Suchergebnisse

Min-Jun Wang,1,* Jia-Jia Chen,1,* Shao-Hua Song,2,* Jing Su,1,* Ling-Hao Zhao,3 Qing-Gui Liu,1 Tao Yang,1 Zhiwen Chen,4 Chang Liu,4 Zhi-Ren Fu,2 Yi-Ping Hu,1 Fei Chen1 1Department of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University (Navy Medical University), Shanghai, People's Republic of China; 2Department of General Surgery, Liver Transplantation Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China; 3National Center for Liver Cancer, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People's Republic of China; 4State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, People's Republic of China*These authors contributed equally to this workCorrespondence: Fei Chen Yi-Ping HuDepartment of Cell Biology, Center for Stem Cell and Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433, ChinaTel +86-21-81870943Email feelchen@smmu.edu.cn; yphu9@yeah.netPurpose: Cancer stem cells (CSCs) have been considered involving in tumorigenesis, local recurrence, and therapeutic drug resistance of hepatocellular carcinoma (HCC). To investigate novel and effective methods for targeting hepatic CSCs is crucial for a permanent cure of liver cancer.Methods: The expression level of SIRT1 was detected in CSCs of HCC tissues and cancer cell lines. Expression of CSC markers, the self-renewal and tumorigenic ability of liver CSCs were analyzed with SIRT1 inhibition. Cellular senescence-related markers were used to detect CSCs senescence after inhibition of SIRT1.Results: SIRT1 was highly expressed in CSCs of HCC cell lines and human HCC tissues. In vitro study revealed that decreasing of SIRT1 level significantly downregulated the stemness-associated genes of liver CSCs and reduced the CSC stemness properties. Also, downregulated SIRT1 suppressed liver CSCs proliferation by decreasing their self-renewal abilities. Furthermore, CSCs with decreased SIRT1 expression showed limited tumorigenicity and formed smaller HCC tumor in vivo. And SIRT1 decreased CSCs became more susceptible to chemotherapeutic drugs. Mechanistically, SIRT1 decreased CSCs became senescence through the activation of p53-p21 and p16 pathway. The data further indicated that the tumor formed from SIRT1-knockdown CSCs exhibited higher senescence-associated β-galactosidase (SA-β-Gal) activity but lower proliferative capacity.Conclusion: Taken together, these findings pointed that induction of senescence in liver CSCs is an effective tumor suppression method for HCC, and SIRT1 may be served as a promising target for HCC treatment.Keywords: SIRT1, hepatocellular carcinoma, liver cancer stem cells, cellular senescence, stemness, self-renewal

University of Nottingham ; Biotechnology and Biological Sciences Research Council, United Kingdom ; Department for International Development, United Kingdom ; Scottish Government ; Bill & Melinda Gates Foundation ; King Saud University ; King Abdulaziz City for Science and Technology ; Peer Review

Hepatic myelopathy is a complication seen in patients with chronic liver failure with physiologic or iatrogenic portosystemic shunting. The main symptom is progressive lower limb dyskinesia. The role of the brain motor control center in hepatic myelopathy is unknown. This study aimed to investigate the gray matter changes in patients with hepatic myelopathy secondary to transjugular intrahepatic portosystemic shunt and to examine their clinical relevance. This was a cross-sectional study. Twenty-three liver failure patients with hepatic myelopathy (hepatic myelopathy group), 23 liver failure patients without hepatic myelopathy (non-hepatic myelopathy group) after transjugular intrahepatic portosystemic shunt, and 23 demographically matched healthy volunteers were enrolled from March 2014 to November 2016 at Xijing Hospital, Air Force Military Medical University (Fourth Military Medical University), China. High-resolution magnetization-prepared rapid gradient-echo brain imaging was acquired. Group differences in regional gray matter were assessed using voxel-based morphometry analysis. The relationship between aberrant gray matter and motor characteristics was investigated. Results demonstrated that compared with the non-hepatic myelopathy group, gray matter volume abnormalities were asymmetric, with decreased volume in the left insula (P = 0.003), left thalamus (P = 0.029), left superior frontal gyrus (P = 0.006), and right middle cingulate cortex (P = 0.021), and increased volume in the right caudate nucleus (P = 0.017), corrected with open-source software. The volume of the right caudate nucleus in the hepatic myelopathy group negatively correlated with the lower limb clinical rating of the Fugl-Meyer Assessment (r = –0.53, P = 0.01). Compared with healthy controls, patients with and without hepatic myelopathy exhibited overall increased gray matter volume in both thalami, and decreased gray matter volume in both putamen, as well as in the globus pallidus, cerebellum, and vermis. The gray matter abnormalities ...

Anti-Retroviral Therapy (ART) is the recommended first line therapy for patients with HIV. Since 2004, Chinese government has provided free Chinese herbal medicine (CHM) for Chinese HIV/AIDS patients. Data of living patients with HIV from the NFTCMP database and Center for Disease Control (CDC) database during 2003-2016 in Guangxi province was obtained and compared. Patients were divided into 3 groups according to their recorded treatment regimens. A total of 2954 patients with their treatment recorded in the two databases were included for analysis, their median age was 46 years (IQR = 36-59), and 64.63% were male. CHM regimens users had baseline CD4 cell counts (380.11±240.59 cell/μL), approximately 100 cell/μL significantly higher than patients receiving CHM combined with ART regimens or only ART regimens. There was no significant difference in mortality among groups. All three regimens improved patients' CD4 cell counts. Compared to the sharp improvement in ART group during the first 6 months, CD4 cell counts of patients in CHM group and CHM combined with ART group showed a smooth and steady rise. CD4 counts of the combined group remained much lower than ART group in the first 3 years, but overtook ART group in the fourth year.