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Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 35-42页

作者： Li-Li Miao Jing-Wen Wang Hui-Hui Liu Shuai Gao Yu-Chen Fan Kai Wang Department of hepatology Qilu Hospital of Shandong UniversityJinan 250012China Experimental Center Shandong University of Traditional Chinese MedicineJinan 250355China institute of hepatology Shandong UniversityJinan 250012China

Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

关键词： Hepatocellular carcinoma Glycine dehydrogenase DNA methylation Peripheral blood mononuclear cells

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Bioinformatics analysis and experimental validation of cystathionine-gamma-lyase as a potential prognosis biomarker in hepatocellular carcinoma

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BIOCELL 2024年第3期48卷 463-471页

作者： YANAN MA SHANSHAN WANG HUIGUO DING Department of Gastroenterology and hepatology Beijing You’an Hospital Affiliated with Capital Medical UniversityBeijing100069China Beijing institute of hepatology Beijing You’an Hospital Affiliated with Capital Medical UniversityBeijing100069China

Background:Hepatocellular carcinoma(HCC)is a common malignant tumor with poor prognosis and high mortality *** cystathionine-gamma-lyase(CSE)plays an important role in the development of multiple tumors,the clinical implication and potential mechanisms of CSE in HCC development remain ***:In our study,the CSE expression in HCC was analyzed in Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)datasets and further conﬁrmed by RT-qPCR and immunohistochemistry assays in HCC ***,the associations between CSE expression and HCC malignancy as well as survival were analyzed in GSE14520 and validated in HCC ***,the biological functions of CSE in HCC cells was assessed by CCK-8,ﬂow cytometry and Western ***:Lower transcriptional and proteomic CSE expressions were found in HCC tissues in contrast to adjacent normal *** CSE mRNA expression was signiﬁcantly associated with advanced clinicopathological features and poor outcomes in HCC patients from public database and our *** univariate and multivariate analyses of GSE14520 data showed that CSE expression was an independent prognostic indicator for the overall survival(OS)and recurrence-free survival(RFS)of HCC *** vitro experiments further explained that CSE might trigger HCC cell apoptosis by ***:In summary,the present study identiﬁed the relationship between CSE expression and HCC malignancy as well as OS and RFS,indicating that CSE might be a potential prognostic biomarker and a novel therapeutic target for HCC.

关键词： Hepatocellular carcinoma Cystathionine-gamma-lyase Hydrogen sulfide Prognosis Apoptosis

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Targeting muscle to treat Charcot-Marie-Tooth disease

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Neural Regeneration Research 2024年第8期19卷 1653-1654页

作者： David Villarroel-Campos James N.Sleigh Department of Neuromuscular Diseases and ucl Queen Square Motor Neuron Disease Centre UCL Queen Square Institute of NeurologyUniversity College LondonLondonUK UK Dementia Research institute University College LondonLondonUK

Charcot-Marie-Tooth disease(CMT)is a hereditary peripheral neuropathy causing muscle weakness/wasting and sensory dysfunction predominantly in limb *** patients display gait abnormalities,foot deformities,loss of sens... 详细信息

关键词： Marie sensation neuropathy

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Dynamic ultrasonography for optimizing treatment position in superior mesenteric artery syndrome:Two case reports and review of literature

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World Journal of Gastroenterology 2024年第5期30卷 499-508页

作者： Nobuaki Hasegawa Akihiko Oka Muyiwa Awoniyi Yuri Yoshida Hiroshi Tobita Norihisa Ishimura Shunji Ishihara Department of Internal Medicine II Shimane University Faculty of MedicineIzumo 693-8501ShimaneJapan Department of Gastroenterology Hepatology and NutritionDigestive Disease and Surgery InstituteHepatology SectionCleveland ClinicClevelandOH 44195United States Clinical Laboratory Division Shimane University HospitalIzumo 693-8501ShimaneJapan Division of hepatology Shimane University HospitalIzumo 693-8501Japan

BACKGROUND Superior mesenteric artery(SMA)syndrome is a rare cause of duodenal obstruction by extrinsic compression between the SMA and the aorta(SMA-Ao).Although the left lateral recumbent position is considered effective in the treatment of SMA syndrome,individual variations in the optimal patient position have been *** this report,we present two elderly cases of SMA syndrome that exhibited rapid recovery due to ultrasonographic dynamic evaluation of the optimal position for each *** SUMMARY Case 1:A 90-year-old man with nausea and *** diagnosis of SMA syndrome by computed tomography(CT),ultrasonography(US)revealed the SMA-Ao distance in the supine position(4 mm),which slightly improved in the lateral position(5.7–7.0 mm)without the passage of duodenal ***,in the sitting position,the SMA-Ao distance was increased to 15 mm accompanied by improved content ***,US indicated enhanced passage upon abdominal massage on the right *** day 2,the patient could eat comfortably with the optimal position and *** 2:An 87-year-old woman with *** the diagnosis of SMA syndrome and aspiration pneumonia by CT,dynamic US confirmed the optimal position(SMA-Ao distance was improved to 7 mm in forward-bent position,whereas it remained at 5 mm in the supine position).By day 7 when her pneumonia recovered,she could eat with the optimal *** The optimal position for SMA syndrome varies among *** US appears to be a valuable tool in improving patient outcomes.

关键词： Superior mesenteric artery syndrome Wilkie’s syndrome Cast syndrome Aorto-mesenteric compass syndrome Ultrasonography Case report

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Targeting therapy for hepatocellular carcinoma by delivering microRNAs as exosomal cargo

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World Journal of Gastroenterology 2024年第17期30卷 2369-2370页

作者： Takeshi Suda Department of Gastroenterology and hepatology Uonuma Institute of Community MedicineNiigata University Medical and Dental HospitalMinami Uonuma 949-7302NiigataJapan

Exosomes,the smallest extracellular vesicles,have gained significant attention as key mediators in intercellular communication,influencing both physiological and pathological processes,particularly in cancer progression.A recent review article by Wang et al was published in a timely manner to stimulate future research and facilitate practical developments for targeted treatment of hepatocellular carcinoma using exosomes,with a focus on the origin from which exosomes *** information about the mechanisms for delivering exosomes to specific cells is incorporated,the concept of targeted therapy for hepatocellular carcinoma using exosomes could be more comprehensively understood.

关键词： Exosomal delivery Therapeutic targets MicroRNAs Hepatocellular carcinoma

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Portal hypertension in patients with nonalcoholic fatty liver disease:Current knowledge and challenges

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World Journal of Gastroenterology 2024年第4期30卷 290-307页

作者： Anita Madir Ivica Grgurevic Emmanuel A Tsochatzis Massimo Pinzani Department of Gastroenterology Hepatology and Clinical NutritionUniversity Hospital DubravaZagreb 10000Croatia School of Medicine University of ZagrebZagreb 10000Croatia Faculty of Pharmacy and Biochemistry University of ZagrebZagreb 10000Croatia ucl institute for Liver and Digestive Health Royal Free Hospital and University College LondonLondon NW32PFUnited Kingdom

Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver *** early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver *** compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of *** spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with ***,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of *** theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this *** and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing *** change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the comp

关键词： Non-alcoholic fatty liver disease Portal hypertension Mechanotransduction Endothelial dysfunction Hepatic venous pressure gradient

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Insm1:orchestrating cellular mimicry in the thymus medulla

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Cellular & Molecular Immunology 2024年第4期21卷 414-416页

作者： K.D.James J.E.Cowan ucl institute of Immunity and Transplantation The Pears BuildingRowland Hill StreetLondonNW32PPUK

The thymus is the primary production site for a functional and self-tolerant T-cell *** establishment of immune tolerance is mediated by the generation and presentation of tissue-restricted self-antigens(TRAs)by medullary thymic epithelial cells(mTECs),which screen T-cell receptors for self-reactivity to eliminate autoreactive T *** studies have extended our understanding of mTEC heterogeneity by examining the mechanisms by which mTECs mimic the peripheral self[1].

关键词： medullary eliminate restricted

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Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio:Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 577-582页

作者： Qiu-Yu Jiang Ru-Yi Xue Department of Gastroenterology and hepatology Zhongshan HospitalShanghai Institute of Liver DiseaseFudan UniversityShanghai 200032China Department of Gastroenterology and hepatology Shanghai Baoshan District Wusong Central Hospital(Zhongshan Hospital Wusong BranchFudan University)Shanghai 200940China

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting ***,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers *** and PLR are promising markers for clinical *** models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite ***,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

关键词： Neutrophil-to-lymphocyte ratio Platelet-to-lymphocyte ratio Immunecheckpoint inhibitor Immune-related adverse event

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Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第9期21卷 813-825页

作者： Jiaxin Han Wentao Kuai Liu Yang Xuemei Tao Yuekui Wang Minghui Zeng Yuqin Li Yuqiang Mi Ningning Zhang Wei Lu Liang Xu Clinical School of the Tianjin Second People's Hospital Tianjin Medical University Department of hepatology Tianjin Second People's Hospital Tianjin institute of hepatology Department of Hepatobiliary Oncology Liver Cancer Center Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD) on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods: A total of 155 patients with CHB-related HCC who received ICI±based therapy(in the Department of hepatology, Tianjin Second People's Hospital and Department of Hepatobiliary Oncology, Tianjin Medical University Cancer institute & Hospital) between April 2021 and December 2023 were *** were divided into two groups: MASLD concurrent with CHB [MASLD-CHB](n = 38), and CHB(n = 117).Results: The median progression-free survival(PFS, 6.9 months vs.9.3 months; P = 0.001), progressive disease(57.89% vs.37.61%; P = 0.028), and disease control rate(42.11% vs.62.39%; P = 0.028) in the MASLD-CHB group were significantly worse than the CHB *** median overall survival was not *** percentage of CD4+PD1+(17.56% vs.8.89%; P < 0.001) and CD8+PD1+ T cells(10.50% vs.7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB *** MASLD [hazard ratio(HR) = 1.921; 95% CI, 1.138±3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment(HR = 2.412; 95% CI, 1.360±4.279; P = 0.003) were independent risk factors for PFS in all ***: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

关键词： Metabolic dysfunction-associated steatotic liver disease chronic hepatitis B efficacy hepatocellular carcinoma immunotherapy

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Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease:Opportunities and challenges

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World Journal of hepatology 2024年第5期16卷 731-750页

作者： Chencheng Xie Naim Alkhouri Mohamed A Elfeki Department of Internal Medicine University of South Dakota Sanford School of MedicineSioux FallsSD 57105United States Department of hepatology Avera Mckennan University Hospital and Transplant InstituteSioux FallsSD 57105United States Department of hepatology Arizona Liver HealthChandlerAZ 85712United States Department of hepatology Avera McKennan University Hospital and Transplant InstituteSioux FallsSD 57105United States

Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most common chronic liver disease worldwide,paralleling the rising pandemic of obesity and type 2 *** to the growing global health burden and com-plex pathogenesis of MASLD,a multifaceted and innovative therapeutic approach is *** receptor agonists,which were initially developed for diabetes management,have emerged as promising candidates for MASLD *** review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists:glucagon-like peptide-1 receptor agonists,glucose-dependent insulinotropic polypeptide receptor agonists,and glucagon receptor *** and glucagon directly or indirectly impact various organs,including the liver,brain,pancreas,gastro-intestinal tract,and adipose ***,these agents significantly improve glycemic control and weight management and mitigate MASLD ***,this study provides a summary of clinical trials analyzing the effect-iveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function,hepatic steatosis,and intrahepatic *** are emerging challenges associated with the use of these medications in the real world,particularly adverse events,drug-drug interactions,and barriers to access,which are discussed in ***,this review highlights the evolving role of incretin receptor agonists in MASLD management and suggests future research directions.

关键词： Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis Glucagon-like peptide-1 Glucose-dependent inulinotropic polypeptide Glucagon Incretin Receptor agonist

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