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Paclitaxel-induced Immune Dysfunction and Activation of Transcription Factor AP-1 Facilitate Hepatitis B Virus Replication

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Journal of Clinical and Translational Hepatology 2024年第5期12卷 457-468页

作者： Shi Chen Benhua Li Wei Luo Adeel ur Rehman Miao He Qian Yang Shunyao Wang Jinjun Guo Ling Chen Xiaosong Li Clinical Molecular Medicine Testing Center The First Affiliated HospitalChongqing Medical UniversityChongqingChina Affiliated Traditional Chinese Medicine Hospital of Southwest medical university LuzhouSichuanChina Laboratory Animal Center of chongqing medical university ChongqingChina Bishan Hospital of chongqing Bishan Hospital of Chongqing Medical UniversityChongqingChina The Center of Experimental Teaching Management Chongqing Medical UniversityChongqingChina

Background and Aims:Hepatitis B virus(HBV)reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug ***(PTX)treatment has been identified as a potential trigger for HBV *** study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo,which may inform new strategies for HBV antiviral ***:The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay,dual-luciferase reporter assay,quantitative real-time PCR,chromatin immunoprecipitation,and immunohistochemical *** sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic ***:PTX enhanced the levels of HBV 3.5-kb mRNA,HBV DNA,HBeAg,and HBsAg both in vitro and in *** also promoted the activity of the HBV core promoter and transcription factor *** of AP-1 gene expression markedly suppressed PTX-induced HBV *** sequencing revealed that PTX activated the immune-related signaling networks such as IL-17,NF-􀇉B,and MAPK signaling pathways,with the pivotal common key molecule being *** 16S rRNA sequencing revealed that PTX induced dysbiosis of gut ***:PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor *** findings propose a novel molecular mechanism,underscoring the critical role of AP-1 in PTX-induced HBV reactivation.

关键词： Paclitaxel HBV reactivation Transcription factor AP-1 Immune system Gut microbiota

Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

Classifying hepatitis B therapies with insights from covalently closed circular DNA dynamics

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Virologica Sinica 2024年第1期39卷 9-23页

作者： Jie-Li Hu Ai-Long Huang Key Laboratory of Molecular Biology on Infectious Diseases Ministry of EducationChongqing Medical UniversityChongqing400016China

The achievement of a functional cure for chronic hepatitis B(CHB)remains limited to a minority of patients treated with currently approved *** primary objective in developing new anti-HBV drugs is to enhance the functional cure rates for CHB.A critical prerequisite for the functional cure of CHB is a substantial reduction,or even eradication of covalently closed circular DNA(cccDNA).Within this context,the changes in cccDNA levels during treatment become as a pivotal *** have previously analyzed the factors influencing cccDNA dynamics and introduced a preliminary classification of hepatitis B treatment strategies based on these *** this review,we employ a systems thinking perspective to elucidate the fundamental aspects of the HBV replication cycle and to rationalize the classification of treatment strategies according to their impact on the dynamic equilibrium of *** upon this foundation,we categorize current anti-HBV strategies into two distinct groups and advocate for their combined use to significantly reduce cccDNA levels within a well-defined timeframe.

关键词： Hepatitis B cccDNA Functional cure Dynamics Treatment Strategy

JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1

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Genes & Diseases 2023年第5期10卷 2167-2178页

作者： Junping Liu Yutong Shi Minmin Wu Fengmei Zhang Mengqi Xu Zhiqiang He Min Tang Key Laboratory of Laboratory medical Diagnostics Designated by the Chinese Ministry of Education Chongqing Medical UniversityChongqing 400016China

Despite significant improvements in five-year survival rates due to early diagnosis and combination therapy, triple-negative breast cancer (TNBC) treatment remains a major challenge. Finding new and effective targets for diagnosis and drug therapy is urgent for TNBC patients. Jagged-1 (JAG1), one of the canonical ligands of the Notch signaling pathway, is involved in vascular budding and is a poor prognostic factor of TNBC. In this study, combined with quantitative real-time PCR, database analysis, animal experiments, and other means, JAG1 was confirmed to be related to the poor prognosis of TNBC patients. JAG1 was highly expressed in MDA-MB-231 Bone (231B) cells, with stronger invasion and metastasis ability than MDA-MB-231 (231) cells. Treatment of human vascular endothelial cells (HUVEC) with TNBC conditioned medium showed that TNBC JAG1 promoted the angiogenesis of HUVEC. Next, we detected the exosomes extracted from TNBC conditioned medium and found that JAG1 promoted the exosome secretion from 231 cells via ALIX-RAB11A/RAB35. In addition, we also found that the exosomes from JAG1 overexpressed TNBC cells contained more long non-coding RNA (lncRNA) MALAT1 , and MALAT1 promoted angiogenesis of HUVEC by targeting miR-140-5p . Finally, the angiogenesis-promoting effect of JAG1 in TNBC was further investigated by matrix gel assay. In conclusion, we reveal that JAG1 has a pro-invasion effect on TNBC and is involved in microenvironment angiogenesis by promoting exosome secretion and the MALAT1-miR-140-5p-JAG1/VEGFA pathway.

关键词： Angiogenesis Exosome JAG1 lncRNAMALAT1 Triple-negative breast cancer

Small-cell neuroendocrine carcinoma of the rectum—a rare tumor type with poor prognosis:A case report and review of literature

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World Journal of Clinical Cases 2020年第23期8卷 6095-6102页

作者： Zhen-Zhou Chen Wang Huang Zheng-Qiang Wei Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400000China

BACKGROUND Small-cell neuroendocrine carcinoma(SNEC)of the rectum is a rare tumor associated with poor *** SUMMARY We report a case of a 77-year-old male who came into our hospital because of blood with his *** endoscopy revealed a cauliflower-like neoplasm in his *** examination showed that the lesion in the upper rectum was likely rectal cancer,and there was no evidence of *** patient was treated with *** examination confirmed SNEC of the rectum and an R0 resection was ***,1 mo after the operation,the patient developed intestinal and ureteral obstructions due to peritoneal ***,the patient died from renal *** SNEC of the rectum is a high-grade carcinoma with an aggressive phenotype,and surgery should be cautiously considered.

关键词： Case report Small-cell neuroendocrine carcinoma Rectum Treatment Prognosis Rare tumor

Contrast enhanced ultrasound in diagnosing liver lesion that spontaneously disappeared:A case report

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World Journal of Clinical Cases 2021年第21期9卷 5948-5954页

作者： Zong-Ding Wang Salameen Haitham Jian-Ping Gong Zi-Li Pen Department of Surgery Fengjie People’s HospitalChongqing 400010China Department of Hepatobiliary Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Focal liver lesions(FLLs)are abnormal masses that are distinguishable from the surrounding liver parenchyma,solid or cystic and may be benign or *** are usually detected incidentally on abdominal *** classification of FLLs is very important as it directly determines the diagnosis and treatment of *** SUMMARY A 46-year-old male patient was admitted into the hospital with tarry stool,during the investigation of this issue an incidental FLL was *** further investigation of this“incidentaloma”computerized tomography and magnetic resonance imaging reached contradictory *** lesion was then further investigated using contrast-enhanced ultrasound(CEUS)with an initial diagnosis of idiopathic FLL was acquired and observation of the FLL over time need for final diagnosis,however in the follow up the FLL disappeared *** CEUSs value for characterization of FLLs is undeniable,especially when other methods produce inconsistent results,is undeniable but with its *** and how the FLL disappeared is not known,and can be only hypothesized it was a pseudolesion.

关键词： Liver Ultrasonography Tomography Contrast enhanced ultrasound Focal liver lesions Case report

Does chronic kidney disease affect the complications and prognosis of patients after primary colorectal cancer surgery?

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World Journal of Gastrointestinal Oncology 2022年第6期14卷 1199-1209页

作者： Xiao-Yu Liu Bin Zhang Yu-Xi Cheng Wei Tao Chao Yuan Zheng-Qiang Wei Dong Peng Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND The effect of chronic kidney disease(CKD)on the outcomes of colorectal cancer(CRC)patients after primary CRC surgery is *** To analyze whether CKD had specific effect on the outcomes after CRC *** We searched the PubMed,Embase,Cochrane Library databases and CNKI,from inception to March 14,***-Ottawa Scale was used for the quality assessment in this meta-analysis,and we used RevMan 5.3 was used for data *** A total of nine studies including 47771 patients were eligible for this *** significant difference was found in terms of overall postoperative complications[odds ratio(OR)=1.78,95%CI:0.64-4.94,P=0.27].We analyzed the specific complications and found that the CKD group had higher rates of pulmonary infection(OR=2.70,95%CI:1.82-4.00,P<0.01),cardiovascular complications(OR=3.39,95%CI:2.34-4.91,P<0.01)and short-term death(OR=3.01,95%CI:2.20-4.11,P<0.01).After pooling the hazard ratio(HR),the CKD group had worse overall survival(OS)(HR=1.51,95%CI:1.04-2.20,P=0.03).We performed subgroup analyses of the dialysis and non-dialysis groups,and no significant difference was found in the non-dialysis group(HR=1.20,95%CI:0.98-1.47,P=0.08).The dialysis group had worse OS(HR=3.36,95%CI:1.92-5.50,P<0.01)than the non-dialysis *** CKD group had worse disease-free survival(DFS)(HR=1.41,95%CI:1.12-1.78,P<0.01),and in the subgroup analysis of the dialysis and non-dialysis groups,no significant difference was found in the non-dialysis group(HR=1.27,95%CI:0.97-1.66,P=0.08).The dialysis group had worse OS(HR=1.95,95%CI:1.23-3.10,P<0.01)than the non-dialysis *** Preexisting CKD was associated with higher rates of pulmonary infection,higher rates of shortterm death,and worse OS and poorer DFS following CRC surgery.

关键词： Chronic kidney disease Colorectal cancer Outcome Prognosis Meta-analysis

Heparin-induced thrombocytopenia in renal insufficiency undergoing dialysis and percutaneous coronary intervention after acute myocardial infarction:A case report

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World Journal of Cardiology 2020年第12期12卷 634-641页

作者： Jing Wang Song-Bai Deng Qiang She Department of Cardiology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Heparin-induced thrombocytopenia(HIT)is a rare complication of heparin therapy,and is characterized by arteriovenous thrombosis and bleeding *** incidence of HIT after percutaneous coronary intervention(PCI)in patients with myocardial infarction complicated with renal failure is rarely *** SUMMARY We report a 73-year-old man with acute myocardial infarction and renal failure who underwent hemodialysis and PCI,and developed a progressive decline in platelets and subcutaneous hemorrhage of both upper limbs after heparin *** addition to a gradual decrease in platelets,the patient’s 4T's score was 7,and HIT antibody was positive,confirming the diagnosis of *** Patients receiving heparin combined with antiplatelet therapy should be monitored closely,especially for their platelet *** the case of thrombocytopenia,HIT should be highly *** the diagnosis of HIT is confirmed,timely individualized treatment should be delivered.

关键词： Thrombocytopenia Heparin Percutaneous coronary intervention Myocardial infarction Chronic renal insufficiency Case report

Particle Size-Controlled Oxygen Reduction and Evolution Reaction Nanocatalysts Regulate Ru(bpy)_(3)^(2+)’s Dual-potential Electrochemiluminescence for Sandwich Immunoassay

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Research 2023年第4期2023卷 701-715页

作者： Shijun Wang Shu Zhu Ziqi Kang Xiangxiu Wang Zixin Deng Kun Hu Jianjun Hu Xiancheng Liu Guixue Wang Guangchao Zang Yuchan Zhang Institute of Life Science and Laboratory of Tissue and Cell Biology Lab Teaching&Management CenterChongqing Medical UniversityChongqing 400016China Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing 400030China Jinfeng Laboratory Chongqing 401329China Department of Pathophysiology Chongqing Medical UniversityChongqing 400016China Department of Pathology Guizhou Provincial People’s HospitalGuiyangGuizhou 550002China

Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their *** this study,we synthesized a series of gold nanoparticles(AuNPs)/reduced graphene oxide(Au/rGO)composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2′-bipyridine)ruthenium(II)(Ru(bpy)_(3)^(2+))’s multisignal *** the increase in the diameter of AuNPs(3 to 30 nm),their ability to promote Ru(bpy)_(3)^(2+)’s anodic ECL was first impaired and then strengthened,and cathodic ECL was first enhanced and then ***/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)_(3)^(2+)’s cathodic and anodic luminescence,***,the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)_(3)^(2+)***,we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)_(3)^(2+)’s luminescence promoter rather than luminophores as tags of antibodies to achieve signal *** method avoids signal cross talk between luminophores and their respective co-reactants,which achieved a good linear range of 10−7 to 10−1 ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic *** study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)_(3)^(2+),broadening its application in biomaterial ***,the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)_(3)^(2+)could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)_(3)^(2+)luminescence enhancers or applications of Au/rGOs to other *** work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their

关键词： luminescence potential reactant