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BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/ Stat3 pathway in mesenchymal stem cells

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Genes & Diseases 2024年第3期11卷 468-483页

作者： Jie Zhang Jinhai Jiang Hang Liu Shiyu Wang Kaixin Ke Siyuan Liu Yue Jiang Lu Liu Xiang Gao Baicheng He Yuxi Su department of Pharmacology School of PharmacyChongqing Medical UniversityChongqing 400016China Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing Chongqing Medical UniversityChongqing 400016China department of Orthopedics Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China orthopedics department Children's Hospital of Chongqing Medical UniversityChongqing 400014China China International science and Technology Cooperation Base of Child Development and Critical Disorders Jiangxi Hospital Affiliated Children's Hospital of Chongqing Medical UniversityJiangxi 330000China National clinical Research Center for Child Health and Disorders China

Bone defects and non-union are prevalent in clinical orthopedy,and the outcomes of current treatments are often *** tissue engineering offers a promising approach to treating these conditions *** morphogenetic protein 9(BMP9)can commit mesenchymal stem cells to osteogenic lineage,and a knowledge of the underlying mechanisms may help advance the field of bone tissue ***-rich repeats con-taining G protein-coupled receptor 4(LGR4),a member of G protein-coupled receptors,is essential for modulating bone *** study is aimed at investigating the impact of LGR4 on BMP9-induced osteogenesis in mesenchymal stem cells as well as the underlying *** marrow stromal cells from BMp9-knockout mice exhibited diminished LGR4 expression,and exogenous LGR4 clearly restored the impaired osteogenic potency of the bone marrow stromal ***,LGR4 expression was increased by BMP9 in C3H10T1/2 ***4 augmented the benefits of BMP9-induced osteogenic markers and bone formation,whereas LGR4 inhibition restricted these ***,the BMP9-induced li-pogenic markers were increased by LGR4 *** protein levels of Raptor and p-Stat3 were elevated by *** knockdown or p-Stat3 suppression attenuated the osteoblastic markers and LGR4 expression brought on by ***4 significantly reversed the blocking ef-fect of Raptor knockdown or p-Stat3 suppression on the BMP9-induced osteoblastic *** interacts with p-Stat3,and p-Stat3 activates the LGR4 promoter *** conclusion,LGR4 boosts BMP9 osteoblastic potency in mesenchymal stem cells,and BMP9 may up-regulate LGR4 via the mTORC1/Stat3 signal activation.

关键词： BMP9 LGR4 mTORC1 Osteogenic differentiation Stat3

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Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma(PRP)

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animal Models and Experimental Medicine 2024年第2期7卷 106-113页

作者： Qian Zhang Yanan Wang Cheng Ran Yingmei Zhou Zigang Zhao Tianhua Xu Hongwei Hou Yuan Lu Beijing Life science Academy BeijingChina department of Pathology Affiliated Hospital of Hebei UniversityBaodingChina department of Otolaryngology Affiliated Hospital of Hebei UniversityBaodingChina department of Dermatology Huazhong University of Science and Technology Union Shenzhen HospitalShenzhenChina department of Dermatology Hainan Hospital of PLA General HospitalSanyaChina department of Chemical Engineering Tsinghua UniversityBeijingChina

Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its role in the process of hair loss remains unclear,and the relationship between PRP and the microbiome needs further ***,the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota ***:We performed PRP treatment on 14 patients with AGA,observed their clinical efficacy,and collected scalp swab samples before and after *** scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial ***:The results showed that PRP was effective in the treatment of AGA patients,and the hair growth increased *** results of relative abundance analysis of microbiota showed that after treatment,g_Cutibacterium increased and g_Staphylococcus decreased,which played a stable role in scalp *** addition,g_Lawsonella decreased,indicating that the scalp oil production decreased after ***:The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

关键词： androgenic alopecia microbiome platelet-rich plasma scalp

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On implications of somatostatin in diabetic retinopathy

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Neural Regeneration Research 2024年第9期19卷 1984-1990页

作者： Yanhong Fang Qionghua Wang Youjian Li Li Zeng Jian Liu Kepeng Ou department of Ophthalmology Chongqing University Jiangjin HospitalChongqingChina College of Pharmacy National&Local Joint Engineering Research Center of Targeted and Innovative TherapeuticsIATTIChongqing University of Arts and SciencesChongqingChina Shandong Provincial Hospital Shandong Laboratory Animal CenterScience and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinanShandong ProvinceChina Academic Unit of Ophthalmology Bristol Medical SchoolUniversity of BristolBristolUK

Somatostatin,a naturally produced neuroprotective peptide,depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the *** this review,we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar *** neuroprotection,which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy,triggers retinal neurovascular unit impairment and microvascular *** replacement is a promising treatment for retinal neurodegeneration in diabetic *** pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been *** one such trial(EUROCONDOR),topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction,but had no impact on the onset of diabetic ***,we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage *** order to achieve early prevention of diabetic retinopathy initiation,and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy,several issues need to be *** include the needs to:a)update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration,b)identify patient subgroups who would benefit from somatostatin analog supplementation,c)elucidate the interactions of somatostatin,particularly exogenously-delivered somatostatin analogs,with other retinal peptides in the context of hyperglycemia,and d)design safe,feasible,low cost,and effective administration routes.

关键词： diabetes retinopathy excitotoxicity growth hormone insulin like growth factor irisin neurodegeneration neuroinflammation neuroprotection neurovascular unit octreotide oxidative stress somatostatin

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Correlation between Intestinal Health and Coccidiosis Prevalence in Broilers during Different Seasons of the Year in Brazil from 2012 to 2018

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Food and Nutrition sciences 2024年第3期15卷 179-198页

作者： Fabio Luis Gazoni Gabriela Miotto Galli Marcel Manente Boiago Lenita Moura Stefani Aline Zampar Marco A. Juárez-Estrada Guillermo Tellez-Isaias Aleksandro S. da Silva animal Health and Reproduction Veterinary Medicine Graduate Program Federal University of Santa Maria (UFSM) Santa Maria Brazil animal science Graduate Program Federal University of Rio Grande do Sul (UFRGS) Porto Alegre Brazil animal science Graduate Program Santa Catarina State University (UDESC) Chapecó Brazil Departamento de Medicina y Zootecnia de Aves Facultad de Medicina Veterinaria y Zootecnia Universidad Nacional Autonoma de Mexico Ciudad Universitaria Ciudad de Mexico Mexico department of Poultry science Division of Agriculture University of Arkansas Fayetteville AR USA

Coccidiosis is a disease caused by intracellular protozoan parasites, specifically belonging to the genus Eimeria. These parasites target the gastrointestinal tract in different types of hosts, causing sores in the intestinal lining. The presence of these lesions reduces the animal’s ability to digest and absorb nutrients, significantly impacting their overall performance. The current study aimed to explore the potential correlation between seasonal variations and the incidence of Eimeria spp-induced lesions in broiler chickens’ gastrointestinal tracts in Brazil from 2012 to 2018. A total of 8,607 broiler chickens, aged 14 to 42 days, were sampled from 103 poultry integrated companies in Brazil to conduct intestinal health examinations. The sampling process involved selecting 3 to 6 chickens from each poultry house for examination. The assessment included various abnormalities such as shedding of intestinal cells and excessive fluid and mucus presence, thickening and tension of the intestines, food movement, roughened mucosal surface resembling a Turkish towel in the small intestine, tissue death, duodenal inflammation, intestinal inflammation, gizzard erosion, presence of worms and bedding material, and ingestion of mealworms. During the seasons, winter exhibited the highest average occurrence of Eimeria maxima microorganisms at 52.83%, with E. acervulina following closely at 26.42% in second place. In spring, E. maxima had an occurrence of 11.31%, while in fall, E. tenella had the lowest occurrence at 6.74%. When analyzing the seasonal occurrence of Eimeria, it was observed that E. maxima micro was more common during winter compared to summer (P = 0.0491). However, no discernible variation was observed in the occurrence of the remaining species across different seasons. Research findings suggest that subclinical coccidiosis is most prevalent during the winter season in Brazil. Likewise, clinical disease caused by E. acervulina is also prevalent during this time. I

关键词： Eimeria Epidemiology Intestinal Pathology Broiler Chickens Brazil

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PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

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Zoological Research 2024年第3期45卷 535-550页

作者： Laidong Yu Fangfang Zeng Mengshu Fan Kexuan Zhang Jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang Jialong Yuan Xinxin Pang Yan Huang Yangzhou Zhang Jia-Da Li Zhuohua Zhang Zhonghua Hu Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China National clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Provincial clinical Research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Key Laboratory of animal Models for Human Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China MOE Key Lab of Rare Pediatric Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain *** abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric *** 17(PCDH17)is associated with major mood disorders,including bipolar disorder and ***,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain *** this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory *** overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in ***,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)***,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine ***,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

关键词： Synapse development Dendritic spine Mood disorder Actin cytoskeleton animal behavior

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Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2024年第5期25卷 438-450页

作者： Yu ZHANG Xinliang GU Yang LI Xun LI Yuejiao HUANG Shaoqing JU Medical School of Nantong University Nantong UniversityNantong 226001China department of Laboratory Medicine Affiliated Hospital of Nantong UniversityNantong 226001China Research Center of clinical Medicine Affiliated Hospital of Nantong UniversityNantong 226001China department of Medical Oncology Affiliated Hospital of Nantong UniversityNantong 226001China

Gastric cancer(GC)is one of the most common gastrointestinal *** a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in *** previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for *** this work,we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation,migration,and invasion of GC cells in *** dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3'untranslated region(UTR)site of acyl-coenzyme A dehydrogenase short/branched chain(ACADSB).In addition,ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC ***,we used Gene Ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ***,we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level,as well as the changes in reactive oxygen species(ROS)levels by flow *** summary,this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB,thereby promoting GC *** provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens upnew possibilities for treatment.

关键词： Transfer RNA(tRNA)-derived small RNA(tsRNA) Gastric cancer(GC) Acyl-coenzyme A dehydrogenase short/branched chain(ACADSB) Molecular mechanism Treatment Ferroptosis

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MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2024年第7期25卷 594-604页

作者： Yanjin WANG Yifei CHEN Fuji YANG Xiaolong YU Ying CHU Jing ZHOU Yongmin YAN Jianbo XI department of Laboratory Medicine Wujin Hospital Affiliated with Jiangsu UniversityJiangsu UniversityChangzhou 213017China department of Laboratory Medicine School of MedicineJiangsu UniversityZhenjiang 212013China Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine Wujin Clinical College of Xuzhou Medical UniversityChangzhou 213017China

Liver fibrosis is a significant health burden,marked by the consistent deposition of ***,the currently available treatment approaches for this condition are far from *** oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver *** stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver *** studies have found that MSC-sEV can be used for microRNA delivery into target cells or *** is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC ***,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver *** study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis *** results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in ***,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in ***-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse ***-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 *** conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.

关键词： Mesenchymal stem cell(MSC) small extracellular vesicle(sEV) MicroRNA-4465(miR-4465) Hepatic stellate cell(HSC) Liver fibrosis

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Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

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World Journal of clinical Cases 2024年第9期12卷 1685-1690页

作者： Xuan Xu Jing-Wen Jiang Bing-Yun Lu Xia-Xi Li department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhen 518100Guangdong ProvinceChina The First clinical Medical School Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological *** is currently no consensus on the treatment of refractory *** have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating ***,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and *** SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to *** patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four *** on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory *** particular,the patient showed primary nonresponse to infliximab and *** on the patient’s history and recurrent disease,we decided to administer *** hospitalisation,the patient was received upadacitinib under our *** weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved *** notable adverse reactions have been reported to *** Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

关键词： Upadacitinib Refractory ulcerative colitis Primary nonresponse Infliximab Vedolizumab Case report

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Targeted therapies for lupus nephritis:Current perspectives and future directions

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Chinese Medical Journal 2024年第1期137卷 34-43页

作者： Xiuzhi Jia Yuewen Lu Xunhua Zheng Ruihan Tang Wei Chen department of Nephrology The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510080China NHC Key Laboratory of clinical Nephrology(Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhouGuangdong 510080China

Lupus nephritis(LN),a severe manifestation of systemic lupus erythematosus,poses a substantial risk of progression to end-stage renal disease,with increased *** therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids,mycophenolate mofetil,and calcineurin *** therapeutic regimens have evolved over the years,they have inherent limitations,including non-specific targeting,substantial adverse effects,high relapse rates,and prolonged maintenance and remission *** drawbacks underscore the need for targeted therapeutic strategies for *** advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced *** review provides an overview of the current evidence on targeted therapies for LN,elucidates the biological mechanisms of responses and failure,highlights the challenges ahead,and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

关键词： Lupus nephritis Molecular targeted therapies Adaptive immunity Immunity,Innate Cytokines

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Regeneration of the heart:f rom molecular mechanisms to clinical therapeutics

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Military Medical Research 2024年第1期11卷 80-97页

作者： Qian-Yun Guo Jia-Qi Yang Xun-Xun Feng Yu-Jie Zhou Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease Beijing Institute of Heart Lung and Blood Vessel DiseaseClinical Center for Coronary Heart DiseaseDepartment of CardiologyBeijing Anzhen HospitalCapital Medical UniversityBeijing 100029China

Heart injury such as myocardial infarction leads to cardiomyocyte loss,fibrotic tissue deposition,and scar *** changes reduce cardiac contractility,resulting in heart failure,which causes a huge public health *** personnel,compared with civilians,is exposed to more stress,a risk factor for heart diseases,making cardiovascular health management and treatment innovation an important topic for military *** far,medical intervention can slow down cardiovascular disease progression,but not yet induce heart *** the past decades,studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart *** have emerged from studies in animal models and early clinical *** interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart *** this review,we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

关键词： Heart regeneration Cardiac disease Therapeutics Signaling mechanisms

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