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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden department of Biosciences and nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

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Trefoil factor-3 is not a useful marker of mucosal healing in Crohn's disease treated with anti-TNF-α antibodies

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World Journal of gastroenterology 2017年第1期23卷 135-140页

作者： Piotr Eder Kamila Stawczyk-Eder Katarzyna Korybalska Natasza Czepulis Joanna Luczak Liliana Lykowska-Szuber Iwona Krela-Kazmierczak Krzysztof Linke Janusz Witowski department of gastroenterology Human Nutrition and Internal DiseasesPoznan University of Medical Sciences department of Pathophysiology Poznan University of Medical Sciences

AIMTo evaluate whether repeated serum measurements of trefoil factor-3 (TFF-3) can reliably reflect mucosal healing (MH) in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor-α (anti-TNF-α) *** TFF-3 was measured before and after anti-TNF-α induction therapy in 30 CD patients. The results were related to clinical, biochemical and endoscopic parameters. MH was defined as a ≥ 50% decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD).RESULTSSES-CD correlated significantly with CD clinical activity and several standard biochemical parameters (albumin, leukocyte and platelet counts, C-reactive protein, erythrocyte sedimentation rate, fibrinogen). In contrast, SES-CD did not correlate with TFF-3 (P = 0.54). Moreover, TFF-3 levels did not change significantly after therapy irrespectively of whether the patients achieved MH or not. Likewise, TFF-3 did not correlate with changes in fecal calprotectin, which has been proposed as another biochemical marker of mucosal damage in *** TFF-3 is not a convenient and reliable surrogate marker of MH during therapy with TNF-α antagonists in CD.

关键词： Adalimumab Crohn’ s disease Infliximab Mucosal healing Trefoil factors

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Can Emax and platelet count truly differentiate between benign and malignant liver lesions?

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World Journal of gastroenterology 2025年第3期31卷 120-122页

作者： Manjeet Kumar Goyal Omesh Goyal department of gastroenterology and human nutrition Unit All India Institute of Medical SciencesNew Delhi 110029DelhiIndia department of gastroenterology Dayanand Medical College and HospitalLudhiana 141001PunjabIndia

This letter critically evaluates Jiang et al's article on the differentiation of benign and malignant liver lesions using Emax and platelet *** notable findings,significant methodological and interpretative limitations are *** study lacks detailed assay conditions for Emax measurement,employs inadequate statistical methods without robust multivariate analysis,and does not provide clinically relevant threshold *** nomogram's reliance on Emax as a major diagnostic contributor is questionable due to attenuation in hepatocellular carcinoma patients with ***,the study's limitations,such as selection bias and confounding factors,are not adequately *** research should adopt more rigorous methodologies,including prospective studies with larger cohorts and standardized protocols for biomarker measurement,to enhance validity and clinical applicability.

关键词： Emax Platelet count Benign liver lesions Malignant liver lesions Hepatocellular carcinoma Cirrhosis Diagnostic biomarkers Shear wave elastography Methodological limitations Clinical utility

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Intestinal permeability and its association with the patient and disease characteristics in Crohn's disease

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World Journal of gastroenterology 2008年第9期14卷 1399-1405页

作者： Jaya Benjamin Govind K Makharia Vineet Ahuja Mani Kalaivan Yogendra K Joshi department of gastroenterology & human nutrition All India Institute of Medical SciencesAnsari NagarNew Delhi 110029India department of Biostatistics All India Institute of Medical SciencesAnsari NagarNew Delhi 110029India department of gastroenterology & human nutrition All India Institute of Medical SciencesAnsari NagarNew Delhi 110029India

AIM:To assess the intestinal permeability (IP) in patients with Crohn's disease (CD) and study the association of IP with the patient and disease characteristics. METHODS: One hundred and twenty five consecutive patients of CD (Males: 66) were diagnosed on the basis of a combination of standard clinical, endoscopic, imaging and histological features. CD activity index (CDAI) was used to calculate the activity of the disease while the behavior of the disease was assessed by the modified Montreal classification. IP was measured by the ratio of the percentage excretion of ingested doses of lactulose and mannitol in urine (LMR). The upper limit of normality of LMR (0.037) was derived from 22 healthy controls. RESULTS: Thirty six percent of patients with CD had increased IP. There was no significant difference in mannitol excretion (patients vs controls = 12.5% vs 14.2%, P = 0.4652), but lactulose excretion was significantly higher in patients compared to healthy controls (patients vs controls = 0.326% vs 0.293%, P = 0.0391). The mean LMR was also significantly higher in the patients as compared to healthy controls [0.027 (0.0029-0.278) vs 0.0164 (0.0018-0.0548), P = 0.0044]. Male patients had a higher LMR compared to females [0.036 (95% CI 0.029, 0.046) vs 0.022 (95% CI 0.0178, 0.028) (P = 0.0024), though there was no difference in the number of patients with abnormal IP in boththe sexes. Patients with an ileo-colonic disease had a higher LMR than those with only colonic disease [0.045 (95% CI 0.033, 0.06) vs 0.021 (95% CI 0.017, 0.025) (P < 0.001)]. Of patients with ileo-colonic disease, 57.8% had an abnormal IP, compared to 26.7% with colonic and 15.6% with small intestinal disease. Patients with a stricturing disease had significantly higher LMR compared to non-fistulising non-stricturing disease [0.043 (95% CI 0.032, 0.058) vs 0.024 (95% CI 0.019, 0.029) (P = 0.0062)]. There was no correlation of IP with age, disease activity, duration of illness, D-xylose absorptio

关键词： Lactulose mannitol ratio Crohn's disease Inflammatory bowel disease Intestinal barrier Crohn's disease activity index Intestinal permeability

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Coronavirus Disease-2019(COVID-19)and the Liver

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 247-255页

作者： Anshuman Elhence Manas Vaishnav Sagnik Biswas Ashish Chauhan Abhinav Anand Shalimar department of gastroenterology and human nutrition Unit All India Institute of Medical SciencesNew DelhiIndia department of gastroenterology Indira Gandhi Medical CollegeShimlaIndia

Within a year of its emergence,coronavirus disease-2019(COVID-19)has evolved into a *** has emerged during the past 1 year is that,apart from its potentially fatal respiratory presentation from which the severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)derives its name,it presents with a myriad of gastrointestinal(GI)and liver *** of the angiotensinconverting enzyme-2(ACE-2)receptor throughout the GI tract and liver,which is the receptor for the SARS-CoV-2,may be responsible for the GI and liver *** acting directly via the ACE-2 receptor,the virus triggers a potent immune response,which might have a role in *** virus leads to derangement in liver function tests in close to 50%of the *** impact of these derangements in patients with a normal underlying liver seems to be *** clinical presentations include acute decompensation and acute-on-chronic liver failure in a patient with chronic liver disease,leading to high *** data suggests that,contrary to intuition,liver transplant recipients and patients with autoimmune liver disease on immunosuppression do not have increased *** exact mechanism underlying why immunosuppressed patients fare well as compared to other patients remains to be *** newer variants of COVID-19,which can spread faster than the original strain,the data on hepatic manifestations needs to be updated to keep a step ahead of the virus.

关键词： Transaminitis Cirrhosis Vaccine ACLF

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Special Considerations in the Management of Autoimmune Hepatitis in COVID-19 Hotspots:A Review

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Journal of Clinical and Translational Hepatology 2021年第4期9卷 568-575页

作者： Deepak Madhu Sanchit Sharma Ashish Agarwal Anoop Saraya department of gastroenterology Aster MIMS CalicutKeralaIndia department of gastroenterology Caritas HospitalKottayamKeralaIndia department of gastroenterology and human nutrition All India Institute of Medical SciencesNew DelhiIndia department of gastroenterology All India Institute of Medical SciencesJodhpurRajasthanIndia

The ongoing coronavirus disease-2019(COVID-19)pandemic has necessitated special considerations in the management of *** way presence of pre-existing diseases or treatment for it predisposes to,alters course of,and changes the management of COVID-19,is of relevance and is being extensively *** hepatitis(AIH)is unique in that it is an autoimmune disease mandating treatment with immunosuppressive drugs,as well as a liver disease with potential for varying degrees of underlying *** use of immunosuppressive drugs could alter the risk of acquiring COVID-19,the clinical course and severity of COVID-19 and the degree of underlying liver fibrosis could alter the clinical outcomes of patients with *** this review,we try to summarize key areas relevant in understanding and improving the clinical care of patients with AIH in the current *** considerations required in the management of patients with AIH in COVID-19 hotspots have been outlined based on the current evidence.

关键词： Hepatitis Autoimmune Liver cirrhosis COVID-19 SARS-CoV-2 infection Immunosuppressive agents

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Critical analysis of the effects of proton pump inhibitors on inflammatory bowel disease:An updated review

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World Journal of gastroenterology 2024年第37期30卷 4160-4162页

作者： Omesh Goyal Manjeet Kumar Goyal department of gastroenterology Dayanand Medical College and HospitalLudhiana 141001PunjabIndia department of gastroenterology and human nutrition All India Institute of Medical SciencesNew Delhi 110029DelhiIndia

This letter critically evaluates the effects of proton pump inhibitors(PPIs)on inflammatory bowel disease,particularly focusing on Crohn's disease(CD)and ulcerative colitis(UC),as discussed in Liang et al’s recent *** the review provides significant insights,it relies heavily on cross-sectional and observational studies,which limits the ability to draw causal *** heterogeneous study populations and inconsistent definitions of long-term PPI use further complicate the *** letter also highlights the need for rigorous control of confounding factors and considers the potential publication bias in the existing *** implications of these issues are discussed in the context of both CD and UC,and future research directions are proposed to address these shortcomings.

关键词： Proton pump inhibitors Inflammatory bowel disease Gut microbiota Intestinal mucosal barrier Immune cell function

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Transfusion transmitted virus: A review on its molecular characteristics and role in medicine

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World Journal of gastroenterology 2006年第32期12卷 5122-5134页

作者： M Irshad YK Joshi Y Sharma I Dhar Clinical Biochemistry Division department of Laboratory Medicine All India Institute of Medical SciencesNew Delhi-110029India department of gastroenterology and human nutrition All India Institute of medical sciences New Delhi-110029India

The present review gives an updated overview of transfusion transmitted virus （TTV）, a novel agent, in relation to its molecular characteristics, epidemiological features, modes of transmission, tissue tropism, pathogenesis, role in various diseases and its eradication from the body. TTV, a DNA virus, is a single stranded, non-enveloped, 3.8 kb long DNA virus with a small and covalently closed circular genome comprising 3852 bases. It was tentatively designated Cirdnoviridae *** genome sequence is heterogeneous and reveals the existence of six different genotypes and several subtypes. TTV has been reported to transmit not only via parenteral routes, but also via alternate routes. This virus has been detected in different non-human primates as well. At present, TTV is detected by polymerase chain reaction （PCR） with no other available diagnostic assays. It shows its presence globally and was detected in high percent populations of healthy persons as well as in various disease groups. Initially it was supposed to have strong association with liver disease; however, there is little evidence to show its liver tropism and contribution in causing liver diseases. It shows high prevalence in hemodialysis patients, pointing towards its significance in renal diseases. In addition,TTV is associated with several infectious and non-infectious diseases. Though, its exact pathogenesis is not yet clear, TTV virus possibly resides and multiplies in bone marrow cells and peripheral blood mononuclear cells （PBMCs）. Recently, attempts have been made to eradicate this virus with interferon treatment. More information is still needed to extricate various mysteries related to TTV.

关键词： Transfusion transmitted virus DNA Virus Hepatitis Transfusion

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Test-based exclusion diets in gastro-esophageal reflux disease patients:A randomized controlled pilot trial

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World Journal of gastroenterology 2014年第45期20卷 17190-17195页

作者： Michele Caselli Giovanni Zuliani Francesca Cassol Nadia Fusetti Elena Zeni Natalina Lo Cascio Cecilia Soavi Sergio Gullini department of medical sciences Internal Medicine Institute University of Ferrara department of gastroenterology School of Gastroenterology University of Ferrara Center Study Association on Food Intolerance and nutrition of Ferrara

AIM: To investigate the clinical response of gastro-esophageal reflux disease (GERD) symptoms to exclusion diets based on food intolerance tests.

关键词： Gastro-esophageal reflux disease Food intolerance Leukocytotoxic test Exclusion diet Treatment

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Dietary carbohydrate intake and risk of type 2 diabetes:a 16-year prospective cohort study

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Science China Life sciences 2025年

作者： Lu Gan Yi Yang Bin Zhao Kai Yu Kehua Guo Fang Fang Zhiguang Zhou Demetrius Albanes Jiaqi Huang Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University CSU-Sinocare Research Center for Nutrition and Metabolic Health Xiangya School of Public Health Central South UniversityFurong Laboratory Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Department of Health and Human Services School of Computer Science and Engineering Central South University Institute of Environmental Medicine Karolinska Institute National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University

Despite considerable research underscoring the importance of carbohydrate intake in relation to the risk of type 2 diabetes(T2D), a comprehensive assessment of this relationship is currently lacking. We aimed to examine the associations of various types and food sources of dietary carbohydrate intake with the risk of T2D, to evaluate potential effect modification by other factors, including genetic susceptibility,and to explore the potential mediators for such associations. The present study included 161,872 participants of the UK Biobank who were free of prevalent cancer, cardiovascular disease, or diabetes, and had at least one validated 24-h dietary recall assessment. Multivariableadjusted age-stratified Cox proportional hazard regression models were applied to estimate hazard ratios(HRs) and 95% confidence intervals(CI) for the associations of various types and food sources of dietary carbohydrate intake with risk of T2D. During a median follow-up of13.6 years, 4,176 incident cases of T2D were identified. In the multivariable-adjusted models, a greater intake of fiber, carbohydrates from whole grains, and carbohydrates from non-starchy vegetables was significantly associated with a lower risk of T2D(highest vs. lowest quantile, HR [95% CI]=0.70 [0.62–0.79], 0.74 [0.67–0.82], and 0.83 [0.75–0.92], respectively, all P for trend <0.005). In contrast, a higher intake of starch and carbohydrate from starchy vegetables was associated with an increased risk of T2D(highest vs. lowest quantile, HR [95%CI]=1.31 [1.16–1.48] and 1.19 [1.09–1.31], respectively, both P for trend <0.005). Replacing one serving of refined grains or starchy vegetables with an equal amount of whole grains or non-starchy vegetables was associated with 4% to 10% lower risk of T2D(all P values <0.001).The observed associations were generally similar across population subgroups, including individuals with different genetic susceptibility to T2D. Mediation analyses of the inverse association between T

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