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Phosphatidic acid-enabled MKL1 contributes to liver regeneration:Translational implication in liver failure

Acta Pharmaceutica Sinica B 2024年第1期14卷 256-272页

作者： Jiawen Zhou Xinyue Sun Xuelian Chen Huimin Liu Xiulian Miao Yan Guo Zhiwen Fan Jie Li Yong Xu Zilong Li State Key Laboratory of Natural medicine. Department of PharmacologyChina Pharmaceutical UniversityNanjing 211198China Institute of Biomedical Research Liaocheng UniversityLiaocheng 252200China department of Pathology Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China department of infectious diseases Nanjing Drum Tower Hospital Affiliated with Nanjing University Medical SchoolNanjing 210008China Institute of Viruses and infectious diseases Nanjing UniversityNanjing 210008China

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver *** the present study we investigated the contribution of megakaryocytic leukemia 1(MKL1),a transcriptional modulator,to liver *** report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure *** with MKL1 deletion exhibited defective regenerative response in the *** analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative ***2 mediated phosphorylation primed MKL1 for its interaction with *** interest,phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid(PA).PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver ***,PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure *** conclusion,our data reveal a novel mechanism whereby MKL1 contributes to liver *** for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

关键词： Liver failure Liver regeneration Transcription regulation Transcription factor Hepatocytes Phosphatidic acid Phospholipase d2 Translational medicine

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Rocahepevirus ratti: An underrecognised cause of acute hepatitis

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World Journal of Hepatology 2024年第8期16卷 1084-1090页

作者： George S Gherlan department of infectious diseases “Carol Davila”University of Medicine and PharmacyBucharest 050474Romania

Zoonoses are responsible for many of all emerging infectious diseases as well as for those already *** ratti is a rat-originated virus related to the hepatitis E virus(Paslahepevirus balayani)but highly divergent genetically from this,with a high cross-species infection potential and zoonotic *** can infect humans,leading to acute hepatitis,and is primarily transmitted through the consumption of contaminated *** ratti was first discovered in Germany in *** first human case was described in 2017 in Hong Kong in an immune-compromised *** first case of chronic infection with Rocahep-evirus ratti was described in 2023.A meta-analysis based on 38 studies published between 2000 and 2023 identified 21 cases in humans described up to this date and 489 infections in different *** awareness regarding this virus is essential,as there are probably many cases that remain undiagnosed,and the virus even has the ability to produce chronic infections in selected patients.

关键词： Hepatitis Rocahepevirus ratti Rats Zoonoses Hepeviridae Liver

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Isolation and characterization of mpox virus from the first mpox case in Shenzhen,China

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Virologica Sinica 2024年第2期39卷 335-337页

作者： Lin Cheng Liuqing Yang Miao Wang Yabo Peng Haiyan Wang Xiaoxiang Yang Juanjuan Zhao Mingxia Zhang Fuxiang Wang Zheng Zhang Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalShenzhen518112China department of infectious diseases Shenzhen Third People's HospitalShenzhen 518112China The Second Affiliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China

Dear Editor,Unlike previous outbreaks of the mpox(previously known as monkeypox),which were localized in Africa and resulted in small numbers of infections due to limited human-to-human transmission,the current outbreak beginning in May 2022,has spread rapidly primarily through human-to-human transmission in non-endemic countries(Gong et al.,2022).As of 27 Sep 2023,115 countries and regions have reported cases of mpox to the World Health Organization(WHO),bringing the total number of confirmed cases to 90,618 including 125 *** the number of new cases has decreased in most WHO regions in the second half of 2022,the curves reveal a long outbreak tail in different subregions of the *** worrying,106 mpox cases were reported in the mainland of China in June 2023.

关键词： mainland bringing

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Unveiling sinus venosus atrial septal defect and partial anomalous pulmonary venous return in an elderly patient

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Journal of Geriatric Cardiology 2024年第4期21卷 462-464页

作者： Cristina M Font Anamarys Blanco Fernandez Dinesh Kadariya department of medicine Division of CardiologyUniversity of Florida College of MedicineJacksonvilleFloridaUSA

Sinus venosus defect(SVD) accounts for 4%–11% of all atrial septal defects(ASD) and may present with dyspnea, heart failure(HF), palpitations, or angina.^[1] The malformation typically involves an interatrial communication due to a deficiency in the common wall connecting the right pulmonary veins and the superior vena cava(SVC) and often accompanies anomalous pulmonary venous connection of some or all of the pulmonary veins.

关键词： atrial septal venous

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Intermittent fasting and the liver: Focus on the Ramadan model

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World Journal of Hepatology 2024年第8期16卷 1070-1083页

作者： Mohamed H Emara Hanan Soliman Ebada M Said Hassan Elbatae Mostafa Elazab Shady Elhefnawy Tarik I Zaher Ahmed Abdel-Razik Mohamed Elnadry department of Hepatology Gastroenterology and Infectious DiseasesKafrelsheikh UniversityKafr-Elshikh 33516Egypt department of medicine Alyousif HospitalAlkhobar 34622Saudi Arabia department of Tropical medicine.and infectious diseases Tanta UniversityTanta 31512Egypt department of Hepatology Gastroenterology and Infectious DiseasesBenha UniversityBenha 13511Egypt department of Tropical medicine Zagazig UniversityZagazig 44519Egypt department of Tropical medicine Mansoura UniversityMansoura 35516Egypt department of Hepato-Gastroenterology and infectious diseases Al-Azhar UniversityCairo 11651Egypt

Intermittent fasting(IF)is an intervention that involves not only dietary modific-ations but also behavioral changes with the main core being a period of fasting alternating with a period of controlled *** duration of fasting differs from one regimen to *** fasting(RF)is a religious fasting for Muslims,it lasts for only one month every one lunar *** this model of fasting,observers abstain from food and water for a period that extends from dawn to *** period of daily fasting is variable(12-18 hours)as Ramadan rotates in all seasons of the ***,longer duration of daily fasting is observed during the *** fact,RF is a peculiar type of *** is a dry IF as no water is allowed during the fasting hours,also there are no calorie restrictions during feeding hours,and the mealtime is exclusively *** three variables of the RF model are believed to have a variable impact on different liver *** was evaluated by different observational and interventional studies among patients with non-alcoholic fatty liver disease and it was associated with improve-ments in anthropometric measures,metabolic profile,and liver biochemistry regardless of the calorie restriction among lean and obese *** situation is rather different for patients with liver *** was associated with adverse events among patients with liver cirrhosis irrespective of the underlying etiology of *** patients developed new ascites,ascites were increased,had higher serum bilirubin levels after Ramadan,and frequently developed hepatic encephalopathy and acute upper gastrointestinal *** complications were higher among patients with Child class B and C cirrhosis,and some fatalities occurred due to *** transplant recipients as a special group of patients,are vulnerable to dehydration,fluctuation in blood immunosuppressive levels,likelihood of deterioration and hence observing RF without special precautions

关键词： Intermittent fasting Ramadan fasting Non-alcoholic fatty liver disease Liver cirrhosis Peptic ulcer Liver transplantation Gilbert syndrome

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Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1514-1531页

作者： Yong Pan Yi-Ru Zhang Ling-Yun Wang Li-Na Wu Ying-Qiu Ma Zhou Fang Shi-Bo Li department of infectious Disease Zhoushan HospitalWenzhou Medical UniversityZhoushan 316021Zhejiang ProvinceChina State Key Laboratory for the Diagnosis and Treatment of infectious diseases The First Affiliated Hospital of Zhejiang UniversityHangzhou 310003Zhejiang ProvinceChina department of infectious Disease The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035Zhejiang ProvinceChina

BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in ***,the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma(HCC)remain *** To establish a cyclin dependent kinase inhibitor 2A(CDKN2A)-related ceRNA network and recognize potential prognostic indicators for *** The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal *** expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC *** targeted microRNAs were predicted by lncBasev3.0,and the targeted mRNAs were predicted by miRDB,and Targetscan *** univariate and multivariate analysis were utilized to identify independent prognostic *** CDKN2A was frequently mutated and deleted in *** single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle *** CDKN2A-related ceRNA network-growth arrest specific 5(GAS5)/miR-25-3p/SRY-box transcription factor 11(SOX11)was successfully ***5 was recognized as an independent prognostic biomarker,whose overexpression was correlated with a poor prognosis in HCC *** association between GAS5 expression and methylation,immune infilt-ration was ***,traditional Chinese medicine.effective components targeting GAS5 were *** This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and ***,GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

关键词： Hepatocellular carcinoma Competitive endogenous RNA Molecular mechanism Prognosis Biomarker

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Computed tomography for prediction of esophageal variceal bleeding

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World Journal of Gastrointestinal Endoscopy 2024年第3期16卷 175-177页

作者： Mohammed Elhendawy Ferial Elkalla department of Tropical medicine.and infectious diseases Tanta UniversityTanta 31111Egypt

This letter to the editor relates to the study entitled“The role of computed tomography for the prediction of esophageal variceal bleeding:Current status and future perspectives”.Esophageal variceal bleeding(EVB)is one of the most common and severe complications related to portal hypertension(PH).Despite marked advances in its management during the last three decades,EVB is still associated with significant morbidity and *** risk of first EVB is related to the severity of both PH and liver disease,and to the size and endoscopic appearance of esophageal ***,hepatic venous pressure gradient(HVPG)and esophagogastroduodenoscopy(EGD)are currently recognized as the“gold standard”and the diagnostic reference standard for the prediction of EVB,***,HVPG is an invasive,expensive,and technically complex procedure,not widely available in clinical practice,whereas EGD is mainly limited by its invasive *** this scenario,computed tomography(CT)has been recently proposed as a promising modality for the non-invasive prediction of *** CT serves solely as a diagnostic tool and cannot replace EGD or HVPG for delivering therapeutic and physiological information,it has the potential to enhance the prediction of EVB more effectively when combined with liver disease scores,HVPG,and ***,to date,evidence concerning the role of CT in this setting is still lacking,therefore we aim to summarize and discuss the current evidence concerning the role of CT in predicting the risk of EVB.

关键词： Esophageal variceal bleeding Variceal upper gastrointestinal bleeding Portal hypertension Computed tomography Computed tomography angiography

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Inhibition of hepatitis B virus via selective apoptosis modulation by Chinese patent medicine.Liuweiwuling Tablet

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World Journal of Gastroenterology 2024年第13期30卷 1911-1925页

作者： Fei-Lin Ge Yan Yang Lan-Lan Si Yuan-Hua Li Meng-Zhen Cao Jun Wang Zhao-Fang Bai Zhi-Gang Ren Xiao-He Xiao Yan Liu department of Chinese medicine State Key Laboratory of Antiviral DrugsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina The Fifth Medical Center of Chinese PLA General Hospital Beijing 100039China College of Traditional Chinese medicine Chongqing Medical UniversityChongqing 400010China Beijing Key Laboratory of Emerging infectious diseases Peking University Ditan Teaching HospitalBeijing 100015China department of infectious diseases State Key Laboratory of Antiviral Drugsthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine.approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)*** studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains *** To investigate the potential mechanism of action of LWWL against *** In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell *** in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV *** and metabolomics were used to investigate the underlying mechanisms of action of *** In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,*** inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,*** of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups

关键词： Hepatitis B virus Chinese patent medicine Antiviral activity Antiviral mechanism Selective apoptosis

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Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee Bong-Ki Hong Saseong Lee Naeun Lee Seung-Whan Kim Donghyun Kim Wan-Uk Kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea department of Biomedicine.Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea department of Pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical Institute of Technology University of UlsanSeoul 05505Republic of Korea department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea Institute of infectious diseases Seoul National University College of MedicineSeoul 03080Republic of Korea division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the *** receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains ***,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory ***,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic ***,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active *** note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in *** ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in *** with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling ***,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

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Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B:A meta-analysis

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World Journal of Hepatology 2024年第3期16卷 465-476页

作者： Shi-Yi Liu Dian Wang Jing Liu Lu-Ping Yang Gong-Ying Chen department of medicine Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina department of medicine Hangzhou Normal UniversityHangzhou 310011Zhejiang ProvinceChina department of infectious and Hepatology diseases Affiliated Hospital of Hangzhou Normal UniversityHangzhou 310015Zhejiang ProvinceChina

BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver *** number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has *** To analyze the effect of NAFLD on the response to antiviral treatment in patients with *** Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October *** in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were *** Of the 2502 retrieved studies,11 articles were finally *** response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB *** Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

关键词： Nonalcoholic fatty liver disease Hepatitis B virus Antiviral treatment effect Meta-analysis

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