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Evidence-based pathogenesis and treatment of ulcerative colitis:A causal role for colonic epithelial hydrogen peroxide

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World Journal of Gastroenterology 2022年第31期28卷 4263-4298页

作者： Jay Pravda Disease pathogenesis Inflammatory Disease Research CentrePalm Beach GardensFL 33410United States

In this comprehensive evidence-based analysis of ulcerative colitis(UC),a causal role is identified for colonic epithelial hydrogen peroxide(H_(2)O_(2))in both the pathogenesis and relapse of this debilitating inflammatory bowel *** have shown that H_(2)O_(2) production is significantly increased in the non-inflamed colonic epithelium of individuals with UC.H_(2)O_(2) is a powerful neutrophilic chemo-tactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular“trail”that attracts adjacent intra-vascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC.A novel therapy aimed at removing the inappropriate H_(2)O_(2) mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one(biopsy-proven)histologic remission lasting 14 years to *** evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H_(2)O_(2) mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this *** data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse *** is the aim of this paper to present experimental and clinical evidence that identifies H_(2)O_(2) produced by the colonic epithelium as the causal agent in the pathogenesis of UC.A detailed explanation of a novel therapeutic intervention to normalize colonic H_(2)O_(2),its rationale,components,and formulation is also provided.

关键词： Ulcerative colitis pathogenesis,Treatment Hydrogen peroxide

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pathogenesis of Cerebral Ischemia Based on brain-heart interaction

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South China Journal of Cardiology 2022年第2期23卷 129-141,152页

作者：于长江邓刚 Muqaddas Masood 欧阳情何茵茹陈寄梅朱平 Moussa Ide Nasser Guangdong Cardiovascular Institute Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouZhongshan RoadGuangzhouPR China510080 Guangdong Provincial Key Laboratory of pathogenesis Targeted Prevention and Treatment of Heart DiseaseAdd:106 Zhongshan Er RoadGuangzhouPR China510080

Over the last few years,neuro-cardiology has grown the awareness of the relationship between the brain and the heart,contributing to developing a modern interdisciplinary field of *** enhance the awareness of the relationship between the brain and the heart,we concentrate on the brain function disability that results from cardiac dysfunction and the brain function impairment that results from cardiac *** is usual for patients with cerebral ischemia to be preceded by cardiac *** main triggers of cerebral ischemia involve arrhythmia,atrial fibrillation,etc.,reflecting a strong connection between the heart and the *** ischemia is linked to how the heart and brain communicate and affect each other at the pathophysiological *** formation of the heart-brain axis mechanism is important in its incidence and *** analysis explores the etiology and pathogenesis of cerebral ischemia centered on the heart-brain axis neuronal pathway and the mechanism of the relationship between the heart and brain,which offers important enrichment to the hypothesis of combined care of brain and heart and is extremely useful for gaining new knowledge for research and production of multi-target drugs for the prevention and treatment of cerebral ischemia.

关键词： Brain Heart.neuro-cardiology Cerebral Ischemia

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Roles of SET7/9 and LSD1 in the pathogenesis of Arsenicinduced Hepatocyte Apoptosis

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 364-372页

作者： Bing Han Yi Yang Lei Tang Qin Yang Rujia Xie Department of Pathophysiology College of Basic Medical SciencesGuizhou Medical UniversityGuiyangGuizhouChina Guizhou Provincial Key Laboratory of pathogenesis and Drug Research on Common Chronic Diseases Guizhou Medical UniversityGuiyangGuizhouChina Medical College of Guizhou University GuiyangGuizhouChina

Background and Aims:Multiple regulatory mechanisms play an important role in arsenic-induced liver *** investigate whether histone H3 lysine 4(H3K4)methyltransferase(SET7/9)and histone H3K4 demethyltransferase(LSD1/KDM1A)can regulate endoplasmic reticulum stress(ERS)-related apoptosis by modulating the changes of H3K4 methylations in liver cells treated with ***:Apoptosis,proliferation and cell cycles were quantified by flow cytometry and real-time cell *** expression of ERS-and epigenetic-related proteins was detected by Western blot *** antisense SET7/9 expression vector and the overexpressed LSD1 plasmid were used for transient transfection of LO_(2) *** effects of NaAsO_(2) on the methylation of H3 in the promoter regions of 78 kDa glucose-regulated protein,activating transcription factor 4 and C/EBP-homologous protein were evaluated by chromatin immunoprecipitation ***:The protein expression of LSD1(1.25±0.08 vs.1.77±0.08,p=0.02)was markedly decreased by treatment with 100μM NaAsO_(2),whereas the SET7/9(0.68±0.05 vs.1.10±0.13,p=0.002)expression level was notably increased,which resulted in increased H3K4me1/2(0.93±0.64,1.19±0.22 vs.0.71±0.13,0.84±0.13,p=0.03 and p=0.003).After silencing SET7/9 and overexpressing LSD1 by transfection,apoptosis rate(in percentage:3.26±0.34 vs.7.04±0.42,4.80±0.32 vs.7.52±0.38,p=0.004 and p=0.02)was significantly decreased and proliferation rate was notably increased,which is reversed after inhibiting LSD1(in percentage:9.31±0.40 vs.7.52±0.38,p=0.03).Furthermore,the methylation levels of H3 in the promoter regions of GRP78(20.80±2.40 vs.11.75±2.47,20.46±2.23 vs.14.37±0.91,p=0.03 and p=0.01)and CHOP(48.67±4.04 vs.16.67±7.02,59.33±4.51 vs.20.67±3.06,p=0.004 and p=0.001)were significantly increased in LO_(2) cells exposed to 100μM NaAsO_(2) for 24 ***:Histone methyltransferase SET7/9 and histone demethyltransferase LSD1 jointly regulate the changes of H3K4me1/me2 levels in

关键词： Arsenic SET7/9 LSD1 H3K4me1/2 ER stress

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A rat model of multicompartmental traumatic injury and hemorrhagic shock induces bone marrow dysfunction and profound anemia

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Animal Models and Experimental Medicine 2024年第3期7卷 367-376页

作者： Lauren S.Kelly Jennifer A.Munley Erick E.Pons Kolenkode B.Kannan Elizabeth M.Whitley Letitia E.Bible Philip A.Efron Alicia M.Mohr Department of Surgery and Sepsis and Critical Illness Research Center University of Florida College of MedicineGainesvilleFloridaUSA pathogenesis LLCGainesvilleFloridaUSA

Background:Severe trauma is associated with systemic inflammation and organ *** rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human *** aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic ***:Male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock(LCHS),multicompartmental polytrauma(PT)(unilateral lung contusion,hemorrhagic shock,cecectomy,bifemoral pseudofracture),or na?ve ***,plasma toll-l ike receptor 4(TLR4),hemoglobin,spleen to body weight ratio,bone marrow(BM)erythroid progenitor(CFU-GEMM,BFU-E,and CFU-E)growth,plasma granulocyte colony-stimulating factor(G-CSF)and right lung histologic injury were assessed on day 7,with significance defined as p values<0.05(*).Results:Polytrauma resulted in markedly more profound inhibition of weight gain compared to LCHS(p=0.0002)along with elevated plasma TLR4(p<0.0001),lower hemoglobin(p<0.0001),and enlarged spleen to body weight ratios(p=0.004).Both LCHS and PT demonstrated suppression of CFU-E and BFU-E growth compared to naive(p<0.03,p<0.01).Plasma G-CSF was elevated in PT compared to both na?ve and LCHS(p<0.0001,p=0.02).LCHS and PT demonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial ***:Multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia,splenic tissue enlargement,weight loss,and increased inflammatory activity compared to a less severe *** may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.

关键词： anemia i nflammation polytrauma pseudofracture shock

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Going only half the way:cell cycle exit after the G1 restriction point

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Signal Transduction and Targeted Therapy 2024年第1期9卷 1-2页

作者： Lisa Muller Tony Gutschner Mechthild Hatzfeld Department of Pathobiochemistry Institute of Molecular MedicineMartin Luther University Halle-WittenbergCharles Tanford Protein Research CenterHalleGermany Department of RNA Biology and pathogenesis Institute of Molecular MedicineMartin Luther University Halle-WittenbergCharles Tanford Protein Research CenterHalleGermany

In a recent article published in Nature,James *** et *** that cyclin A2 levels determine whether cells will make an entrance into mitosis or whether cells will leave the cell cycle after having passed the G1/restriction(R)-point implicating that the decision is fully reversible(Fig.1).This ground-breaking study could impact future approaches for cancer treatment by targeting the mitotic clock.

关键词： point cycle

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Comparison of the early curative effect in patients undergoing mechanical vs. bioprosthetic aortic valve replacement with concomitant annuloplasty by the Nicks procedure

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South China Journal of Cardiology 2024年第1期25卷 29-37页

作者：吴浩向鸿谟王露朱平 Guangdong Cardiovascular Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510100China Guangdong Provincial Key Laboratory of pathogenesis Targeted Prevention and Treatment of Heart DiseaseGuangzhou Key Laboratory of Cardiac Pathogenesis and PreventionGuangzhouGuangdong 510100China

Background The probability of prosthesis-patient mismatch(PPM)is high in aortic valve replacement surgery for small aortic valve annulus,which increases the postoperative prosthetic valve transvalvular pressure *** aortic annuloplasty is a commonly applied surgical procedure,but there is currently no uniform standard or guideline on the type of prosthetic valve that should be used during ***,this study aimed to analyze whether there was any difference in the short-term prognosis between the choice of mechanical valves and bioprosthetic valves during aortic valve replacement surgery with concomitant aortic annuloplasty by the Nicks *** A retrospective analysis was conducted based on the clinical data from 55 patients undergoing aortic valve replacement surgery with concomitant annuloplasty by the Nicks procedure at the Cardiac Surgery Department of Guangdong Provincial People’s Hospital from November 2021 to December *** this study,all patients received aortic annuloplasty by the Nicks *** these patients,30 were in the mechanical valve group,while the other 25 were in the bioprosthetic valve *** including left ventricular end-diastolic/endsystolic diameters,left ventricular ejection fraction,interventricular septal thickness,left ventricular posterior wall thickness,transvalvular pressure gradient,left ventricular fractional shortening,and left ventricular mass index were collected 1 week preoperatively and 1 week and 3 months *** on gender,age,body surface area,types of perioperative complications,operation time,complication rates,and outcomes was also *** Among the 55 patients enrolled in this study,4 *** main causes of death included postoperative low cardiac output syndrome,severe pulmonary infection,and multi-organ ***,there was a statistically significant difference in left ventricular end-diastolic diameter between the mechanical valv

关键词： Valve replacement Small aortic annulus Nicks procedure Prosthesis-patient mismatch Mechani-cal valve Bioprosthetic valve

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Portal vein embolization combined with ex vivo liver resection and autotransplantation: A novel treatment strategy for end-stage and metastatic hepatic alveolar echinococcosis

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 210-216页

作者： Qiang Guo Mao-Lin Wang Kai Zhong Jia-Long Li Tie-Min Jiang Hao Wen Tuerganaili Aji Ying-Mei Shao Department of Hepatobiliary and Echinococcosis Surgery Digestive and Vascular Surgery CenterFirst Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054China Clinical Medical Research Center of Echinococcosis and Hepatobiliary Disease of Xinjiang Uygur Autonomous Region Urumqi 830054China State Key Laboratory of pathogenesis Prevention and Treatment of High Incidence Diseases in Central AsiaXinjiang Medical UniversityUrumqi 830054China

Alveolar echinococcosis(AE)is a lethal parasitic disease caused by Echinococcus multilocularis larvae,and more than 90%of pri-mary AE lesions occur in the *** of the affected individ-uals remain asymptomatic and the disease is often diagnosed at an advanced *** infection may spread to organs adjacent to the liver or distant locations,eventually causing end-stage multi-ple organ *** metastasis of AE is the most fatal with an inci-dence rate of 0.2%[1].

关键词： organs echinococcosis metastasis

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Click chemistry and natural products

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Chinese Journal of Natural Medicines 2024年第2期22卷 97-99页

作者： ZHANG Chen WU Jianbing ZHANG Yihua HUANG Zhangjian State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesCenter of Drug DiscoveryChina Pharmaceutical UniversityNanjing 210009China State Key Laboratory of pathogenesis Prevention and Treatment of High Incidence Diseases in Central AsiaXinjiang Key Laboratory of Natural Medicines Active Components and Drug Release TechnologySchool of PharmacyXinjiang Medical UniversityUrumqi 830054China

The 2022 Nobel Prize in Chemistry was awarded to American scientists Carolyn Bertozzi,*** Sharpless,and Danish scientist Morten *** for their contributions to the development of click chemistry and bioorthogonal chemi... 详细信息

关键词： Click chemistry Natural product Target identification Drug discovery

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Gut microbiota: a potential target for hyperuricemia and gout

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Food Science and Human Wellness 2024年

作者： Feiyan Zhao Shuying Yang Laiyu Kwok Hongbin Li Heping Zhang Zhihong Sun Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering Key Laboratory of Dairy Products Processing Ministry of Agriculture and Rural Affairs Key Laboratory of Dairy Biotechnology and Engineering Ministry of Education Inner Mongolia Agricultural University Department of Rheumatology and Immunology The Affiliated Hospital of Inner Mongolia Medical University Inner Mongolia Key Laboratory for pathogenesis and Diagnosis of Rheumatic and Autoimmune Diseases

Modern lifestyle and diet have increased the incidence rate of uric acid (UA) metabolism-related diseases like hyperuricemia (HUA) and gout， posing heavy economic burden to individual patients and their families and the society. Uric acid metabolism is a complex physiological process involving the kidney， intestine， and other organs. A number of factors together regulate UA metabolism， including genetics， diet， hormones， and the gut microbiota. This review summaries the gut microbiota features in subjects with HUA and gout， and the therapeutic effects of implementing microecological therapies (probiotics， prebiotics， or fecal microbiota transplant) that target modulate the gut microbiota and its downstream metabolism on the disease. Current evidence shows that these strategies are safe and promising in alleviate inflammation， reduce UA， and restoring a healthy gut microbiota in subjects with UA metabolism-related diseases. However， most clinical data are generated by animal studies. Therefore， we propose that vigorous human intervention trials should be conducted in the future to evaluate the therapeutic effects of microecological therapies in managing HUA and gout.

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The combined detection of carcinoembryonic antigen,carcinogenic antigen 125,and carcinogenic antigen 19-9 in colorectal cancer patients

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2073-2079页

作者： Ling-Zhen Gong Qian-Wen Wang Jie-Wen Zhu Department of Clinical Laboratory Huangshi Central Hospital(Affiliated Hospital of Hubei Polytechnic University)Hubei Key Laboratory of Kidney Disease Pathogenesis and InterventionHuangshi Tumor Molecular Diagnosis and Treatment Key LaboratoryHuangshi 435000Hubei ProvinceChina

BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)*** predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is *** To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of *** The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January *** CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver *** addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic *** The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone ***,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL *** 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL *** addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(P<0.05).ROC curve analysis results showed that the areas under the ROC curves of CEA,CA125 and CA19-9 were 0.607,0.692 and *** These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.

关键词： Colorectal cancer Liver metastasis Serum markers Carcinoembryonic antigen Cancer antigen 125 Cancer antigen 19-9 Receiver operating characteristic analysis

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