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3'-Sialyllactose regulates glucose and lipid metabolic disorders via the gut–liver axis in mice fed a high-fat die

Food Science and Human Wellness 2024年

作者： Wei Zhang Meizhen Zhu Kelsang Dekyi Linxi Zheng Yichen Zhang Youping Lv Dongbei Guo Xiaoxuan Chen Lili Pan Xinyue Wang Hongwei Li State Key laboratory of Vaccines for Infectious diseases， Xiang An Biomedicine laboratory， School of Public Health， Xiamen University State Key laboratory of Molecular Vaccinology and Molecular diagnostics，National Innovation Platform for Industry-Education Integration in Vaccine Research， Xiamen University Department of Nutrition， Zhongshan Hospital (Xiamen)， Fudan University Xiamen Clinical Research Center for Cancer Therapy

Recent research has indicated that sialic acid， such as free sialic acid (N-acetylneuraminic acid， Neu5Ac) and bound sialic acid (3'-sialyllactose， 3'-SL)， can ameliorate disorders associated with glycolipid metabolism， although the underlying mechanisms have yet to be determined. We examined the effects of 3'-SL on glycolipid metabolism in mice fed a high-fat diet. Male C57BL/6J mice were divided into six groups: two model control groups (normal and high-fat diets) and four intervention groups [Neu5Ac， and low-，moderate-， and high-dose 3'-SL]. After 8 weeks of continuous gavage intervention， mice in the 3'-SL intervention groups had lower body weight and total fat content; reduced fasting blood glucose， triglycerides， low-density lipoproteins and oxidized-low-density lipoproteins; and increased high-density lipoproteins，but no dosage-dependent of 3'-SL intervention was found， 3’-SL＿M intervention as optimal for further exploration. 3'-SL intervention could increase respiratory exchange ratio， energy expenditure， and amount of exercise performed. 3'-SL increased the colonic abundances of Akkermansia， Lactobacillus， and Bacteroides， and reduced those of Erysipelatoclostridium， Faecalibaculum， and Aldercreutzia. Changes were also observed in colonic metabolites， and liver gene transcript and metabolites， which were mainly enriched in bile secretion， taurine and hypotaurine metabolism， and insulin resistance. Additionally， 3'-SL was observed to regulate genes associated with physiological rhythms， including clock， per2， cry1， and bhihe41. Collectively， our findings indicate that 3'-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets. Compared with Neu5Ac， 3'-SL intervention can ameliorate intestinal flora disorders， enhance bile acid circulation， increase tissue energy expenditure， and reduce lipid synthesis， thereby promoting lipid-lowering effects mediated via the liver–gut axis， and can a

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Laccase/caffeic acid-catalyzed crosslinking coupled with galactomannan alters the conformational structure of ovalbumin and alleviates Th2-mediated allergic asthma

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Food Science and Human Wellness 2024年第4期13卷 1962-1973页

作者： Ishfaq Ahmed Suidong Ouyang Shengquan Wu Haochang Song Miaoyuan Zhang Renxing Luo Peishan Lu Jiaqi Deng Tingting Zheng Yanyan Wang Xinguang Liu Gonghua Huang Guangdong Provincial Key laboratory of Medical Molecular diagnostics The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan 523808China Haide College Ocean University of ChinaLaoshan CampusQingdao 266100China School of Medical Technology Guangdong Medical UniversityDongguan 523808China

Ovalbumin(OVA)is the major allergenic protein that can induce T helper 2(Th2)-allergic reactions,for which current treatment options are *** this study,we developed a polymerized hypoallergenic OVA product via laccase/caffeic acid(Lac/CA)-catalyzed crosslinking in conjunction with galactomannan(Man).The formation of high molecular weight crosslinked polymers and the Ig G-binding were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Western *** study indicated that Lac/CA-catalyzed crosslinking plus Man conjugation substantially altered secondary and tertiary structures of OVA along with the variation in surface *** digestion stability assay indicated that crosslinked OVA exhibited less resistance in simulated gastric fluid(SGF)and simulated intestinal fluid(SIF).Mouse model study indicated that Lac-Man/OVA ameliorated eosinophilic airway inflammatory response and efficiently downregulated the expression of Th2-related cytokines(interleukin(IL)-4,IL-5,and IL-13),and upregulated IFN-γand IL-10 *** of bone marrow-derived dendritic cells with Lac-Man/OVA suppressed the expression of phenotypic maturation markers(CD80 and CD86)and MHC class II molecules,and suppressed the expression levels of proinflammatory *** knowledge obtained in the present study offers an effective way to acquire a hypoallergenic OVA product that can have a therapeutic effect in alleviating OVA-induced allergic asthma.

关键词： Ovalbumin Laccase Galactomannan Conformational structure Asthma

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Antibiotic-induced gut bacteria depletion has no effect on HBV replication in HBV immune tolerance mouse model

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Virologica Sinica 2023年第3期38卷 335-343页

作者： Yanan Bu Kaitao Zhao Zaichao Xu Yingcheng Zheng Rong Hua Chuanjian Wu Chengliang Zhu Yuchen Xia Xiaoming Cheng State Key laboratory of Virology and Hubei Province Key laboratory of Allergy and Immunology Hubei Jiangxia LaboratoryInstitute of Medical VirologyTaiKang Center for Life and Medical SciencesTaiKang Medical SchoolWuhan UniversityWuhan430071China Department of Clinical laboratory Renmin Hospital of Wuhan UniversityWuhan430060China Department of Pathology Center for Pathology and Molecular DiagnosticsHubei Clinical Center and Key Laboratory of Intestinal and Colorectal DiseasesZhongnan Hospital of Wuhan UniversityTaiKang Medical SchoolWuhan UniversityWuhan430071China

Commensal microbiota is closely related to Hepatitis B virus(HBV)*** bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse ***,the effect of gut bacteria on HBV replication in recombinant adeno-associated virus(AAV)-HBV mouse model with immune tolerance remains *** aim to investigate its role on HBV replication in AAV-HBV mouse model.C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures(ABX)to deplete gut bacteria and intravenously injected with AAV-HBV to establish persistent HBV *** microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA(rRNA)gene *** replication markers in blood and liver were determined by ELISA,qPCR assay and Western blot at indicated time *** response in AAV-HBV mouse model was activated through HDI of HBV plasmid or poly(I:C)and then detected by quantifying the percentage of IFN-γ^(+)/CD8^(+)T cells in the spleen via flow cytometry as well as the splenic IFN-γmRNA level via qPCR *** found that antibiotic exposure remarkably decreased gut bacteria abundance and *** treatment failed to alter the levels of serological HBV antigens,intrahepatic HBV RNA transcripts and HBc protein in AAV-HBV mouse model,but contributed to HBsAg increase after breaking of immune ***,our data uncovered that antibiotic-induced gut bacteria depletion has no effect on HBV replication in immune tolerant AAV-HBV mouse model,providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic HBV infection.

关键词： Hepatitis B virus(HBV) Gut bacteria Antibiotic mixtures(ABX) Adeno-associated virus(AAV)-HBV mouse model Persistent HBV replication Chronic HBV infection

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Relevance of Medical Imaging in the Pre-Therapeutic Evaluation of Acute intestinal Obstruction at CIMED

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Open Journal of Medical Imaging 2024年第1期14卷 31-41页

作者： Mamoudou Camara Aly Mampan Koundouno Siré Nabe Toumin Camara Ousmane Aminata Bah Center for Medical Imaging Exploration and Diagnostics University of Conakry Conakry Guinea General Surgery Department of the Kankan Regional Hospital Kankan Guinea Ministry of Health and Public Hygiene Conakry Guinea General Medicine Department of the Siguiri Prefectural Hospital Siguiri Guinea CIRA Conakry Guinea

Objective: We initiated this work with the aim of studying the contribution of imaging in the diagnosis of acute intestinal obstruction at CIMED. Patients and methods: This was a prospective, descriptive and analytical study involving 96 patients collected at the radiology and medical imaging department of CIMED, from January 2022 to January 2023. Result: The age of our patients varied between 11 and 86 years with an average age of 36 years. There was a male predominance of 64.6% compared to 35.4% for women, i.e. a sex ratio of 1.82. The notion of previous surgery was found in 61.5% of our patients. Pain was present in all patients. Radiography of the ASP was performed in 89.6% of patients. It showed hydro-aerial levels in 96.5% of patients. Abdominopelvic CT was performed in 12 patients and made it possible to make the diagnosis of occlusion in all patients. The results of the positive diagnosis were concordant with those intraoperatively in 92% of cases. 8% of our patients, compared to the treatment, spontaneously resumed their transit, 91% benefited from surgical treatment and 1% died before surgery. The outcome was favorable in 80 patients or 83.3%, poor with death in 16 patients or 16.7% of cases. Conclusion: Acute intestinal obstruction remains a serious pathology for which ASP radiography often remains the only radiological examination performed urgently. However, abdominopelvic CT seems widely indicated thanks to its contribution both for the positive diagnosis and for the serious and etiological diagnoses. However, this imaging technique is largely underused in our practice due to its high cost and lack of availability.

关键词： Imaging Acute intestinal Obstruction CIMED

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Patients with functional bowel disorder have disaccharidase deficiency:A single-center study from Russia

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World Journal of Clinical Cases 2021年第17期9卷 4178-4187页

作者： Saria Dbar Olga Akhmadullina Elena Sabelnikova Nikolai Belostotskiy Asfold Parfenov Svetlana Bykova Sergey Bakharev Elena Baulo Alexandra Babanova Lilia Indeykina Tatyana Kuzmina Tatiana Kosacheva Aleksey Spasenov Alina Makarova Non-inflammatory Bowel diseases Moscow Health DepartmentMoscow Clinical Scientific Center n.a.A.S.LoginovMoscow 111123Russia Moscow Health Department Moscow Clinical Scientific Center n.a.A.S.LoginovMoscow 111123Russia Pre-Clinical Research laboratory Moscow Clinical Scientific Center Named after A.S.Loginov MHDMoscow 111123Russia Department of Bowel Pathology Moscow Health DepartmentMoscow Clinical Scientific Center n.a.A.S.LoginovMoscow 111123Russia laboratory of functional diagnostics of intestinal diseases Moscow Health DepartmentMoscow Clinical Scientific Center n.a.A.S.LoginovMoscow 111123Russia Nutraceuticals laboratory Moscow Health DepartmentMoscow Clinical Scientific Center n.a.A.S.LoginovMoscow 111123Russia Department of Medical Statistics Moscow Health DepartmentMoscow Clinical Scientific Center n.a.A.S.LoginovMoscow 111123Russia

BACKGROUND functional bowel disorder(FBD)may be caused by a decrease in disaccharidase ***,the timely diagnosis of disaccharidase deficiency could lead to a better prognosis in patients with this *** To determine the potential value of intestinal disaccharidases glucoamylase,maltase,sucrase,and lactase in understanding the etiology and pathogenesis of *** A total of 82 FBD patients were *** to the Rome IV criteria(2016),23 patients had diarrhea-predominant irritable bowel syndrome(IBS),33 had functional diarrhea,10 had constipation-predominant IBS,4 had functional constipation,and 12 had mixed *** Dahlqvist method was used to measure disaccharidase activity in the brush-border membrane of mature enterocytes of the small intestine,in duodenal biopsies obtained during *** Lactase deficiency was detected in 86.5%of patients,maltase deficiency in 48.7%,sucrase deficiency in 50%,and glucoamylase deficiency in 84.1%.The activities of all enzymes were reduced in 31.7%of patients,and carbohydrase deficiency was detected in 63.5%of *** low activity of enzymes involved in membrane digestion in the small intestine was found in 95.2%of *** In 78 of the 82 patients with FBD,gastrointestinal symptoms were associated with disaccharidase deficiency.

关键词： functional bowel disorder Irritable bowel syndrome Disaccharidase deficiency Maltase deficiency Sucrase deficiency Lactase deficiency

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Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis

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World Journal of Gastroenterology 2010年第31期16卷 3936-3943页

作者： Nicole Acosta Andrés Quiroga Pilar Delgado María Mercedes Bravo Carlos Jaramillo Molecular diagnostics and Bioinformatics laboratory Biological Sciences DepartmentLos Andes University Infectious Agents and Cancer Research Group National Cancer Institute(Colombia)

AIM: To investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies. METHODS: One hundred and twenty-two clinical isolates of H. pylori cultured from gastric biopsies obtained from Colombian patients with dyspepsia were included as study material. DNA extracted from isolates was used to determine cagA status, amplifying the C-terminal cagA gene region by polymerase chain reaction. One hundred and six strains with a single amplicon were sequenced and results were used to characterize the 3' variable region of the cagA gene. To establish the number and type of tyrosine phosphorylation motifs Glutamine acid-Proline-Isoleucine-Tyrosine-Alanine (EPI-YA) bioinformatic analysis using Amino Acid Sequence Analyzer-Amino Acid Sequence Analyzer software was conducted. Analysis of the association between the number of EPIYA motifs and the gastric pathology was performed using χ2 test and analysis of the presence of EPIYA-C motifs in relation to the pathology was made by logistic regression odds ratios. Comparisons among EPIYA types found and those reported in GenBank were performed using a proportion test in Statistix Analytical Software version 8.0. RESULTS: After amplification of the 3' of the cagA gene, 106 from 122 isolates presented a single amplicon and 16 showed multiple amplicons. As expected, diversity in the size of the cagA unique fragments among isolates was observed. The 106 strains that presented a single amplicon after 3' cagA amplification came from patients with gastritis (19 patients), atrophic gastritis (21), intestinal metaplasia (26), duodenal ulcer (22) and gastric cancer. DNA sequence analysis showed that the differences in size of 3' cagA unique fragments was attributable to the number of EPIYA motifs: 1.9% had two EPIYA motifs, 62.3% had three, 33.0% had four and 2.8% had five motifs. The majority of tested clinical strains (62.3%) were found to harbor

关键词： Helicobacter pylori CagA-protein polymorphisms Molecular characterization Bioinformatic analysis Pathogenesis Cancer

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Clostridium difficile Toxin B: Insights into Its Target Genes

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Open Journal of Applied Sciences 2022年第3期12卷 368-386页

作者： Junyi Hu Yunjie Shan Huan Yang Xuzhou Key laboratory of laboratory diagnostics School of Medical Technology Xuzhou Medical University Xuzhou China

Clostridium difficile is a grossly Gram-positive anaerobic bacterium that has been a key factor in inducing imbalances in the gut microbiota in recent years, leading to intestinal-associated inflammation. The main pathogenic toxins of Clostridium difficile are toxin A (TcdA) and toxin B (TcdB). TcdB is the main pathogenic factor of Clostridium difficile infection. This review revealed the pathogenic mechanism of Clostridium difficile toxin B, expounded the impact of Clostridium difficile on the intestinal system, and predicted the genes on which TcdB may act, thereby providing a new therapeutic target for Clostridium difficile infection, offering theoretical basis and new strategies for clinical prevention and control.

关键词： Clostridium difficile Infection TcdB Gene Regulation

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Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1573-1584页

作者： Cheng Kong Xuebing Yan Yongqiang Liu Linsheng Huang Yefei Zhu Jide He Renyuan Gao Matthew F.Kalady Ajay Goel Huanlong Qin Yanlei Ma Department of Gastrointestinal Surgery Shanghai Tenth People's HospitalTongji UniversityShanghaiChina Research Institute of intestinal diseases Tongji University School of MedicineShanghaiChina Department of Cancer Biology Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Oncology Affiliated Hospital of Yangzhou UniversityYangzhou UniversityYangzhouChina sDepartment of Coloreaal Surgery Digestive Disease and Surgery InstituteCleveland ClinicClevelandOHUSA Department of Molecular diagnostics and Experimental Therapeutics Beckman Research Institute of City of Hope Comprehensive Cancer CenterDuarteCAUSA Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiChina

Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain *** performed a series of systematic studies using a dextran sulfate sodium(DSS)animal model of inflammatory *** were fed with a KD,low-carbohydrate diet(LCD),or normal diet(ND).Germ-free mice were utilized in validation *** tissues were analyzed by transcriptome sequencing,RT2 profiler PCR array,histopathology,and *** samples were analyzed by metabolic assay *** samples were analyzed by 16S rRNA gene sequencing,liquid chromatography-mass spectrometry and gas chromatography-mass *** observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from *** diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia,whereas the opposite was observed for Escherichia/*** colitis induction,the KD protected intestinal barrier function,and reduced the production of R0Ryt+CD3_group 3 innate lymphoid cells(ILC3s)and related inflammatory cytokines(IL-17a,IL-18,IL-22,Ccl4).Finally,fecal microbiota transplantation into germ-free mice revealed that the KD-mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut *** together,our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment,and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.

关键词： colitis lymphoid consequences

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Patient-derived organoids for therapy personalization in inflammatory bowel diseases

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World Journal of Gastroenterology 2022年第24期28卷 2636-2653页

作者： Marianna Lucafò Antonella Muzzo Martina Marcuzzi Lorenzo Giorio Giuliana Decorti Gabriele Stocco Advanced Translational diagnostics laboratory Institute for Maternal and Child Health-IRCCS“Burlo Garofolo”Trieste 34137Italy Department of Medicine Surgery and Health SciencesUniversity of TriesteTrieste 34127Italy Department of Life Sciences University of TriesteTrieste 34127Italy

Inflammatory bowel diseases(IBDs)are chronic inflammatory disorders of the intestinal tract that have emerged as a growing problem in industrialized *** of IBD pathogenesis is still incomplete,and the most widely-accepted interpretation considers genetic factors,environmental stimuli,uncontrolled immune responses and altered intestinal microbiota composition as determinants of IBD,leading to dysfunction of the intestinal epithelial *** vitro models commonly used to study the intestinal barrier do not fully reflect the proper intestinal *** important innovation is represented by organoids,3D in vitro cell structures derived from stem cells that can self-organize into functional organ-specific *** may be generated from induced pluripotent stem cells or adult intestinal stem cells of IBD patients and therefore retain their genetic and transcriptomic *** models are powerful pharmacological tools to better understand IBD pathogenesis,to study the mechanisms of action on the epithelial barrier of drugs already used in the treatment of IBD,and to evaluate novel target-directed molecules which could improve therapeutic *** aim of this review is to illustrate the potential use of organoids for therapy personalization by focusing on the most significant advances in IBD research achieved through the use of adult stem cells-derived intestinal organoids.

关键词： Inflammatory bowel disease Organoids intestinal epithelium 3D cell cultures Personalized medicine

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Resistance to activated protein C is a risk factor for fibrostenosis in Crohn’s disease

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World Journal of Gastroenterology 2006年第37期12卷 6026-6031页

作者： Gottfried Novacek Wolfgang Miehsler Julia Palkovits Walter Reinisch Thomas Waldhr Center of Public Health Department of Epidemiology Medical University of Vienna Vienna Austria Stylianos Kapiotis Alfred Gangl Harald Vogelsang Department of Internal Medicine Ⅳ Division of Gastroenterology andHepatology Medical University of Vienna Vienna Austria Clinical Institute of Medical and Chemical laboratory diagnostics Medical University of Vienna Vienna Austria

AIM: To evaluate the effect of resistance to activated protein C (aPCR), the most common known inherited thrombophilic disorder, on the risk of intestinal operation of fi brostenosis in patients with Crohn’s disease (CD). METHODS: In a previous study, we assessed the prevalence of aPCR in CD. In a retrospective case- controlled study, 8 of these CD patients with aPCR were now compared with 24 CD patients without aPCR, matched by gender, age at diagnosis and duration of disease in a 1:3 fashion. The primary end point was the occurrence of an intestinal CD-related operation with evidence of fibrostenosis in the bowel resection specimen. RESULTS: The Kaplan-Meier analysis revealed that patients with aPCR had a lower probability of remaining free of operation with f ibrostenosis than patients without aPCR (P = 0.0372; exact log-rank test) resulting in a signifi cantly shorter median time interval from diagnosis of CD to the fi rst operation with fi brostenosis (32 vs 160 mo). At 10 years, the likelihood of remaining free of operation with fi brostenosis was 25% for patients with aPCR and 57.8% for patients without aPCR. CONCLUSION: CD patients with aPCR are at higher risk to undergo intestinal operation of fi brostenosis than those without aPCR. This supports our hypothesis of aPCR being a possible risk factor for fi brostenosis in CD.

关键词： Fibrostenosis Resistance to activated protein C Factor V Leiden intestinal surgery Crohn's disease

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