Publications by authors named "B Y Santosh Kumar"

2,926 Publications

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Investigation of indole functionalized pyrazoles and oxadiazoles as anti-inflammatory agents: Synthesis, in-vivo, in-vitro and in-silico analysis.

Bioorg Chem 2021 Jun 8;114:105068. Epub 2021 Jun 8.

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, Ferozpur G.T. Road MOGA-142001, Punjab, India. Electronic address:

There are several potential side and adverse effects are found to be associated with the anti-inflammatory drugs in clinical practice. The long-term use of these clinical agents highly unsafe. It encouraged the development of novel heterocyclic compounds with potential anti-inflammatory activity and low to no toxicity. In present investigation, a total of 12 indole functionalized pyrazole and oxadiazole derivatives were designed, synthesized and evaluated for the in-vivo anti-inflammatory and analgesic potential. These compounds displayed comparable anti-inflammatory and analgesic potential to the reference drugs. Finally, molecular docking analysis was performed considering different anti-inflammatory targets to determine the mechanistic target of the designed molecules. Detailed analysis suggested that the molecules inhibit COX-2, preferably over other anti-inflammatory targets. The results suggested that two compounds (15c and 15f) were found promising candidates for the development of novel anti-inflammatory agents.
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http://dx.doi.org/10.1016/j.bioorg.2021.105068DOI Listing
June 2021

Maintenance of the human memory T cell repertoire by subset and tissue site.

Genome Med 2021 Jun 14;13(1):100. Epub 2021 Jun 14.

Department of Microbiology and Immunology, Columbia University, New York, NY, USA.

Background: Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating effector-memory (TEM), central memory (TCM), or terminal effector (TEMRA) subsets in blood and tissues. The relationship between circulating and tissue resident T cell subsets in humans remains elusive, and is important for promoting site-specific protective immunity.

Methods: We analyzed the TCR repertoire of the major memory CD4 and CD8T cell subsets (TEM, TCM, TEMRA, and TRM) isolated from blood and/or lymphoid organs (spleen, lymph nodes, bone marrow) and lungs of nine organ donors, and blood of three living individuals spanning five decades of life. High-throughput sequencing of the variable (V) portion of individual TCR genes for each subset, tissue, and individual were analyzed for clonal diversity, expansion and overlap between lineage, T cell subsets, and anatomic sites. TCR repertoires were further analyzed for TRBV gene usage and CDR3 edit distance.

Results: Across blood, lymphoid organs, and lungs, human memory, and effector CD8T cells exhibit greater clonal expansion and distinct TRBV usage compared to CD4T cell subsets. Extensive sharing of clones between tissues was observed for CD8T cells; large clones specific to TEMRA cells were present in all sites, while TEM cells contained clones shared between sites and with TRM. For CD4T cells, TEM clones exhibited the most sharing between sites, followed by TRM, while TCM clones were diverse with minimal sharing between sites and subsets. Within sites, TRM clones exhibited tissue-specific expansions, and maintained clonal diversity with age, compared to age-associated clonal expansions in circulating memory subsets. Edit distance analysis revealed tissue-specific biases in clonal similarity.

Conclusions: Our results show that the human memory T cell repertoire comprises clones which persist across sites and subsets, along with clones that are more restricted to certain subsets and/or tissue sites. We also provide evidence that the tissue plays a key role in maintaining memory T cells over age, bolstering the rationale for site-specific targeting of memory reservoirs in vaccines and immunotherapies.
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http://dx.doi.org/10.1186/s13073-021-00918-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204429PMC
June 2021

Assessing the in situ bacterial diversity and composition at anthropogenically active sites using the environmental DNA (eDNA).

Mar Pollut Bull 2021 Jun 11;170:112593. Epub 2021 Jun 11.

National Centre for Coastal Research, Ministry of Earth Sciences (MoES), Government of India, Chennai 600100, India.

In this study, we identified the in situ bacterial groups and their community structure in coastal waters influenced by anthropogenic inputs. The use of environmental DNA (eDNA) and high throughput sequencing (HTS) were employed to derive accurate and reliable information on bacterial abundance. The V3 and V4 hypervariable regions of the 16S rRNA gene were amplified and the sequences were clustered into operational taxonomic units to analyze the site-specific variations in community composition. The percentage composition within the bacterial orders varied significantly among nearshore anthropogenic hotspots and offshore (5 km) samples. The microbial network constructed taking the bacterial abundance as nodes displayed strong positive and negative correlations within the bacterial families. Overall, the use of eDNA coupled with HTS is an incredible means for monitoring and assessing the abundance of bacterial communities and also serves as a biomonitoring tool to understand the degree of anthropogenic contamination in coastal waters.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112593DOI Listing
June 2021

Glitazones Activate PGC-1α Signaling via PPAR-γ: A Promising Strategy for Antiparkinsonism Therapeutics.

ACS Chem Neurosci 2021 Jun 14. Epub 2021 Jun 14.

Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Mysuru, Karnataka 570 015, India.

Understanding various aspects of Parkinson's disease (PD) by researchers could lead to a better understanding of the disease and provide treatment alternatives that could significantly improve the quality of life of patients suffering from neurodegenerative disorders. Significant progress has been made in recent years toward this goal, but there is yet no available treatment with confirmed neuroprotective effects. Recent studies have shown the potential of PPARγ agonists, which are the ligand activated transcriptional factor of the nuclear hormone superfamily, as therapeutic targets for various neurodegenerative disorders. The activation of central PGC-1α mediates the potential role against neurogenerative diseases like PD, Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Further understanding the mechanism of neurodegeneration and the role of glitazones in the activation of PGC-1α signaling could lead to a novel therapeutic interventions against PD. Keeping this aspect in focus, the present review highlights the pathogenic mechanism of PD and the role of glitazones in the activation of PGC-1α via PPARγ for the treatment of neurodegenerative disorders.
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http://dx.doi.org/10.1021/acschemneuro.1c00085DOI Listing
June 2021

Impact of Intravenous Vitamin C Administration in Reducing Severity of Symptoms in Breast Cancer Patients During Treatment.

Cureus 2021 May 6;13(5):e14867. Epub 2021 May 6.

Internal Medicine, Jinnah Postgraduate Medical Centre, Karachi, PAK.

Introduction Alternative medicine during treatment is often used to make the quality of life (QoL) better. Women with early-stage breast cancer, particularly the ones who possess lower QoL, are more prone to opt for complementary medicine. This study aims to explore the effects exerted by intravenous vitamin C (IVC) on symptoms and adverse events associated with breast cancer treatment. Methods This single-center, parallel-group, single-blind interventional study was conducted in the oncology ward of a tertiary care hospital in Pakistan. For this study, after informed consent was taken, breast cancer patients with Union for International Cancer Control stages IIA to IIIb were included in the study. Three hundred and fifty (n = 350) patients were randomized into two groups at a ratio of 1:1. Study group was randomized to receive 25 grams per week of IVC at a rate of 15 grams per hour for four weeks in addition to their current standard treatment, and the control group received placebo (normal saline drip with label removed) in addition to their current standard treatment. Results In patients who had received IVC, there was a significant decrease in the mean severity score after 28 days for the following symptoms: nausea (2.65 ± 0.62 vs. 2.59 ± 0.68; p-value: 0.0003), loss of appetite (2.26 ± 0.51 vs. 2.11 ± 0.52; p-value: 0.007), tumor pain (2.22 ± 0.45 vs. 1.99 ± 0.40, p-value: <0.0001), fatigue (3.11 ± 0.32 vs. 2.87 ± 0.29; p-value: <0.0001), and insomnia (2.59 ± 0.35 vs. 2.32 ± 0.36, p-value: <0.0001). Conclusion Our study showed improvement in the mean severity score of nausea, fatigue, tumor pain, loss of appetite, and fatigue. More studies are also needed to assess the long-term effects of IVC in the cancer management. This shall help incorporate the use of IVC in standard practice to make the journey of cancer management comfortable for the patients.
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http://dx.doi.org/10.7759/cureus.14867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177022PMC
May 2021