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Use of induced pluripotent stem cell-derived brain cells,organoids,assembloids,and blood-brain barrier models in understanding alcohol and anesthetic-induced brain injuries:an emerging perspective

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Neural Regeneration Research 2024年第5期19卷 953-954页

作者： Xiaowen Bai department of Cell Biology Neurobiology&AnatomyMedical College of WisconsinMilwaukeeWIUSA

Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts *** extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain *** perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general *** models could also be used to develop protective and therapeutic approaches.

关键词： injuries protective drugs

Changes in structural plasticity of hippocampal neurons in an animal model of multiple sclerosis

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Zoological Research 2024年第2期45卷 398-414页

作者： Poornima D.E.Weerasinghe-Mudiyanselage Sohi Kang Joong-Sun Kim Sung-Ho Kim Hongbing Wang Taekyun Shin Changjong Moon department of Veterinary anatomy and Animal Behavior College of Veterinary Medicine and BK21 FOUR ProgramChonnam National UniversityGwangju 61186Republic of Korea department of anatomy and Convergence Medical Science Institute of Health SciencesCollege of MedicineGyeongsang National UniversityJinju 52727Republic of Korea department of Physiology and Neuroscience Program Michigan State UniversityEast LansingMI 48824USA department of Veterinary anatomy College of Veterinary Medicine and Veterinary Medical Research InstituteJeju National UniversityJeju 63243Republic of Korea

Structural plasticity is critical for the functional diversity of neurons in the *** autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE *** the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic *** complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early ***,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic ***,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic ***,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC *** cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory ***,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hi

关键词： Activity-regulated cytoskeleton-associated protein Anxiety-like behavior Experimental autoimmune encephalomyelitis Hippocampal dysfunction Neuroinflammation

Understanding the spectrum of non-motor symptoms in multiple sclerosis:insights from animal models

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Neural Regeneration Research 2024年第1期19卷 84-91页

作者： Poornima D.E.Weerasinghe-Mudiyanselage Joong-Sun Kim Taekyun Shin Changjong Moon department of Veterinary anatomy and Animal Behavior College of Veterinary Medicine and BK21 FOUR programChonnam National UniversityGwangjuRepublic of Korea department of Veterinary anatomy College of Veterinary Medicine and Veterinary Medical Research InstituteJeju National UniversityJejuRepublic of Korea

Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic,physically debilitating neurological *** addition to experiencing motor disability,patients with multiple sclerosis also experience a variety of nonmotor symptoms,including cognitive deficits,anxiety,depression,sensory impairments,and ***,the pathogenesis and treatment of such non-motor symptoms in multiple scle rosis are still under *** studies for multiple sclerosis benefit from the use of disease-appropriate animal models,including experimental autoimmune *** to understanding the pathophysiology and developing treatments for non-motor symptoms,it is critical to chara cterize the animal model in terms of its ability to replicate certain non-motor features of multiple *** such,no single animal model can mimic the entire spectrum of *** review focuses on the non-motor symptoms that have been investigated in animal models of multiple sclerosis as well as possible underlying ***,we highlighted gaps in the literature to explain the nonmotor aspects of multiple sclerosis in expe rimental animal models,which will serve as the basis for future studies.

关键词： anxiety cognitive deficit depression experimental autoimmune encephalomyelitis motor disability neurological disorder pain pathophysiology preclinical study sensory impairments

Korean red ginseng alleviates benign prostatic hyperplasia by dysregulating androgen receptor signaling and inhibiting DRP1-mediated mitochondrial fission

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Chinese Journal of Natural Medicines 2024年第7期22卷 599-607页

作者： HONG Geum-Lan KIM Kyung-Hyun CHO Sung-Pil LEE Hui-Ju KIM Yae-Ji JUNG Ju-Young department of Veterinary Medicine&Institute of Veterinary Science Chungnam National UniversityDaejeon 34134Korea department of anatomy College of MedicineKonyang UniversityDaejeon 35365Korea

Panax ginseng(***.)has been traditionally employed in Korea and China to alleviate fatigue and digestive *** particular,Korean red ginseng(KRG),derived from streamed and dried ***,is known for its anti-aging and anti-inflammatory ***,its effects on benign prostatic hyperplasia(BPH),a representative aging-related disease,and the underlying mechanisms remain *** study aims to elucidate the therapeutic effects of KRG on BPH,with a particular focus on mitochondrial dynamics,including fission and fusion *** effects of KRG on cell proliferation,apoptosis,and mitochondrial dynamics and morphology were evaluated in a rat model of testosterone propionate(TP)-induced BPH and TP-treated LNCaP cells,with mdivi-1 as a *** results revealed that KRG treatment reduced the levels of androgen receptors(AR)and prostate-specific antigens in the BPH *** inhibited cell proliferation by downregulating cyclin D and proliferating cell nuclear antigen(PCNA)levels,and it promoted apoptosis by increasing the ratio of B-cell lymphoma protein 2(Bcl-2)-associated X protein(Bax)to Bcl-2 ***,KRG treatment enhanced the phosphorylation of dynamin-related protein 1(DRP-1,serine 637)compared with that in the BPH group,which inhibited mitochondrial fission and led to mitochondrial *** modulation of mitochondrial dynamics was associated with decreased cell proliferation and increased *** dysregulating AR signaling and inhibiting mitochondrial fission through enhanced DRP-1(ser637)phosphorylation,KRG effectively reduced cell proliferation and induced *** findings suggest that KRG’s regulation of mitochondrial dynamics offers a promising clinical approach for the treatment of BPH.

关键词： Androgen Benign prostatic hyperplasia Fission Korean red ginseng Mitochondria

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon Kim Deok Ryong Kim department of Biochemistry and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea department of anatomy and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

Activation of NRF2 by celastrol increases antioxidant functions and prevents the progression of osteoarthritis in mice

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Chinese Journal of Natural Medicines 2024年第2期22卷 137-145页

作者： LIU Mingming GUO Jiatian ZHAO Jing LI Hongye FENG Xiaoxiao LIU Haojun ZHANG Hao JIA Xuejun WEI Rushuai LI Fang CHEN Chong HOU Mingzhuang LV Nanning XU Haiyan department of human anatomy Xuzhou Medical UniversityXuzhou 221004China department of Orthopedic Surgery The Affiliated Lianyungang Clinical College of Xuzhou Medical University(The Second People’s Hospital of Lianyungang)Lianyungang 222003China department of Orthopaedics The First Afliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Institute of Hematology Xuzhou Medical UniversityXuzhou 221004China

Excessive oxidative stress impairs cartilage matrix metabolism balance,significantly contributing to osteoarthritis(OA)***(CSL),a drug derived from Tripterygium wilfordii,has recognized applications in the treatment of cancer and immune system disorders,yet its antioxidative stress mechanisms in OA remain *** study aimed to substantiate CSL’s chondroprotective effects and unravel its underlying *** investigated CSL’s impact on chondrocytes under both normal and inflammatory *** vitro,CSL mitigated interleukin(IL)-1β-induced activation of proteinases and promoted cartilage extracellular matrix(ECM)*** vivo,intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA ***,it was found that inhibiting nuclear factor erythroid 2-related factor 2(NRF2)abrogated CSL-mediated antioxidative functions and exacerbated the progression of *** study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2,offering a novel therapeutic avenue for arthritis therapy.

关键词： Osteoarthritis Celastrol Articular cartilage Extracellular matrix NRF2

Unveiling health rights:A call to action for sex workers'HIV care in the Philippines

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Asian Pacific Journal of Tropical Medicine 2024年第1期17卷 45-46页

作者： Sheikh Mohd Saleem Shah Sumaya Jan Health Section International NGONew DelhiIndia department of anatomy Govt.Medical CollegeSrinagarIndia

We are writing in response to the article titled“Addressing the needs and rights of sex workers for HIV healthcare services in the Philippines”[1].The article calls for attention on the significant challenges faced by sex workers in the Philippines in accessing HIV *** appreciate the article’s effort to examine these issues in *** would like to present a constant flow of thoughts in this letter while highlighting the positive aspects,potential obstacles,and additional points that contribute to this ongoing discussion.

关键词： workers action letter

Revealing the role of honokiol in human glioma cells by RNA-seq analysis

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BIOCELL 2024年第6期48卷 945-958页

作者： YUNBAO GUO XU LIU QI XU XIAOTONG ZHOU JIAWEI LIU YANYAN XU YAN LU HAIYAN LIU The department of Neurosurgery First Hospital of Jilin UniversityChangchun130021China The department of anatomy College of Basic Medical SciencesJilin UniversityChangchun130021China The Third college of Clinical Medicine Jilin UniversityChangchun130021China

Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve *** is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae *** also has anti-infection,antitumor,and immunomodulatory *** this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and ***,the mechanism through which honokiol regulates glioma cell apoptosis is still ***:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control ***-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative ***,MAPK signaling and ferroptosis were detected via western ***:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased *** of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were veriﬁ***:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling *** data could lead to new ideas for future research and therapy for patients with glioma.

关键词： human glioma Honokiol RNA-seq Apoptosis Ferroptosis MAPK

Cytokine landscapes of pregnancy:mapping gestational immune phases

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Gynecology and Obstetrics Clinical Medicine 2024年第1期4卷 56-64页

作者： Sulagna Dutta Pallav Sengupta Fong Fong Liew Basic Medical Sciences department College of MedicineAjman UniversityAjmanUAE department of Biomedical Sciences Gulf Medical UniversityAjmanUAE department of preclinical Sciences Faculty of DentistryMAHSA UniversityKuala LumpurMalaysia

Background Synchronised physiological adaptations occur during pregnancy to achieve systemic,immune and neuroendocrine equilibrium in the mother's body,allowing semiallogenic fetal *** text Depending on the cytokine profile alterations occurring through pregnancy,the latter can be divided into three distinct *** the first immunological phase of pregnancy,proinflammatory cytokines promote inflammatory reactions needed for *** the second phase,a possible change from proinflammatory to anti-inflammatory cytokines creates a symbiosis between maternal and fetal components,ensuring fetal *** the third phase,inflammatory and cytolytic cytokines operate again to reinforce an inflammatory environment for *** article offers a detailed account of immune adaptations during pregnancy and highlights the distinctive cytokine profiles that mark each *** By providing a simplified depiction of pregnancy phases based on cytokine profiles,the article aims to inspire more research in reproductive immunology and improve the management of pregnancy-related inflammation and infection.

关键词： pregnancy mother alterations