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      • KCI등재후보

        Impact of type 2 diabetes variants identified through genome-wide association studies in early-onset type 2 diabetes from South Indian population

        Liju, Samuel,Chidambaram, Manickam,Mohan, Viswanathan,Radha, Venkatesan Korea Genome Organization 2020 Genomics & informatics Vol.18 No.3

        The prevalence of early-onset type 2 diabetes (EOT2D) is increasing in Asian countries. Genome-wide association studies performed in European and various other populations have identified associations of numerous variants with type 2 diabetes in adults. However, the genetic component of EOT2D which is still unexplored could have similarities with late-onset type 2 diabetes. Here in the present study we aim to identify the association of variants with EOT2D in South Indian population. Twenty-five variants from 18 gene loci were genotyped in 1,188 EOT2D and 1,183 normal glucose tolerant subjects using the MassARRAY technology. We confirm the association of the HHEX variant rs1111875 with EOT2D in this South Indian population and also the association of CDKN2A/2B (rs7020996) and TCF7L2 (rs4506565) with EOT2D. Logistic regression analyses of the TCF7L2 variant rs4506565(A/T), showed that the heterozygous and homozygous carriers for allele 'T' have odds ratios of 1.47 (95% confidence interval [CI], 1.17 to 1.83; p = 0.001) and 1.65 (95% CI, 1.18 to 2.28; p = 0.006) respectively, relative to AA homozygote. For the HHEX variant rs1111875 (T/C), heterozygous and homozygous carriers for allele 'C' have odds ratios of 1.13 (95% CI, 0.91 to 1.42; p = 0.27) and 1.58 (95% CI, 1.17 to 2.12; p = 0.003) respectively, relative to the TT homozygote. For CDKN2A/2B variant rs7020996, the heterozygous and homozygous carriers of allele 'C' were protective with odds ratios of 0.65 (95% CI, 0.51 to 0.83; p = 0.0004) and 0.62 (95% CI, 0.27 to 1.39; p = 0.24) respectively, relative to TT homozygote. This is the first study to report on the association of HHEX variant rs1111875 with EOT2D in this population.

      • KCI등재

        Picroside II attenuates fatty acid accumulation in HepG2 cells via modulation of fatty acid uptake and synthesis

        ( Hiteshi Dhami-shah ),( Rama Vaidya ),( Shobha Udipi ),( Srividhya Raghavan ),( Shiny Abhijit ),( Viswanathan Mohan ),( Muthuswamy Balasubramanyam ),( Ashok Vaidya ) 대한간학회 2018 Clinical and Molecular Hepatology(대한간학회지) Vol.24 No.1

        Background/Aims: Hepatic steatosis is caused by an imbalance between free fatty acids (FFAs) uptake, utilization, storage, and disposal. Understanding the molecular mechanisms involved in FFAs accumulation and its modulation could drive the development of potential therapies for Nonalcoholic fatty liver disease. The aim of the current study was to explore the effects of picroside II, a phytoactive found in Picrorhiza kurroa, on fatty acid accumulation vis-a-vis silibinin, a known hepatoprotective phytoactive from Silybum marianum. Methods: HepG2 cells were loaded with FFAs (oleic acid:palmitic acid/2:1) for 20 hours to mimic hepatic steatosis. The FFAs concentration achieving maximum fat accumulation and minimal cytotoxicity (500 μM) was standardized. HepG2 cells were exposed to the standardized FFAs concentration with and without picroside II pretreatment. Results: Picroside II pretreatment inhibited FFAs-induced lipid accumulation by attenuating the expression of fatty acid transport protein 5, sterol regulatory element binding protein 1 and stearoyl CoA desaturase. Preatreatment with picroside II was also found to decrease the expression of forkhead box protein O1 and phosphoenolpyruvate carboxykinase. Conclusions: These findings suggest that picroside II effectively attenuated fatty acid accumulation by decreasing FFAs uptake and lipogenesis. Picroside II also decreased the expression of gluconeogenic genes. (Clin Mol Hepatol 2018;24:77-87)

      • KCI등재

        The impact of yoga on stress, metabolic parameters, and cognition of Indian adolescents: A cluster randomized controlled trial

        Ranjani Harish,Jagannathan Narayanaswamy,Rawal Tina,Vinothkumar Radhakrishnan,Tandon Nikhil,Vidyulatha Jayaram,Mohan Viswanathan,Gupta Yashdeep,Anjana Ranjit Mohan 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.3

        Background: This project aimed to assess the impact of yoga on stress, metabolic parameters and cognition (attention & concentration) in adolescents, aged 13–15 years from public and private schools in two cities (Chennai and New Delhi) in India. Methods: The study recruited 2000 adolescents from 24 schools in a cluster randomized controlled trial design. The yoga group participants underwent 17 yoga sessions, which included: pranayama, basic asanas, meditation and relaxation exercises. Yoga sessions, were held in the school premises once a week. A total of five awareness talks on healthy lifestyle were delivered once a month to the education group. ADOlescence Stress Scale (ADOSS), salivary cortisol, metabolic and clinical parameters and Letter Cancellation Test (LCT) score were measured at baseline and post-intervention (5–6 months). Results: The yoga group showed statistically significant differences in the mean ADOSS score, metabolic parameters, salivary cortisol, and LCT scores compared to the education group. In the intention- to- treat analysis, a significant reduction [5.11, 95% CI (4.78, 5.36), p = 0.001] in ADOSS score was seen in the yoga group compared to education. Conclusion: Implementation of a 17-week standardized yoga program at the school level significantly decreased stress, improved attention and concentration, metabolic and clinical parameters in Indian adolescents.

      • KCI등재

        Metformin Reduces the Progression of Atherogenesis by Regulating Sestrin2-mTOR Pathway in Obese and Diabetic Rats

        Saravanakumar Sundararajan,Isaivani Jayachandran,Gautam Kumar Pandey,Saravanakumar Venkatesan,Anusha Rajagopal,Kuppan Gokulakrishnan,Muthuswamy Balasubramanyam,Viswanathan Mohan,Nagaraj Manickam 한국지질동맥경화학회 2023 지질·동맥경화학회지 Vol.12 No.3

        Objective: In previous research, we found that Sestrin2 has a strong association with plasma atherogenicity and combats the progression of atherogenesis by regulating the AMPK-mTOR pathway. Metformin, an activator of AMPK, is widely used as a first-line therapy for diabetes, but its role in preventing atherosclerosis and cardiac outcomes is unclear. Hence, we aimed to assess the effect of metformin on preventing atherosclerosis and its regulatory role in the Sestrin2-AMPK -mTOR pathway in obese/diabetic rats. Methods: Animals were fed a high-fat diet to induce obesity, administered streptozotocin to induce diabetes, and then treated with metformin (150 mg/kg body weight) for 14 weeks. Aorta and heart tissues were analyzed for Sestrin2 status by western blotting and immunohistochemistry, AMPK and mTOR activities were investigated using western blotting, and atherogenicity-related events were evaluated using reverse transcription quantitative polymerase chain reaction and histology. Results: Obese and diabetic rats showed significant decrease in Sestrin2 levels and AMPK activity, accompanied by increased mTOR activity in the heart and aorta tissues. Metformin treatment significantly restored Sestrin2 and AMPK levels, reduced mTOR activity, and restored the altered expression of inflammatory markers and adhesion molecules in obese and diabetic rats to normal levels. A histological analysis of samples from obese and diabetic rats showed atherosclerotic lesions both in aorta and heart tissues. The metformin-treated rats showed a decrease in atherosclerotic lesions, cardiac hypertrophy, and cardiomyocyte degeneration. Conclusion: This study presents further insights into the beneficial effects of metformin and its protective role against atherosclerosis through regulation of the Sestrin2-AMPK-mTOR pathway.

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