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TET1 Participates in Complete Freund’s Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model

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Neuroscience Bulletin 2024年第6期40卷 707-718页

作者： Dengcheng Zhan Jingjing Zhang Songxue Su Xiuhua Ren Sen Zhao Weidong Zang Jing Cao department of human anatomy School of Basic Medical SciencesZhengzhou UniversityZhengzhou450001China Neuroscience Research Institute Zhengzhou UniversityZhengzhou450001China

Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely *** this study,we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1(TET1)and the voltage-gated K^(+)channel Kv7.2(encoded by Kcnq2)to orofacial inflammatory pain in *** found that complete Freund’s adjuvant(CFA)injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion(TG)and induced orofacial inflammatory *** involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or ***,TET1 knockdown in Tet1^(flox/flox)mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like ***,TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical *** data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.

关键词： Facial pain KCNQ2 potassium channel TET1 protein

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

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

Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn D.Roseborough Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead department of anatomy and Cell Biology Western UniversityLondonONCanada Schulich School of Medicine and Dentistry Western UniversityLondonONCanada Deparment of clinical Neurological Sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

Neuroprotective effect of liraglutide and memantine in a rat model of Alzheimer’s disease

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 207-214页

作者： Duaa M.Bakhshwin Foziya W.Alhalabi Mohamad Omar Barasheed Ahmed M.Bakhshwin Maha H.Jamal Mohammed A.Bazuhair Fatemah O.Kamel Rania M.Magadmi Zoheir A Damanhouri Samar M.Alsaggaf department of clinical Pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia Hera General Hospital MakkahSaudi Arabia department of Pathology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of clinical anatomy Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia

Objective:To assess the effect of memantine combined with liraglutide on aluminum chloride(AlCl_(3))and D-galactose(D-GAL)-induced neurotoxicity in ***:Male Wistar rats were divided into 5 groups of 5 animals each:the positive control,the negative control,the memantine-treated group,the liraglutide-treated group,and the combination group treated with memantine and ***_(3)and D-GAL were used to induce *** tests,brain beta-amyloid protein,and oxidative stress biomarkers were ***:The Morris water maze test indicated an enhanced memory in the combination ***,the combination treatment of liraglutide and memantine resulted in a remarkable reduction in the beta-amyloid protein level in the brain *** inflammation and oxidative stress biomarkers were significantly reduced,and the levels of antioxidant parameters were ***:The combination of liraglutide and memantine exerts neuroprotective effects and enhances memory and cognitive functions in rats with Alzheimer’s disease.

关键词： Alzheimer’s disease Cognitive function Glucagonlike peptide-1 Liraglutide Memantine

Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 241-254页

作者： Chenjun Hu Yiqun Yan Yanhong Jin Jun Yang Yongmei Xi Zhen Zhong department of Neurology of the Second Afliated Hospital and department of human anatomy Histology and EmbryologyZhejiang University School of MedicineHangzhou 310058China department of Physiology and department of Cardiology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Division of human Reproduction and Developmental Genetics Women’s Hospital and Institute of GeneticsZhejiang University School of MedicineHangzhou 310006China

The accumulation and spread of prion-like proteins is a key feature of neurodegenerative diseases(NDs)such as Alzheimer’s disease,Parkinson's disease,or Amyotrophic Lateral *** a process known as‘seeding’,prion-like proteins such as amyloid beta,microtubule-associated protein tau,α-synuclein,silence superoxide dismutase 1,or transactive response DNA-binding protein 43 kDa,propagate their misfolded conformations by transforming their respective soluble monomers into *** and molecular evidence of prion-like propagation in NDs,the clinical relevance of their‘seeding’capacities,and their levels of contribution towards disease progression have been intensively studied over recent *** review unpacks the cyclic prion-like propagation in cells including factors of aggregate internalization,endo-lysosomal leaking,aggregate degradation,and *** on the importance of the role of prion-like protein aggregates in NDs,whether causal or consequent,are also *** lead to a greater understanding of ND pathogenesis and increased potential for therapeutic strategies.

关键词： Neurodegenerative diseases Prion-like propagation Seeding Endocytosis Endolyosomal leaking Degradation

Pre-activated macrophage membrane-encased aggregationinduced emission featuring nanoparticles:a novel possibility for tuberculosis treatment

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2848-2850页

作者： Qiang Cai Yihao Tian Quazi T.H.Shubhra department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanChina department of human anatomy and Histology and Embryology School of Basic Medical SciencesWuhan UniversityWuhanChina Institute of Chemistry University of Silesia in KatowiceSzkolna 9KatowicePoland

In a recent study published in Nature Nanotechnology,Li et *** the synthesis of a novel photosensitizer with unique aggregation-induced emission(AIE)characteristics.1 They microencapsulated this photosensitizer inside engineered nanoparticles(NPs)coated with pre-activated macrophage cell membranes(CMs),an innovative approach marking a significant leap in nanomedicine by offering a pathway to potent tuberculosis(TB)treatments that bypass antibiotic resistance with unparalleled precision.

关键词： tuberculosis macrophage aggregation

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

PPP1R14A is Associated with Immunotherapy Resistance in Head and Neck Squamous Cell Carcinoma Identified by Single-Cell and Bulk RNA-Sequencing

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Chinese Medical Sciences Journal 2024年第2期39卷 111-121页

作者： Jun-Jie Ma Lei Zhang Jin Lu Hao-Xuan Zhang department of clinical Medicine Bengbu Medical UniversityBengbu 233030AnhuiChina department of General Surgery The Second Affiliated Hospital of Bengbu Medical UniversityBengbu 233030AnhuiChina department of human anatomy Bengbu Medical UniversityBengbu 233030AnhuiChina Anhui Key Laboratory of Computational Medicine and Intelligent Health Bengbu Medical UniversityBengbu 233030AnhuiChina

Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing *** The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R *** Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab *** enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes *** relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were *** We found 83 *** were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor *** six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC ***,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.

关键词： PPP1R14A head and neck squamous cell carcinoma immunotherapy drug resistance