Biology subjects

K, S.

Publications and source records attributed to K, S..

At least 19 recordsLinked to original sources

bioRxiv2026

UT-018 Accelerates Wound Repair and Hair Follicle Regeneration in Murine Models

UT-018, a stem cell chemoattractant formulation, demonstrated significant regenerative activity across independent murine wound-healing and hair-regeneration studies. Topical treatment accelerated wound closure, enhanced granulation tissue formation, improved collagen organization, increased fibroblast proliferation, and enhanced dermal vascularization. Separate hair-growth studies demonstrated increased follicular density, deeper follicular penetration, enhanced dermal vascularization, and induction of anagen-phase transition by UT-018. Mechanistic studies demonstrated strong intracellular cAMP generation and activation-associated {beta}-catenin phosphorylation consistent with GPCR-mediated regenerative signaling.

pharmacology and toxicology↗

bioRxiv2026

Stress Granules Buffers Inflammation by Restricting dsRNA-led Mitochondrial Fragmentation

Stress granules (SGs) are dynamic RNA-RBP condensates that form during stress and inflammation, yet how they modulate inflammatory signalling remains unclear. We uncover a rapid, protective SG-mediated mechanism that preserves mitochondrial integrity. During stress and translation inhibition, mitochondrial fragmentation releases double-stranded RNA (dsRNA), which activates PKR and its downstream effector DRP1, generating a self-amplifying loop of mitochondrial fragmentation and inflammation. We find that released dsRNA nucleates nanoSGs within minutes at ER-mitochondria contact sites--the very sites of mitochondrial division. These nanoSGs grow into macroSGs, effectively sequestering PKR-activating dsRNA from the cytosol. By depleting dsRNA, SGs suppress PKR-DRP1-driven positive-feedback inflammation and maintain mitochondrial integrity and function. Our findings reveal SGs as key guardians of mitochondrial homeostasis and position condensate biology at the centre of chronic mitochondrial-driven inflammation relevant to autoimmunity, ageing, and neurodegenerative disease.

cell biology↗

bioRxiv2026

An Indian Diet Relevant Rat Screening Model for Hypertriglyceridemia Associated Fatty Liver

Hypertriglyceridemia is a dominant and early metabolic abnormality underlying fatty liver disease in Indian populations, often preceding obesity, insulin resistance, or inflammatory liver injury. Many diet-induced rodent models of hepatic steatosis rely on extreme obesogenic or fructose-rich diets that poorly reflect real-world Indian dietary patterns. Here, we describe a diet-induced rat screening model designed to reflect typical Indian cereal-rich, visible-fat dietary exposure and to preferentially induce triglyceride-centric hepatic lipid accumulation. The model reproducibly induces hepatic triglyceride deposition with preserved liver architecture and minimal inflammatory features, aligning with early-stage fatty liver observed clinically in Indian patients. This work does not propose a novel disease model nor evaluate therapeutic efficacy, but establishes a translationally relevant screening tool for prioritizing lipid-modulating interventions in hypertriglyceridemia-associated fatty liver. We show that the high-fat diet increased serum triglycerides [~]1.8 -fold versus chow (normalized index 1.0 vs 1.8), with organ weights remaining within [~]0.95-1.00 of reference (normalized indices), supporting screening tolerability. Secondary changes in liver morphology and histopathology were indicative of fatty liver.

pharmacology and toxicology↗

bioRxiv2026

NexaSweet Attenuates DSS-Induced Colitis and Preserves Colon Architecture in BALB/c Mice

We evaluated NexaSweet(R), a nutraceutical comprising fructooligosaccharides (FOS) combined with UT18 (a composition of selected amino acids and organic acid), in a dextran sulfate sodium (DSS)-induced colitis model in male BALB/c mice. Compared with DSS controls, NexaSweet improved bodyweight preservation ([~]13.4% relative improvement), reduced Disease Activity Index (DAI) by[~] 57.9%, increased colon length by[~] 32.1%, and reduced composite colon histopathology severity by[~] 53.1%, without adverse safety signals. These data support NexaSweet as a regenerationoriented, foodgrade intervention for mucosal repair. . Based on these data and by comparing with steroid therapy reported in literature, NexaSweet could be a favorable disease modifying ( not just symptomatic relief) therapeutic for gut diseases and wellness.

pharmacology and toxicology↗

bioRxiv2024

Human like severe hypertriglyceridemia in a high fat fed chicken model

Cardiovascular disease (CVD) is the biggest cause of mortality globally. Controlling the risk factors for CVD such as blood cholesterol and triglycerides is the hallmark of primary prevention of CVD. There are several drugs to control cholesterol that are available but not many approaches to reducing triglycerides safely are available. High blood triglycerides or hypertriglyceridemia in humans is classified as moderate (200-400 mg/dl plasma levels) severe (400-800 mg/dl) and very severe (>800 mg/dl). There are not many appropriate in vivo models to study human like severe hypertriglyceridemia. We show here that high fat fed chickens rapidly and in a sustained manner respond by demonstrating triglyceride levels reminiscent of severe hypertriglyceridemia in humans. Such a model could be useful in better understanding this human disease as well as serve to test new therapies.

pharmacology and toxicology↗

bioRxiv2023

Robust acidic pH and digestive enzyme stability of anti-SarsCov2 IgY antibodies: Implications for treatment of viral transmission thru gastrointestinal, ocular, nasal and skin tissues

There are many paths for the transmission of SarsCov2 virus. The main routes are nasal and oral and the droplets carrying the virus can also be transmitted thru ocular and skin tissues. The gastrointestinal (small intestine), nasal, ocular and skin tissues all present an acidic pH milieu and therefore any treatment with antibodies thru these routes has to have the antibodies remain active at acid pH as well as be resistant to typical protease digestion. To this end we profiled our anti-SarasCov2 receptor binding domain IgY antibodies for retention of activity at acidic and basic pHs and trypsin digestion. We find that the IgY are strongly resistant to denaturation at acid pH as well as not digested by trypsin. Our data strongly support the use of these IgY in treatment of viral transmission thru the GI, nasal, ocular and skin all tissues where the pH is acidic. We also provide an enabling platform to rapidly asses the suitability of any antibody or protein therapeutic for use at acidic pH.

pharmacology and toxicology↗

bioRxiv2023

Metformin an anti-diabetic drug, possess ACE-2 receptor-SARS- Cov-2 RBD binding antagonist activity, anti-inflammatory and cytokine inhibitory properties suitable for treatment of COVID-19

Metformin is a widely used and is a safe anti-diabetic drug. It has also been shown to have anti-inflammatory and anti-viral activities in humans and animal models. Specifically we explored its activity in SARS-CoV-2 initiated COVID19 disease. Here we show that metformin 1. blocks the binding of SARS-CoV-2 spike protein receptor binding domain RBD to human ACE2 receptor 2. We also show that it has anti-inflammatory effects and reduces cytokine secretion as well as blocks the recruitment of monocytes to endothelial cells 3. Finally we show its activity in a hamster in vivo model of SARS-CoV-2 infection as a nasal formulation. Based on the safety and the therapeutic properties relevant to COVID-19 it is feasible to propose a nasal spray of metformin that can be used in treatment of this disease. A nasal spray would deliver the drug to the target organ lung and spare other organs which get exposed upon oral dosing.

pharmacology and toxicology↗

bioRxiv2023

An Anti-diabetic Nutraceutical enhances muscle cell glucose uptake of cardiometabolic drugs

Type 2 diabetes is currently treated by multiple drugs that are often combined to achieve maximum blood glucose lowering in patients. Yet more than 50% of patients are unable to attain target glucose levels. There is clear need for agents which can be added to current drugs to help patients achieve their target blood glucose levels safely. To this end we tested an anti-diabetic nutraceutical for its ability to enhance glucose uptake in muscle cells in combination with currently used cardiometabolic drugs. We show here that the nutraceutical is able to effectively improve glucose uptake of multiple drugs suggesting that it may help in enhancement of glucose lowering by the drugs in patients and achieve optimal glucose levels.

pharmacology and toxicology↗

bioRxiv2022

Suppression of insulin stimulated muscle glucose uptake by non-caloric sweetener sucralose and its reversal by an antidiabetic nutraceutical supplement

Non caloric sweeteners (NCS) have been used for decades now as sugar substitutes in foods and beverages. The market for such products has grown immensely over time. There are human studies which report their negative effects on glucose metabolism with various results of disturbances in glucose metabolism, weight gain etc. No studies to the best of our knowledge have directly addressed the impact of the NCS on muscle glucose uptake. Muscle tissue can account for over 70 percent of whole-body glucose uptake. Therefore, we examined directly the effect of NCS on muscle cell glucose uptake. We find that aspartame moderately increased insulin stimulated glucose uptake by muscle cells in vitro. But sucralose, saccharin and stevia suppressed insulin stimulated glucose uptake. Sucralose is one of the most often used sweetener in foods and beverages globally it is important to understand its effects on glucose metabolism. Therefore, we explored the mechanism of its inhibition of glucose uptake by using an anti-diabetic nutraceutical which is known to target insulin mediated glucose uptake and metabolism pathways. We show here that the nutraceutical is able to relieve the suppression by sucrose in muscle uptake by a novel mechanism of action. We propose that such nutraceuticals may be useful to combine with sucralose containing products to offset negative effects of the NCS on glucose metabolism.

pharmacology and toxicology↗

bioRxiv2022

De-differentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development

Collateral arteries act as natural bypasses which re-route blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called Artery Reassembly, aids complete cardiac regeneration in neonatal hearts, but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries, like in cardiomyocytes, is dictated by their ability to de-differentiate. We performed single cell RNA sequencing of coronary endothelial cells and identified differences in molecular profiles of neonatal and adult endothelial cells. Neonates show significant increase in actively cycling artery cells that expressed prominent de-differentiation markers. Using both, in silico pathway analyses and in vivo experiments, we show that cell cycle re-entry of pre-existing artery cells, subsequent collateral artery formation and cardiac function is dependent on arterial VegfR2. This sub-population of de-differentiated and proliferating artery cells is absent in non-regenerative P7 or adult hearts. Together, our data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to de-differentiate and proliferate.

developmental biology↗

bioRxiv2022

Nutraceutical supplement targeting multiple molecular steps synergistically enhances muscle glucose uptake and improves in vivo oral glucose disposal

Pre diabetes and type 2 diabetes are increasingly becoming rampant world wide. While there are medications to control blood glucose in type 2 diabetics, currently there are no interventions prescribed for pre diabetes. Alternate strategies to control blood glucose are needed either to act alone in pre diabetes or as supplement to the existing drugs for type 2 diabetes. We report here the targeting of critical molecular steps in muscle glucose uptake and metabolism to result in glucose lowering using a combination of safe vitamins. Our in vitro and in vivo data support the potential for using such vitamin combination for glucose control in pre diabetes and as a supplement in type 2 diabetics.

pharmacology and toxicology↗

bioRxiv2022

A 3-Dimensional bioprinted human gut-liver axis model for studying Alcoholic Liver Disease

Gut-liver axis is the interaction between the gut, its microbiome and the liver. The crosstalk and interaction between these organs plays an important role in their individual health and disease. Alcoholic liver disease (ALD) is a case in point where dysfunction of intestine actively promotes liver damage by alcohol. A flashpoint in ALD is the breach of intestinal integrity caused by gut bacteria Enterococcus faecalis (E.Faecalis). More specifically, Cytolysin, a toxin secreted by this bacteria may have a central role in the genesis of ALD. 3-D bioprinted human simulations of the gut-liver axis may help better understand the genesis of ALD. Here we developed a 3 dimensional bioprinted in vitro model composed of human origin intestinal and liver cells to explore the role of Cytolysin and ethanol in intestinal and liver damage. We find that neither Cytolysin or ethanol are sufficient for cell damage but a combination of the two act in concert to cause maximum breach in intestinal integrity. Secondly we find that enhanced transport of macromolecules thru the intestinal layer is not caused by overt cell toxicity but occurs through potentially paracellular/transcellular pathways. Our model will be used to test repurposed and new drugs/ biologics for treatment of ALD as well as other intestinal inflammatory diseases.

pharmacology and toxicology↗

bioRxiv2022

Differential Activity of Repurposed Drugs as Receptor Binding Domain Antagonists for Omicron and Native Strains of SarsCov2

Omicron strain is the latest variant of concern of SarsCov2 virus. The mutations in this strain in the S protein Receptor Binding domain (RBD) enable it to be more transmissible as well as escape neutralizing activity by antibodies in response to vaccine. Thus, Omicron specific strategies are need to counter infection by this strain. We investigated a collection of approved drugs shown to antagonize the binding of native strain RBD to human ACE2, for their ability to antagonize binding to Omicron strain RBD. While most of the drugs the drugs that antagonize binding to native RBD are also active for Omicron RBD but some were inactive, namely drugs that contain iodine are completely inactive against Omicron RBD. Our data strongly indicate that presence of a single iodine molecule in the drug renders it inactive against Omicron strain. Thus, there is molecular specificity of drugs for antagonizing Omicron strain RBD versus native strain RBD of this virus. Such information will pave way for specific drugs for Omicron. A pragmatic message from our data is that the often-used iodine containing mouth wash and rises may be ineffective in antagonizing receptor binding of Omicron strain.

pharmacology and toxicology↗

bioRxiv2021

Mechanistic Model of Telomere Length Homeostasisin Yeast

Cells maintain homeostatic telomere length, and this homeostatic disruption leads to various types of diseases. Presently, it is not clear how telomeres achieve homeostasis. One of the prevailing hypotheses is a protein-counting model with a built-in sensor mechanism that counts proteins that directly regulate the telomeric length. However, it does not explain telomere length regulation at the mechanistic level. Here, we present a mathematical model based on the underlying molecular mechanisms of length regulation needed to establish telomere length homeostasis in yeast. We perform both deterministic and stochastic simulations to validate the models with the experimental data of Teixeira et al., rate-balance plot, and phase plane analysis to understand the nature of dynamics exhibited by the models. For global analysis, we constructed bifurcation diagrams. The model explains the role of negative and positive feedback loops and a delay between telomerase and telomere-bound proteins, leading to oscillations in telomere length. We map these in-silico results to Teixeiras proposition of telomeres making a transition between extendible and non-extendible states.

systems biology↗

bioRxiv2021

An Evaluation of Curriculum change in Physiology: A Mixed method research design

IntroductionThe quality of both teaching and learning techniques in health sciences determines the competency of the doctors produced and the patient care. Realizing the necessity of active learning at the undergraduate level, curricular reforms were crucial to ensure that students play an active role in the learning process and imbibe all the prerequisite qualities of a competent health professional. The objective of this study was to implement and evaluate case-based learning in the physiology curriculum. MethodsThe study included 150 first-year MBBS students. We followed a mixed research design in this study. A short lecture on anemia was followed by two sessions of CBL with a gap of one week. A structured questionnaire on a 5-point Likert scale was used to collect students perceptions. The internal consistency of the questionnaire was Cronbach -statistic = 0.8. Faculties feedback was collected through Focus Group Discussion (FGD). ResultsOut of 145 participants, 117 responded to feedback. Students perceived that the CBL method was effective in understanding anemia topic (71%); promoted meaningful learning (83%); encouraged teamwork (69%); improved communication skills (65%); helps in future application of knowledge (81%); motivated self-directed learning (66%); helped to understand physiology concepts better (72%); leads to the development of problem-solving abilities (70%); and better student-teacher relationship (72%). Faculties suggested developing an assessment plan for future CBL sessions. ConclusionIn our experience, CBL is an effective, active teaching-learning tool that improves students understanding of basic concepts, clinical knowledge, problem-solving abilities, teamwork, communication skills, student-teacher relationship, and self-directed learning.

scientific communication and education↗

bioRxiv2020

Assessment of heterotic potential and combining ability of immortal restorer lines derived from an elite rice hybrid, KRH-2, for the development of superior rice hybrids

Present investigation was carried out to assess the heterotic potential and combining ability of immortal restorer lines [consisting of two recombinant inbred lines (RILs) and two doubled haploid lines (DHLs)] developed from an elite rice hybrid, KRH-2 by crossing them with three popular WA-CMS lines, IR58025A, CRMS32A and APMS6A through line x tester analysis. The doubled haploid line 1 (DHL-1) was observed to be a good general combiner for total grain yield per plant (YLD) and other yield component traits and among the CMS lines, IR58025A was observed to be the best combiner as it showed positive significant values for the traits viz., total grain yield per plant, panicle length and spikelet fertility. Higher preponderance of the variance associated with specific combining ability (SCA) as compared to general combining ability (GCA) variance was observed for most of the traits indicated the predominant role of non-additive gene action in the expression of the traits. Out of twelve novel crosses between the immortal restorer lines derived from KRH-2 and the WA-CMS lines, 66.66% (eight crosses) showed significant and desirable SCA effects for the traits viz., total grain yield per plant, days to fifty percent flowering, plant height, flag leaf length, flag leaf width, number of filled grains per panicle and spikelet fertility. Two crosses IR58025A/RIL-24 and CRMS32A/RIL-24 were observed to be the most promising cross combinations showing standard heterosis of >50% for YLD trait (as compared with KRH-2) with higher prevalence of GCA and SCA, respectively. Heterotic yield advantage of IR58025A/RIL-24 and CRMS32A/RIL-24 was 77.05% and 54.74%, respectively over KRH-2 and these can be utilized for developing commercial hybrids. The present study also indicates the potentiality of RILs in providing useful parental lines for developing heterotic hybrids which are hard to get from outside sources in the new intellectual property regime.

genetics↗

bioRxiv2020

Osteogenic differentiation potential and marker gene expression of different porcine bone marrow mesenchymal stem cell subpopulations selected in different basal media

Multipotent porcine mesenchymal stem cells (pMSC) are indispensable for research and therapeutic use. Derivation and culture media might affect the selection of MSC subpopulation and thus the differentiation potential of cells. In this study we evaluated the effects of MEM, aDMEM, M199, MEM/M199, aDMEM/M199 and MEM/aDMEM media on porcine bone marrow MSC derivation; pre-differentiation expression of ALP, COL1A1, SPP1 and BGLAP osteogenic marker genes at passage 5 and 10 pMSC; and differentiation potential of passage 5 pMSC. Morphological changes and matrix formation in osteogenic cells were evaluated by microscopical examination and calcium deposit in osteocytes was confirmed by Alizarin Red S staining. Results indicated media independent selection of different bone marrow MSC subpopulations with different surface marker gene expressions. Many pMSC subpopulations in different media had CD14+ expressing cells. We also observed basal media dependent changes in osteogenic markers expression and differentiation potential of pMSC. The MEM/aDMEM media grown pMSC showed best osteogenic differentiation potential. We thus recommended the testing of MEM/aDMEM mixed media in other species for pre-differentiation MSC culture that are intended for better osteogenic differentiation. SummaryPre-differentiation basal media influence osteogenic differentiation potential of mesenchymal stem cells (MSC). Among the tested media, MEM/aDMEM was the best for pre-differentiation porcine MSC culture intending to use in osteogenesis.

molecular biology↗

bioRxiv2019

Coconut inflorescence sap mediated synthesis of silver nanoparticles and its diverse antimicrobial properties

Green synthesis of nanoparticles (NPs) involves the use of diverse extracts of biological origin as substrates to synthesize nanoparticles and can overcome the hazards associated with chemical methods. Coconut inflorescence sap, which is unfermented phloem sap obtained by tapping of coconut inflorescence, is a rich source of sugars and secondary metabolites. In this study, coconut inflorescence sap was used to synthesize silver nanoparticles (AgNPs). We have initially undertaken metabolomic profiling of coconut inflorescence sap from West Coast Tall cultivar to delineate its individual components. Secondary metabolites constituted the major portion of the inflorescence sap along with sugars, lipids and, peptides. The concentration of silver nitrate, inflorescence sap and incubation temperature for synthesis of AgNPs were optimized. Incubating the reaction mixture at 40{degrees}C was found to enhance AgNP synthesis. The AgNPs synthesized were characterized using UV-Visible spectrophotometry, X-Ray Diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM) and Transmission Electron Microscopy (TEM). Antimicrobial property of AgNP was tested in tissue culture of arecanut (Areca catechu L.) where bacterial contamination (Bacillus pumilus) was a frequent occurrence. Significant reduction in the contamination was observed when plantlets were treated with aqueous solutions of 0.01, 0.02 and 0.03% of AgNPs for one hour. Notably, treatment with AgNPs did not affect growth and development of the arecanut plantlets. Cytotoxicity of AgNPs was quantified in HeLa cells. Viability (%) of HeLa cells declined significantly at 10 ppm concentration of AgNP and complete mortality was observed at 60 ppm. Antimicrobial properties of AgNPs synthesized from inflorescence sap were also evaluated and confirmed in human pathogenic bacteria viz., Salmonella sp., Vibrio parahaemolyticus, and Escherichia coli. The study concludes that unfermented inflorescence sap, with above neutral pH, serves as an excellent reducing agent to synthesize AgNPs from Ag+.\n\nO_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC=\"FIGDIR/small/775940v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (64K):\norg.highwire.dtl.DTLVardef@3c3f1forg.highwire.dtl.DTLVardef@1540f6borg.highwire.dtl.DTLVardef@1c069aborg.highwire.dtl.DTLVardef@159772c_HPS_FORMAT_FIGEXP M_FIG Graphical abstract\n\nC_FIG

plant biology↗