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Biology subjects

Singh, A. R.

Publications and source records attributed to Singh, A. R..

4 recordsLinked to original sources

Bio-Templated Zinc Oxide Nanotherapeutics from Flemingia macrophylla kuntze Ex Merr: In Vivo Anti-Diabetic and Anti-Inflammatory Efficacy in Drosophila melanogaster

Nanotechnology has a major impact on the creation of novel and effective therapies for the treatment of several diseases, including diabetes and cancer. The current work is a report on the use of the aqueous extract from the leaves of the Flemingia macrophylla plant as a capping and reducing agent in the green synthesis of zinc oxide nanoparticles (ZnO-NPs).The synthesized ZnO-NPs were subjected to characterization through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM) scanning electron microscopy (SEM), and ultraviolet-visible spectroscopy (UV-Vis). Dose-dependent in vivo effects were investigated using Drosophila melanogaster subjected to a high-sugar diet (HSD) to induce a diabetic-like model. In vitro anti-oxidant, anti-diabetic, anti-inflammatory assay, survival, locomotor function, neuroanatomical integrity, ovary and testis morphology, egg-laying capacity, and male fertility were evaluated. The most prominent UV-visible peak was detected at around 370 nm. Structural and morphological analysis via XRD and electron microscopy confirmed the hexagonal phase of the ZnO-NPs, indicating an average calcined particle size of around 47 nm at 500 degree C. The manuscript reports significant anti-diabetic and anti-inflammatory effects in vitro and in the in vivo Drosophila model, together with antioxidant activity. The in vivo results indicate that green-synthesized ZnO-NPs mitigate adverse phenotypes triggered by a high-sugar diet and also potential as an anti-diabetic intervention and warrant further mechanistic and preclinical investigation. Keywords: Flemingia macrophylla; Green ZnO-NPs; Drosophila melanogaster; high-sugar diet; nanobiotechnology

pharmacology and toxicology↗

Protein diffusion controls how single cells respond to electric fields

Cells sense and respond to electric fields, using these fields as a guidance cue in wound healing and development. This sensing is done by redistribution of charged membrane proteins on the cells surface ("sensors") via electrophoresis and electroosmotic flow. If membrane proteins have to physically rearrange on the cells surface, how quickly can a cell respond to an applied signal? What limits the cells ability to respond? Are galvanotaxing cells, like chemotaxing cells, limited by stochasticity from the finite number of molecules? Here, we develop a model for the response dynamics of galvanotaxing cells and show that, for weak enough field strengths, two relevant timescales emerge: the time for the cells sensors to rearrange, which depends on their diffusion across the cell, and the time for the cells orientation to respond to an applied field, which may be very different. We fit this model to experimental measurements on the recently-identified sensor galvanin (TMEM154) in neutrophil-like HL-60 cells, finding that given the dynamics of a cell responding to an applied field, we can predict the dynamics of the cell after the field is turned off. This fit constrains the noise of the galvanotaxis process, demonstrating that HL-60 is not limited by the stochasticity of finite sensor number. Our model also allows us to explain the effect of media viscosity on cell dynamics, and predict how cells respond to pulsed DC fields. These results place constraints on the ability to guide cells with pulsed fields, predicting that a field on half of the time is no better than a field that is always on with half the magnitude.

cell biology↗

BESFA: Bioinformatics based Evolutionary, Structural & Functional Analysis of Prostrate, Placenta, Ovary, Testis, and Embryo (POTE) Paralogs

The POTE family comprises 14 paralogues and is primarily expressed in Prostrate, Placenta, Ovary, Testis, Embryo (POTE), and cancerous cells. The prospective function of the POTE protein family under physiological conditions is less understood. We systematically analyzed their cellular localization and molecular docking analysis to elucidate POTE proteins structure, function, and Adaptive Divergence. Our result discerns that group three POTE paralogs (POTEE, POTEF, POTEI, POTEJ, and POTEKP (a pseudogene)) exhibits significant variation among other members could be because of their Adaptive Divergence. Furthermore, our molecular docking studies on POTE protein revealed the highest binding affinity with NCI-approved anticancer compounds. Additionally, POTEE, POTEF, POTEI, and POTEJ were subject to an explicit molecular dynamic simulation for 50ns. MM-GBSA and other essential electrostatics were calculated that showcased that only POTEE and POTEF have absolute binding affinities with minimum energy exploitation. Thus, this studys outcomes are expected to drive cancer research to successful utilization of POTE genes family as a new biomarker, which could pave the way for the discovery of new therapies.

cancer biology↗

Patient-derived endometrial organoids from MRKH patients: Insight in disease causing pathways

The uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focusses on DNA-sequencing efforts and, so far, failed to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully hormone responsive. Transcriptome analyses, however, identified an array of dysregulated genes that point at potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.

developmental biology↗