Prof. Jiye Cai
Department of Chemistry, Jinan University, Guangzhou, China
State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau
· Single molecule in situ detection on cell membrane
· Cell ultrastructures
Title: Atomic force microscopy study of the immunomodulatory effects of polysaccharide compounds in macrophages
Abstract: Polysaccharide compounds (PCs), which composed of different kinds of polysaccharides always isolated from different kinds of traditional Chinese medicine, are now attracting more and more attentions due to their strong immunomodulatory activities beyond the corresponding one-component polysaccharides. In this study, we demonstrated for the first time that PCs-1 and PCs-2 had strong immunomodulatory effects on macrophages both in in vitro and in vivo models by high resolution atomic force microscopy (AFM). PCs-1 and PCs-2 were found to inhibit LPS induced cell surface particle size and roughness increase in RAW264.7 macrophages, demonstrating the anti-inflammatory effects of PCs-1 and PCs-2 on macrophages. PCs-1 and PCs-2 could also induce the increase of surface particle size and roughness in RAW264.7 macrophages, demonstrating the activation effects of PCs-1 and PCs-2 on macrophages. And additionally, PCs-1 and PCs-2 were also found to reverse surface particle size and roughness decrease of peritoneal macrophages from cyclophosphamide induced immunosuppressive mice, also suggesting the activation effects of PCs-1 and PCs-2 on immunosuppressive macrophages. These results further enhanced our understanding of macrophage activations by direct imaging of cell surface ultrastructure and also highlighted AFM as a novel nanotool for macrophage detections. And most importantly, these results also indicated the outstanding immunomodulatory effects of PCs on macrophages, which therefore suggested that PCs could be served as a kind of novel immunomodulatory agents that would benefit human health.
Dr. Jinsong Bian
Department of Pharmacology, National University of Singapore
· Biology of endogenous mediators (e.g. hydrogen sulfide)
· Mechanisms for cardioprotection
· Mechanisms for neurodegenerative diseases and opioid addiction
Title: Hydrogen sulfide and its releasing compounds: when bad guy turns good
Hydrogen sulfide was thought to be a toxic gas and is now recognized to be an endogenous biological gaseous mediator. It produces multiple benefit effects in various biological systems. These include cardioprotective, antihypertension, neuroprotective, renal protection and so on. H2S was also reported to be used to treat different diseases with different animal models. However, NaHS or Na2S was commonly used as a H2S donor in most of these studies. Recently, there are several hydrogen sulfide releasing compounds were developed. I will focus on discussing the new discoveries of the biological functions of this gas in cardiovascular and central nervous systems. The therapeutic effects of several H2S-releasing compounds will also be discussed.
Prof. Baojun Xu
Food Science and Technology Program, Beijing Normal University–Hong Kong Baptist University United International College
Health benefits (targeted at aging, cancers, obesity, diabetes, and inflammatory diseases) assessment of phytochemicals from legumes, fruits, vegetables, traditional Chinese medicines through in vitro animal cell models
· Cellular and molecular mechanisms of bioactive food components in disease prevention
· Development of novel health promoting products and cosmeceuticals
· Lab-scale and pilot scale extraction techniques of natural functional polysaccharides
Title: Daphnetin protects INS-1 pancreatic β-cells from streptozotocin-induced apoptosis
Abstract: Background: Excessive loss of pancreatic β-cell, mainly due to apoptosis is major causes in the development of diabetes hyperglycemia in both type 1 and 2 diabetes mellitus. Pancreatic β-cell apoptosis is initiated by stimuli such as inflammation and hyperglycemia. Numerous epidemiological studies have demonstrated that excessive human consumption of diet rich phytochemicals attenuates effect of diabetes. Daphnetin (7,8-dihydrocoumarin), a naturally present such as fruits, Daphne koreane Nakai and Daphne odora var. marginata, has shown significant biological effects of antioxidant and antiflammatrory activities. Objective: The objective of the present study was to evaluate the mechanism behind its antidiabetic property in streptozotocin (STZ)-induced diabetic in INS-1 cell line. Methods: The INS-1 rat insulinoma cell line was cultured. INS-1 cells were pretreated with daphetin (1, 10, 20 and 40 µM) for 24 h, cells were exposed to STZ (3 mM) for 12h. STZ induced cell damage was estimated by MTT assay, glucose stimulated insulin secretion assay, lipid peroxidation (thiobarbituric acid reactive substance and lipid hydroperoxide), antioxidant status (SOD, CAT, GPx, and GST), apoptosis stainings (DAPI, Hoechst33342, AO/EB, ROS) by fluorescence microscopy and annexin V and propidium iodide double staining by flow cytometry. Results: The exposure to STZ for 12h significantly reduced the viability of INS-1 cells, compared to control cells in culture media, while pretreated with daphnetin for 24h resulted in a significant improve of cell viability as determined by MTT. Daphnetin was tested for its effects on insulin secretion by INS-1 cells cultured in low and high glucose medium; we found that daphnetin pretreatment improved glucose stimulated insulin secretion. STZ cause increased levels of lipid peroxidation and decreased antioxidant status of diabetic in INS-1 cells. Daphnetin pretreatment significantly reduced the levels of lipid peroxidation markers and improved antioxidant status in STZ induced INS-1 cells. STZ-induced cells showed less live cells and highly condensed chromatin in nuclei. However, daphnetin obviously decreased the apoptotic ratio in comparison with STZ-induced diabetic in INS-1 cells. Conclusion: The results suggest that daphnetin may be used in treating diabetes mellitus by considering its insulin stimulating property and subsequent regulation of apoptotic pathway.
Dr. Wenhua Zheng
Faculty of Health Science, University of Macau
Neuro- and ocular pharmacology
Aging, neuronal degenerative disorders including Alzheimer's disease and degenerative retinal diseases
Molecular mechanisms of neuronal death and survival
New drug developments
Title: The role of FoxO3a on NGF-induced neuronal differentiation and its underlying mechanisms
Abstract: Forkhead box O3 (FoxO3a) is a forkhead family transcription factor playing important roles in non-neuronal differentiation, metabolism, proliferation, and survival, but its role in neuronal differentiation remains unclear. In the present study, we investigated the role of FoxO3a in neuronal differentiation and its underlying mechanisms. Our results showed that overexpression of FoxO3a inhibited neuronal differentiation of PC12 cells induced by nerve growth factor (NGF) while knockdown of FoxO3a by siRNA enhanced NGF-induced differentiation. DNA microarray analysis and quantitative reverse transcription PCR (RT-PCR) showed that the overexpression of FoxO3a significantly attenuated expression of neurochondrin (NCDN), a neurite outgrowth-related protein, in PC12 cells, while knocking down the expression of FoxO3a had the opposite effect. Bioinformatic studies found that the regulatory region of NCDN promoter contained multiple FoxO3a binding sites. Dual-luciferase reporter assay with report gene containing NCDN promoter showed that FoxO3a significantly decreased the transcription activity of NCDN promoter. These results indicate that NCDN is a direct downstream target of FoxO3a which negatively regulates the expression of NCDN. Interestingly, NGF-induced NCDN expression and cell differentiation was blocked by the inhibition of phosphatidylinositol-3-kinase (PI3K)-protein kinase B (PKB, Akt) signal pathway (activation of FoxO3a) and overexpression of FoxO3a. Moreover, knockdown of NCDN by siRNA blocked NGF-induced neuronal differentiation of PC12 cells while overexpression of NCDN significantly promoted neurite outgrowth. These results put together demonstrate that NCDN plays an important role in NGF-induced neuronal differentiation and suggest that FoxO3a inhibits NGF-induced neuronal differentiation, at least in part, by suppressing the expression of NCDNSupported by National Natural Science Fund of China (31371088), SRG2015-00004-FHS from University of Macau and the Science and Technology Development Fund (FDCT) of Macao (FDCT 021/2015/A1).
· Biomaterials for surgical applications
· Laryngeal physiology, acoustics, and biomechanics
· Solid mechanics (soft tissue mechanics)
· Tissue engineering and regenerative medicine
· Viscoelasticity and biorheology
Title: Controlled release of growth factors from xenogeneic, acellular extracellular matrix scaffolds for soft tissue reconstruction
Abstract: Xenogeneic, acellular extracellular matrix (ECM) scaffolds have been found to facilitate constructive tissue remodeling in a variety of tissue engineering applications, including the reconstruction of soft connective tissues like tendons, ligaments, heart valves, and vocal folds. Growth factors such as hepatocyte growth factor (HGF) have been shown to have strong anti-fibrotic effects in connective tissue ECM. The loading and release kinetics of HGF was examined in vitro, and the potential of a bovine ECM-based acellular scaffold as a timed-release system for the delivery of HGF in vivo was investigated. With a rat model of laryngeal injury, bilateral wounds were created in the posterior vocal folds of rats, with HGF-loaded acellular ECM scaffolds implanted into the wounds unilaterally, and scaffolds without HGF implanted into the contralateral vocal folds as control. The rats were humanely sacrificed after 3, 7, 30, and 90 days, with their larynges examined histologically and immunohistochemically. Expressions of key matrix proteins in the vocal fold coronal sections were quantified by digital image analysis. Results demonstrated a gradual, sustained release of HGF for at least 7 days in vitro, consistent with the detection of glycosaminoglycans inherent of the scaffold. In rat vocal folds implanted with HGF-loaded scaffolds, fewer inflammatory cells were observed 3 days after surgery when compared to the control. The mean relative densities of collagen III and hyaluronic acid were significantly lower than those of the control 7 days after surgery. Scaffold implants were apparently degraded by 3 months in all animals, with no evidence of fibrosis or calcification. These data suggested that the bovine acellular ECM scaffold could be promising for the exogenous delivery of select growth factors in vivo.