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The innate immune receptor NLRP12 maintains intestinal homeostasis by regulating microbiome diversity

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Cellular & Molecular Immunology 2018年第3期15卷 193-195页

作者： Jenny Moi-Fong Lau Yvonne Dombrowski Centre for experimental medicine Wellcome-Wolfson Institute for Experimental MedicineQueen’s University BelfastBelfastBT97BLUK

Inflammatory bowel disease(IBD)is on the rise in the western world.1 The dynamic interplay between genetic susceptibility,the gut microbiome and host inflammatory reactions underlying IBD are still *** light onto these complex interactions in IBD,Chen et al.2 identified a key role for the negative immune regulator NLRP12 in shaping the composition of the gut microbiome and maintaining intestinal *** finding,published in the most recent issue of Nature Immunology,2 can advance the development of much needed microbiome-based therapies for IBD patients.

关键词： homeostasis Immunology maintain

FHL2 deficiency aggravates Candida albicans infection through decreased myelopoiesis

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Science China Life Sciences 2025年

作者： Rongmei Gao Kanchao Chen Yimin Wang Rongxia Guo Xiaoyu Zhang Peng Wu Weili Wang Qingxiang Huang Xuemei Xie Shangda Yang Yanling Lü Qian Ren Fei Liu Song Chen Fengxia Ma Tao Cheng Hui Cheng State Key Laboratory of experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College CAMS Center for Stem Cell medicine PUMC Department of Stem Cell and Regenerative Medicine

Hematopoiesis is a finely tuned process that generates all blood cell types through self-renewal and differentiation, which is crucial for maintaining homeostasis. Acute infections can prompt a hematopoietic response known as emergency myelopoiesis. In this study, using a Candida albicans (C. albicans) infection model, we demonstrated for the first time that disruption of Fhl2 led to increased fungal burden,heightened inflammatory response and reduced survival rates. Impaired myeloid hematopoiesis and immune cell production were evident, as proved by the decreased numbers of hematopoietic stem and progenitor cells (HSPCs) and granulocytes in the bone marrow of Fhl2-deficient mice. In conclusion, FHL2 regulated emergency myelopoiesis in response to C. albicans, affecting the host’s defense against pathogens.

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Treatment for diabetic macular oedema:looking further into the evidence

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Annals of Eye Science 2018年第1期3卷 7-13页

作者： Noemi Lois wellcome-wolfson Centre for experimental medicine School of MedicineDentistry and Biomedical SciencesQueen’s UniversityBelfastUK

Throughout the years,people with diabetic macular oedema(DMO)have seen the number of options for their treatment *** photocoagulation was the first of these and great experience is behind it;intraocular steroids followed and more recently anti-vascular endothelial growth factor(anti-VEGF)agents came to *** face now the dilemma of determining which may be the best therapeutic strategy for each particular patient based on best available *** article summarises data available from randomised clinical trials(RCTs)on treatments for DMO and provides some facts about this condition and its treatments that need to be taken into consideration when treatment decisions are made.

关键词： Diabetic macular edema(DME) diabetic macular oedema(DMO) anti-vascular endothelial growth factor(anti-VEGF) laser photocoagulation randomised clinical trials(RCTs) retina diabetic retinopathy

Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-Belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

Simultaneous occurrence of autoimmune pancreatitis and pancreatic cancer in patients resected for focal pancreatic mass

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World Journal of Gastroenterology 2017年第12期23卷 2185-2193页

作者： Peter Macinga Adela Pulkertova Lukas Bajer Jana Maluskova Martin Oliverius Martin Smejkal Maria Heczkova Julius Spicak Tomas Hucl Department of Gastroenterology and Hepatology Institute for Clinical and Experimental Medicine Department of Pathology Institute for Clinical and Experimental Medicine Department of Transplant Surgery Institute for Clinical and Experimental Medicine Department of Radiodiagnostics and Interventional Radiology Institute for Clinical and Experimental Medicine Center for experimental medicine Institute for Clinical and Experimental Medicine

AIM To assess the occurrence of autoimmune pancreatitis(AIP) in pancreatic resections performed for focal pancreatic *** We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic *** Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients(5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma(PC) was also present in six patients with AIP(40%), all six were men. Patients with AIP + PC were significantly older(60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes(67% vs 11%, P = 0.09), and had experienced greater weight loss(15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case. CONCLUSION The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC.

关键词： Chronic pancreatitis Pancreatic cancer Ig G4related disease Autoimmune pancreatitis Malignancy

Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease

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World Journal of Gastroenterology 2018年第43期24卷 4939-4949页

作者： Lukas Bajer Antonij Slavcev Peter Macinga Eva Sticova Jan Brezina Matej Roder Radim Janousek Pavel Trunecka Julius Spicak Pavel Drastich Department of Gastroenterology and Hepatology Institute for Clinical and Experimental MedicinePrague Department of Immunogenetics Institute for Clinical and Experimental Medicine Department of Clinical and Transplant Pathology Institute for Clinical and Experimental MedicinePrague Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental MedicinePrague

AIM To evaluate risk factors for primary sclerosing cholangitis(PSC) recurrence(rPSC) after orthotopic liver transplantation(OLT) in patients with well-preserved colons. METHODS We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with followup of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen(HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical *** Altogether, 31 men and 16 women with a median(range) age of 36(15-68) years at the time of OLT and a median follow-up of 122(60-249) mo were included. rPSC was confirmed in 21/47(44.7%) of patients, a median 63(12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio(HR): 4.02, 95% confidence interval(CI): 1.58-10.98] and history of acute cellular rejection(rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis(r PSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor(r PSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04(rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03(rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07(rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective *** De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.

关键词： Primary sclerosing cholangitis Inflammatory bowel disease Liver transplantation Acute cellular rejection Autoimmune hepatitis Human leukocyte antigen Immunosuppression

Behavioral Abnormality along with NMDAR-related CREB Suppression in Rat Hippocampus after Shortwave Exposure

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Biomedical and Environmental Sciences 2019年第3期32卷 189-198页

作者： YU Chao BAI Yan Xin XU Xin Ping GAO Ya Bing HAO Yan Hui WANG Hui TAN Sheng Zhi LI Wen Chao ZHANG Jing YAO Bin Wei DONG Ji ZHAO Li PENG Rui Yun Department of experimental Pathology Beijing Institute of Radiation Medicine

Objective To estimate the detrimental effects of shortwave exposure on rat hippocampal structure and function and explore the underlying mechanisms. Methods One hundred Wistar rats were randomly divided into four groups(25 rats per group) and exposed to 27 MHz continuous shortwave at a power density of 5, 10, or 30 m W/cm^2 for 6 min once only or underwent sham exposure for the control. The spatial learning and memory, electroencephalogram(EEG), hippocampal structure and Nissl bodies were analysed. Furthermore, the expressions of N-methyl-D-aspartate receptor(NMDAR) subunits(NR1, NR2 A, and NR2 B), c AMP responsive element-binding protein(CREB) and phosphorylated CREB(p-CREB) in hippocampal tissue were analysed on 1, 7, and 14 days after exposure. Results The rats in the 10 and 30 m W/cm^2 groups had poor learning and memory, disrupted EEG oscillations, and injured hippocampal structures, including hippocampal neurons degeneration, mitochondria cavitation and blood capillaries swelling. The Nissl body content was also reduced in the exposure groups. Moreover, the hippocampal tissue in the 30 m W/cm^2 group had increased expressions of NR2 A and NR2 B and decreased levels of CREB and p-CREB. Conclusion Shortwave exposure(27 MHz, with an average power density of 10 and 30 m W/cm^2) impaired rats' spatial learning and memory and caused a series of dose-dependent pathophysiological changes. Moreover, NMDAR-related CREB pathway suppression might be involved in shortwave-induced structural and functional impairments in the rat hippocampus.

关键词： Shortwave exposure Learning and memory Hippocampus NMDAR CREB

Turning to myelin turnover

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Neural Regeneration Research 2019年第12期14卷 2063-2066页

作者： Tobias J.Buscham Maria A.Eichel Sophie B.Siems Hauke B.Werner Department of Neurogenetics Max Planck Institute of Experimental Medicine

Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but constantly turn over their pre-existing myelin sheaths, thereby establishing an equilibrium of replenishment and degradation that may also be subject to adaptation with consequences for nerve conduction velocity. In this short review we highlight selected approaches to the normal turnover of adult myelin in vivo, from injecting radioactive precursors of myelin constituents in the 1960s to current strategies involving isotope labeling and tamoxifen-induced gene targeting.

关键词： oligodendrocyte myelin plasticity and turnover degradation tamoxifen metabolic labeling isotope labeling neural plasticity myelinoid bodies central nervous system

Relevance of low viral load in haemodialysed patients with chronic hepatitis C virus infection

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World Journal of Gastroenterology 2015年第18期21卷 5496-5504页

作者： Jan Sperl Sona Frankova Renata Senkerikova Magdalena Neroldova Vaclav Hejda Miroslava Volfova Dusan Merta Ondrej Viklicky Julius Spicak Milan Jirsa Department of Hepatogastroenterology Institute for Clinical and Experimental Medicine Laboratory of experimental Hepatology Institute for Clinical and Experimental Medicine Department of Internal medicine Division of Gastroenterology and Hepatology Charles University Medical School and Teaching Hospital Hepato-gastroenterology 50012 Hradec Kralove Czech Republic Department of Anesthesiology Resuscitation and Intensive Care Institute for Clinical and Experimental Medicine Department of Nephrology Institute for Clinical and Experimental Medicine

AIM: To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype ***: The sustained virological response(SVR) rate, IL28 B genotype, IFNL4 genotype, initial viral load(IVL) and other pretreatment variables in 39 endstage renal disease patients(ESRD) on maintenance haemodialysis(HD) infected with hepatitis C virus(HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment nave and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a(Peg IFN-α) weekly and a reduced dose of ribavirin(RBV) was administered to 23/39 patients with an initial haemoglobin level > 10 g/d L. Control group patients were given standard doses of Peg IFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ2 testcompared the *** regression was used to determine significant predictors of *** values for continuous variables were obtained from Receiver Operating Characteristic ***:The distribution of IL28B rs12979860 CC,CT and TT genotypes in the ESRD group was 28.2%,64.1%and 7.7%,respectively,and 19.3%,62.4%and18.3%in the *** IFNL4 genotype was in almost absolute linkage disequlibrium with *** proportion of patients with a low IVL(<600000 IU/m L)was significantly higher in the ESRD group than in the controls(28/39,71.8%vs 51/109,46.8%,P=0.009),as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group(10/11,90.9%vs 18/28,64.3%,P=0.0035).This difference was not found in the controls(7/22,31.8%vs 44/87,50.6%,P=0.9).The overall SVR rate was 64.1%(25/39)in the ESRD group and 50.5%(55/109)in the control group(P=0.19).11/11(100%)and 19/22(86.4%)IL28B CC patients achieved SVR in the

关键词： End-stage renal disease Hepatitis C virus genotype 1 Interferon alpha IFNL4 Ribavirin