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| 1 | Complement C3 activation regulates the production of tRNA-derived fragments Gly-tRFs and promotes alcohol-induced liver injury and steatosis显示文摘Complement is known to play a role in alcoholic fatty liver disease (AFLD), but the underlying mechanisms are poorly understood, thereby constraining the development of a rational approach for therapeutic intervention in the complement system. C3 deficiency has been shown to impart protective effects against ethanol-induced hepatic steatosis and inflammation. Here we demonstrate a protection effect in wild-type mice by treatment with CR2-Crry, a specific inhibitor of C3 activation. The expression of glycine transfer (t) RNA-derived fragments (Gly-tRFs) is upregulated in ethanol-fed mice and inhibition of Gly-tRFs in vivo decreases chronic ethanol feeding-induced hepatosteatosis without affecting inflammation. The expression of Gly-tRF was downregulated in C3-deficient or CR2-Crry-treated mice, but not in C5-deficient mice;Gly-tRF expression was restored by the C3 activation products C3a or Asp (C3a-des-Arg) via the regulation of CYP2E1. Transcriptome profiling of hepatic tissues showed that Gly-tRF inhibitors upregulate the expression of sirtuin1 (Sirt1) and subsequently affect downstream lipogenesis and β-oxidation pathways. Mechanistically, Gly-tRF interacts with AGO3 to downregulate Sirt1 expression via sequence complementarity in the 3′ UTR. Notably, the expression levels of C3d, CYP2E1 and Gly-tRF are upregulated, whereas Sirt1 is decreased in AFLD patients compared to healthy controls. Collectively, our findings suggest that C3 activation products contribute to hepatosteatosis by regulating the expression of Gly-tRF. Complement inhibition at the C3 activation step and treatment with Gly-tRF inhibitors may be potential and precise therapeutic approaches for AFLD. | Fudi Zhong Zhigao Hu Keqing Jiang Biao Lei Zhan Wu Guandou Yuan Hongliang Luo Chunqiang Dong Bo Tang Chaowen Zheng Shuai Yang Yonglian Zeng Zhenya Guo Shuiping Yu Huizhao Su Guo Zhang Xiaoqiang Qiu Stephen Tomlinson Songqing He | 2019 | Cell Research2019，29，7： | 14 |
| 2 | Effect of Dahuang Zhechong pills on long non-coding RNA growth arrest specific 5 in rat models of hepatic fibrosis显示文摘OBJECTIVE: To investigate the involvement of growth arrest specific 5(GAS5), a long non-coding RNA, in the anti-hepatic fibrosis process induced by Dahuang Zhechong pill(DHZCP) in rats.METHODS: Thirty adult rats were divided into three groups, including a control group, a CCl4-induced fibrosis group and a DHZCP-treated fibrosis group. Hematoxylin-eosin and Masson staining were used for histopathological study. Serum enzymes, cytokines and cell proliferation were assayed using commercially available kits. A GAS5 lenti-virus vector was constructed to further investigate the role of GAS5 in the anti-hepatic fibrosis effect of DHZCP in rats.RESULTS: Our results revealed that the proliferation of hepatic stellate cells cultured in serum derived from rats treated with DHZCP was significantly decreased, compared with cells treated with serum from the untreated rats. DHZCP alleviated the CCl4-induced hepatic fibrosis. Additionally, DHZCP can restore the expression of GAS5,which was significantly decreased in the CCl4-induced group, and markedly suppress the expression of p-p38 and p-Erk induced by CCl4, but not p-Jnk. Cell proliferation was significantly arrested when cells overexpressed GAS5. Thus,DHZCP can inhibit the expression of p-p38 and p-Erk, while GAS5 can only inhibit the expression of p-Erk.CONCLUSIONS: DHZCP can alleviate hepatic fibrosis by increasing the expression of GAS5 to suppress p-Erk and regulating other factors to inhibit p-p38. | Gong Zhenghua Deng Chaowen Xiang Tianxin Tao Lili Xiao Hongbo Peng Yanzhong Zheng Jie Hu Guoxin | 2018 | Journal of Traditional Chinese Medicine2018，38，2： | 6 |
| 3 | A nomogram for individualized estimation of survival among adult patients with adrenocortical carcinoma after surgery:a retrospective analysis and multicenter validation study显示文摘Background:Clinical outcome of adrenocortical carcinoma(ACC)varies because of its heterogeneous nature and reliable prognostic prediction model for adult ACC patients is limited.The objective of this study was to develop and externally validate a nomogram for overall survival(OS)prediction in adult patients with ACC after surgery.Methods:Based on the data from the Surveillance Epidemiology,and End Results(SEER)database,adults patients diagnosed with ACC between January 1988 and December 2015 were identified and classified into a training set,comprised of 404 patients diagnosed between January 2007 and December 2015,and an internal validation set,com-prised of 318 patients diagnosed between January 1988 and December 2006.The endpoint of this study was OS.The nomogram was developed using a multivariate Cox proportional hazards regression algorithm in the training set and its performance was evaluated in terms of its discriminative ability,calibration,and clinical usefulness.The nomogram was then validated using the internal SEER validation,also externally validated using the Cancer Genome Atlas set(TCGA,82 patients diagnosed between 1998 and 2012)and a Chinese multicenter cohort dataset(82 patients diag-nosed between December 2002 and May 2018),respectively.Results:Age at diagnosis,T stage,N stage,and M stage were identified as independent predictors for OS.A nomo-gram incorporating these four predictors was constructed using the training set and demonstrated good calibration and discrimination(C-index 95%confidence interval[CI],0.715[0.679-0.751]),which was validated in the internal validation set(C-index[95%CI],0.672[0.637-0.707]),the TCGA set(C-index[95%CI],0.810[0.732-0.888])and the Chi-nese multicenter set(C-index[95%CI],0.726[0.633-0.819]),respectively.Encouragingly,the nomogram was able to successfully distinguished patients with a high-risk of mortality in all enrolled patients and in the subgroup analyses.Decision curve analysis indicated that the nomogram was clinically useful and applicable.Conclusions:The study presents a nomogram that incorporates clinicopathological predictors,which can accurately predict the OS of adult ACC patients after surgery.This model and the corresponding risk classification system have the potential to guide therapy decisions after surgery. | Jianqiu Kong Junjiong Zheng Jinhua Cai Shaoxu Wu Xiayao Diao Weibin Xie Xiong Chen Chenyi Liao Hao Yu Xinxiang Fan Chaowen Huang Zhuowei Liu Wei Chen Qiang Lv Haide Qin Jian Huang Tianxin Lin | 2019 | Cancer Communications2019，39，1： | 3 |
| 4 | Projection from the Anterior Cingulate Cortex to the Lateral Part of Mediodorsal Thalamus Modulates Vicarious Freezing Behavior显示文摘Emotional contagion, a primary form of empathy, is present in rodents. Among emotional contagion behaviors, social transmission of fear is the most studied.Here, we modified a paradigm used in previous studies to more robustly assess the social transmission of fear in rats that experienced foot-shock. We used resting-state functional magnetic resonance imaging to show that foot-shock experience enhances the regional connectivity of the anterior cingulate cortex(ACC). We found that lesioning the ACC specifically attenuated the vicarious freezing behavior of foot-shock-experienced observer rats. Furthermore, ablation of projections from the ACC to the mediodorsal thalamus(MDL) bilaterally delayed the vicarious freezing responses, and activation of these projections decreased the vicarious freezing responses.Overall, our results demonstrate that, in rats, the ACC modulates vicarious freezing behavior via a projection to the MDL and provide clues to understanding the mechanisms underlying empathic behavior in humans. | Chaowen Zheng Yanwang Huang Binshi Bo Lei Wei Zhifeng Liang Zuoren Wang | 2020 | Neuroscience Bulletin2020，36，3： | 0 |
| 5 | Correction to:Projection from the Anterior Cingulate Cortex to the Lateral Part of Mediodorsal Thalamus Modulates Vicarious Freezing Behavior显示文摘The original version of this article unfortunately contained some mistakes.The authors found that in this article,the left panel of Figure 6B was a wrong placed figure (it was duplicated with the left panel of Figure 5A),and the corrected Figure 6 was shown as follow. | Chaowen Zheng Yanwang Huang Binshi Bo Lei Wei Zhifeng Liang Zuoren Wang | 2020 | Neuroscience Bulletin2020，36，9： | 0 |
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