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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei Institute of Clinical pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China department of Clinical pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex ***-derived macrophages(MDMs)infiltration are associated with RA *** have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor ***,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been ***,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)*** inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)*** experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting *** further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγ***,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 ***,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and ***,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular *** GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

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Unraveling the potential of acute intermittent hypoxia as a strategy for inducing robust repair in multiple sclerosis

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Neural Regeneration Research 2024年第11期19卷 2339-2340页

作者： Valerie M.K.Verge Nataliya Tokarska Justin M.Naniong department of Anatomy Physiology and PharmacologyUniversity of SaskatchewanSaskatoonSKCanada Cameco MS Neuroscience Research Center University of SaskatchewanSaskatoonSKCanada

Multiple sclerosis(MS)is a debilitating inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration that contribute to *** efficient and effective repair programs following demyelination is a major goal and challenge in *** MS therapies focus largely on modulating the immune aspects of the disease contributing to *** this alleviates some symptoms and mitigates damage,it does not tackle the fundamental challenge of effective remyelination,which few MS patients experience,especially in the progressive phase of the disease.

关键词： sclerosis degeneration damage

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Prenatal amoxicillin exposure induces developmental toxicity in fetal mice and its characteristics

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Journal of Environmental Sciences 2024年第3期137卷 287-301页

作者： Yongguo Dai Yu Peng Wen Hu Yi Liu Hui Wang department of pharmacology Wuhan University School of Basic Medical SciencesWuhan 430071China department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Provincial Key Laboratory of Developmentally Originated Disease Wuhan 430071China

Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse ***,systematic studies about the developmental toxicity of amoxicillin are still *** explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the ***,PAmE altered multiple maternal/fetal serum phenotypes,especially in *** multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>*** analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response *** conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.

关键词： Amoxicillin Prenatal exposure Fetal development Organ function Developmental toxicity

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Potential Adverse Outcome Pathways of Chlorinated Organophosphate Flame Retardants

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China CDC weekly 2024年第23期6卷 542-546,I0008-I0011页

作者： Meiyu Zhou Huilin Zhang Qi Xiao Kexin Li Xiaoting Li Haiyan Chu department of Environmental Genomics Jiangsu Key Laboratory of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjing CityJiangsu ProvinceChina department of Genetic toxicology The Key Laboratory of Modern Toxicology of Ministry of EducationCenter of Global HealthSchool of Public HealthNanjing Medical UniversityNanjing CityJiangsu ProvinceChina department of Nutrition and Food Safety School of Public HealthNanjing Medical UniversityNanjing CityJiangsu ProvinceChina

What is already known about this topic?Chlorinated organophosphate flame retardants(Cl-OPFRs)are frequently detected chemicals in the environment and biological samples,yet there is a lack of systematic evaluation regarding the adverse effects and toxicological mechanisms of *** is added by this report?This study utilizes the adverse outcome pathway(AOP)framework to assess the health implications and mechanisms of Cl-OPFRs,identifying multi-system toxicity,with a particular emphasis on reproductive issues and the possible toxic *** are the implications for public health practice?These results enhance knowledge of the health hazards linked to Cl-OPFRs,supporting the creation of focused risk evaluations and suitable regulatory actions.

关键词： utilize supporting Chlorin

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Agmatine ameliorates diabetes type 2-induced nephropathy in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第1期14卷 8-16页

作者： Fatemah O.Kamel Ohoud Shagroud Mai AAlim A.Sattar Ahmad Gamal S Abd El-Aziz Abdulhadi S.Burzangi Duaa Bakhshwin Maha Jamal Shahid Karim department of Clinical pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddah 21589Saudi Arabia department of Anatomy Faculty of MedicineKing Abdulaziz UniversityJeddah 21589Saudi Arabia

Objective:To assess the nephroprotective potential of agmatine in a rat model of streptozotocin-induced diabetic ***:A single dose of streptozotocin(40 mg/kg)coupled with a fructose diet induced diabetes in Wistar ***(40 and 80 mg/kg)was administered to rats for 12 *** body weight and fasting blood glucose were measured *** level,urine output,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C were also determined at the end of the ***,superoxide dismutase,glutathione,interleukin-1β,interleukin-6,and tumor necrosis factor-alpha were evaluated in kidney *** study was also performed using hematoxylin and eosin ***:Agmatine at both doses significantly increased final body weight,and lowered fasting blood glucose,urine output,insulin,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C levels compared with the diabetic group(P<0.05).Inflammatory markers and antioxidant effect were significantly improved in agmatine-treated ***,the histopathological changes in renal structure were ameliorated by agmatine ***:Agmatine alleviates diabetic nephropathy by improving renal functions and reducing inflammation and oxidative *** molecular mechanisms of its nephroprotective actions need to be investigated in future study.

关键词： Agmatine Type 2 diabetes Nephropathy Oxidative stress Nephroprotection

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Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda department of Medical Oncology Showa UniversityTokyo 1428555Japan department of Clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic ***,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently *** SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe *** tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated *** RAS or BRAF mutations were *** Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was *** drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly ***,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse *** Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

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Probiotics: Shaping the gut immunological responses

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World Journal of Gastroenterology 2024年第15期30卷 2096-2108页

作者： Eirini Filidou Leonidas Kandilogiannakis Anne Shrewsbury George Kolios Katerina Kotzampassi Faculty of Medicine Laboratory of PharmacologyDemocritus University of ThraceAlexandroupolis 68100Greece department of Surgery Aristotle University of ThessalonikiThessaloniki 54636Greece

Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate *** the most popular and adequately studied probiotics are bacteria from the families Lactobacillaceae,Bifidobacteriaceae and *** of them have been shown,both in vitro and in vivo studies of intestinal inflammation models,to provide favorable results by means of improving the gut microbiota composition,promoting the wound healing process and shaping the immunological *** intestinal conditions,such as inflammatory bowel diseases(IBD),are characterized by an imbalance in microbiota composition,with decreased diversity,and by relapsing and persisting inflammation,which may lead to mucosal *** the results of the clinical studies investigating the effect of probiotics on patients with IBD are still controversial,it is without doubt that these microorganisms and their metabolites,now named postbiotics,have a positive influence on both the host’s microbiota and the immune system,and ultimately alter the topical tissue *** influence is achieved through three axes:(1)By dis-placement of potential pathogens via competitive exclusion;(2)by offering protection to the host through the secretion of various defensive mediators;and(3)by supplying the host with essential *** will analyze and discuss almost all the in vitro and in vivo studies of the past 2 years dealing with the possible favorable effects of certain probiotic genus on gut immunological responses,highlighting which species are the most beneficial against intestinal inflammation.

关键词： Probiotics Lactobacillaceae Bifidobacteriaceae Saccharomyces Intestinal inflammation Immune responses

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Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system

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Neural Regeneration Research 2024年第7期19卷 1437-1445页

作者： Steinunn Sara Helgudóttir Anne Skøttrup Mørkholt Jacek Lichota Preben Bruun-Nyzell Mads Christian Andersen Nanna Marie Juhl Kristensen Amanda Krøger Johansen Mikela Reinholdt Zinn Hulda Maria Jensdóttir John Dirk Vestergaard Nieland 2N Pharma ApS NOVI Science ParkAalborgDenmark Molecular pharmacology Group Department of Health Science and TechnologyAalborg UniversityAalborgDenmark

Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s *** the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these *** considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological *** innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers *** this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative *** provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ***,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter ***,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

关键词： brain disease carnitine palmitoyl transferase 1 epigenetics metabolism gut microbiome mitochondrial dysfunction neurodegeneration oxidative stress

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MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

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Neural Regeneration Research 2025年第7期20卷 1957-1970页

作者： Bridget Martinez Philip V.Peplow department of pharmacology University of Nevada-RenoRenoNVUSA department of Medicine University of Nevada-RenoRenoNVUSA department of Anatomy University of OtagoDunedinNew Zealand

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life ***,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress *** addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate *** suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress *** performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December *** included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum *** of these studies had also used whole *** studies were excluded as they did not involve microRNA *** of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult *** measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString *** six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to *** miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/

关键词： biomarker diagnosis microRNA peripheral blood mononuclear cells plasma extracellular vesicles/exosomes post-traumatic stress disorder serum exosomes whole blood whole plasma

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Cellular interplay to 3D in vitro microphysiological disease model:cell patterning microbiota-gut-brain axis

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Bio-Design and Manufacturing 2024年第3期7卷 320-357页

作者： Kamare Alam Lakshmi Nair Souvik Mukherjee Kulwinder Kaur Manjari Singh Santanu Kaity Velayutham Ravichandiran Sugato Banerjee Subhadeep Roy department of pharmacology and toxicology National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India department of Pharmaceutical Sciences Assam UniversitySilchar 788011India department of Pharmaceutical Sciences Guru Ghasidas UniversityKoniBilaspur 495009C.G.India School of Pharmacy and Biomolecular Sciences RCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Tissue Engineering Research Group Department of Anatomy and Regenerative MedicineRCSI University of Medicine and Health SciencesDublin D02 YN77Ireland department of Pharmaceutics National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India department of Natural Products National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India

The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the *** between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological *** most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune ***,each pathway is intertwined with a complex *** the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative *** paper briefly retraces the possible communication pathways between the gut microbiome and the *** further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the *** diseases also decrease patients’quality of ***,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the *** of MGBA in the laboratory uses many molecular technologies and biomaterial *** and organoids provide a more realistic picture of the cell and tissue structure than *** them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between ***-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

关键词： Microbiota-gut-brain axis Neurodegeneration 3D disease model Organoid Transwell system

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