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Oroxylum indicum , of the Bignoniaceae family, has various ethnomedical uses such as an astringent, anti-inflammatory, anti-bronchitis, anti-helminthic and anti-microbial, including anticancer properties. The druggability of OI stem bark extract was determined by its molecular docking interactions with PARP and Caspase-3, two proteins involved in cell survival and death. Note that 50 µg/mL of Oroxylum indicum extract (OIE) showed a significant ( p < 0.05%) toxicity to HSC-3 cells. MTT aided cell viability and proliferation assay demonstrated that 50 µg/mL of OIE displayed significant ( p < 0.5%) reduction in cell number at 4 h of incubation time. Cell elongation and spindle formation was noticed when HSC-3 cells were treated with 50 µg/mL of OIE. OIE initiated DNA breakage and apoptosis in HSC-3 cells, as evident from DNA ladder assay and calcein/EB staining. Apoptosis potential of OIE is confirmed by flow cytometer and triple-staining (live cell/apoptosis/necrosis) assay. Caspase-3/7 fluorescence quenching (LANCE) assay demonstrated that 50 µg/mL of OIE significantly enhanced the RFU of caspases-3/7, indicating that the apoptosis potential of OIE is probably through the activation of caspases. Immuno-cytochemistry of HSC-3 cells treated with 50 µg/mL of OIE showed a significant reduction in mitochondrial bodies as well as a reduction in RFU in 60 min of incubation time. Immunoblotting studies clearly showed that treatment of HSC-3 cells with OI extract caused caspase-3 activation and PARP deactivation, resulting in apoptotic cell death. Overall, our data indicate that OIE is an effective apoptotic agent for human squamous carcinoma cells and it could be a future cancer chemotherapeutic target.

Exosomes are the master transporters of genes, RNAs, microRNAs, proteins, and lipids. They have applications in major diseases, including cancer, cardiovascular diseases, neurological disorders, and diabetes mellitus. Delivery of the exosomes to recipient cells is governed by the functional heterogenicity of the tissues. Engineered exosomes are promising tools in tissue regeneration. In addition to their role as intracellular communication cargos, exosomes are increasingly primed as standard biomarkers in the progression of diseases, thereby solving the diagnostic dilemma. Futuristic empowerment of exosomes with OMICS strategy can undoubtedly be a bio-tool in translational medicine. This review discusses the advent transformation of exosomes in regenerative medicine and limitations that are caveats to broader applications in clinical use.

The present study investigated the effect of polysaccharide gel (PG) extracted from the rind of durian fruit which is encapsulated with Bacillus subtilis as a feed and co-inoculation with Artemia nauplii in the induction of immune response in Danio rerio after Vibrio immersion challenge (5 days). The total RBC count, lysozyme activity test, weight, and length analysis revealed that the zebra fishes fed with the PG encapsulated probiotics had more immune induction activity, survival, and growth than the non-encapsulated groups. When the expression of the immune-related genes was measured, the studies revealed the significant upregulation (P < 0 .05) of interleukin 1 beta (Il1b), lysozyme (lyz), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) genes in fish fed with PG encapsulated probiotics with A. nauplii showed an immense effect on the induction of immune response compared to other feeds., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Published by Elsevier Ltd.)

Objective: We examined regional specificity of microglial activation in the developing rat brain for 72 hours after hypoxia-ischemia (HI) and the effect of acetylcholine receptor (AChR) agonist on microglial activation., Study Design: Seven-day-old Wistar rats were divided into two groups: one receiving a single dose of AChR agonist just before hypoxia (carbachol; 0.1mg/kg) to investigate the reducing effect on brain damage with decreasing activation of microglia and the other group receiving saline as a control. Rats were subjected to left carotid artery ligation followed by 8% hypoxia. Brains were analyzed immunohistochemically at 24, 48, and 72 hours after HI. TNFα production was measured at respective times after HI., Results: Activation of microglia on the hippocampus of the control group was strong for the first 48 hours and then weakened. In contrast, activation of microglia on white matter and the cortex was weak at 24 hours and then became stronger. A single dose of carbachol significantly reduced brain damage with a marked reduction of microglial activation on the hippocampus, whereas it was less effective regarding microglial activation on white matter and the cortex. TNFα production was low in both groups., Conclusion: Regional specificity was observed for both microglial activation and susceptibility to carbachol for the first 72 hours after HI. Our data suggested that timely intervention along with region-specific microglial activation, apart from TNFα production, may be critical for the prevention of further brain damage after HI in the newborn., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In the present investigation, we examined the effect of Hyuganatsu (Citrus tamurana) extract (HE) on skin fibroblast (TIG-119) proliferation and migration during in vitro wound healing. HE selectively inhibited proliferation of TIG-119 cells at higher concentration (>1.0 mg/mL); at lower concentrations (0.1, 0.25, 0.5, and 0.75 mg/mL), it exhibited linear and time-dependent cell proliferation. In vitro scratch wound healing studies showed that the HE also accelerated the migration of cells towards the wounded region. Cytometric analysis demonstrated that HE extract did not alter G1/0 and S phases of cell cycle in any concentration studied; however, G2/M phases of cell cycle were significantly (P < 0.05) accelerated at 0.75 mg/mL dose. RT-PCR and Western blotting analysis indicated that HE markedly overexpressed levels of Rac-1, Rho-A, and Cdc-42 mRNA and the respective proteins. Cyclin-dependent kinases (Cdk-1 and -2) gene expression activity was significantly (P < 0.05) increased, but protein content decreased during treatment with HE. The induction of Cdk-1 and -2 by HE was abolished by inhibitors, transcription (DRB), and translation (CHX), implying transcriptional regulation that required de novo protein synthesis.

Urokinase plasminogen activator (uPA) system, comprising of uPA, its receptor uPAR and inhibitor, type 1 plasminogen activator inhibitor (PAI-1), plays a vital role in various biological processes involving extracellular proteolysis, fibrinolysis, cell migration and proliferation. The timely occurence of these processes are essential for normal wound healing. This study examines the regulation of uPA and PAI-1 by a natural polyphenol-rich compound, grape seed extract (GSE). GSE is reported to have beneficial effects in promoting wound healing. Fibroblast cells exposed to different doses of GSE for 18hours were processed for further studies such as ELISA, RT-PCR, western blotting, fibrinolytic assay, cell surface plasmin activity assay and in vitro wound healing assay. GSE treatment caused a significant downregulation of uPA and PAI-1 expression, both at the RNA and protein levels. ELISA also revealed a dose-dependent decrease in uPA and PAI-1 activities. Functional significance of the downregulation was evident in decreased fibrinolytic activity, concomittant with decreased cell-surface plasmin activity. In vitro wound healing studies showed that GSE also retarded the migration of cells towards the wounded region.