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| 1 | Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury显示文摘Neuronal regeneration and functional recovery are severely compromised following traumatic brain injury(TBl).Treatment options,including cell transplantation and drug therapy,have been shown to benefit TBl,although the underlying mechanisms remain elusive.In this study,neural stem cells(NSCs)are transplanted into TBl-challenged mice,together with olfactory ensheathing cells(OECs)or followed by valproic acid(VPA)treatment.Both OEC grafting and VPA treatment facilitate the differentiation of NSCs into neurons(including endogenous and exogenous neurons)and significantly attenuate neurological functional defects in TBl mice.Combination of NSCs with OECs or VPA administration leads to overt improvement in axonal regeneration,synaptogenesis,and synaptic plasticity in the cerebral cortex in TBl-challenged mice,as shown by retrograde corticospinal tract tracing,electron microscopy,growth-associated protein 43(GAP43),and synaptophysin(SYN)analyses.However,these beneficial effects of VPA are reversed by local delivery of N-methyl-D-aspartate(NMDA)into tissues surrounding the injury epicenter in the cerebral cortex,accompanied by a pronounced drop in axons and synapses in the brain.Our findings reveal that increased axonal regeneration and synaptogenesis evoked by cell grafting and VPA fosters neural repair in a murine model of TBl.Moreover,VPA-induced neuroprotective roles are antagonized by exogenous NMDA administration and its concomitant decrease in the number of neurons of local brain,indicating that increased neurons induced by VPA treatment mediate axonal regeneration and synaptogenesis in mice after TBl operation.Collectively,this study provides new insights into NSC transplantation therapy for TBI. | Sujuan Liu Haili Tian Yanmei Niu Chunxia Yu Lingjian Xie Zhe Jin Wenyan Niu Jun Ren Li Fu Zhi Yao | 2022 | Acta Biochimica et Biophysica Sinica2022，54，9： | 1 |
| 2 | 1,5-Anhydroglucitol Predicts Mortality in Patients with HBV-Related Acute-on-chronic Liver Failure显示文摘Background and Aims:1,5-Anhydroglucitol(1,5AG)activ-ity has been reported in chronic liver disease.Hepatitis B vi-rus(HBV)-related acute-on-chronic liver failure(HBV-ACLF)patients have a high mortality.We aimed to discover the re-lationship between serum 1,5AG and the prognosis of HBV-ACLF.Methods:Serum 1,5AG levels were determined in 333 patients with HBV-ACLF,300 without diabetes were allo-cated to derivation(n=206)and validation cohorts(n=94),and 33 were recruited to evaluate 1,5AG in those with diabe-tes.Forty patients with chronic hepatitis B,40 with liver cir-rhosis,and 40 healthy people were controls in the validation cohort.Results:In the derivation and validation cohorts,serum 1,5AG levels were significantly lower in nonsurvivors than in survivors.The AUC of 1,5AG for 28-day mortality was 0.811.In patients with diabetes,serum 1,5AG levels were also significantly lower in nonsurvivors than in survi-vors.In multivariate Cox regression analysis,serum 1,5AG levels were independently associated with 28-day mortal-ity.A novel predictive model(ACTIG)based on 1,5AG,age,TB,cholesterol,and INR was derived to predict mortality.In ACTIG,the AUC for 28-day mortality was 0.914,which was superior to some prognostic score models.ACTIG was also comparable to those prognostic score models in pre-dicting 6-month mortality.In mice with D-galactosamine/lipopolysaccharide-induced liver failure,1,5AG levels were significantly reduced in serum and significantly increased in urine and liver tissue.Conclusions:Serum 1,5AG levels are a promising predictor of short-term mortality in HBV-ACLF patients.The 1,5AG distribution changed in mice with D-galactosamine/lipopolysaccharide-induced liver failure. | Lingjian Zhang Yalei Zhao Zhongyang Xie Lanlan Xiao Qingqing Hu Qian Li Shima Tang Jie Wang Lanjuan Li | 2022 | Journal of Clinical and Translational Hepatology2022，10，4： | 1 |
| 3 | Integrative proteomics reveals the role of E3 ubiquitin ligase SYVN1 in hepatocellular carcinoma metastasis显示文摘Background:Tumor metastasis is a major factor for poor prognosis of hepatocellular carcinoma(HCC),but the relationship between ubiquitination and metastasis need to be studiedmore systematically.We analyzed the ubiquitinome of HCC in this study to have a more comprehensive insight into human HCC metastasis.Methods:The protein ubiquitination levels in 15 HCC specimens with vascular invasion and 15 without vascular invasion were detected by ubiquitinome.Proteins with significantly different ubiquitination levels between HCCs with and without vascular invasion were used to predict E3 ubiquitin ligases associated with tumor metastasis.The topological network of protein substrates and corresponding E3 ubiquitin ligaseswas constructed to identify the key E3 ubiquitin ligase.Besides,the growth,migration and invasion ability of LM3 and HUH7 hepatoma cell lines with andwithout SYVN1 expression interferencewere measured by cell proliferation assay,subcutaneous tumor assay,umphal vein endothelium tube formation assay,transwell migration and invasion assays.Finally,the interacting proteins of SYVN1 were screened and verified by protein interaction omics,immunofluorescence,and immunoprecipitation.Ubiquitin levels of related protein substrates in LM3 and HUH7 cells were compared in negative control,SYVN1 knockdown,and SYVN1 overexpression groups.Results:In this study,our whole-cell proteomic dataset and ubiquitinomic dataset contained approximately 5600 proteins and 12,000 ubiquitinated sites.We discovered increased ubiquitinated sites with shorter ubiquitin chains during the progression ofHCC metastasis.In addition,proteomic and ubiquitinomic analyses revealed that high expression of E3 ubiquitin-protein ligase SYVN1 is related with tumor metastasis.Furthermore,we found that SYVN1 interacted with heat shock protein 90(HSP90)and impacted the ubiquitination of eukaryotic elongation factor 2 kinase(EEF2K).Conclusions:The ubiquitination profiles of HCC with and without vascular invasion were significantly different.SYVN1 was the most important E3 ubiquitin-protein ligase responsible for this phenomenon,and itwas related with tumormetastasis and growth.Therefore,SYVN1might be a potential therapeutic target for HCC. | Feiyang Ji Menghao Zhou Zeyu Sun Zhengyi Jiang Huihui Zhu Zhongyang Xie Xiaoxi Ouyang Lingjian Zhang Lanjuan Li | 2021 | Cancer Communications2021，41，10： | 0 |
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