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        Ginsenoside Rd alleviates mouse acute renal ischemia/reperfusion injury by modulating macrophage phenotype

        Ren, Kaixi,Jin, Chao,Ma, Pengfei,Ren, Qinyou,Jia, Zhansheng,Zhu, Daocheng The Korean Society of Ginseng 2016 Journal of Ginseng Research Vol.40 No.2

        Background: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits anti-inflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10-100 mg/kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with $CD11b^+$, $iNOS^+$/interleukin-12/tumor necrosis factor-${\alpha}$ labeling. For the in vitro study, GSRd ($10-100{\mu}g/mL$) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylin-eosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-${\alpha}$. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion: These findings demonstrate that GSRd possess a protective function against renal ischemia/reperfusion injury via downregulating M1 macrophage polarization.

      • KCI등재

        Ginsenoside Rd alleviates mouse acute renal ischemia/reperfusion injury by modulating macrophage phenotype

        Kaixi Ren,Chao Jin,Pengfei Ma,Qinyou Ren,Zhansheng Jia,Daocheng Zhu 고려인삼학회 2016 Journal of Ginseng Research Vol.40 No.2

        Background: Ginsenoside Rd (GSRd), a main component of the root of Panax ginseng, exhibits antiinflammation functions and decreases infarct size in many injuries and ischemia diseases such as focal cerebral ischemia. M1 Macrophages are regarded as one of the key inflammatory cells having functions for disease progression. Methods: To investigate the effect of GSRd on renal ischemia/reperfusion injury (IRI) and macrophage functional status, and their regulatory role on mouse polarized macrophages in vitro, GSRd (10e100 mg/ kg) and vehicle were applied to mice 30 min before renal IRI modeling. Renal functions were reflected by blood serum creatinine and blood urea nitrogen level and histopathological examination. M1 polarized macrophages infiltration was identified by flow cytometry analysis and immunofluorescence staining with CD11bþ, iNOSþ/interleukin-12/tumor necrosis factor-a labeling. For the in vitro study, GSRd (10 e100 mg/mL) and vehicle were added in the culture medium of M1 macrophages to assess their regulatory function on polarization phenotype. Results: In vivo data showed a protective role of GSRd at 50 mg/kg on Day 3. Serum level of serum creatinine and blood urea nitrogen significantly dropped compared with other groups. Reduced renal tissue damage and M1 macrophage infiltration showed on hematoxylineeosin staining and flow cytometry and immunofluorescence staining confirmed this improvement. With GSRd administration, in vitro cultured M1 macrophages secreted less inflammatory cytokines such as interleukin-12 and tumor necrosis factor-a. Furthermore, macrophage polarization-related pancake-like morphology gradually changed along with increasing concentration of GSRd in the medium. Conclusion: These findings demonstrate that GSRd possess a protective function against renal ischemia/ reperfusion injury via downregulating M1 macrophage polarization.

      • Daclatasvir plus Asunaprevir in Interferon (± Ribavirin)- Ineligible/Intolerant Asian Patients with Chronic HCV Genotype-1b Infection

        ( Lai Wei ),( Mingxiang Zhang ),( Min Xu ),( Wan-Long Chuang ),( Wei Lu ),( Wen Xie ),( Zhansheng Jia ),( Guozhong Gong ),( Yueqi Li ),( Si Hyun Bae ),( Yong-Feng Yang ),( Qing Xie ),( Shumei Lin ),( 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

        Aims: The efficacy/safety of daclatasvir (pan-genotypic NS5A inhibitor) plus asunaprevir (NS3 protease inhibitor) in interferon (± ribavirin)- ineligible/intolerant patients with chronic HCV genotype-1b infection from mainland China, Korea and Taiwan was investigated in a phase 3, open-label study. Methods: Patients received daclatasvir 60 mg (tablet) once daily plus asunaprevir 100 mg (soft capsule) twice daily for 24 weeks. The primary endpoint was sustained virologic response at post-treatment Week 24 (SVR24). Results: This study treated 159 patients from mainland China (80%), Korea (11%) and Taiwan (9%), including patients with cirrhosis (33%), IL28B non-CC genotypes (40%), and aged ≥70 years (4%). SVR24 was achieved by 91% of patients (100% concordance with SVR12) and was similarly high in all subgroups, e.g. cirrhotic patients (90%), and in patients from mainland China (91%), Korea (94%) and Taiwan (87%). SVR24 was higher in patients without baseline NS5A (L31M/Y93H) resistance-associated variants (RAVs) (n=137/139 [99%]), regardless of the presence (98%) or absence (99%) of cirrhosis, and lower in patients with baseline NS5A RAVs (n=8/19 [42%]). All serious adverse events (AEs) (n=5/159 [3.1%]), grade 4 laboratory abnormalities (n=3/159 [1.9%]) and deaths (n=1/159 [0.6%]) that occurred on-treatment were unrelated to the study drugs; two patients discontinued due to AEs. Treatment was generally well tolerated regardless of cirrhosis status. Conclusions: Daclatasvir plus asunaprevir achieved a high SVR24 rate of 91%, rising to 99% in patients without baseline NS5A RAVs, and was generally well tolerated in cirrhotic and non-cirrhotic interferon (± ribavirin)-ineligible/intolerant patients with HCV genotype-1b infection from mainland China, Korea and Taiwan.

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