Gelatin, one of the most abundant, naturally derived biomacromolecules from collagen, is widely applicable in food additives, cosmetic ingredients, drug formulation, and wound dressing based on their non-toxicity and biodegradability. In parallel, polyvinyl alcohol (PVA), a synthetic polymer, has been commonly applied as a thickening agent for coating processes in aqueous systems and a major component in healthcare products for cartilage replacements, eye lubrication, and contact lenses. In this study, a new type of mixed hydrogel nanofiber was fabricated from gelatin and polyvinyl alcohol by electrospinning under a feasible range of polymer compositions. To determine the optimal composition of gelatin and polyvinyl alcohol in nanofiber fabrication, several key physicochemical properties of mixed polymer solutions such as viscosity, surface tension, pH, and electrical conductance were thoroughly characterized by a viscometer, surface tensiometer, water analyzer, and carbon electron probe. Moreover, the molecular structures of polymeric chains within mixed hydrogel nanofibers were investigated with Fourier-transform infrared spectroscopy. The morphologies and surface elemental compositions of the mixed hydrogel nanofibers were examined by the scanning electron microscope and energy-dispersive X-ray spectroscopy, respectively. The measurement of water contact angles was performed for measuring the hydrophilicity of nanofiber surfaces. Most importantly, the potential cytotoxicity of the electrospun nanofibers was evaluated by the in vitro culture of 3T3 fibroblasts. Through our extensive study, it was found that a PVA-rich solution (a volumetric ratio of gelatin/polyvinyl alcohol <1) would be superior for the efficient production of mixed hydrogel nanofibers by electrospinning techniques. This result is due to the appropriate balance between the higher viscosity (~420–~4300 10⁻² poise) and slightly lower surface tension (~35.12–~32.68 mN/m²) of the mixed polymer solution. The regression on the viscosity data also found a good fit by the Lederer–Rougier’s model for a binary mixture. For the hydrophilicity of nanofibers, the numerical analysis estimates that the value of interfacial energy for the water contact on nanofibers is around ~−0.028 to ~−0.059 J/m².

The NS5A protein of the hepatitis C virus (HCV) is an integral component of the viral replicase. It also modulates cellular signaling and perturbs host interferon responses. The multifunctional characteristics of NS5A are mostly attributed to its ability to interact with various cellular proteins. This study aimed to identify the novel cellular factors that interact with NS5A and decipher the significance of this interaction in viral replication. The NS5A-interacting proteins were purified by the tandem affinity purification (TAP) procedure from cells expressing NS5A and identified by mass spectrometry. The chaperone protein Hsp72 was identified herein. In vivo protein-protein interaction was verified by co-immunoprecipitation and an in situ proximity ligation assay. In addition to NS5A, Hsp72 was also associated with other members of the replicase complex, NS3 and NS5B, suggesting that it might be directly involved in the HCV replication complex. Hsp72 plays a positive regulatory role in HCV RNA replication by increasing levels of the replicase complex, which was attributed either to the increased stability of the viral proteins in the replicase complex or to the enhanced translational activity of the internal ribosome entry site of HCV. The fact that the host chaperone protein Hsp72 is involved in HCV RNA replication may represent a therapeutic target for controlling virus production.

In the tumor microenvironment hypoxia and nutrient deprived states can induce endoplasmic reticulum (ER) stress. If ER stress is not relieved, the tumor cells may become apoptotic. Therefore, targeting ER homeostasis is a potential strategy for cancer treatment. Various chemotherapeutic agents including histone deacetylase (HDAC) inhibitors can induce ER stress to cause cell death in cancers. Some HDAC inhibitors can prevent HDAC from binding to the specificity protein 1-binding site of the promoter of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and up-regulate RECK expression. Up-regulation of RECK expression by HDAC inhibitors has been observed in various cancer types. RECK is a tumor and metastasis suppressor gene and is critical for regulating tumor cell invasiveness and metastasis. RECK also modulates ER stress via binding to and sequestering glucose-regulated protein 78 protein, so that the transmembrane sensors, such as protein kinase RNA-like ER kinase are released to activate eukaryotic translational initiation factor 2α phosphorylation and enhance ER stress. Therefore, HDAC inhibitors may directly induce ER stress or indirectly induce this stress by up-regulating RECK in cancer cells.

Stroke is one of the leading causes of mortality, with a high incidence of severe morbidity in survivors. The treatment to minimize tissue injury after stroke is still unsatisfactory and it is mandatory to develop effective treatment strategies for stroke. The pathophysiology of ischemic stroke is complex and involves many processes including energy failure, loss of ion homeostasis, increased intracellular calcium level, platelet aggregation, production of reactive oxygen species, disruption of blood brain barrier, and inflammation and leukocyte infiltration, etc. Tetrandrine, a bisbenzylisoquinoline alkaloid, has many pharmacologic effects including anti-inflammatory and cytoprotective effects. In addition, tetrandrine has been found to protect the liver, heart, small bowel and brain from ischemia/reperfusion injury. It is a calcium channel blocker, and can inhibit lipid peroxidation, reduce generation of reactive oxygen species, suppress the production of cytokines and inflammatory mediators, inhibit neutrophil recruitment and platelet aggregation, which are all devastating factors during ischemia/reperfusion injury of the brain. Because tetrandrine can counteract these important pathophysiological processes of ischemic stroke, it has the potential to be a protective agent for ischemic stroke.