Characteristics of Bone Marrow Derived Mesenchymal Stem Cells in Patients with Liver Cirrhosis

( Haripriya Gupta ),( Sang Jun Yoon ),( Dae Hee Han ),( Na Young Lee ),( Ki Tae Suk ),( Dong Joon Kim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Cirrhosis is the end stage of chronic liver disease, which may lead to severe hepatic dysfunction and even life-threatening conditions. The beneficial impact of mesenchymal stem cells (MSCs) transplantation on liver diseases has been confirmed on several studies include our previous clinical trial for autologous bone marrow-derived mesenchymal stem cells (BM MSCs) transplantation to patients with liver cirrhosis, which have shown the ability of MSCs to reduce liver cirrhosis and improve liver function. We aimed to identify secreted factors by undifferentiated BM-MSCs in order to describe related pathways potentially targeted gene by MSC in liver cirrhosis. Methods: Human BM-MSCs from normal and patients who had liver cirrhosis after autologous BM-MSCs transplanted and cultured specific medium condition for mesenchymal stem cells. We evaluated the potential of differentiation to osteoblast and adipocytes, morphological changes and cell proliferation depending on culture period, and immunophenotyping assay with flow cytometer with CD14, CD34, CD45, CD73 and CD105. At passage 4-5 of BM-MSCs were used for cDNA microarrays to identify secreted genes and related pathway that differentially expressed in specific stem cell population in liver cirrhosis and identified by biomathmatical analysis. Results: On immunophenotyping analysis to determine mesenchymal function, CD14, CD34 and CD45 were 0.88%, 0.68% and 0.78%, respectively, however CD73 and CD105 for specific antigen of MSCs were 99.81% and 99.92%. BM MSCs secreted different factors in normal and patients with liver cirrhosis. We found 2968 genomes of 15 maps in KEGG pathway include Metabolic pathways, TGF-beta signaling pathway, Wnt signaling pathway, Cytokine-cytokine receptor interaction, HIF- 1 signaling pathway, Ras signaling pathway and Natural killer cell mediated cytotoxicity. Within these pathways, functionally up-regulated genes were 7 genes and down-regulated genes were 9. In particular, we were able to identify potential specific genes might have typical function for regulation of liver cirrhosis and regeneration (FBN2, P4HA1 and STC1), and KIR3DL2, which is gene for regulation of immune system process. Conclusions: Based on our previous clinical trial for autologous BM MSCs transplantation to patients with liver cirrhosis, the results have shown the ability of MSCs to reduce liver cirrhosis and improve liver function. Application of MSCs might target a widespread pattern of biological, cellular compositional and molecular functional event in the liver. MSC secreted genes and proteins can be differ depending on pathways and molecular mechanisms. Genes involved liver cirrhosis are able to release hepatotropic factors from transplanted MSCs, also potentially supporting liver regenerations.

Gut Microbiome and Metabolomic Signatures in Alco-holic Liver Disease

( Raja Ganesan ),( Haripriya Gupta ),( Ye Rin Choi ),( Hyeong Seop Kim ),( Sang Jun Yoon ),( Yoseph Asmelash Gebru ),( Satya Priya Sharma ),( Dong Joon Kim ),( Ki Tae Suk ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

The Poverty Reduction in India and The Global Corporate Citizenship of Korean Companies

Han, In-Soo,Haripriya Gundimeda 한국외국어대학교 인도연구소 2013 남아시아연구 Vol.19 No.2

한국기업의 글로벌 전개가 가속화될수록 글로벌 사회적 책임(CSR)이나 글로벌 기업시민(global corporate citizenship)활동의 중요성이 증가하고 있다. 그리고 이러한 활동은 진출국의 시급한 문제에 동참하는 전략적 전개가 요망된다. 한국기업의 진출이 크게 늘 것으로 예상되는 인도는 빈곤이라는 심각한 사회적 과제를 안고 있어 빈곤감소는 국가적 과제의 매우 높은 우선순위를 차지하고 있다. 인도에 진출한 한국기업은 이러한 국가과제의 해결에 동참하는 자세를 보일 때 지속가능 성장을 유지할 수 있을 것으로 예상된다. 인도에서의 빈곤감소와 관련된 한국기업의 기업시민활동은 자원의 제약 상 교육과 건강 이슈에 집중될 필요가 있다. 전자는 빈곤감소와 장기적으로 그리고 후자는 보다 단기적으로 연결될 것이다. 그리고 본 연구에서는 빈곤감소와 관련된 개별기업의 활동 외에 한국기업의 이미지를 장기적으로 제고할 수 있는 방안의 하나로 인도 진출 한국기업들이 매출액의 일부를 출연하여 참여하는 빈곤감소 기금을 제안하고 있다. 여기에는 국가적 지원도 첨가되어야 할 것이다.

Impact of Probiotics in NAFLD in Mice with Western Diet

( Sang Jun Yoon ),( Dae Hee Han ),( Haripriya Gupta ),( Na Young Lee ),( Ki Tae Suk ),( Dong Joon Kim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide. However, definitive medical treatment has not been established with the exception of lifestyle modification. Probiotics can be used as a promising mediation targeting gut-liver axis in NAFLD. The aim of study was to evaluate the impact of some strains in Western diet induced NAFLD mice model. Methods: We used 6-week aged C57BL/6 mouse and mice were divided into 8 groups (n=10/group; normal diet group, Western diet for 8 weeks group, and 6 Western diet with probiotics administration groups [10⁹ CFU/g, for 8 weeks]). Used probiotics strains are Lactobacillus reuteri, L. salivarius, L. gasseri, Bifidobacterium lactis, B. breve, and B. longum. We compared liver/body weight ratio, histology (fatty liver and hepatitis), liver enzymes (AST, ALT, and bilirubin), and cholesterol. Results: In the analysis of liver/body weight ratio, L. salivarius (5.73±0.52, P=0.028), B. breve (5.27±0.47, P=0.001), and B. longum (4.85±0.57, P<0.001) groups showed significant improvement compared with that of Western group (6.33±0.63). In comparison of histology (fatty liver score/ hepatitis score), L. salivarius (1.9±0.3/1.0±0.0, P<0.001), B. breve (1.2±0.7/0.9±0.6, P<0.001), L. gasseri (1.9±0.3/1.0±0.3, P<0.001), B. lactis (2.1±0.3/1.2±0.4, P<0.001), and B. longum (1.2±0.4/0.8±0.4, P<0.001) groups reveled significant improvement compared with that of Western group (3.0±0.4/1.9±0.3). Especially, B. breve and B. longum showed liver histology like that of normal control. All strains are effective in improvement of liver enzyme (ASTT or ALT, P<0.05). In case of B. longum, mean cholesterol level was significantly decreased after administration of B. longum (0.9±0.5/0.3±0.2, P<0.001) Conclusions: Gut-liver axis plays an important role in the NAFLD and probiotics effectively reduce inflammation and steatosis of the liver in NAFLD. In addition, B. longum can be used in the treatment of dyslipidemia.

Compositional Shift of Gut Microbiome According to the Complications In Patients With Liver Cirrhosis

( Satya Priya Sharma ),( Raja Ganesan ),( Haripriya Gupta ),( Ye Rin Choi ),( Hyeong Seop Kim ),( Sang Jun Yoon ),( Yoseph Asmelash Gebru ),( Dong Joon Kim ),( Ki Tae Suk ) 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Bifidobacterium Breve and Bifidobacterium longum Attenuate Western Diet Induced Nonalcoholic Fatty Liver Disease in Mice

( Sang Jun Yoon ),( Yoseph Asmelash ),( Raja Ganesan ),( Haripriya Gupta ),( Sung Min Won ),( Eun Ju Park ),( Satyapriya Sharma ),( Hyeong Seop Kim ),( Ye Rin Choi ),( Byeong Hyun Min ),( Min Kyo Jeon 대한간학회 2021 춘·추계 학술대회 (KASL) Vol.2021 No.1

Effects of Probiotics for the Treatment of Non-Alcoholic Fatty Liver Disease in Mice Model

( Dae Hee Han ),( Sang Jun Yoon ),( Haripriya Gupta ),( Na Young Lee ),( Ki Tae Suk ),( Dong Joon Kim ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, comprises a spectrum of diseases ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis, and cirrhosis. Currently, there are no Food and Drug Administration-approved therapies for NAFLD. The aim of this study is to find beneficial probiotics and assess the improvement in NAFLD animal model. Methods: Six-week male C57BL/6J mice were used in this study. Mice were randomly assigned to normal diet, Western-diet, and 9 Western diet+probiotics groups (n=10/group). Used probiotics strains are Lactobacillus acidophilus, L. plantarum, L. casei, L. paracasei, L. fermentum, L. helveticus, L. bulgaricus, Bifidobacterium bifidum, Pediococcus pentosaceus KID7). Each probiotics were administered to mice in the drinking water at concentration of 1 Х 10⁹ colony forming units(CFU)/g/day for 8 weeks. Liver/body weight ratio, liver enzyme (ALT, AST), cholesterol, and histologic findings (hepatitis and steatosis score)) were analyzed. Results: In the analysis of liver/body weight ratio, L. acidophilus (5.5±0.4, P<0.001), L. bulgaricus (5.1±0.5, P<0.001), P. pentosaceus KID7 (5.5±0.5, P=0.009), L. paracasei (5.7±0.4, P=0.032), and L. helveticus (5.2±0.4, P<0.001) groups showed significant improvement compared with that of Western group (6.2±0.6). All strains except B. bifidum were effective in improvement of liver enzyme (AST or ALT, P<0.05). All strains except B. bifidum and L. casei significantly reduced the level of cholesterol (P<0.05). In comparison of histology (hepatitis score/steatosis score), L. helveticus (1.3±0.5/1.7±0.7, P<0.001), L. fermentum (1.8±0.4/2.7±0.5, P=0.042), L. paracasei (1.6±0.5/2.1±0.9, P=0.035), P. pentosaceus KID7 (1.3±0.5/1.4±0.5, P<0.001), B. bifidum (1.6±0.5/2.5±0.8, P=0.037), L. bulgaricus (0.7±0.7/0.7±0.7, P<0.001), L. casei (1.8±0.4/2.1±0.6, P<0.001), L. plantarum (1.8±0.6/2.3±0.7, P=0.003), and L. acidophilus (1.6±0.7/1.8±0.6, P<0.001) groups reveled significant improvement compared with that of Western group (3.1±0.3/2.0±0.0). Conclusion: Our selected probiotics have beneficial effects on weight reduction, dyslipidemia, and liver inflammation and steatosis. Therefore, probiotics might be effective in the treatment of NALD by regulating the gut-liver axis.

Sufficient Calorie Intake Ameliorates Cognitive Impairment in Alcoholic Liver Disease

( Ye Rin Choi ),( Min Jea Shin ),( Gi Soo Youn ),( Sang Jun Yoon ),( Haripriya Gupta ),( Na Young Lee ),( Hyeong Seop Kim ),( Dong Joon Kim ),( Ki Tae Suk ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Alcoholic liver disease (ALD) is the most common cause of chronic liver disease. And cognitive dysfunction is one of the complications and associated with calorie intake in ALD. However, relation between nutrition and cognitive function has not been fully evaluated. The aim of this study is to explore the effect of diet on cognitive function in ALD. Methods: A total of 43 patients were enrolled and neuropsychological tests assessed according to the nutritional state (BMI<21.7 and BMI≥21.7). In animal study, mice were sub-divided into 4 groups (n=9/group; control (5% EtOH liquid diet), low fat (5% EtOH+low fat diet), high fat (5% EtOH+high fat diet), and high protein (5% EtOH+high protein diet)) for 8 weeks. For the cognitive function, we performed T-maze study weekly before and after alcohol binge. Results: In the comparison of cognitive function (BMI<21.7 and BMI≥21.7), language score of Korea mini-mental state (7.37 ± 1.4 and 7.85 ± 0.4 P=0.04), rey-complex figure (72.0±25.9 and 58.4±33.6, P=0.05), boston naming (11.7±2.7 and 13.0±1.8, P=0.02), forward digit span (6.7±1 .8 and 7.5±1.6, P=0.04), Korean-color word stroop (24.2±26.5 and 43.6±32.4, P=0.006), interference score (33.9±31.9 and 52.3±33.9, P=0.02) showed high scores in BMI≥21.7 group. In the animal study on day 40, all groups shortened the time to find feed (low fat: P=0.004, high fat: P=0.02) compared to the control group. Interestingly, binge drinking mice reduced the time than before trained mice. Conclusions: ALD patients with BMI<21.7 enhance their cognitive dysfunction. Although it needs more studies which correlation of calorie intake and cognitive function, this study indicates that sufficient intake of calories provides major benefits for preventing cognitive dysfunction.

Poster Session : PS 0465 ; Genetics ; A Study on XRCC1, P53 Gene Polymorphisms in Patients with Hepatocellular Carcinoma (HCC) in Southern India

( Vellingiri Balachandar ),( Subramaniam Mohana Devi ),( Meyyazhagan Arun ),( S Haripriya ),( Iyer Mahalakshmi ),( Sn Dharwadkar ),( Keshavarao Sasikala ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Hepatocellular carcinoma (HCC) ids one of the most common cancer worldwide. Polymorphism in p53 and XRCC1 genes were associated with increased risk of early-onset HCC. We thus hypothesized that, these polymorphism could be more likely in South Indian population. However the status of these mutations in South Indian HCC had not been studied. Methods: In the present study 130 HCC patients and 130 control subjects were analyzed for known polymorphisms in the p53 and XRCC1 genes. Results: In the Arg194Trp polymorphism of p53 gene, we found 19.05% with Arg- 399Trp (heterozygous variant) genotype and 1.6% with 399Trp (homozygous variant) in comparison to controls who exhibited 90.39% with wild type genotype. In Arg399Gln polymorphism of XRCC1 gene, 46.17% were found to have Arg399Gln (heterozygous variant) genotype and 10.11% were found to have 399Gln (homozygous variant) genotype in comparison to controls who exhibited 55% individuals with heterozygous variant genotype and 16.75% with homozygous variant genotype. This polymorphic incidence revealed signifi cant association with advanced stages of the HCC and also well differentiated tumor. Conclusions: Thus the results of our study provide the genetic variations of p53 and XRCC1 which may contribute to the susceptibility to HCC in South India. The results suggest that, these genes could play a signifi cant role in HCC and the combined effect of these variants may interact to increase the risk of HCC in Indian population.

Gut Lactobacillus and Probiotics Lactobacillus lactis/rhamnosis Ameliorate Liver Fibrosis in Prevention and Treatment

Won Sung Min,Lee Na Young,Oh Ki-Kwang,Gupta Haripriya,Sharma Satya Priya,Kim Kyung Hwan,Kim Byoung Kook,Joung Hyun Chae,Jeong Jin Ju,Ganesan Raja,Han Sang Hak,Yoon Sang Jun,Kim Dong Joon,Suk Ki Tae 한국미생물학회 2023 The journal of microbiology Vol.61 No.2

The progression and exacerbation of liver fibrosis are closely related to the gut microbiome. It is hypothesized that some probiotics may slow the progression of liver fibrosis. In human stool analysis [healthy group (n = 44) and cirrhosis group (n = 18)], difference in Lactobacillus genus between healthy group and cirrhosis group was observed. Based on human data, preventive and therapeutic effect of probiotics Lactobacillus lactis and L. rhamnosus was evaluated by using four mice fibrosis models. L. lactis and L. rhamnosus were supplied to 3,5-diethoxycarbonyl-1,4-dihydrocollidine or carbon tetrachloride-induced liver fibrosis C57BL/6 mouse model. Serum biochemical measurements, tissue staining, and mRNA expression in the liver were evaluated. The microbiome was analyzed in mouse cecal contents. In the mouse model, the effects of Lactobacillus in preventing and treating liver fibrosis were different for each microbe species. In case of L. lactis, all models showed preventive and therapeutic effects against liver fibrosis. In microbiome analysis in mouse models administered Lactobacillus, migration and changes in the ratio and composition of the gut microbial community were confirmed. L. lactis and L. rhamnosus showed preventive and therapeutic effects on the progression of liver fibrosis, suggesting that Lactobacillus intake may be a useful strategy for prevention and treatment.