Publications by authors named "S N Sinha"

4,967 Publications

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Caviunin glycoside (CAFG) from Dalbergia sissoo attenuates osteoarthritis by modulating chondrogenic and matrix regulating proteins.

J Ethnopharmacol 2021 Jun 8:114315. Epub 2021 Jun 8.

Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India. Electronic address:

Ethnopharmacological Relevance: Dalbergia sissoo DC. (Indian rosewood or Sheesham) is a traditional medicinal plant, reported since time immemorial for its analgesic, anti-nociceptive, anti-inflammatory, and immuno-modulatory properties. D. sissoo DC (DS). is being used traditionally to cure joint inflammation and joint pain.

Aim: To study the potential of DS leaves and its derived novel compound CAFG to treat the clinical symptoms of osteoarthritis (OA) and its underlying mechanism.

Methods: The chemical profile of DS extract (DSE) with isoflavonoids and isoflvaonoid glycosides from the DS was established by UHPLC-PDA and UHPLC-MS/MS. Monosodium iodoacetate (MIA) was injected into the knee joint to develop the OA model in rats. DSE were given orally for 28 days daily at 250 and 500 mg.kgday. For in-vitro experiments, chondrocytes were isolated from joint articular cartilage were negatively induced with interleukin-1β (IL-1β) and CAFG was given to the cells as a co-treatment.

Results: Chondrocytes undergo apoptosis following inflammation and proteoglycan synthesis affected in MIA injected knees. DSE administration prevented these effects as assessed by H&E and Toluidine blue staining. Micro-CT analysis showed that subchondral bone loss was restored. DSE decreased elevated serum levels of cartilage-bone degradation (CTX-I, CTX-II, and COMP), inflammation markers IL-1β, and matrix-degrading MMP-3 and 13. The effects of IL-1β on gene expression of chondrocytes were reversed by CAFG treatment at 1 μM.

Conclusion: Data showed that DSE protected joint cartilage and deterioration in subchondral bone in vivo while in in-vitro, its active ingredient CAFG prevented interleukin-1β induced effects and inhibited OA. This finding suggest that DSE and CAFG could be used as a possible therapeutic to treat osteoarthritis.
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http://dx.doi.org/10.1016/j.jep.2021.114315DOI Listing
June 2021

Unregulated online sales of cardiac implantable electronic devices in the United States: A six-month assessment.

Heart Rhythm O2 2020 Oct 12;1(4):235-238. Epub 2020 Jul 12.

Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Background: An estimated 1 million patients require cardiac implantable electronic devices (CIEDs) but go without annually. This disparity exists in low-to-middle-income nations largely owing to the cost of CIED hardware. of CIEDs has been shown to be safe and feasible. However, recent publications have raised concern that promotion of CIED reuse may foster a CIED "black market," to the dismay of manufacturers, regulators, and clinicians alike.

Objective: To determine if unregulated CIED sales for potential human use is a real issue by investigating unregulated public online CIED sale listings in the United States of America.

Methods: An observational study was undertaken over 6 months using multiple internet search engines from May 1 to November 1, 2019. We cataloged (still in packaging, manufactured <7 years) and pricing. Manufacturers were contacted to determine status of sellers and using model/serial numbers.

Results: In total, 58 CIEDs-47 implantable cardioverter-defibrillators and 11 permanent pacemakers-from 4 manufacturers were listed for sale on 3 websites. During the study period, 8 of 11 pacemakers and 37 of 47 implantable cardioverter-defibrillators were sold (price range: $100-$1500 [US dollars]). No new listings were seen in the last 3 months of observation, possibly owing to concomitant industry investigation.

Conclusion: There does exist a public online market for unregulated CIED sales in the United States. This specific market seems to be small and unlikely to significantly expand with active monitoring by manufacturers and regulators.
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http://dx.doi.org/10.1016/j.hroo.2020.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183896PMC
October 2020

Altered vascular permeability but not angiogenesis may play a role in the epileptogenesis of human hippocampal sclerosis.

Epileptic Disord 2021 Jun 8. Epub 2021 Jun 8.

Department of Neurology, NIMHANS, Bangalore, India.

Objective: We investigated the role of angiogenesis and vascular permeability in the pathogenesis of human drug-resistant epilepsy due to hippocampal sclerosis.

Methods: Resected hippocampi from 30 histologically confirmed cases of hippocampal sclerosis and 30 age-matched post-mortem controls were examined by immunohistochemical quantitation of vascular endothelial markers, CD31 and CD105 (markers of newly formed vessels), and data were analysed relative to MR volumetry. The blood-brain barrier was evaluated based on immunohistochemistry for IgG, albumin, VEGF and AQP4.

Results: Mean vascular density in the hippocampus was 8.71/mm in hippocampal sclerosis samples compared to 7.94/mm in age-matched controls. No statistically significant increase in vascular density was found in hippocampal sclerosis samples. Although no neoangiogenesis was found in hippocampal sclerosis samples based on CD105, breakdown of the blood-brain barrier, enhanced neuronal expression of VEGF, and perivascular seepage of IgG and albumin with uptake within neurons and astrocytes were found. Redistribution of the water channel protein, AQP4, reflected by change from normal punctate labelling to intense diffuse staining in hippocampal sclerosis samples, indicated an altered glia-vascular interface, disrupting blood-brain barrier permeability.

Significance: Our data show no objective histological evidence of angiogenesis in hippocampal sclerosis samples. When controlled for the confounding variable of hippocampal area, there was no difference in vascular density between cases and controls. A leaky blood-brain barrier and redistribution of AQP4 were identified which may contribute to epileptogenesis. This constitutes the largest study in the published literature evaluating a role of vascular permeability and angiogenesis in human hippocampal sclerosis.
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http://dx.doi.org/10.1684/epd.2021.1290DOI Listing
June 2021

Correction to: Effect of shunt type on rates of tube-cornea touch and corneal decompensation after tube shunt surgery in uveitic glaucoma.

Graefes Arch Clin Exp Ophthalmol 2021 Jun 7. Epub 2021 Jun 7.

Wills Eye Hospital, Glaucoma Research Center, 840 Walnut Street, Suite 1140, Philadelphia, PA, 19107, USA.

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http://dx.doi.org/10.1007/s00417-021-05263-4DOI Listing
June 2021

Integration of Dual Stress Transcriptomes and Major QTLs from a Pair of Genotypes Contrasting for Drought and Chronic Nitrogen Starvation Identifies Key Stress Responsive Genes in Rice.

Rice (N Y) 2021 Jun 5;14(1):49. Epub 2021 Jun 5.

ICAR-National Institute for Plant Biotechnology, Pusa Campus, New Delhi, 110012, India.

We report here the genome-wide changes resulting from low N (N-W+), low water (N+W-)) and dual stresses (N-W-) in root and shoot tissues of two rice genotypes, namely, IR 64 (IR64) and Nagina 22 (N22), and their association with the QTLs for nitrogen use efficiency. For all the root parameters, except for root length under N-W+, N22 performed better than IR64. Chlorophyll a, b and carotenoid content were higher in IR64 under N+W+ treatment and N-W+ and N+W- stresses; however, under dual stress, N22 had higher chlorophyll b content. While nitrite reductase, glutamate synthase (GS) and citrate synthase assays showed better specific activity in IR64, glutamate dehydrogenase showed better specific activity in N22 under dual stress (N-W-); the other N and C assimilating enzymes showed similar but low specific activities in both the genotypes. A total of 8926 differentially expressed genes (DEGs) were identified compared to optimal (N+W+) condition from across all treatments. While 1174, 698 and 903 DEGs in IR64 roots and 1197, 187 and 781 in N22 roots were identified, nearly double the number of DEGs were found in the shoot tissues; 3357, 1006 and 4005 in IR64 and 4004, 990 and 2143 in N22, under N-W+, N+W- and N-W- treatments, respectively. IR64 and N22 showed differential expression in 15 and 11 N-transporter genes respectively, under one or more stress treatments, out of which four showed differential expression also in N+W- condition. The negative regulators of N- stress, e.g., NIGT1, OsACTPK1 and OsBT were downregulated in IR64 while in N22, OsBT was not downregulated. Overall, N22 performed better under dual stress conditions owing to its better root architecture, chlorophyll and porphyrin synthesis and oxidative stress management. We identified 12 QTLs for seed and straw N content using 253 recombinant inbred lines derived from IR64 and N22 and a 5K SNP array. The QTL hotspot region on chromosome 6 comprised of 61 genes, of which, five were DEGs encoding for UDP-glucuronosyltransferase, serine threonine kinase, anthocyanidin 3-O-glucosyltransferase, and nitrate induced proteins. The DEGs, QTLs and candidate genes reported in this study can serve as a major resource for both rice improvement and functional biology.
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http://dx.doi.org/10.1186/s12284-021-00487-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179884PMC
June 2021