Aboulkheyr Es, H, Aref, AR & Warkiani, ME 2022, 'Generation and Culture of Organotypic Breast Carcinoma Spheroids for the Study of Drug Response in a 3D Microfluidic Device', Methods in Molecular Biology, vol. 2535, pp. 49-57.
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Breast cancer (BC) is a leading cause of cancer death among women worldwide. To better understand and predict therapeutic response in BC patient developing a fast, low-cost, and reliable preclinical tumor from patient's tumor specimen is needed. Here, we describe the development of a preclinical model of BC through the generation and ex vivo culture of patient-derived organotypic tumor spheroids (PDOTS) in a 3D microfluidic device. Moreover, the real-time screening of conventional chemotherapy agents on cultured PDOTS is also described.
Afrose, D, Chen, H, Ranashinghe, A, Liu, C-C, Henessy, A, Hansbro, PM & McClements, L 2022, 'The diagnostic potential of oxidative stress biomarkers for preeclampsia: systematic review and meta-analysis', Biology of Sex Differences, vol. 13, no. 1, p. 26.
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Abstract Background Preeclampsia is a multifactorial cardiovascular disorder of pregnancy. If left untreated, it can lead to severe maternal and fetal outcomes. Hence, timely diagnosis and management of preeclampsia are extremely important. Biomarkers of oxidative stress are associated with the pathogenesis of preeclampsia and therefore could be indicative of evolving preeclampsia and utilized for timely diagnosis. In this study, we conducted a systematic review and meta-analysis to determine the most reliable oxidative stress biomarkers in preeclampsia, based on their diagnostic sensitivities and specificities as well as their positive and negative predictive values. Methods A systematic search using PubMed, ScienceDirect, ResearchGate, and PLOS databases (1900 to March 2021) identified nine relevant studies including a total of 343 women with preeclampsia and 354 normotensive controls. Results Ischemia-modified albumin (IMA), uric acid (UA), and malondialdehyde (MDA) were associated with 3.38 (95% CI 2.23, 4.53), 3.05 (95% CI 2.39, 3.71), and 2.37 (95% CI 1.03, 3.70) odds ratios for preeclampsia diagnosis, respectively. The IMA showed the most promising diagnostic potential with the positive predictive ratio (PPV) of 0.852 (95% CI 0.728, 0.929) and negative predictive ratio (NPV) of 0.811 (95% CI 0.683, 0.890) for preeclampsia. Minor between-study heterogeneity was reported for these biomarkers (Higgins’ I2 = 0–15.879%). Conclusions This systematic review and meta-analysis identifie...
Alghalayini, A, Cranfield, CG, Cornell, BA & Valenzuela, SM 2022, 'Preparing Ion Channel Switch Membrane-Based Biosensors', Methods in Molecular Biology, vol. 2402, pp. 13-20.
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Monitoring the changes in membrane conductance using electrical impedance spectroscopy is the platform of membrane-based biosensors in order to detect a specific target molecule. These biosensors represent the amalgamation of an electrical conductor such as gold and a chemically tethered bilayer lipid membrane with specific incorporated ion channels such as gramicidin-A that is further functionalized with detector molecules of interest.
Asadniaye Fardjahromi, M, Nazari, H, Ahmadi Tafti, SM, Razmjou, A, Mukhopadhyay, S & Warkiani, ME 2022, 'Metal-organic framework-based nanomaterials for bone tissue engineering and wound healing', Materials Today Chemistry, vol. 23, pp. 100670-100670.
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Over the past decade, tremendous growth has been witnessed in the synthesis of scaffolds fabricated by natural or synthetic, composite, or hybrid biomaterials to enhance wound healing, repair of bone fractures, and pathological loss of bones. However, the current limitations of using these scaffolds in tissue engineering are impaired cellular proliferation, poor differentiation, low mechanical stability, and bioactivity. Recent advances in the fabrication of nanoscale metal-organic framework (nano-MOF) scaffolds have provided golden opportunities to enhance the properties of scaffolds in bone and wound tissue engineering. In the past few years, studies have shown that incorporating nano-MOFs into scaffolds can be highly favorable in the regeneration of imperfect tissues owing to their unique properties such as high internal surface areas, high porosity, good mechanical stability, biocompatibility, and tunability. Moreover, the nanoscale structural and topological properties of nano-MOFs enhance the physicochemical properties of scaffolds, enrich them with drug-loading and ion-releasing capacity, and regulate stem cell attachment, proliferation, and differentiation after transplantation. This review initially introduces the various nano-MOFs incorporated into scaffolds for tissue engineering. Recent applications of nanoMOFs for bone and wound healing are comprehensively discussed. The unique properties of nano-MOFs for improving osteoconductivity, osteoinductivity, and wound healing, such as high antibacterial activity, high drug loading capacity (i.e., bioactive molecules and growth factors), and controlled drug release, are discussed. Finally, challenges, clinical barriers, and considerations for implementing these nanomaterials in different scaffolds, tissue-like structures, implants, fillers, and dressers in the orthopedic and wound clinics are comprised.
Augustine, R, S, A, Nayeem, A, Salam, SA, Augustine, P, Dan, P, Maureira, P, Mraiche, F, Gentile, C, Hansbro, PM, McClements, L & Hasan, A 2022, 'Increased complications of COVID-19 in people with cardiovascular disease: Role of the renin–angiotensin-aldosterone system (RAAS) dysregulation', Chemico-Biological Interactions, vol. 351, pp. 109738-109738.
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The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19), has had a dramatic negative impact on public health and economies worldwide. Recent studies on COVID-19 complications and mortality rates suggest that there is a higher prevalence in cardiovascular diseases (CVD) patients. Past investigations on the associations between pre-existing CVDs and susceptibility to coronavirus infections including SARS-CoV and the Middle East Respiratory Syndrome coronavirus (MERS-CoV), have demonstrated similar results. However, the underlying mechanisms are poorly understood. This has impeded adequate risk stratification and treatment strategies for CVD patients with SARS-CoV-2 infections. Generally, dysregulation of the expression of angiotensin-converting enzyme (ACE) and the counter regulator, angiotensin-converting enzyme 2 (ACE2) is a hallmark of cardiovascular risk and CVD. ACE2 is the main host receptor for SARS-CoV-2. Although further studies are required, dysfunction of ACE2 after virus binding and dysregulation of the renin-angiotensin-aldosterone system (RAAS) signaling may worsen the outcomes of people affected by COVID-19 and with preexisting CVD. Here, we review the current knowledge and outline the gaps related to the relationship between CVD and COVID-19 with a focus on the RAAS. Improved understanding of the mechanisms regulating viral entry and the role RAAS may direct future research with the potential to improve the prevention and management of COVID-19.
Bordhan, P, Razavi Bazaz, S, Jin, D & Ebrahimi Warkiani, M 2022, 'Advances and enabling technologies for phase-specific cell cycle synchronisation', Lab on a Chip, vol. 22, no. 3, pp. 445-462.
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Schematic illustration of conventional (left) and microfluidics-based (right) phase-specific cell cycle synchronization strategies.
Bradbury, P, Cidem, A, Mahmodi, H, Davies, JM, Spicer, PT, Prescott, SW, Kabakova, I, Ong, HX & Traini, D 2022, 'Timothy Grass Pollen Induces Spatial Reorganisation of F-Actin and Loss of Junctional Integrity in Respiratory Cells', Inflammation, vol. 45, no. 3, pp. 1209-1223.
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Grass pollens have been identified as mediators of respiratory distress, capable of exacerbating respiratory diseases including epidemic thunderstorm asthma (ETSA). It is hypothesised that during thunderstorms, grass pollen grains swell to absorb atmospheric water, rupture, and release internal protein content to the atmosphere. The inhalation of atmospheric grass pollen proteins results in deadly ETSA events. We sought to identify the underlying cellular mechanisms that may contribute towards the severity of ETSA in temperate climates using Timothy grass (Phleum pratense). Respiratory cells exposed to Timothy grass pollen protein extract (PPE) caused cells to undergo hypoxia ultimately triggering the subcellular re-organisation of F-actin from the peri junctional belt to cytoplasmic fibre assembly traversing the cell body. This change in actin configuration coincided with the spatial reorganisation of microtubules and importantly, decreased cell compressibility specifically at the cell centre. Further to this, we find that the pollen-induced reorganisation of the actin cytoskeleton prompting secretion of the pro-inflammatory cytokine, interleukin-8. In addition, the loss of peri-junctional actin following exposure to pollen proteins was accompanied by the release of epithelial transmembrane protein, E-cadherin from cell-cell junctions resulting in a decrease in epithelial barrier integrity. We demonstrate that Timothy grass pollen regulates F-actin dynamics and E-cadherin localisation in respiratory cells to mediate cell-cell junctional integrity highlighting a possible molecular pathway underpinning ETSA events.
Chen, C & Jin, D 2022, 'Giant nonlinearity in upconversion nanoparticles', Nature Photonics, vol. 16, no. 8, pp. 553-554.
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Chen, H, Aneman, I, Nikolic, V, Karadzov Orlic, N, Mikovic, Z, Stefanovic, M, Cakic, Z, Jovanovic, H, Town, SEL, Padula, MP & McClements, L 2022, 'Maternal plasma proteome profiling of biomarkers and pathogenic mechanisms of early-onset and late-onset preeclampsia', Scientific Reports, vol. 12, no. 1, p. 19099.
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AbstractPreeclampsia is still the leading cause of morbidity and mortality in pregnancy without a cure. There are two phenotypes of preeclampsia, early-onset (EOPE) and late-onset (LOPE) with poorly defined pathogenic differences. This study aimed to facilitate better understanding of the mechanisms of pathophysiology of EOPE and LOPE, and identify specific biomarkers or therapeutic targets. In this study, we conducted an untargeted, label-free quantitative proteomic analyses of plasma samples from pregnant women with EOPE (n = 17) and LOPE (n = 11), and age, BMI-matched normotensive controls (n = 18). Targeted proteomics approach was also employed to validate a subset of proteins (n = 17). In total, there were 26 and 20 differentially abundant proteins between EOPE or LOPE, and normotensive controls, respectively. A series of angiogenic and inflammatory proteins, including insulin-like growth factor-binding protein 4 (IGFBP4; EOPE: FDR = 0.0030 and LOPE: FDR = 0.00396) and inter-alpha-trypsin inhibitor heavy chain H2-4 (ITIH2-4), were significantly altered in abundance in both phenotypes. Through validation we confirmed that ITIH2 was perturbed only in LOPE (p = 0.005) whereas ITIH3 and ITIH4 were perturbed in both phenotypes (p < 0.05). Overall, lipid metabolism/transport proteins associated with atherosclerosis were highly abundant in LOPE, however, ECM proteins had a more pronounced role in EOPE. The complement cascade and binding and uptake of ligands by scavenger receptors, pathways, were associated with both EOPE and LOPE.
Chen, H, Tesic, M, Nikolic, VN, Pavlovic, M, Vucic, RM, Spasic, A, Jovanovic, H, Jovanovic, I, Town, SEL, Padula, MP & McClements, L 2022, 'Systemic Biomarkers and Unique Pathways in Different Phenotypes of Heart Failure with Preserved Ejection Fraction', Biomolecules, vol. 12, no. 10, pp. 1419-1419.
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Heart failure with preserved ejection fraction (HFpEF) accounts for around 50% of all heart failure cases. It is a heterogeneous condition with poorly understood pathogenesis. Here, we aimed to identify unique pathogenic mechanisms in acute and chronic HFpEF and hypertrophic cardiomyopathy (HCM). We performed unbiased, comprehensive proteomic analyses of plasma samples from gender- and BMI-matched patients with acute HFpEF (n = 8), chronic HFpEF (n = 9) and HCM (n = 14) using liquid chromatography–mass spectrometry. Distinct molecular signatures were observed in different HFpEF forms. Clusters of biomarkers differentially abundant between HFpEF forms were predominantly associated with microvascular inflammation. New candidate protein markers were also identified, including leucine-rich alpha-2-glycoprotein 1 (LRG1), serum amyloid A1 (SAA1) and inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3). Our study is the first to apply systematic, quantitative proteomic screening of plasma samples from patients with different subtypes of HFpEF and identify candidate biomarkers for improved management of acute and chronic HFpEF and HCM.
Chen, J, Yao, B, Yang, Z, Shi, W, Luo, T, Xi, P, Jin, D & Li, Y 2022, 'Ratiometric 4Pi single-molecule localization with optimal resolution and color assignment', Optics Letters, vol. 47, no. 2, pp. 325-325.
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4Pi single-molecule localization microscopy (4Pi-SMLM) with two opposing objectives achieves sub-10 nm isotropic 3D resolution when as few as 250 photons are collected by each objective. Here, we develop a new ratiometric multi-color imaging strategy for 4Pi-SMLM that employs the intrinsic multi-phase interference intensity without increasing the complexity of the system and achieves both optimal 3D resolution and color separation. By partially linking the photon parameters between channels with an interference difference of π during global fitting of the multi-channel 4Pi single-molecule data, we show via simulated data that the loss of localization precision is minimal compared with the theoretical minimum uncertainty, the Cramer–Rao lower bound.
Chen, Y, Shimoni, O, Huang, G, Wen, S, Liao, J, Duong, HTT, Maddahfar, M, Su, QP, Ortega, DG, Lu, Y, Campbell, DH, Walsh, BJ & Jin, D 2022, 'Upconversion nanoparticle‐assisted single‐molecule assay for detecting circulating antigens of aggressive prostate cancer', Cytometry Part A, vol. 101, no. 5, pp. 400-410.
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AbstractSensitive and quantitative detection of molecular biomarkers is crucial for the early diagnosis of diseases like metabolic syndrome and cancer. Here we present a single‐molecule sandwich immunoassay by imaging the number of single nanoparticles to diagnose aggressive prostate cancer. Our assay employed the photo‐stable upconversion nanoparticles (UCNPs) as labels to detect the four types of circulating antigens in blood circulation, including glypican‐1 (GPC‐1), leptin, osteopontin (OPN), and vascular endothelial growth factor (VEGF), as their serum concentrations indicate aggressive prostate cancer. Under a wide‐field microscope, a single UCNP doped with thousands of lanthanide ions can emit sufficiently bright anti‐Stokes' luminescence to become quantitatively detectable. By counting every single streptavidin‐functionalized UCNP which specifically labeled on each sandwich immune complex across multiple fields of views, we achieved the Limit of Detection (LOD) of 0.0123 ng/ml, 0.2711 ng/ml, 0.1238 ng/ml, and 0.0158 ng/ml for GPC‐1, leptin, OPN and VEGF, respectively. The serum circulating level of GPC‐1, leptin, OPN, and VEGF in a mixture of 10 healthy normal human serum was 25.17 ng/ml, 18.04 ng/ml, 11.34 ng/ml, and 1.55 ng/ml, which was within the assay dynamic detection range for each analyte. Moreover, a 20% increase of GPC‐1 and OPN was observed by spiking the normal human serum with recombinant antigens to confirm the accuracy of the assay. We observed no cross‐reactivity among the four biomarker analytes, which eliminates the false positives and enhances the detection accuracy. The developed single upconversion nanoparticle‐assisted single‐molecule assay suggests its potential in clinical usage for prostate cancer detection by monitoring tiny concentration differences in a panel of serum biomarkers.
Cranfield, CG, Le Brun, AP, Garcia, A, Cornell, BA & Holt, SA 2022, 'Langmuir-Schaefer Deposition to Create an Asymmetrical Lipopolysaccharide Sparsely Tethered Lipid Bilayer', Methods in Molecular Biology, vol. 2402, pp. 21-30.
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Because they are firmly anchored to a noble metal substrate, tethered bilayer lipid membranes (tBLMs) are considerably more robust than supported lipid bilayers such as black lipid membranes (BLMs) (Cranfield et al. Biophys J 106:182-189, 2014). The challenge to rapidly create asymmetrical tBLMs that include a lipopolysaccharide outer leaflet for bacterial model membrane research can be overcome by the use of a Langmuir-Schaefer deposition protocol. Here, we describe the procedures required to assemble and test asymmetric lipopolysaccharide (LPS) tethered lipid bilayers.
Di, X, Wang, D, Su, QP, Liu, Y, Liao, J, Maddahfar, M, Zhou, J & Jin, D 2022, 'Spatiotemporally mapping temperature dynamics of lysosomes and mitochondria using cascade organelle-targeting upconversion nanoparticles', Proceedings of the National Academy of Sciences, vol. 119, no. 45, p. e2207402119.
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The intracellular metabolism of organelles, like lysosomes and mitochondria, is highly coordinated spatiotemporally and functionally. The activities of lysosomal enzymes significantly rely on the cytoplasmic temperature, and heat is constantly released by mitochondria as the byproduct of adenosine triphosphate (ATP) generation during active metabolism. Here, we developed temperature-sensitive LysoDots and MitoDots to monitor the in situ thermal dynamics of lysosomes and mitochondria. The design is based on upconversion nanoparticles (UCNPs) with high-density surface modifications to achieve the exceptionally high sensitivity of 2.7% K −1 and low uncertainty of 0.8 K for nanothermometry to be used in living cells. We show the measurement is independent of the ion concentrations and pH values. With Ca 2+ ion shock, the temperatures of both lysosomes and mitochondria increased by ∼2 to 4 °C. Intriguingly, with chloroquine (CQ) treatment, the lysosomal temperature was observed to decrease by up to ∼3 °C, while mitochondria remained relatively stable. Lastly, with oxidative phosphorylation inhibitor treatment, we observed an ∼3 to 7 °C temperature increase and a thermal transition from mitochondria to lysosomes. These observations indicate different metabolic pathways and thermal transitions between lysosomes and mitochondria inside HeLa cells. The nanothermometry probes provide a powerful tool for multimodality functional imaging of subcellular organelles and interactions with high spatial, temporal, and thermal dynamics resolutions.
Ding, L, Razavi Bazaz, S, Asadniaye Fardjahromi, M, McKinnirey, F, Saputro, B, Banerjee, B, Vesey, G & Ebrahimi Warkiani, M 2022, 'A modular 3D printed microfluidic system: a potential solution for continuous cell harvesting in large-scale bioprocessing', Bioresources and Bioprocessing, vol. 9, no. 1.
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AbstractMicrofluidic devices have shown promising applications in the bioprocessing industry. However, the lack of modularity and high cost of testing and error limit their implementation in the industry. Advances in 3D printing technologies have facilitated the conversion of microfluidic devices from research output to applicable industrial systems. Here, for the first time, we presented a 3D printed modular microfluidic system consisting of two micromixers, one spiral microfluidic separator, and one microfluidic concentrator. We showed that this system can detach and separate mesenchymal stem cells (MSCs) from microcarriers (MCs) in a short time while maintaining the cell’s viability and functionality. The system can be multiplexed and scaled up to process large volumes of the industry. Importantly, this system is a closed system with no human intervention and is promising for current good manufacturing practices. Graphical Abstract
Ding, L, Razavi Bazaz, S, Hall, T, Vesey, G & Ebrahimi Warkiani, M 2022, 'Giardia purification from fecal samples using rigid spiral inertial microfluidics', Biomicrofluidics, vol. 16, no. 1, pp. 014105-014105.
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Giardia is one of the most common waterborne pathogens causing around 200 × 106 diarrheal infections annually. It is of great interest to microbiological research as it is among the oldest known eukaryotic cells. Purifying Giardia from fecal samples for both research and diagnostic purposes presents one of the most difficult challenges. Traditional purification methods rely on density gradient centrifugation, membrane-based filtration, and sedimentation methods, which suffer from low recovery rates, high costs, and poor efficiency. Here, we report on the use of microfluidics to purify Giardia cysts from mouse feces. We propose a rigid spiral microfluidic device with a trapezoidal cross section to effectively separate Giardia from surrounding debris. Our characterizations reveal that the recovery rate is concentration-dependent, and our proposed device can achieve recovery rates as high as 75% with 0.75 ml/min throughput. Moreover, this device can purify Giardia from extremely turbid samples to a level where cysts are visually distinguishable with just one round of purification. This highly scalable and versatile 3D printed microfluidic device is then capable of further purifying or enhancing the recovery rate of the samples by recirculation. This device also has the potential to purify other gastrointestinal pathogens of similar size, and throughput can be significantly increased by parallelization.
Ding, L, Razavi Bazaz, S, Shrestha, J, A. Amiri, H, Mas-hafi, S, Banerjee, B, Vesey, G, Miansari, M & Ebrahimi Warkiani, M 2022, 'Rapid and Continuous Cryopreservation of Stem Cells with a 3D Micromixer', Micromachines, vol. 13, no. 9, pp. 1516-1516.
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Cryopreservation is the final step of stem cell production before the cryostorage of the product. Conventional methods of adding cryoprotecting agents (CPA) into the cells can be manual or automated with robotic arms. However, challenging issues with these methods at industrial-scale production are the insufficient mixing of cells and CPA, leading to damage of cells, discontinuous feeding, the batch-to-batch difference in products, and, occasionally, cross-contamination. Therefore, the current study proposes an alternative way to overcome the abovementioned challenges; a highly efficient micromixer for low-cost, continuous, labour-free, and automated mixing of stem cells with CPA solutions. Our results show that our micromixer provides a more homogenous mixing of cells and CPA compared to the manual mixing method, while the cell properties, including surface markers, differentiation potential, proliferation, morphology, and therapeutic potential, are well preserved.
Ding, L, Shan, X, Wang, D, Liu, B, Du, Z, Di, X, Chen, C, Maddahfar, M, Zhang, L, Shi, Y, Reece, P, Halkon, B, Aharonovich, I, Xu, X & Wang, F 2022, 'Lanthanide Ion Resonance‐Driven Rayleigh Scattering of Nanoparticles for Dual‐Modality Interferometric Scattering Microscopy', Advanced Science, vol. 9, no. 32, pp. e2203354-2203354.
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AbstractLight scattering from nanoparticles is significant in nanoscale imaging, photon confinement. and biosensing. However, engineering the scattering spectrum, traditionally by modifying the geometric feature of particles, requires synthesis and fabrication with nanometre accuracy. Here it is reported that doping lanthanide ions can engineer the scattering properties of low‐refractive‐index nanoparticles. When the excitation wavelength matches the ion resonance frequency of lanthanide ions, the polarizability and the resulted scattering cross‐section of nanoparticles are dramatically enhanced. It is demonstrated that these purposely engineered nanoparticles can be used for interferometric scattering (iSCAT) microscopy. Conceptually, a dual‐modality iSCAT microscopy is further developed to identify different nanoparticle types in living HeLa cells. The work provides insight into engineering the scattering features by doping elements in nanomaterials, further inspiring exploration of the geometry‐independent scattering modulation strategy.
dos Remedios, C, Cranfield, C, Whelan, D, Cox, C, Shearwin, K, Ho, J, Allen, T, Shibuya, R, Hibino, E, Hayashi, K & Li, A 2022, 'A special issue of the Australian society for Biophysics', Biophysical Reviews, vol. 14, no. 1, pp. 1-2.
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Elsemary, MT, Maritz, MF, Smith, LE, Warkiani, M, Bandara, V, Napoli, S, Barry, SC, Coombs, JT & Thierry, B 2022, 'Inertial Microfluidic Purification of CAR‐T‐Cell Products', Advanced Biology, vol. 6, no. 1, pp. e2101018-e2101018.
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AbstractChimeric antigen receptor T (CAR‐T) cell therapy is rapidly becoming a frontline cancer therapy. However, the manufacturing process is time‐, labor‐ and cost‐intensive, and it suffers from significant bottlenecks. Many CAR‐T products fail to reach the viability release criteria set by regulators for commercial cell therapy products. This results in non‐recoupable costs for the manufacturer and is detrimental to patients who may not receive their scheduled treatment or receive out‐of‐specification suboptimal formulation. It is demonstrated here that inertial microfluidics can, within minutes, efficiently deplete nonviable cells from low‐viability CAR‐T cell products. The percentage of viable cells increases from 40% (SD ± 0.12) to 71% (SD ± 0.09) for untransduced T cells and from 51% (SD ± 0.12) to 71% (SD ± 0.09) for CAR‐T cells, which meets the clinical trials’ release parameters. In addition, the processing of CAR‐T cells formulated in CryStor yields a 91% reduction in the amount of the cryoprotectant dimethyl sulfoxide. Inertial microfluidic processing has no detrimental effects on the proliferation and cytotoxicity of CAR‐T cells. Interestingly, ≈50% of T‐regulatory and T‐suppressor cells are depleted, suggesting the potential for inertial microfluidic processing to tune the phenotypical composition of T‐cell products.
Fang, G, Lu, H, Al-Nakashli, R, Chapman, R, Zhang, Y, Ju, LA, Lin, G, Stenzel, MH & Jin, D 2022, 'Enabling peristalsis of human colon tumor organoids on microfluidic chips', Biofabrication, vol. 14, no. 1, pp. 015006-015006.
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Abstract Peristalsis in the digestive tract is crucial to maintain physiological functions. It remains challenging to mimic the peristaltic microenvironment in gastrointestinal organoid culture. Here, we present a method to model the peristalsis for human colon tumor organoids on a microfluidic chip. The chip contains hundreds of lateral microwells and a surrounding pressure channel. Human colon tumor organoids growing in the microwell were cyclically contracted by pressure channel, mimicking the in vivo mechano-stimulus by intestinal muscles. The chip allows the control of peristalsis amplitude and rhythm and the high throughput culture of organoids simultaneously. By applying 8% amplitude with 8 ∼ 10 times min−1, we observed the enhanced expression of Lgr5 and Ki67. Moreover, ellipticine-loaded polymeric micelles showed reduced uptake in the organoids under peristalsis and resulted in compromised anti-tumor efficacy. The results indicate the importance of mechanical stimuli mimicking the physiological environment when using in vitro models to evaluate nanoparticles. This work provides a method for attaining more reliable and representative organoids models in nanomedicine.
Fernandez, TT, Johnston, B, Gross, S, Cozic, S, Poulain, M, Mahmodi, H, Kabakova, I, Withford, M & Fuerbach, A 2022, 'Ultrafast laser inscribed waveguides in tailored fluoride glasses: an enabling technology for mid-infrared integrated photonics devices', Scientific Reports, vol. 12, no. 1, p. 14674.
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AbstractZirconium fluoride (ZBLAN) glass, the standard material used in fiber-based mid-infrared photonics, has been re-designed to enable the fabrication of high index-contrast low-loss waveguides via femtosecond laser direct writing. We demonstrate that in contrast to pure ZBLAN, a positive index change of close to 10−2 can be induced in hybrid zirconium/hafnium (Z/HBLAN) glasses during ultrafast laser inscription and show that this can be explained by an electron cloud distortion effect that is driven by the existence of two glass formers with contrasting polarizability. High numerical aperture (NA) type-I waveguides that support a well confined 3.1 μm wavelength mode with a mode-field diameter (MFD) as small as 12 μm have successfully been fabricated. These findings open the door for the fabrication of mid-infrared integrated photonic devices that can readily be pigtailed to existing ZBLAN fibers.
Fernandez, TT, Johnston, B, Mahmodi, H, Privat, K, Kabakova, I, Gross, S, Withford, M & Fuerbach, A 2022, 'Thermally stable high numerical aperture integrated waveguides and couplers for the 3 μm wavelength range', APL Photonics, vol. 7, no. 12, pp. 126106-126106.
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The femtosecond laser direct write technique was used to fabricate mid-infrared compatible waveguide couplers into Suprasil 3001, a fused silica glass with an OH content of as low as ≤1 ppm. Smooth positive step-index change multi-scan waveguides were produced with a high index contrast of 1 × 10−2, measured directly using quadriwave lateral shearing interferometry. Waveguides were annealed at 400 °C for 15 h and found to be highly stable, with only <5% reduction in positive index change. Brillouin microscopy and cathodoluminescence are introduced as novel tools that complement Raman mapping and electron microscopy for the investigation of the laser-induced structural changes within the glass matrix, and it was found that although a uniform step index profile is observed across the entire guiding region, different physical mechanisms underpin the index change in the upper and lower sections of the waveguide cross-section, respectively. Waveguides were optimized for mode-matching with optical fibers for the 3.2 μm wavelength range, and evanescent four-port directional couplers with coupling ratios ranging from 5:95 to 50:50 were designed and fabricated. This demonstration opens the door to the development of fully integrated and temperature-stable hybrid chip/fiber systems for the important mid-infrared spectral range.
Francis, I, Shrestha, J, Paudel, KR, Hansbro, PM, Warkiani, ME & Saha, SC 2022, 'Recent advances in lung-on-a-chip models', Drug Discovery Today, vol. 27, no. 9, pp. 2593-2602.
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Fu, L, Shi, B, Wen, S, Morsch, M, Wang, G, Zhou, Z, Mi, C, Sadraeian, M, Lin, G, Lu, Y, Jin, D & Chung, R 2022, 'Aspect Ratio of PEGylated Upconversion Nanocrystals Affects the Cellular Uptake In Vitro and In Vivo', Acta Biomaterialia, vol. 147, pp. 403-413.
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The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a physical barrier to regulate and prevent the uptake of endogenous metabolites and xenobiotics. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. Therefore, there is considerable interest in identifying drug carriers that can maintain the biostability of therapeutic molecules and target their transport across the BBB. In this regard, upconversion nanoparticles (UCNPs) have become popular as a nanoparticle-based solution to this problem, with the additional benefit that they display unique properties for in vivo visualization. The majority of studies to date have explored basic spherical UCNPs for drug delivery applications. However, the biophysical properties of UCNPs, cell uptake and BBB transport have not been thoroughly investigated. In this study, we described a one-pot seed-mediated approach to precisely control longitudinal growth to produce bright UCNPs with various aspect ratios. We have systematically evaluated the effects of the physical aspect ratios and PEGylation of UCNPs on cellular uptake in different cell lines and an in vivo zebrafish model. We found that PEGylated the original UCNPs can enhance their biostability and cell uptake capacity. We identify an optimal aspect ratio for UCNP uptake into several different types of cultured cells, finding that this is generally in the ratio of 2 (length/width). This data provides a crucial clue for further optimizing UCNPs as a drug carrier to deliver therapeutic agents into the CNS. STATEMENT OF SIGNIFICANCE: The central nervous system (CNS) is protected by the blood-brain barrier (BBB), which acts as a highly selective semipermeable barrier of endothelial cells to regulate and prevent the uptake of toxins and pathogens. However, the BBB prevents most non-lipophilic drugs from reaching the CNS following systematic administration. The proposed...
Ghalehno, AD, Saeedi, M, Bazaz, SR, Asadi, P, EbrahimiWarkiani, M & Yazdian-Robati, R 2022, 'Nano aptasensors for detection of streptomycin: A review', Nanomedicine Journal, vol. 9, no. 1, pp. 24-33.
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This review provides a literature update of the progress in optical and electrochemical aptasensors for the detection of streptomycin in human sera and animal-derived foods. The uncontrolled use of antibiotics and rising resistance to them, has created a global problem. Therefore, the detection and quantitation of antibiotics, i.e., streptomycin by robust, easy, and sensitive methods is in great demand. Among different strategies, new analytical methods for the efficient detection and quantitative determination of streptomycin have been developed. Aptasensors or aptamer-based biosensors have attracted more attention due to their unique recognition, simple fabrication, and significant selectivity, sensitivity, and specificity. Advantages of aptasensors will be highlighted in this review, with emphasis on methodological technique and specific properties of aptasensors developed for STR determination. In this review paper, we will focus on the recent development of aptasensors for streptomycin detection, considering the papers summarized in the data bases scopus and google scholar covering the period of time from 2013 till 2021.
Ghalehno, AD, Saeedi, M, Bazaz, SR, Asadi, P, EbrahimiWarkiani, M & Yazdian-Robati, R 2022, 'Nano aptasensors for detection of streptomycin: A review', NANOMEDICINE JOURNAL, vol. 9, no. 1, pp. 24-33.
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This review provides a literature update of the progress in optical and electrochemical aptasensors for the detection of streptomycin in human sera and animal-derived foods. The uncontrolled use of antibiotics and rising resistance to them, has created a global problem. Therefore, the detection and quantitation of antibiotics, i.e., streptomycin by robust, easy, and sensitive methods is in great demand. Among different strategies, new analytical methods for the efficient detection and quantitative determination of streptomycin have been developed. Aptasensors or aptamer-based biosensors have attracted more attention due to their unique recognition, simple fabrication, and significant selectivity, sensitivity, and specificity. Advantages of aptasensors will be highlighted in this review, with emphasis on methodological technique and specific properties of aptasensors developed for STR determination. In this review paper, we will focus on the recent development of aptasensors for streptomycin detection, considering the papers summarized in the data bases scopus and google scholar covering the period of time from 2013 till 2021.
Guan, M, Wang, M, Zhanghao, K, Zhang, X, Li, M, Liu, W, Niu, J, Yang, X, Chen, L, Jing, Z, Zhang, MQ, Jin, D, Xi, P & Gao, J 2022, 'Polarization modulation with optical lock-in detection reveals universal fluorescence anisotropy of subcellular structures in live cells', Light: Science & Applications, vol. 11, no. 1, p. 4.
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AbstractThe orientation of fluorophores can reveal crucial information about the structure and dynamics of their associated subcellular organelles. Despite significant progress in super-resolution, fluorescence polarization microscopy remains limited to unique samples with relatively strong polarization modulation and not applicable to the weak polarization signals in samples due to the excessive background noise. Here we apply optical lock-in detection to amplify the weak polarization modulation with super-resolution. This novel technique, termed optical lock-in detection super-resolution dipole orientation mapping (OLID-SDOM), could achieve a maximum of 100 frames per second and rapid extraction of 2D orientation, and distinguish distance up to 50 nm, making it suitable for monitoring structural dynamics concerning orientation changes in vivo. OLID-SDOM was employed to explore the universal anisotropy of a large variety of GFP-tagged subcellular organelles, including mitochondria, lysosome, Golgi, endosome, etc. We found that OUF (Orientation Uniformity Factor) of OLID-SDOM can be specific for different subcellular organelles, indicating that the anisotropy was related to the function of the organelles, and OUF can potentially be an indicator to distinguish normal and abnormal cells (even cancer cells). Furthermore, dual-color super-resolution OLID-SDOM imaging of lysosomes and actins demonstrates its potential in studying dynamic molecular interactions. The subtle anisotropy changes of expanding and shrinking dendritic spines in live neurons were observed with real-time OLID-SDOM. Revealing previously unobservable fluorescence anisotropy in various samples and indicating their underlying dynamic molecular structural changes, OLID-SDOM expands the toolkit for live cell research.
Hanaei, S, Takian, A, Majdzadeh, R, Maboloc, CR, Grossmann, I, Gomes, O, Milosevic, M, Gupta, M, Shamshirsaz, AA, Harbi, A, Burhan, AM, Uddin, LQ, Kulasinghe, A, Lam, C-M, Ramakrishna, S, Alavi, A, Nouwen, JL, Dorigo, T, Schreiber, M, Abraham, A, Shelkovaya, N, Krysztofiak, W, Ebrahimi Warkiani, M, Sellke, F, Ogino, S, Barba, FJ, Brand, S, Vasconcelos, C, Salunke, DB & Rezaei, N 2022, 'Emerging Standards and the Hybrid Model for Organizing Scientific Events During and After the COVID-19 Pandemic', Disaster Medicine and Public Health Preparedness, vol. 16, no. 3, pp. 1172-1177.
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AbstractSince the beginning of 2020, the coronavirus disease (COVID-19) pandemic has dramatically influenced almost every aspect of human life. Activities requiring human gatherings have either been postponed, canceled, or held completely virtually. To supplement lack of in-person contact, people have increasingly turned to virtual settings online, advantages of which include increased inclusivity and accessibility and a reduced carbon footprint. However, emerging online technologies cannot fully replace in-person scientific events. In-person meetings are not susceptible to poor Internet connectivity problems, and they provide novel opportunities for socialization, creating new collaborations and sharing ideas. To continue such activities, a hybrid model for scientific events could be a solution offering both in-person and virtual components. While participants can freely choose the mode of their participation, virtual meetings would most benefit those who cannot attend in-person due to the limitations. In-person portions of meetings should be organized with full consideration of prevention and safety strategies, including risk assessment and mitigation, venue and environmental sanitation, participant protection and disease prevention, and promoting the hybrid model. This new way of interaction between scholars can be considered as a part of a resilience system, which was neglected previously and should become a part of routine practice in the scientific community.
Hartmann, LM, Garcia, A, Deplazes, E & Cranfield, CG 2022, 'Determining the Pore Size of Multimeric Peptide Ion Channels Using Cation Conductance Measures of Tethered Bilayer Lipid Membranes', pp. 81-92.
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Hossain, KR, Escobar Bermeo, JD, Warton, K & Valenzuela, SM 2022, 'New Approaches and Biomarker Candidates for the Early Detection of Ovarian Cancer', Frontiers in Bioengineering and Biotechnology, vol. 10, p. 819183.
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Hu, B, Bao, G, Xu, X & Yang, K 2022, 'Topical hemostatic materials for coagulopathy', Journal of Materials Chemistry B, vol. 10, no. 12, pp. 1946-1959.
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We present a thorough analysis on the hemostatic mechanisms and the design principles of hemostatic materials for coagulopathy, survey their remarkable success, and briefly discuss the challenges and perspectives for their clinical translation.
Huang, G, Zhu, Y, Wen, S, Mei, H, Liu, Y, Wang, D, Maddahfar, M, Su, QP, Lin, G, Chen, Y & Jin, D 2022, 'Single Small Extracellular Vesicle (sEV) Quantification by Upconversion Nanoparticles', Nano Letters, vol. 22, no. 9, pp. 3761-3769.
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Cancer-derived small extracellular vesicles (sEVs) are potential circulating biomarkers in liquid biopsies. However, their small sizes, low abundance, and heterogeneity in molecular makeups pose major technical challenges for detecting and characterizing them quantitatively. Here, we demonstrate a single-sEV enumeration platform using lanthanide-doped upconversion nanoparticles (UCNPs). Taking advantage of the unique optical properties of UCNPs and the background-eliminating property of total internal reflection fluorescence (TIRF) imaging technique, a single-sEV assay recorded a limit of detection 1.8 × 106 EVs/mL, which was nearly 3 orders of magnitude lower than the standard enzyme-linked immunosorbent assay (ELISA). Its specificity was validated by the difference between EpCAM-positive and EpCAM-negative sEVs. The accuracy of the UCNP-based single-sEV assay was benchmarked with immunomagnetic-beads flow cytometry, showing a high correlation (R2> 0.99). The platform is suitable for evaluating the heterogeneous antigen expression of sEV and can be easily adapted for biomarker discoveries and disease diagnosis.
Johnson, B, Zhuang, L, Rath, EM, Yuen, ML, Cheng, NC, Shi, H, Kao, S, Reid, G & Cheng, YY 2022, 'Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response', Cancers, vol. 14, no. 19, pp. 4784-4784.
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Malignant pleural mesothelioma (MPM) is a deadly thoracic malignancy and existing treatment options are limited. Chemotherapy remains the most widely used first-line treatment regimen for patients with unresectable MPM, but is hampered by drug resistance issues. The current study demonstrated a modest enhancement of MPM cell sensitivity to chemotherapy drug treatment following microRNA (miRNA) transfection in MPM cell lines, albeit not for all tested miRNAs. This effect was more pronounced for FAK (PND-1186) small molecule inhibitor treatment; consistent with previously published data. We previously established that MPM response to survivin (YM155) small molecule inhibitor treatment is unrelated to basal survivin expression. Here, we showed that MPM response to YM155 treatment is enhanced following miRNA transfection of YM155-resistant MPM cells. We determined that YM155-resistant MPM cells secrete a higher level of exosomes in comparison to YM155-sensitive MPM cells. Despite this, an exosome inhibitor (GW4896) did not enhance MPM cell sensitivity to YM155. Additionally, our study showed no evidence of a correlation between the mRNA expression of inhibitor of apoptosis (IAP) gene family members and MPM cell sensitivity to YM155. However, two drug transporter genes, ABCA6 and ABCA10, were upregulated in the MPM cell lines and correlated with poor sensitivity to YM155.
Kapeleris, J, Ebrahimi Warkiani, M, Kulasinghe, A, Vela, I, Kenny, L, Ladwa, R, O’Byrne, K & Punyadeera, C 2022, 'Clinical Applications of Circulating Tumour Cells and Circulating Tumour DNA in Non-Small Cell Lung Cancer—An Update', Frontiers in Oncology, vol. 12, p. 859152.
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Despite efforts to improve earlier diagnosis of non-small cell lung cancer (NSCLC), most patients present with advanced stage disease, which is often associated with poor survival outcomes with only 15% surviving for 5 years from their diagnosis. Tumour tissue biopsy is the current mainstream for cancer diagnosis and prognosis in many parts of the world. However, due to tumour heterogeneity and accessibility issues, liquid biopsy is emerging as a game changer for both cancer diagnosis and prognosis. Liquid biopsy is the analysis of tumour-derived biomarkers in body fluids, which has remarkable advantages over the use of traditional tumour biopsy. Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) are two main derivatives of liquid biopsy. CTC enumeration and molecular analysis enable monitoring of cancer progression, recurrence, and treatment response earlier than traditional biopsy through a minimally invasive liquid biopsy approach. CTC-derived ex-vivo cultures are essential to understanding CTC biology and their role in metastasis, provide a means for personalized drug testing, and guide treatment selection. Just like CTCs, ctDNA provides opportunity for screening, monitoring, treatment evaluation, and disease surveillance. We present an updated review highlighting the prognostic and therapeutic significance of CTCs and ctDNA in NSCLC.
Kapeleris, J, Müller Bark, J, Ranjit, S, Irwin, D, Hartel, G, Warkiani, ME, Leo, P, O'Leary, C, Ladwa, R, O'Byrne, K, Hughes, BGM & Punyadeera, C 2022, 'Prognostic value of integrating circulating tumour cells and cell-free DNA in non-small cell lung cancer', Heliyon, vol. 8, no. 7, pp. e09971-e09971.
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BACKGROUND: Non-small cell lung cancer (NSCLC) often presents at an incurable stage, and majority of patients will be considered for palliative treatment at some point in their disease. Despite recent advances, the prognosis remains poor, with a median overall survival of 12-18 months. Liquid biopsy-based biomarkers have emerged as potential candidates for predicting prognosis and response to therapy in NSCLC patients. This pilot study evaluated whether combining circulating tumour cells and clusters (CTCs) and cell-free DNA (cfDNA) can predict progression-free survival (PFS) in NSCLC patients. METHODS: CTC and cfDNA/ctDNA from advanced stage NSCLC patients were measured at study entry (T0) and 3-months post-treatment (T1). CTCs were enriched using a spiral microfluidic chip and characterised by immunofluorescence. ctDNA was assessed using an UltraSEEK® Lung Panel. Kaplan-Meier plots were generated to investigate the contribution of the presence of CTC/CTC clusters and cfDNA for PFS. Cox proportional hazards analysis compared time to progression versus CTC/CTC cluster counts and cfDNA levels. RESULTS: Single CTCs were found in 14 out of 25 patients, while CTC clusters were found in 8 out of the 25 patients at T0. At T1, CTCs were found in 7 out of 18 patients, and CTC clusters in 1 out of the 18 patients. At T0, CTC presence and the combination of CTC cluster counts with cfDNA levels were associated with shorter PFS, p = 0.0261, p = 0.0022, respectively. CONCLUSIONS: Combining CTC cluster counts and cfDNA levels could improve PFS assessment in NSCLC patients. Our results encourage further investigation on the combined effect of CTC/cfDNA as a prognostic biomarker in a large cohort of advanced stage NSCLC patients.
Khan, JU, Sayyar, S, Jin, D, Paull, B & Innis, PC 2022, 'Surface functionalization of low-cost textile-based microfluidics for manipulation of electrophoretic selectivity of charged analytes', Microfluidics and Nanofluidics, vol. 26, no. 12.
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AbstractTextile-based microfluidics offer new opportunities for developing low-cost, open surface-assessable analytical systems for the electrophoretic analysis of complex chemical and biological matrixes. In contrast to electrophoretic fluidic transport in typical chip-based enclosed capillaries where direct access to the sample zone during analysis is a real challenge. Herein, we demonstrate that electrophoretic selectivity could be easily manipulated on these inverted low-cost bespoke textile substrates via a simple surface-functionalization to manipulate, redirect, extract, and characterize charged analytes. This simple approach enables significant improvement in the electrophoretic separation and isotachophoretic (ITP) preconcentration of charged solutes at the surface of open surface-accessible 3D textile constructs. In this work, polyester 3D braided structures have been developed using the conventional braiding technique and used as the electrophoretic substrates, which were modified by dip-coating with polycationic polymers such as chitosan and polyethyleneimine (PEIn). The surface functionalization resulted in the modulation of the electroosmotic flow (EOF) and electrophoretic mobilities of the charged solutes with respect to the unmodified substrates. Chitosan outperformed PEIn in terms of efficient electrophoretic separation and isotachophoretic stacking of an anionic solute. However, PEIn modification resulted in significant suppression of the EOF over a broad range of pH values from 3 to 9 and exhibited fast EOF at acidic pH compared to controlled polyester, which could be promising for the analysis of basic proteins. These findings suggest a great potential for the development of affordable surface-accessible textile-based analytical devices for controlling the specific migration, direction, analysis time, and separation and preconcentration of charged analytes. ...
Kottek, M & Yuen, ML 2022, 'Public health risks from asbestos cement roofing', American Journal of Industrial Medicine, vol. 65, no. 3, pp. 157-161.
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AbstractThere is no identified risk‐free threshold exposure to asbestos. Based on epidemiology and toxicology, asbestos fiber dimensions have been implicated in causing asbestos‐related diseases. Phase‐contrast microscopy provides only a limited index of exposure to fiber dimensions implicated in mesothelioma induction. Installed asbestos‐containing materials (ACMs) create an ongoing risk of intense exposure during natural disasters and remodeling, along with low‐level exposure arising from the continual emission of airborne asbestos into the environment arising from weathering of installed ACM. Epidemiological studies have demonstrated a risk of disease associated with proximity to asbestos cement roofing (ACR), while ongoing environmental emissions of asbestos from installed ACR have also been demonstrated. Owing to the limitations of the available data, a precautionary approach is warranted; asbestos‐free roofing materials should be used in new construction and existing ACR should be removed at the earliest opportunity.
Law, AMK, Chen, J, Colino‐Sanguino, Y, Fuente, LRDL, Fang, G, Grimes, SM, Lu, H, Huang, RJ, Boyle, ST, Venhuizen, J, Castillo, L, Tavakoli, J, Skhinas, JN, Millar, EKA, Beretov, J, Rossello, FJ, Tipper, JL, Ormandy, CJ, Samuel, MS, Cox, TR, Martelotto, L, Jin, D, Valdes‐Mora, F, Ji, HP & Gallego‐Ortega, D 2022, 'ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo', Advanced Science, vol. 9, no. 21, pp. e2103332-2103332.
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AbstractTo fully investigate cellular responses to stimuli and perturbations within tissues, it is essential to replicate the complex molecular interactions within the local microenvironment of cellular niches. Here, the authors introduce Alginate‐based tissue engineering (ALTEN), a biomimetic tissue platform that allows ex vivo analysis of explanted tissue biopsies. This method preserves the original characteristics of the source tissue's cellular milieu, allowing multiple and diverse cell types to be maintained over an extended period of time. As a result, ALTEN enables rapid and faithful characterization of perturbations across specific cell types within a tissue. Importantly, using single‐cell genomics, this approach provides integrated cellular responses at the resolution of individual cells. ALTEN is a powerful tool for the analysis of cellular responses upon exposure to cytotoxic agents and immunomodulators. Additionally, ALTEN's scalability using automated microfluidic devices for tissue encapsulation and subsequent transport, to enable centralized high‐throughput analysis of samples gathered by large‐scale multicenter studies, is shown.
Liao, J, Yang, L, Wu, S, Yang, Z, Zhou, J, Jin, D & Guan, M 2022, 'NIR-II emissive properties of 808 nm-excited lanthanide-doped nanoparticles for multiplexed in vivo imaging', Journal of Luminescence, vol. 242, pp. 118597-118597.
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The second near-infrared window (1000–1700 nm, NIR-II) emissive lanthanide-doped nanoparticles excited by 808 nm laser are ideal for in vivo bioimaging due to their non-heating excitation. The study of 808 nm excited lanthanide-doped nanoparticles not only provides high-quality NIR-II imaging but also can promote in vivo multiplexed bioimaging under single excitation. Herein, we prepared three sets of typical 808 nm excited lanthanide-doped nanoparticles (NaYF4: Nd3+@NaYF4, NaErF4@NaYF4, and NaYbF4: Er3+/Ce3+@NaYbF4@NaYF4: Yb3+/Nd3+) and then systematically compared their optical properties in the NIR-II window. Furthermore, we prepared water-soluble and biocompatible nanoprobes and achieved multiplexed NIR-II in vivo imaging in mice under single 808 nm excitation. These results highlight the potential of 808 nm excited lanthanide probes for physiological studies and biomedical applications.
Liu, B, Liao, J, Song, Y, Chen, C, Ding, L, Lu, J, Zhou, J & Wang, F 2022, 'Multiplexed structured illumination super-resolution imaging with lifetime-engineered upconversion nanoparticles', Nanoscale Advances, vol. 4, no. 1, pp. 30-38.
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We report a tailor-made multiplexed super-resolution imaging method using the lifetime fingerprints from luminescent nanoparticles, which can resolve the particles within the diffraction-limited spots and enable higher multiplexing capacity in space.
Luo, Y, Chen, Z, Wen, S, Han, Q, Fu, L, Yan, L, Jin, D, Bünzli, J-CG & Bao, G 2022, 'Magnetic regulation of the luminescence of hybrid lanthanide-doped nanoparticles', Coordination Chemistry Reviews, vol. 469, pp. 214653-214653.
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The unique optical properties of lanthanide-doped nanomaterials have made them broadly attractive to a wide range of applications in chemical, physical, and biomedical fields. As an external and real-time regulation tool, the magnetic field is highly useful for modulating the luminescence of lanthanide ions by spectral splitting, wavelength shifting, and intensity variation. The dynamic regulation of the luminescence further endows the nanosystems with many valuable optical features, extending their versatility. Here, we analyze the magnetic regulation mechanisms of luminescence, survey the structure design of magnetooptic nanosystems, highlight their advances in imaging agents, responsive probes, nanomagnets and nanogenerators, microrobots, and miniature reactors; we also identify the challenges and future opportunities for hybrid magnetooptic nanosystems.
Mahmud, MAP, Bazaz, SR, Dabiri, S, Mehrizi, AA, Asadnia, M, Warkiani, ME & Wang, ZL 2022, 'Advances in MEMS and Microfluidics‐Based Energy Harvesting Technologies', Advanced Materials Technologies, vol. 7, no. 7, pp. 2101347-2101347.
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AbstractEnergy harvesting from mechanical vibrations, thermal gradients, electromagnetic radiations, and solar radiations has experienced rapid progress in recent times not only to develop an alternative power source that can replace conventional batteries to energize portable and personal electronics smartly but also to achieve sustainable self‐sufficient micro/nanosystems. Utilizing micro‐electromechanical system (MEMS) and microfluidics technologies through selective designs and fabrications effectively, those energy harvesters can be considerably downsized while ensuring a stable, portable, and consistent power supply. Although ambient energy sources such as solar radiation are harvested for decades, recent developments have enabled ambient vibrations, electromagnetic radiation, and heat to be harvested wirelessly, independently, and sustainably. Developments in the field of microfluidics have also led to the design and fabrication of novel energy harvesting devices. This paper reviews the recent advancements in energy harvesting technologies such as piezoelectric, electromagnetic, electrostatic, thermoelectric, radio frequency, and solar to drive self‐powered portable electronics. Moreover, the potential application of MEMS and microfluidics as well as MEMS‐based structures and fabrication techniques for energy harvesting are summarized and presented. Finally, a few crucial challenges affecting the performance of energy harvesters are addressed.
Mathew, M, Rad, MA, Mata, JP, Mahmodi, H, Kabakova, IV, Raston, CL, Tang, Y, Tipper, JL & Tavakoli, J 2022, 'Hyperbranched polymers tune the physicochemical, mechanical, and biomedical properties of alginate hydrogels', Materials Today Chemistry, vol. 23, pp. 100656-100656.
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The current research aimed to fabricate an alginate-hyperbranched polymer (HBP) complex, using a vortex fluidic device (VFD), to control the physicochemical, structural, and mechanical properties of alginate hydrogel; thus, providing a dominant biomaterial system for different biomedical applications. Samples were prepared by mixing alginate (6%w/w) with HBP (0.85 μM) before cross-linking with Ca2+ (100 mM). Magnet stirrer (600 rpm) and VFD (6000 rpm) were used to prepare experimental samples, and alginate was used as control. Comprehensive evaluations of bulk and surface morphology, microstructural analysis, swelling kinetics, mechanical characteristics, cytotoxicity, and formation of hydrogen bonds were conducted. The findings from this study revealed that the addition of HBP to alginate structure led to a higher swelling capability (86%), increased diffusion coefficient (66-fold), and enhanced failure mechanical properties (160% and 20% increases for failure stress and elongation at break, respectively) than control. Traditional mixing affected the surface morphology, while the bulk structure remained unchanged. Moreover, the rate of degradation was not significantly different between alginate and alginate-HBP samples. When VFD was incorporated, a higher swelling ratio (30%) was observed than the control sample and the coefficient of diffusion increased (34-fold). The associated degradation rate increased 30-fold, and the failure stress and elongation at break were increased 310% and 83%, respectively, compared to the control sample. The micromixing of alginate with HBP under high shear stress using a VFD created a micro-hybrid composite formed by alginate microparticles embedded in an alginate sheet.
McClements, L, Richards, C, Patel, N, Chen, H, Sesperez, K, Bubb, KJ, Karlstaedt, A & Aksentijevic, D 2022, 'Impact of reduced uterine perfusion pressure model of preeclampsia on metabolism of placenta, maternal and fetal hearts', Scientific Reports, vol. 12, no. 1, p. 1111.
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AbstractPreeclampsia is a cardiovascular pregnancy complication characterised by new onset hypertension and organ damage or intrauterine growth restriction. It is one of the leading causes of maternal and fetal mortality in pregnancy globally. Short of pre-term delivery of the fetus and placenta, treatment options are limited. Consequently, preeclampsia leads to increased cardiovascular disease risk in both mothers and offspring later in life. Here we aim to examine the impact of the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia on the maternal cardiovascular system, placental and fetal heart metabolism. The surgical RUPP model was induced in pregnant rats by applying silver clips around the aorta and uterine arteries on gestational day 14, resulting in ~ 40% uterine blood flow reduction. The experiment was terminated on gestational day 19 and metabolomic profile of placentae, maternal and fetal hearts analysed using high-resolution 1H NMR spectroscopy. Impairment of uterine perfusion in RUPP rats caused placental and cardiac hypoxia and a series of metabolic adaptations: altered energetics, carbohydrate, lipid and amino acid metabolism of placentae and maternal hearts. Comparatively, the fetal metabolic phenotype was mildly affected. Nevertheless, long-term effects of these changes in both mothers and the offspring should be investigated further in the future.
Merklein, M, Kabakova, IV, Zarifi, A & Eggleton, BJ 2022, '100 years of Brillouin scattering: Historical and future perspectives', Applied Physics Reviews, vol. 9, no. 4, pp. 041306-041306.
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The Year 2022 marks 100 years since Leon Brillouin predicted and theoretically described the interaction of optical waves with acoustic waves in a medium. Accordingly, this resonant multi-wave interaction is referred to as Brillouin scattering. Today, Brillouin scattering has found a multitude of applications, ranging from microscopy of biological tissue, remote sensing over many kilometers, and signal processing in compact photonic integrated circuits smaller than the size of a thumbnail. What allows Brillouin scattering to be harnessed over such different length scales and research domains are its unique underlying properties, namely, its narrow linewidth in the MHz range, a frequency shift in the GHz range, large frequency selective gain or loss, frequency tunability, and optical reconfigurability. Brillouin scattering is also a ubiquitous effect that can be observed in many different media, such as freely propagating in gases and liquids, as well as over long lengths of low-loss optical glass fibers or short semiconductor waveguides. A recent trend of Brillouin research focuses on micro-structured waveguides and integrated photonic platforms. The reduction in the size of waveguides allows tailoring the overlap between the optical and acoustic waves and promises many novel applications in a compact footprint. In this review article, we give an overview of the evolution and development of the field of Brillouin scattering over the last one hundred years toward current lines of active research. We provide the reader with a perspective of recent trends and challenges that demand further research efforts and give an outlook toward the future of this exciting and diverse research field.
Mi, C, Guan, M, Zhang, X, Yang, L, Wu, S, Yang, Z, Guo, Z, Liao, J, Zhou, J, Lin, F, Ma, E, Jin, D & Yuan, X 2022, 'High Spatial and Temporal Resolution NIR-IIb Gastrointestinal Imaging in Mice', Nano Letters, vol. 22, no. 7, pp. 2793-2800.
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Conventional biomedical imaging modalities, including endoscopy, X-rays, and magnetic resonance, are invasive and insufficient in spatial and temporal resolutions for gastrointestinal (GI) tract imaging to guide prognosis and therapy. Here we report a noninvasive method based on lanthanide-doped nanocrystals with ∼1530 nm fluorescence in the near-infrared-IIb window (NIR-IIb, 1500-1700 nm). The rational design of nanocrystals have led to an absolute quantum yield (QY) up to 48.6%. Further benefiting from the minimized scattering through the NIR-IIb window, we enhanced the spatial resolution to ∼1 mm in GI tract imaging, which is ∼3 times higher compared with the near-infrared-IIa (NIR-IIa, 1000-1500 nm) method. The approach also realized a high temporal resolution of 8 frames per second; thus the moment of mice intestinal peristalsis can be captured. Furthermore, with a light-sheet imaging system, we demonstrated a three-dimensional (3D) imaging on the GI tract. Moreover, we successfully translated these advances to diagnose inflammatory bowel disease.
Mohid, SA, Sharma, P, Alghalayini, A, Saini, T, Datta, D, Willcox, MDP, Ali, H, Raha, S, Singha, A, Lee, D, Sahoo, N, Cranfield, CG, Roy, S & Bhunia, A 2022, 'A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation', Biophysical Chemistry, vol. 286, pp. 106802-106802.
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Morshedi Rad, D, Rezaei, M, Radfar, P & Ebrahimi Warkiani, M 2022, 'Microengineered filters for efficient delivery of nanomaterials into mammalian cells', Scientific Reports, vol. 12, no. 1, p. 4383.
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AbstractIntracellular delivery of nanomaterials into the cells of interest has enabled cell manipulation for numerous applications ranging from cell-based therapies to biomedical research. To date, different carriers or membrane poration-based techniques have been developed to load nanomaterials to the cell interior. These biotools have shown promise to surpass the membrane barrier and provide access to the intracellular space followed by passive diffusion of exogenous cargoes. However, most of them suffer from inconsistent delivery, cytotoxicity, and expensive protocols, somewhat limiting their utility in a variety of delivery applications. Here, by leveraging the benefits of microengineered porous membranes with a suitable porosity, we demonstrated an efficient intracellular loading of diverse nanomaterials to different cell types based on inducing mechanical disruption to the cell membrane. In this work, for the first time, we used ultra-thin silicon nitride (SiN) filter membranes with uniform micropores smaller than the cell diameter to load impermeable nanomaterials into adherent and non-adherent cell types. The delivery performance using SiN microsieves has been validated through the loading of functional nanomaterials from a few nanometers to hundreds of nanometers into mammalian cells with minimal undesired impacts. Besides the high delivery efficiency and improved cell viability, this simple and low-cost approach offers less clogging and higher throughput (107 cell min−1). Therefore, it yields to the efficient introduction of exogenous nanomaterials into the large population of cells, illustrating the potential of these microengineered filters to be widely used in the microfiltroporation (MFP) setup.
Nazari, H, Heirani-Tabasi, A, Esmaeili, E, Kajbafzadeh, A-M, Hassannejad, Z, Boroomand, S, Shahsavari Alavijeh, MH, Mishan, MA, Ahmadi Tafti, SH, Warkiani, ME & Dadgar, N 2022, 'Decellularized human amniotic membrane reinforced by MoS2-Polycaprolactone nanofibers, a novel conductive scaffold for cardiac tissue engineering', Journal of Biomaterials Applications, vol. 36, no. 9, pp. 1527-1539.
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In order to regenerate myocardial tissues with functional characteristics, we need to copy some properties of the myocardium, such as its extracellular matrix and electrical conductivity. In this study, we synthesized nanosheets of Molybdenum disulfide (MoS2), and integrated them into polycaprolactone (PCL) and electrospun on the surface of decellularized human amniotic membrane (DHAM) with the purpose of improving the scaffolds mechanical properties and electrical conductivity. For in vitro studies, we seeded the mouse embryonic cardiac cells, mouse Embryonic Cardiac Cells (mECCs), on the scaffolds and then studied the MoS2nanocomposites by scanning electron microscopy and Raman spectroscopy. In addition, we characterized the DHAM/PCL and DHAM/PCL-MoS2by SEM, transmission electron microscopy, water contact angle measurement, electrical conductivity, and tensile test. Besides, we confirmed the scaffolds are biocompatible by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, MTT assay. Furthermore, by means of SEM images, it was shown that mECCs attached to the DHAM/PCL-MoS2scaffold have more cell aggregations and elongated morphology. Furthermore, through the Real-Time PCR and immunostaining studies, we found out cardiac genes were maturated and upregulated, and they also included GATA-4, c-TnT, NKX 2.5, and alpha-myosin heavy chain in cells cultured on DHAM/PCL-MoS2scaffold in comparison to DHAM/PCL and DHAM. Therefore, in terms of cardiac tissue engineering, DHAM nanofibrous scaffolds reinforced by PCL-MoS2can be suggested as a proper candidate.
Nazari, H, Heirani-Tabasi, A, Ghorbani, S, Eyni, H, Razavi Bazaz, S, Khayati, M, Gheidari, F, Moradpour, K, Kehtari, M, Ahmadi Tafti, SM, Ahmadi Tafti, SH & Ebrahimi Warkiani, M 2022, 'Microfluidic-Based Droplets for Advanced Regenerative Medicine: Current Challenges and Future Trends', Biosensors, vol. 12, no. 1, pp. 20-20.
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Microfluidics is a promising approach for the facile and large-scale fabrication of monodispersed droplets for various applications in biomedicine. This technology has demonstrated great potential to address the limitations of regenerative medicine. Microfluidics provides safe, accurate, reliable, and cost-effective methods for encapsulating different stem cells, gametes, biomaterials, biomolecules, reagents, genes, and nanoparticles inside picoliter-sized droplets or droplet-derived microgels for different applications. Moreover, microenvironments made using such droplets can mimic niches of stem cells for cell therapy purposes, simulate native extracellular matrix (ECM) for tissue engineering applications, and remove challenges in cell encapsulation and three-dimensional (3D) culture methods. The fabrication of droplets using microfluidics also provides controllable microenvironments for manipulating gametes, fertilization, and embryo cultures for reproductive medicine. This review focuses on the relevant studies, and the latest progress in applying droplets in stem cell therapy, tissue engineering, reproductive biology, and gene therapy are separately evaluated. In the end, we discuss the challenges ahead in the field of microfluidics-based droplets for advanced regenerative medicine.
Paudel, KR, Patel, V, Vishwas, S, Gupta, S, Sharma, S, Chan, Y, Jha, NK, Shrestha, J, Imran, M, Panth, N, Shukla, SD, Jha, SK, Devkota, HP, Warkiani, ME, Singh, SK, Ali, MK, Gupta, G, Chellappan, DK, Hansbro, PM & Dua, K 2022, 'Nutraceuticals and COVID‐19: A mechanistic approach toward attenuating the disease complications', Journal of Food Biochemistry, vol. 46, no. 12, p. e14445.
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Nutraceuticals have emerged as potential compounds to attenuate the COVID-19 complications. Precisely, these food additives strengthen the overall COVID treatment and enhance the immunity of a person. Such compounds have been used at a large scale, in almost every household due to their better affordability and easy access. Therefore, current research is focused on developing newer advanced formulations from potential drug candidates including nutraceuticals with desirable properties viz, affordability, ease of availability, ease of administration, stability under room temperature, and potentially longer shelf-lives. As such, various nutraceutical-based products such as compounds could be promising agents for effectively managing COVID-19 symptoms and complications. Most importantly, regular consumption of such nutraceuticals has been shown to boost the immune system and prevent viral infections. Nutraceuticals such as vitamins, amino acids, flavonoids like curcumin, and probiotics have been studied for their role in the prevention of COVID-19 symptoms such as fever, pain, malaise, and dry cough. In this review, we have critically reviewed the potential of various nutraceutical-based therapeutics for the management of COVID-19. We searched the information relevant to our topic from search engines such as PubMed and Scopus using COVID-19, nutraceuticals, probiotics, and vitamins as a keyword. Any scientific literature published in a language other than English was excluded. PRACTICAL APPLICATIONS: Nutraceuticals possess both nutritional values and medicinal properties. They can aid in the prevention and treatment of diseases, as well as promote physical health and the immune system, normalizing body functions, and improving longevity. Recently, nutraceuticals such as probiotics, vitamins, polyunsaturated fatty acids, trace minerals, and medicinal plants have attracted considerable attention and are widely regarded as potential alternatives to current the...
Qiao, L, Li, H, Zhong, S, Xu, X, Su, F, Peng, X, Jin, D & Zhanghao, K 2022, 'Laterally swept light-sheet microscopy enhanced by pixel reassignment for photon-efficient volumetric imaging', Advanced Photonics Nexus, vol. 2, no. 01.
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Rad, HS, Shiravand, Y, Radfar, P, Ladwa, R, Perry, C, Han, X, Warkiani, ME, Adams, MN, Hughes, BGM, O'Byrne, K & Kulasinghe, A 2022, 'Understanding the tumor microenvironment in head and neck squamous cell carcinoma', Clinical & Translational Immunology, vol. 11, no. 6, p. e1397.
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AbstractHead and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of tumors. While significant progress has been made using multimodal treatment, the 5‐year survival remains at 50%. Developing effective therapies, such as immunotherapy, will likely lead to better treatment of primary and metastatic disease. However, not all HNSCC tumors respond to immune checkpoint blockade therapy. Understanding the complex cellular composition and interactions of the tumor microenvironment is likely to lead to new knowledge for effective therapies and treatment resistance. In this review, we discuss HNSCC characteristics, predictive biomarkers, factors influencing immunotherapy response, with a focus on the tumor microenvironment.
Rad, MA, Mahmodi, H, Filipe, EC, Cox, TR, Kabakova, I & Tipper, JL 2022, 'Micromechanical characterisation of 3D bioprinted neural cell models using Brillouin microspectroscopy', Bioprinting, vol. 25, pp. e00179-e00179.
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Biofabrication of three-dimensional (3D) in vitro neural cell models that closely mimic the central nervous system (CNS) is an emerging field of research with applications from fundamental biology to regenerative medicine, and far reaching benefits for the economy, healthcare and the ethical use of animals. The micromechanical properties of such models are an important factor dictating the success of modelling outcomes in relation to accurate reproduction of the processes in native tissues. Characterising the micromechanical properties of such models non-destructively and over a prolonged span of time, however, are key challenges. Brillouin microspectroscopy (BM) could provide a solution to this problem since this technology is non-invasive, label-free and is capable of micro-scale 3D imaging. In this work, the micromechanical properties of 3D bioprinted neural cell models consisting of NG 108-15 neuronal cells and Gelatin methacryloyl (GelMA) hydrogels of various concentrations were investigated using BM. We demonstrate changes in the volume-averaged (VA) and local micro-scale mechanical properties of these models over a 7 day period, in which the hydrogel component of the model are found to soften as the cells grow, multiply and form stiffer spheroid-type structures. These findings signify the necessity to resolve in microscopic detail the mechanics of in vitro 3D tissue models and suggest Brillouin microspectroscopy to be a suitable technology to bridge this gap.
Radfar, P, Aboulkheyr Es, H, Salomon, R, Kulasinghe, A, Ramalingam, N, Sarafraz-Yazdi, E, Thiery, JP & Warkiani, ME 2022, 'Single-cell analysis of circulating tumour cells: enabling technologies and clinical applications', Trends in Biotechnology, vol. 40, no. 9, pp. 1041-1060.
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Multimodal analysis of circulating tumour cells (CTCs) has the potential to provide remarkable insight for cancer development and metastasis. CTCs and CTC clusters investigation using single-cell analysis, enables researchers to gain crucial information on metastatic mechanisms and the genomic alterations responsible for drug resistance, empowering treatment, and management of cancer. Despite a plethora of CTC isolation technologies, careful attention to the strengths and weaknesses of each method should be considered in order to isolate these rare cells. Here, we provide an overview of cutting-edge technologies used for single-cell isolation and analysis of CTCs. Additionally, we highlight the biological features, clinical application, and the therapeutic potential of CTCs and CTC clusters using single-cell analysis platforms for cancer management.
Razavi Bazaz, S, Mihandust, A, Salomon, R, Joushani, HAN, Li, W, A. Amiri, H, Mirakhorli, F, Zhand, S, Shrestha, J, Miansari, M, Thierry, B, Jin, D & Ebrahimi Warkiani, M 2022, 'Zigzag microchannel for rigid inertial separation and enrichment (Z-RISE) of cells and particles', Lab on a Chip, vol. 22, no. 21, pp. 4093-4109.
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Overview of the zigzag microchannel for rigid inertial separation and enrichment (Z-RISE). The proposed device has superior performance for particle focusing and separation.
Rzhevskiy, AS, Kapitannikova, AY, Butnaru, DV, Shpot, EV, Joosse, SA, Zvyagin, AV & Ebrahimi Warkiani, M 2022, 'Liquid Biopsy in Diagnosis and Prognosis of Non-Metastatic Prostate Cancer', Biomedicines, vol. 10, no. 12, pp. 3115-3115.
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Currently, sensitive and specific methods for the detection and prognosis of early stage PCa are lacking. To establish the diagnosis and further identify an appropriate treatment strategy, prostate specific antigen (PSA) blood test followed by tissue biopsy have to be performed. The combination of tests is justified by the lack of a highly sensitive, specific, and safe single test. Tissue biopsy is specific but invasive and may have severe side effects, and therefore is inappropriate for screening of the disease. At the same time, the PSA blood test, which is conventionally used for PCa screening, has low specificity and may be elevated in the case of noncancerous prostate tumors and inflammatory conditions, including benign prostatic hyperplasia and prostatitis. Thus, diverse techniques of liquid biopsy have been investigated to supplement or replace the existing tests of prostate cancer early diagnosis and prognostics. Here, we provide a review on the advances in diagnosis and prognostics of non-metastatic prostate cancer by means of various biomarkers extracted via liquid biopsy, including circulating tumor cells, exosomal miRNAs, and circulating DNAs.
Rzhevskiy, AS, Kapitannikova, AY, Vasilescu, SA, Karashaeva, TA, Razavi Bazaz, S, Taratkin, MS, Enikeev, DV, Lekarev, VY, Shpot, EV, Butnaru, DV, Deyev, SM, Thiery, JP, Zvyagin, AV & Ebrahimi Warkiani, M 2022, 'Isolation of Circulating Tumor Cells from Seminal Fluid of Patients with Prostate Cancer Using Inertial Microfluidics', Cancers, vol. 14, no. 14, pp. 3364-3364.
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Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (±3.8%) and 1.7 mL min−1, respectively, while 99% (±0.7%) of sperm cells were disposed of. The introduced approach was further tested in a clinical setting by collecting and processing SF samples of PCa patients. The yield of isolated CTCs measured as high as 613 cells per SF sample in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC numbers with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise in the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.
Sadraeian, M, Junior, FFP, Miranda, M, Galinskas, J, Fernandes, RS, da Cruz, EF, Fu, L, Zhang, L, Diaz, RS, Cabral-Miranda, G & Guimarães, FEG 2022, 'Study of Viral Photoinactivation by UV-C Light and Photosensitizer Using a Pseudotyped Model', Pharmaceutics, vol. 14, no. 3, pp. 683-683.
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Different light-based strategies have been investigated to inactivate viruses. Herein, we developed an HIV-based pseudotyped model of SARS-CoV-2 (SC2) to study the mechanisms of virus inactivation by using two different strategies; photoinactivation (PI) by UV-C light and photodynamic inactivation (PDI) by Photodithazine photosensitizer (PDZ). We used two pseudoviral particles harboring the Luciferase-IRES-ZsGreen reporter gene with either a SC2 spike on the membrane or without a spike as a naked control pseudovirus. The mechanism of viral inactivation by UV-C and PDZ-based PDI were studied via biochemical characterizations and quantitative PCR on four levels; free-cell viral damage; viral cell entry; DNA integration; and expression of reporter genes. Both UV-C and PDZ treatments could destroy single stranded RNA (ssRNA) and the spike protein of the virus, with different ratios. However, the virus was still capable of binding and entering into the HEK 293T cells expressing angiotensin-converting enzyme 2 (ACE-2). A dose-dependent manner of UV-C irradiation mostly damages the ssRNA, while PDZ-based PDI mostly destroys the spike and viral membrane in concentration and dose-dependent manners. We observed that the cells infected by the virus and treated with either UV-C or PDZ-based PDI could not express the luciferase reporter gene, signifying the viral inactivation, despite the presence of RNA and DNA intact genes.
Sadraeian, M, Zhang, L, Aavani, F, Biazar, E & Jin, D 2022, 'Photodynamic viral inactivation assisted by photosensitizers', Materials Today Physics, vol. 28, pp. 100882-100882.
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The deadly viruses, which are spreading worldwide at an alarming rate, are a major challenge for the life sciences. More efficient and cost-effective methods with fewer side effects can provide a good alternative to traditional drug-based methods. Currently, physical phenomena such as light in the form of photodynamic action are increasingly being used to inactivate viruses. Photodynamic inactivation (PDI) uses a photosensitizer (PS), light, and oxygen to generate reactive oxygen species (ROS) to inactivate microorganisms. This article reviews the use of existing PSs, as one of the essential anti-viral agents, and introduces new materials and strategies combined with PDI. Physiochemical properties of PSs and their role in interaction with virus components are discussed. Furthermore, the effectiveness of optical sensitizers with radiation methods to inactivate viruses is highlighted.
Sadraeian, M, Zhang, L, Aavani, F, Biazar, E & Jin, D 2022, 'Viral inactivation by light', eLight, vol. 2, no. 1, p. 18.
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AbstractNowadays, viral infections are one of the greatest challenges for medical sciences and human society. While antiviral compounds and chemical inactivation remain inadequate, physical approaches based on irradiation provide new potentials for prevention and treatment of viral infections, without the risk of drug resistance and other unwanted side effects. Light across the electromagnetic spectrum can inactivate the virions using ionizing and non-ionizing radiations. This review highlights the anti-viral utility of radiant methods from the aspects of ionizing radiation, including high energy ultraviolet, gamma ray, X-ray, and neutron, and non-ionizing photo-inactivation, including lasers and blue light.
Shahrokhi, S, Dubajic, M, Dai, Z, Bhattacharyya, S, Mole, RA, Rule, KC, Bhadbhade, M, Tian, R, Mussakhanuly, N, Guan, X, Yin, Y, Nielsen, MP, Hu, L, Lin, C, Chang, SLY, Wang, D, Kabakova, IV, Conibeer, G, Bremner, S, Li, X, Cazorla, C & Wu, T 2022, 'Anomalous Structural Evolution and Glassy Lattice in Mixed‐Halide Hybrid Perovskites', Small, vol. 18, no. 21, pp. e2200847-2200847.
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AbstractHybrid halide perovskites have emerged as highly promising photovoltaic materials because of their exceptional optoelectronic properties, which are often optimized via compositional engineering like mixing halides. It is well established that hybrid perovskites undergo a series of structural phase transitions as temperature varies. In this work, the authors find that phase transitions are substantially suppressed in mixed‐halide hybrid perovskite single crystals of MAPbI3‐xBrx (MA = CH3NH3+ and x = 1 or 2) using a complementary suite of diffraction and spectroscopic techniques. Furthermore, as a general behavior, multiple crystallographic phases coexist in mixed‐halide perovskites over a wide temperature range, and a slightly distorted monoclinic phase, hitherto unreported for hybrid perovskites, is dominant at temperatures above 100 K. The anomalous structural evolution is correlated with the glassy behavior of organic cations and optical phonons in mixed‐halide perovskites. This work demonstrates the complex interplay between composition engineering and lattice dynamics in hybrid perovskites, shedding new light on their unique properties.
Shi, H, Rath, EM, Lin, RCY, Sarun, KH, Clarke, CJ, McCaughan, BC, Ke, H, Linton, A, Lee, K, Klebe, S, Maitz, J, Song, K, Wang, Y, Kao, S & Cheng, YY 2022, '3-Dimensional mesothelioma spheroids provide closer to natural pathophysiological tumor microenvironment for drug response studies', Frontiers in Oncology, vol. 12, pp. 1-12.
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Traditional studies using cancer cell lines are often performed on a two-dimensional (2D) cell culture model with a low success rate of translating to Phase I or Phase II clinical studies. In comparison, with the advent of developments three-dimensional (3D) cell culture has been championed as the latest cellular model system that better mimics in vivo conditions and pathological conditions such as cancer. In comparison to biospecimens taken from in vivo tissue, the details of gene expression of 3D culture models are largely undefined, especially in mesothelioma – an aggressive cancer with very limited effective treatment options. In this study, we examined the veracity of the 3D mesothelioma cell culture model to study cell-to-cell interaction, gene expression and drug response from 3D cell culture, and compared them to 2D cell and tumor samples. We confirmed via SEM analysis that 3D cells grown using the spheroid methods expressed highly interconnected cell-to-cell junctions. The 3D spheroids were revealed to be an improved mini-tumor model as indicated by the TEM visualization of cell junctions and microvilli, features not seen in the 2D models. Growing 3D cell models using decellularized lung scaffold provided a platform for cell growth and infiltration for all cell types including primary cell lines. The most time-effective method was growing cells in spheroids using low-adhesive U-bottom plates. However, not every cell type grew into a 3D model using the the other methods of hanging drop or poly-HEMA. Cells grown in 3D showed more resistance to chemotherapeutic drugs, exhibiting reduced apoptosis. 3D cells stained with H&E showed cell-to-cell interactions and internal architecture that better represent that of in vivo patient tumors when compared to 2D cells. IHC staining revealed increased protein expression in 3D spheroids ...
Shi, H, Tsai, KH, Ma, D, Wang, X, Desai, R, Parungao, RJ, Hunt, NJ, Cheng, YY, Zhang, H, Xu, Y, Simanainen, U, Tan, Q, Cooper, MS, Handelsman, DJ, Maitz, PK & Wang, Y 2022, 'Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone electrospun scaffolds accelerate burn wound healing', The FASEB Journal, vol. 36, no. 5, p. e22310.
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Wound healing is a complex process involving multiple independent and overlapping sequential physiological mechanisms. In addition to cutaneous injury, a severe burn stimulates physiological derangements that induce a systemic hypermetabolic response resulting in impaired wound healing. Topical application of the anti-androgen drug, flutamide accelerates cutaneous wound healing, whereas paradoxically systemic dihydrotestosterone (DHT) improves burn wound healing. We developed and characterized a PCL scaffold that is capable of controlled release of androgen (DHT) and anti-androgen (F) individually or together. This study aims to investigate whether local modification of androgen actions has an impact on burn injury wound healing. In a full-thickness burn wound healing, mouse model, DHT/F-scaffold showed a significantly faster wound healing compared with F-scaffold or DHT-scaffold. Histology analysis confirmed that DHT/F-scaffold exhibited higher re-epithelization, cell proliferation, angiogenesis, and collagen deposition. Dual release of DHT and F from PCL scaffolds promoted cell proliferation of human keratinocytes and alters the keratinocyte cell cycle. Lastly, no adverse effects on androgen-dependent organs, spleen and liver were observed. In conclusion, we demonstrated DHT plus F load PCL scaffolds accelerated burn wound healing when loading alone did not. These findings point to a complex role of androgens in burn wound healing and open novel therapeutic avenues for treating severe burn patients.
Shi, Y, Wu, Y, Chin, LK, Li, Z, Liu, J, Chen, MK, Wang, S, Zhang, Y, Liu, PY, Zhou, X, Cai, H, Jin, W, Yu, Y, Yu, R, Huang, W, Yap, PH, Xiao, L, Ser, W, Nguyen, TTB, Lin, Y, Wu, PC, Liao, J, Wang, F, Chan, CT, Kivshar, Y, Tsai, DP & Liu, AQ 2022, 'Multifunctional Virus Manipulation with Large‐Scale Arrays of All‐Dielectric Resonant Nanocavities', Laser & Photonics Reviews, vol. 16, no. 5, pp. 2100197-2100197.
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AbstractSpatial manipulation of a precise number of viruses for host cell infection is essential for the extensive studies of virus pathogenesis and evolution. Albeit optical tweezers have been advanced to the atomic level via optical cooling, it is still challenging to efficiently trap and manipulate arbitrary number of viruses in an aqueous environment, being restricted by insufficient strength of optical forces and a lack of multifunctional spatial manipulation techniques. Here, by employing the virus hopping and flexibility of moving the laser position, multifunctional virus manipulation with a large trapping area is demonstrated, enabling single or massive (a large quantity of) virus transporting, positioning, patterning, sorting, and concentrating. The enhanced optical forces are produced by the confinement of light in engineered arrays of nanocavities by fine tuning of the interference resonances, and this approach allows trapping and moving viruses down to 40 nm in size. The work paves the way to efficient and precise manipulation of either single or massive groups of viruses, opening a wide range of novel opportunities for virus pathogenesis and inhibitor development at the single‐virus level.
Shojaei, M, Shamshirian, A, Monkman, J, Grice, L, Tran, M, Tan, CW, Teo, SM, Rodrigues Rossi, G, McCulloch, TR, Nalos, M, Raei, M, Razavi, A, Ghasemian, R, Gheibi, M, Roozbeh, F, Sly, PD, Spann, KM, Chew, KY, Zhu, Y, Xia, Y, Wells, TJ, Senegaglia, AC, Kuniyoshi, CL, Franck, CL, dos Santos, AFR, Noronha, LD, Motamen, S, Valadan, R, Amjadi, O, Gogna, R, Madan, E, Alizadeh-Navaei, R, Lamperti, L, Zuñiga, F, Nova-Lamperti, E, Labarca, G, Knippenberg, B, Herwanto, V, Wang, Y, Phu, A, Chew, T, Kwan, T, Kim, K, Teoh, S, Pelaia, TM, Kuan, WS, Jee, Y, Iredell, J, O’Byrne, K, Fraser, JF, Davis, MJ, Belz, GT, Warkiani, ME, Gallo, CS, Souza-Fonseca-Guimaraes, F, Nguyen, Q, Mclean, A, Kulasinghe, A, Short, KR & Tang, B 2022, 'IFI27 transcription is an early predictor for COVID-19 outcomes, a multi-cohort observational study', Frontiers in Immunology, vol. 13, p. 1060438.
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PurposeRobust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness.MethodsWe conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 (IFI27) in COVID-19 patients.ResultsWe show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For example, in the pandemic H1N1/09 influenza virus infection, IFI27-like genes were highly upregulated in the blood samples of severely infected patients.ConclusionThese data suggest that prognostic biomarkers targeting the family of IFI27
Shrestha, J, Razavi Bazaz, S, Ding, L, Vasilescu, S, Idrees, S, Söderström, B, Hansbro, PM, Ghadiri, M & Ebrahimi Warkiani, M 2022, 'Rapid separation of bacteria from primary nasal samples using inertial microfluidics', Lab on a Chip, vol. 23, no. 1, pp. 146-156.
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Development of an inertial microfluidic device based on a zigzag configuration for rapid separation of bacteria from primary nasal samples.
Su, F, Luo, X, Du, Z, Chen, Z, Liu, Y, Jin, X, Guo, Z, Lu, J & Jin, D 2022, 'High-Contrast Luminescent Immunohistochemistry Using PEGylated Lanthanide Complexes', Analytical Chemistry, vol. 94, no. 50, pp. 17587-17594.
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Immunohistochemistry (IHC) using fluorescent probes provides high resolution with multiplexing capability, but the imaging contrast is limited by the brightness of the fluorescent probe and the intrinsic autofluorescence background from tissues. Herein, we improved the contrast by high-density labeling of long-lifetime lanthanide complexes and time-gated imaging. As the large (∼280 nm) Stokes shift of lanthanide complexes effectively prevents the issue of concentration quenching, we succeeded in conjugating seven europium complexes to an eight-arm hydrophilic poly(ethylene glycol) (PEG) linker for signal amplification with improved water solubility to the level of up to 10 mg/mL. Moreover, we demonstrated that both human epidermal growth factor receptor 2 (HER2) in a formalin-fixed paraffin-embedded (FFPE) tissue section and cytokeratin 18 (CK18) in a frozen section can be resolved with the enhanced contrast by 2-fold and 3-fold, respectively. Furthermore, we show that the PEGylation of multiple lanthanide complexes is compatible with tyramide signal amplification (TSA). This work suggests new opportunities for sensitive imaging of low-abundance biomarkers in a tissue matrix.
Vuitika, L, Prates-Syed, WA, Silva, JDQ, Crema, KP, Côrtes, N, Lira, A, Lima, JBM, Camara, NOS, Schimke, LF, Cabral-Marques, O, Sadraeian, M, Chaves, LCS & Cabral-Miranda, G 2022, 'Vaccines against Emerging and Neglected Infectious Diseases: An Overview', Vaccines, vol. 10, no. 9, pp. 1385-1385.
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Neglected Tropical Diseases (NTDs) are a group of diseases that are highly prevalent in tropical and subtropical regions, and closely associated with poverty and marginalized populations. Infectious diseases affect over 1.6 billion people annually, and vaccines are the best prophylactic tool against them. Along with NTDs, emerging and reemerging infectious diseases also threaten global public health, as they can unpredictably result in pandemics. The recent advances in vaccinology allowed the development and licensing of new vaccine platforms that can target and prevent these diseases. In this work, we discuss the advances in vaccinology and some of the difficulties found in the vaccine development pipeline for selected NTDs and emerging and reemerging infectious diseases, including HIV, Dengue, Ebola, Chagas disease, malaria, leishmaniasis, zika, and chikungunya.
Wang, H, Mao, W, Lou, W, Jin, D, Wu, W, Wang, D, Kuang, T, Rong, Y, Xu, X & Zhang, L 2022, 'PYCR1: A Potential Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma', Journal of Cancer, vol. 13, no. 5, pp. 1501-1511.
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Wang, H, Obeidy, P, Wang, Z, Zhao, Y, Wang, Y, Su, QP, Cox, CD & Ju, LA 2022, 'Fluorescence-coupled micropipette aspiration assay to examine calcium mobilization caused by red blood cell mechanosensing', European Biophysics Journal, vol. 51, no. 2, pp. 135-146.
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AbstractMechanical stimuli such as tension, compression, and shear stress play critical roles in the physiological functions of red blood cells (RBCs) and their homeostasis, ATP release, and rheological properties. Intracellular calcium (Ca2+) mobilization reflects RBC mechanosensing as they transverse the complex vasculature. Emerging studies have demonstrated the presence of mechanosensitive Ca2+ permeable ion channels and their function has been implicated in the regulation of RBC volume and deformability. However, how these mechanoreceptors trigger Ca2+ influx and subsequent cellular responses are still unclear. Here, we introduce a fluorescence-coupled micropipette aspiration assay to examine RBC mechanosensing at the single-cell level. To achieve a wide range of cell aspirations, we implemented and compared two negative pressure adjusting apparatuses: a homemade water manometer (− 2.94 to 0 mmH2O) and a pneumatic high-speed pressure clamp (− 25 to 0 mmHg). To visualize Ca2+ influx, RBCs were pre-loaded with an intensiometric probe Cal-520 AM, then imaged under a confocal microscope with concurrent bright-field and fluorescent imaging at acquisition rates of 10 frames per second. Remarkably, we observed the related changes in intracellular Ca2+ levels immediately after aspirating individual RBCs in a pressure-dependent manner. The RBC aspirated by the water manometer only displayed 1.1-fold increase in fluorescence intensity, whereas the RBC aspirated by the pneumatic clamp showed up to threefold increase. These results demonstrated the water manometer as a gentle tool for cell manipulation with minimal pre-activation, while the high-speed pneumatic clamp as a much stronger pressure actuator to examine cell mechanosensing directly. Together, this multimodal platform enables us to precisely co...
Wang, Z, Kuang, T, Wu, W, Wang, D, Lou, W, Jin, D, Xu, X & Zhang, L 2022, 'GFAT1 is highly expressed in cancer stem cells of pancreatic cancer', Annals of Translational Medicine, vol. 10, no. 10, pp. 544-544.
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Wen, S, Li, D, Liu, Y, Chen, C, Wang, F, Zhou, J, Bao, G, Zhang, L & Jin, D 2022, 'Power-Dependent Optimal Concentrations of Tm3+ and Yb3+ in Upconversion Nanoparticles', The Journal of Physical Chemistry Letters, vol. 13, no. 23, pp. 5316-5323.
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Lanthanide-doped upconversion nanoparticles (UCNPs) have enabled a broad range of emerging nanophotonics and biophotonics applications. Here, we provide a quantitative guide to the optimum concentrations of Yb3+ sensitizer and Tm3+ emitter ions, highly dependent on the excitation power densities. To achieve this, we fabricate the inert-core@active-shell@inert-shell architecture to sandwich the same volume of the optically active section. Our results show that highly doped UCNPs enable an approximately 18-fold enhancement in brightness over that of conventional ones. Increasing the Tm3+ concentration improves the brightness by 6 times and increases the NIR/blue ratio by 11 times, while the increase of Yb3+ concentration enhances the brightness by 3 times and only slightly affects the NIR/blue ratio. Moreover, the optimal doping concentration of Tm3+ varies from 2% to 16%, which is highly dependent on the excitation power density ranging from 102 to 107 W/cm2. This work provides a guideline for designing bright UCNPs under different excitation conditions.
Xu, J, Fang, H, Su, Y, Kang, Y, Xu, D, Cheng, YY, Nie, Y, Wang, H, Liu, T & Song, K 2022, 'A 3D bioprinted decellularized extracellular matrix/gelatin/quaternized chitosan scaffold assembling with poly(ionic liquid)s for skin tissue engineering', International Journal of Biological Macromolecules, vol. 220, pp. 1253-1266.
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Currently, a suitable bioink for 3D bioprinting and capable of mimicking the microenvironment of native skin and preventing bacterial infection remains a major challenge in skin tissue engineering. In this study, we prepared a tissue-specific extracellular matrix-based bioink, and dECM/Gel/QCS (dGQ) 3D scaffold assembling with poly(ionic liquid)s (PILs) (dGQP) was obtained by an extrusion 3D bioprinting technology and dynamic hydrogen bonding method. The morphologies, mechanical properties, porosity, hydrophilicity, biodegradation, hemostatic effect, antibacterial ability, and biocompatibility of the hybrid scaffolds were characterized and evaluated. Results showed that the rapid release (2 h) of PILs on the dGQP scaffold can quickly kill gram-negative (E. coli) and gram-positive (S. aureus) bacteria with almost 100 % antibacterial activity and maintained a stable sterile environment for a long time (7 d), which was superior to the dGQ scaffold. The hemostasis and hemolysis test showed that the dGQP scaffold had a good hemostatic effect and excellent hemocompatibility. In vitro cytocompatibility studies showed that although the cell growth on dGQP scaffold was slow in the early stage, the cells proliferated rapidly since day 4 and had high ECM secretion at day 7. Overall, this advanced dGQP scaffold has a considerable potential to be applied in skin tissue engineering.
York, E, McNaughton, DA, Roseblade, A, Cranfield, CG, Gale, PA & Rawling, T 2022, 'Structure–Activity Relationship and Mechanistic Studies of Bisaryl Urea Anticancer Agents Indicate Mitochondrial Uncoupling by a Fatty Acid-Activated Mechanism', ACS Chemical Biology, vol. 17, no. 8, pp. 2065-2073.
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Targeting the cancer cell mitochondrion is a promising approach for developing novel anticancer agents. The experimental anticancer agent N,N'-bis(3,5-dichlorophenyl)urea (SR4) induces apoptotic cell death in several cancer cell lines by uncoupling mitochondrial oxidative phosphorylation (OxPhos) using a protein-free mechanism. However, the precise mechanism by which SR4 depolarizes mitochondria is unclear because SR4 lacks an acidic functional group typically found in protein-independent uncouplers. Recently, it was shown that structurally related thioureas can facilitate proton transport across lipid bilayers by a fatty acid-activated mechanism, in which the fatty acid acts as the site of protonation/deprotonation and the thiourea acts as an anion transporter that shuttles deprotonated fatty acids across the phospholipid bilayer to enable proton leak. In this paper, we show that SR4-mediated proton transport is enhanced by the presence of free fatty acids in the lipid bilayer, indicating that SR4 uncouples mitochondria through the fatty acid-activated mechanism. This mechanistic insight was used to develop a library of substituted bisaryl ureas for structure-activity relationship studies and subsequent cell testing. It was found that lipophilic electron-withdrawing groups on bisaryl ureas enhanced electrogenic proton transport via the fatty acid-activated mechanism and had the capacity to depolarize mitochondria and reduce the viability of MDA-MB-231 breast cancer cells. The most active compound in the series reduced cell viability with greater potency than SR4 and was more effective at inhibiting adenosine triphosphate production.
Zhang, L, Cao, C, Kaushik, N, Lai, RY, Liao, J, Wang, G, Ariotti, N, Jin, D & Stenzel, MH 2022, 'Controlling the Biological Behaviors of Polymer-Coated Upconverting Nanoparticles by Adjusting the Linker Length of Estrone Ligands', Biomacromolecules, vol. 23, no. 6, pp. 2572-2585.
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The estrone ligand is used for modifying nanoparticle surfaces to improve their targeting effect on cancer cell lines. However, to date, there is no common agreement on the ideal linker length to be used for the optimum targeting performance. In this study, we aimed to investigate the impact of poly(poly ethylene glycol methyl ether methacrylate) (PPEGMEMA) linker length on the cellular uptake behavior of polymer-coated upconverting nanoparticles (UCNPs). Different triblock terpolymers, poly(poly (ethylene glycol) methyl ether methacrylate)-block-polymethacrylic acid-block-polyethylene glycol methacrylate phosphate (PPEGMEMAx-b-PMAAy-b-PEGMP3: x = 7, 15, 33, and 80; y = 16, 20, 18, and 18), were synthesized with different polymer linker chain lengths between the surface and the targeting ligand by reversible addition-fragmentation chain transfer polymerization. The estrone ligand was attached to the polymer via specific terminal conjugation. The cellular association of polymer-coated UCNPs with linker chain lengths was evaluated in MCF-7 cells by flow cytometry. Our results showed that the bioactivity of ligand modification is dependent on the length of the polymer linker. The shortest polymer PPEGMEMA7-b-PMAA16-b-PEGMP3 with estrone at the end of the polymer chain was found to have the best cellular association behavior in the estrogen receptor (ER)α-positive expression cell line MCF-7. Additionally, the anticancer drug doxorubicin•HCl was encapsulated in the nanocarrier to evaluate the 2D and 3D cytotoxicity. The results showed that estrone modification could efficiently improve the cellular uptake in ERα-positive expression cell lines and in 3D spheroid models.
Zhang, L, Rath, EM & Cheng, YY 2022, 'The Use of Epigenetic Biomarkers as Diagnostic and Therapeutic Options', Epigenomes, vol. 6, no. 4, pp. 30-30.
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The last few decades have brought tremendous advances in the mechanisms of epigenetic regulation, with DNA methylation, histone methylation and acetylation, microRNAs and other noncoding RNAs being among the most prominent [...]
Zhang, Q, Liao, J, Huang, Q, Lai, N, Zhang, B, Wen, X, Yang, J, Yang, Y, Wang, J, Zhang, G, Wang, C & Wang, R 2022, 'Regulated broadband visible emission of Bi ions-doped borosilicate glass', Ceramics International, vol. 48, no. 22, pp. 34046-34052.
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Zhang, X, Ekanayake Weeramange, C, Hughes, BGM, Vasani, S, Liu, ZY, Warkiani, ME, Hartel, G, Ladwa, R, Thiery, JP, Kenny, L & Punyadeera, C 2022, 'Application of circulating tumour cells to predict response to treatment in head and neck cancer', Cellular Oncology, vol. 45, no. 4, pp. 543-555.
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Abstract Background Local recurrence and metastasis remain the major causes of death in head and neck cancer (HNC) patients. Circulating tumour cells (CTCs) are shed from primary and metastatic sites into the circulation system and have been reported to play critical roles in the metastasis and recurrence of HNC. Here, we explored the use of CTCs to predict the response to treatment and disease progression in HNC patients. Methods Blood samples were collected at diagnosis from HNC patients (n = 119). CTCs were isolated using a spiral microfluidic device and were identified using immunofluorescence staining. Correlation of baseline CTC numbers to 13-week PET-CT data and multidisciplinary team consensus data were conducted. Results CTCs were detected in 60/119 (50.4%) of treatment naïve HNC patients at diagnosis. Baseline CTC numbers were higher in stage III vs. stage I-II p16-positive oropharyngeal cancers (OPCs) and other HNCs (p = 0.0143 and 0.032, respectively). In addition, we found that baseline CTC numbers may serve as independent predictors of treatment response, even after adjusting for other conventional prognostic factors. CTCs were detected in 10 out of 11 patients exhibiting incomplete treatment responses. Conclusions We found that baseline CTC numbers are correlated with treatment response in patients with HNC. The expression level of cell-surface vimentin (CSV) on CTCs was significantly higher in patients with persistent or progressive disease, thus providing additional prognostic information...
Zhao, H, Cun, Y, Bai, X, Xiao, D, Qiu, J, Song, Z, Liao, J & Yang, Z 2022, 'Entirely Reversible Photochromic Glass with High Coloration and Luminescence Contrast for 3D Optical Storage', ACS Energy Letters, vol. 7, no. 6, pp. 2060-2069.
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Zhao, K, Xu, X, Ren, W, Jin, D & Xi, P 2022, 'Two-photon MINFLUX with doubled localization precision', eLight, vol. 2, no. 1, p. 5.
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AbstractAchieving localization with molecular precision has been of great interest for extending fluorescence microscopy to nanoscopy. MINFLUX pioneers this transition through point spread function (PSF) engineering, yet its performance is primarily limited by the signal-to-background ratio. Here we demonstrate theoretically that two-photon MINFLUX (2p-MINFLUX) could double its localization precision through PSF engineering by nonlinear effect. Cramér-Rao Bound (CRB) is studied as the maximum localization precision, and CRB of two-photon MINFLUX is halved compared to single-photon MINFLUX (1p-MINFLUX) in all three dimensions. Meanwhile, in order to achieve same localization precision with 1p-MINFLUX, 2p-MINFLUX requires only 1/4 of fluorescence photons. Exploiting simultaneous two-photon excitation of multiple fluorophore species, 2p-MINFLUX may have the potential for registration-free nanoscopy and multicolor tracking.
Zhong, X, Zhang, L, van Wezel, GP, Vijgenboom, E & Claessen, D 2022, 'Role for a Lytic Polysaccharide Monooxygenase in Cell Wall Remodeling in Streptomyces coelicolor', mBio, vol. 13, no. 2, p. e0045622.
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Lytic polysaccharide monooxygenases are used in industry for the efficient degradation of recalcitrant polysaccharide substrates. Only recently, we have begun to appreciate some of their important biological roles.
Zuo, Y, Li, R, Zhang, Y, Bao, G, Le, Y & Yan, L 2022, 'Design, synthesis and antitumor activity of 5-trifluoromethylpyrimidine derivatives as EGFR inhibitors', Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 37, no. 1, pp. 2742-2754.
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A new series of 5-trifluoromethylpyrimidine derivatives were designed and synthesised as EGFR inhibitors. Three tumour cells A549, MCF-7, PC-3 and EGFR kinase were employed to evaluate their biological activities. The results were shown that most of the target compounds existed excellent antitumor activities. In particular, the IC50 values of compound 9u (E)-3-((2-((4-(3-(3-fluorophenyl)acrylamido)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylthiophene-2-carboxamide against A549, MCF-7, PC-3 cells and EGFR kinase reached to 0.35 μM, 3.24 μM, 5.12 μM, and 0.091 μM, respectively. Additionally, further researches revealed that compound 9u could induce early apoptosis of A549 cells and arrest the cells in G2/M phase. Taken together, these findings indicated that compound 9u was potential for developing as antitumor reagent.
