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Withania somnifera Dunal, also known as Indian ginseng, has been in use since ancient times in the management of diabetes mellitus (DM). This systematic review and meta-analysis evaluated the efficacy/effectiveness, safety and tolerability of W. somnifera in managing DM. Literature search (published/unpublished) was performed from inception to April 2019 in guidelines recommended databases. A total of 6 in-vitro, 13 pre-clinical and 5 clinical studies were included for systematic evaluation. W. somnifera treatment in DM significantly restored the altered levels of blood glucose (experimental data; mean difference, −196.27; 95% confidence interval [−220.96, −171.58]; p < .00001) glycosylated haemoglobin (HbA1c), insulin, lipid profile, serum and oxidative stress markers with no safety concerns. The results suggest the potential role of W. somnifera in managing DM. However, the available clinical data are not considerably enough to provide novel and sufficiently robust evidence for the use of W. somnifera in managing DM. To further strength the antidiabetic profile of W. somnifera, well-designed randomized-controlled trial(s) with alarger sample size and longer duration is warranted with evaluation of its effect primarily on blood glucose, HbA1c and insulin. Future research also needs to elucidate the molecular mechanism(s) of W. somnifera including its active principles in DM. K E Y W O R D Sdiabetes mellitus, Indian ginseng, meta-analysis, oxidative stress, systematic review

Electrically stimulable nerve conduits are implants that could potentially be utilized in patients with nerve injury for restoring function and limb mobility. Such conduits need to be developed from specialized scaffolds that are both electrically conductive and allow neuronal attachment and differentiation. In this study, we investigate neural cell attachment and axonal differentiation on scaffolds co-woven with poly-(L-lactic acid) (PLLA) yarns and conducting threads. Yarns obtained from electrospun PLLA were co-woven with polypyrrole (PPy)-coated PLLA yarns or ultrathin wires of copper or platinum using a custom built low-resistance semi-automated weaving machine. The conducting threads were first electrically characterized and tested for stability in cell growth media. Suitability of the conducting threads was further assessed via cell viability studies using PC12 cells. Neurite growth was then quantified after electrically stimulating rat dorsal root ganglion (DRG) sensory neurons cultured on the woven scaffolds. Electrical conductivity tests and cellular viability studies demonstrated better bio-tolerability of platinum wires over PPy-coated PLLA yarns and copper wires. Electrically stimulated DRG neurons cultured on platinum-PLLA co-woven scaffolds showed enhanced neurite outgrowth and length. We demonstrate that a woven scaffold design could be utilized to incorporate conducting materials into cell-tolerable polymer yarns for developing electrically stimulable nerve conduits.

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33 34 35 Abbreviations: 36 CFU, colony forming units; DPPH, diphenyl-1-picrylhydrazyl hydrate; FBS, fetal bovine 37 serum; FTIR, Fourier-transform infrared spectroscopy; JFRE, jackfruit rag extract; MBC, 38 minimum bactericidal concentration; MIC, minimum inhibitory concentration; MTT, 3-(4,5, 39 dimethylthiazol2-yl)-2, 5-diphenyltetrazolium bromide; SEM, scanning electron microscope, 40 GC-MS, Gas chromatography mass spectrometry. 41 42 2 Abstract 43The aim of this study was to determine the antibacterial property of extract derived from a part 44 of the Jackfruit called 'rag', that is generally considered as fruit waste. Morpho-physical 45 characterization of the Jackfruit rag extract (JFRE) was performed using gas-chromatography, 46where peaks indicative of furfural; pentanoic acid; and hexadecanoic acid were observed. In 47 vitro biocompatibility of JFRE was performed using the MTT assay, which showed comparable 48 cellular viability between extract-treated and untreated mouse fibroblast cells. Agar well disc 49 diffusion assay exhibited JFRE induced zones of inhibition for a wide variety of laboratory and 50 clinical strains of gram-positive and gram-negative bacteria. Analysis of electron microscope 51 images of bacterial cells suggests that JFRE induces cell death by disintegration of the bacterial 52 cell wall and precipitating intracytoplasmic clumping. The antibacterial activity of the JFREs 53 was further validated in vivo using Shigella dysenteriae infected fly model, where JFRE pre-54 fed flies infected with S. dysenteriae had significantly reduced mortality compared to controls. 55 JFRE demonstrates broad antibacterial property, both in vitro and in vivo, possibly by its 56 activity on bacterial cell wall. This study highlights the importance of exploring alternative 57 sources of antibacterial compounds, especially from plant-derived waste, that could provide 58 economical and effective solutions to current challenges in antimicrobial therapy. 59 60