Biology subjects

Lakshmi, G.

Publications and source records attributed to Lakshmi, G..

3 recordsLinked to original sources

bioRxiv2023

Epigenomic signatures as circulating and predictive biomarkers in sarcomatoid renal cell carcinoma

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are (1) a limited understanding of its gene regulatory programs and (2) difficulty identifying sarcomatoid differentiation on tumor biopsies due to spatial heterogeneity. To address these challenges, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries in tissue and plasma samples from 50 patients with RCC and healthy volunteers. We identified highly recurrent epigenomic reprogramming, as assessed by histone modifications and DNA methylation, that distinguishes sRCC from non-sarcomatoid RCC. Computational analysis of RCC epigenomic profiles and CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs. Analysis of two randomized clinical trials identified FOSL1 expression as a predictive biomarker of response to ICIs in RCC. Finally, we demonstrate that epigenomic signatures of sRCC are detectable in patient plasma, establishing an approach for blood-based diagnosis of this clinically important phenotype. These findings provide a framework for the discovery and non-invasive detection of epigenomic correlates of tumor histology via liquid biopsy.

genomics↗

bioRxiv2023

Interaction studies of Gut metabolite Trimethylene amine Oxide with Bovine Serum Albumin through Spectroscopic, DFT and Molecular Docking Approach

Trimethyleneamine N-oxide (TMAO); a gut microbiota derived metabolite has been involved in human health and diseases. It is enhanced by insulin resistivity and linked with various metabolic syndromes in human being such as renal, neuro-degenerative, and cardiovascular diseases. The primary mechanism through which TMAOs promotes disease is not clear yet. TMAO with MW= 75.11 g/mol is a small biomolecule hence, it becomes crucial to develop the conjugate of TMAO with BSA for aptamer synthesis. The binding interactions among TMAO and BSA were investigated using spectroscopic methods like UV-Vis, photoluminescence, Fourier transform infrared and circular dichroism. Hydrophilicity/Hydrophobicity of the conjugate was monitored by using contact angle ([O]) measurement. Sodium dodecyl sulphate polyacryl amide gel electrophoresis (SDS-PAGE) confirmed the different ratio of conjugate formation with the help of band size. This interaction study reveals that TMAO bind with BSA on two sites and with high affinity on one site. Docking studies also showed TMAO is involved in non-covalent interaction with bovine serum albumin forming stable docking complex with binding score of -3.6 kcal/mol obtained from the docking simulation. TMAO is involved in interaction with BSA via amino acid residues forming the stable docking complex through hydrogen bond and electrostatic interaction. This kind of interaction study may be helpful in making strategies to break the conjugation between serum albumin and uremic toxin and pave the way for the treatment for CKD and other diseases wherein TMAO is implicated. Also, conjugation of TMAO and BSA studied here may also serve as premise to develop aptamers for the detection of TMAO in the body fluids.

biochemistry↗

bioRxiv2022

Optical tuning of polymer functionalized zinc oxide quantum dots as a selective probe for specific detection of antibiotics

It is crucial to monitor the antibiotic levels in the environment like water, food products in the current scenario as the antibiotic concentration above threshold is harmful for the human health. Excess consumption of antibiotics leads to antibiotic resistance that hinders the control and cure of microbial diseases. So, these challenges motivated to devise an optical nano-senor which can sense the ultra-low concentration of antibiotics. In this proposed research work, emphasis is to develop a method which is simple and selective to analyze the detection and presence of antibiotics in various samples like tape water milk etc. using fluorescent ZnO QDs based nano-sensor. For this, fluorescent and different polymers (polyvinylalcohol - PVA and polyvinylpyrrolidine - PVP) capped ZnO QDs were synthesized using modified sol-gel technique. These were used as fluorescent probe to monitor the presence of antibiotics. The optical characterizations of synthesized QDs were performed using UV-Visible absorption & fluorescence spectroscopic methods while structural characteristics were analyzed by using FTIR, XRD and EDX. Charge on the synthesized QDs were obtained with the help of ZETA potential. Here ten different antibiotics were targeted among, Ciprofloxacin and Moxifloxacin have shown excellent sensing and specificity with PVA-ZnO QDs and PVP-ZnO QDs respectively.

biophysics↗