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Functional mechanisms for diabetic nephropathy-associated genetic variants
Hong Xu,Chengxin Gong,Yonghu Xu,Yongfang Fan,Xingzi Liu,Chaopeng Xiong,Luling He,Changle Liu,Shenqiang Rao,Wen Xiao,Lu Ding,Lan Tang,Fangfang Hu,Mengqi Xiong,Mei Yang,Shangdong Liang 한국유전학회 2016 Genes & Genomics Vol.38 No.7
Diabetic nephropathy (DN) is one of the major complications of diabetes. A tremendous amount of genetic variations have been identified to be associated with DN. However, most of them only generate from statistical associations at the DNA level, generally without direct functional evidence regarding their association mechanisms underlying DN. Based on the publicly available datasets and resources, this study performed integrative analyses (expression quantitative trait loci analysis, differential gene expression analysis and functional prediction analysis) to detect the molecular functional mechanisms underlying the associations for DN. Among 150 selected (P\E-4) genetic associations that were archived in the public databases, two single nucleotide polymorphisms (SNPs) (rs3135377 and rs9469220) have been found to act as cis-effect regulators of the ‘‘identified’’ gene (HLADRA and HLA-DRB1). These eQTL genes have differential expression signals in the DN-associated cell groups. These SNPs were predicted as regulatory sites by utilizing online prediction tools. Our data suggest potential mechanistic links underlying the association between DN and two identified SNPs. These results could help us to have a deeper understanding of the functional relevance of genetic variants with susceptibility to DN, which is useful for pursuit of in-depth validation studies to dissect their involvements and molecular functional mechanisms in DN.
Hong-Lin Xu,Guang-Hong Chen,Yu-Ting Wu,Ling-Peng Xie,Zhang-Bin Tan,Bin Liu,Hui-Jie Fan,Hong-Mei Chen,Gui-Qiong Huang,Min Liu,Ying-Chun Zhou 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.1
Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of proinflammatory factors, including TNF-a, IL-6 and IL-1b. Additionally, P. ginseng blocked fluorescence-labeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-kB (NF-kB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/MD2 complex and GRo (KD value of 1.16 × 10<SUP>-9</SUP> M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-kB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.
Xu, Mei Ling,Kim, Hyoung-Jin,Choi, Yoo-Ri,Kim, Hong-Jin The Korean Society of Ginseng 2012 Journal of Ginseng Research Vol.36 No.4
Vaccination is the main strategy for preventing influenza infection. However, vaccine efficacy is influenced by several factors, including age and health status. The efficacy of the influenza vaccine is much lower (17% to 53%) in individuals over 65 yr of age compared with young adults (70% to 90%). Therefore, increasing vaccine efficacy remains a challenge for the influenza vaccine field. In this study, we investigated the impact of supplementing vaccination with the dietary intake of Korean red ginseng (RG) extract and RG saponin. Mice were immunized two times intranasally with inactivated influenza A (H1N1) virus. Mice received RG extract or RG saponin orally for 14 d prior to the primary immunization. After the primary immunization, mice continued to receive RG extract or RG saponin until the secondary immunization. Mice vaccinated in combination with dietary intake of RG extract and RG saponin showed elevated serum anti-influenza A virus IgG titers and improved survival rates in lethal influenza A virus infection: 56% and 63% of mice receiving RG extract or RG saponin survived, respectively, while 38% of mice that only received the vaccine survived. Moreover, mice receiving RG extract supplementation recovered their body weight more quickly than those not receiving RG extract supplementation. We propose that the dietary intake of RG extract and RG saponin enhances the vaccine-induced immune response and aids in providing protection against influenza virus infection.
Mei-Li Lu,Jing Wang,Yang Sun,Cong Li,Tai-Ran Sun,Xu-Wei Hou,Hong-Xin Wang 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.6
Background: Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovasculardisease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-inducedcardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR)signaling pathway. Methods: Mechanical stress was implemented on rats through abdominal aortic constriction (AAC)procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex CollagenI plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca2þ]i, and the expression ofCaSR and calcineurin (CaN) were assayed both on rat and cellular level. Results: Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation inducedby AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1treatment inhibited CaSR expression and increase of [Ca2þ]i, which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-b1 pathways activation. Mechanistic analysis showedthat the CaSR agonist GdCl3 could not further increase the [Ca2þ]i and CaN pathway related proteinexpression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN,inhibited cardiac hypertrophy, cardiac fibrosis, [Ca2þ]i and CaN signaling but had no effect on CaSRexpression. Conclusion: The activation of CaN pathway and the increase of [Ca2þ]i mediated by CaSR are involved incardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardialinjury.
Xu, Jia-Li,Hu, Ling-Min,Huang, Ming-De,Zhao, Wan,Yin, Yong-Mei,Hu, Zhi-Bin,Ma, Hong-Xia,Shen, Hong-Bing,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3
Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.
Xu, Mei Ling,Kim, Hyoung Jin,Kim, Hong-Jin 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.4
Previous studies have revealed that ingestion of bovine colostrum is effective in preventing pathogens from invading through the gastrointestinal tract (GI) and modulating the mucosal immunity of the GI tract, indicating that its effect is principally local. Thus it is unclear if ingestion of bovine colostrum can affect the systemic immune system. In this study, we investigated the effect of taking bovine colostrum (vs phosphate-buffered saline) for 14 days on the behavior of the immune cells of mice. Isolated splenocytes, which are pivotal cells of systemic immunity, were then stimulated with Escherichia coli lipopolysaccharide. Bovine colostrum significantly reduced NK cell and monocyte activities and lymphoproliferaltive responses to LPS stimulation. Thus dietary bovine colostrum renders immune cells less responsive to LPS stimulation. Dietary bovine colostrum thus affects the systemic immune system and may have anti-inflammatory actions.
Mei Ling Xu,Hyoung Jin Kim,Yoo Ri Choi,Hong-Jin Kim 고려인삼학회 2012 Journal of Ginseng Research Vol.36 No.4
Vaccination is the main strategy for preventing infl uenza infection. However, vaccine effi cacy is infl uenced by several factors, including age and health status. The effi cacy of the infl uenza vaccine is much lower (17% to 53%) in individuals over 65 yr of age compared with young adults (70% to 90%). Therefore, increasing vaccine effi cacy remains a challenge for the infl uenza vaccine fi eld. In this study, we investigated the impact of supplementing vaccination with the dietary intake of Korean red ginseng (RG) extract and RG saponin. Mice were immunized two times intranasally with inactivated infl uenza A (H1N1) virus. Mice received RG extract or RG saponin orally for 14 d prior to the primary immunization. After the primary immunization, mice continued to receive RG extract or RG saponin until the secondary immunization. Mice vaccinated in combination with dietary intake of RG extract and RG saponin showed elevated serum anti-infl uenza A virus IgG titers and improved survival rates in lethal infl uenza A virus infection: 56% and 63% of mice receiving RG extract or RG saponin survived, respectively, while 38% of mice that only received the vaccine survived. Moreover, mice receiving RG extract supplementation recovered their body weight more quickly than those not receiving RG extract supplementation. We propose that the dietary intake of RG extract and RG saponin enhances the vaccine-induced immune response and aids in providing protection against infl uenza virus infection.