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Androgens exert multifaceted functions in sex differences analyzed through single-cell transcriptome

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Science China Life Sciences 2024年第11期67卷 2530-2531页

作者： Xinxin Tang Yinkun Fu Zhihui Zou Yue Li Ming He Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases Department of Pathophysiology School of Medicine Shanghai Jiao Tong University department of pathology The Affiliated Hospital of Youjiang Medical University for Nationalities

Sex differences are ubiquitous in human development, aging and disease. For example, the overwhelming majority of non-reproductive system cancers are more common in males(Mauvais-Jarvis et al., 2020), while autoimmune diseases are more common in females. Hormones,especially androgens and oestrogens, contribute to sex-biased phenotypes(Khramtsova et al., 2019).

关键词： PROSTATE CASTRATION

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Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic,periampullary/ampullary,and choledochal adenocarcinomas

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 875-882页

作者： Arzu Hazal Aydın Nesrin Turhan department of pathology Aksaray University Aksaray Training and Research HospitalAksaray 68200Turkey department of pathology University of Health Sciences Ankara City HospitalAnkara 06800Turkey

BACKGROUND Pancreatic,periampullary/ampullary,and choledochal adenocarcinomas are aggressive malignancies with a poor *** checkpoint blockade is a promising treatment option for several tumor types.H long terminal repeatassociating 2(HHLA2),which is analogous to programmed death-ligand 1(PDL1),is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many *** To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to *** Ninety-two adenocarcinoma cases located in the pancreas,ampulla,and distal common bile duct were *** study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and *** was conducted to examine the expression of DNA mismatch repair(MMR),PD-L1,and HHLA2 *** Patients with high HHLA2 expression had a higher mean age than those with low *** HHLA2 expression was associated with high perineural ***2 expression was low in pathological stage T3(pT)3 cases and high in pathological stage T1,T2,and T4 *** was no correlation between HHLA2 expression and the expression of MMR proteins and *** Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.

关键词： H long terminal repeat-associating 2 Programmed death-ligand 1 Adenocarcinoma Pancreas Ampulla of Vater Distal common bile duct

Levisticum officinale extract protects against CCl4-induced hepatotoxicity through anti-inflammatory,anti-fibrotic,and antioxidant properties in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第8期14卷 331-340页

作者： Nahid Ghaedi Iran Pouraboli Mansour Mirtadzadini Mohammad-mehdi Moeini-aghtaie department of Biology Faculty of SciencesShahid Bahonar University of KermanKermanIran department of pathology Pathology and Stem Cell Research CenterAfzalipour Medical FacultyKerman University of Medical SciencesKermanIran

Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced ***:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then rats received a single dose of CCl4(2.5 mL/kg,50%v/v in liquid paraffin).Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and ***,antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were ***:Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure,improved serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea,total bilirubin,and total protein,enhanced glutathione content and superoxide dismutase and catalase activities in the liver,as well as decreased plasma and hepatic malondialdehyde *** results demonstrated that the extract reduced Ki-67 andα-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale ***,Levisticum officinale extract markedly decreased the gene expressions of TNF-α,IL-6,TGF-β1,MCP-1,and ***:Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant,anti-inflammatory,and anti-fibrotic activities.

关键词： Levisticum officinale CCl4 Inflammation Liver toxicity Antioxidant

Mitochondrial DNA methylation and mitochondria-related epigenetics in neurodegeneration

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Neural Regeneration research 2024年第2期19卷 405-406页

作者： Fabio Coppedè department of Translational research and of New Surgical and Medical Technologies Laboratory of Medical GeneticsUniversity of PisaPisaItaly、Interdepartmental Research Center of Biology and Pathology of AgingUniversity of PisaPisaItaly

Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy *** are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.

关键词： impaired neurodegeneration oxidative

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Rhodium-catalyzed enantioselective in situ C（sp3）-H heteroarylation by a desymmetrization approach

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Chinese Chemical Letters 2024年第10期35卷 244-248页

作者： Yujia Shi Yan Qiao Pengfei Xie Miaomiao Tian Xingwei Li Junbiao Chang Bingxian Liu State Key Laboratory of Antiviral Drugs NMPA Key Laboratory for Research and Evaluation of Innovative Drug School of Chemistry and Chemical Engineering Henan Normal UniversityPingyuan Laboratory department of pathophysiology School of Basic Medical Sciences Zhengzhou University

A rhodium-catalyzed desymmetrization reaction for enantioselective methyl C-H arylation is achieved by utilizing an in situ arylating reagent via nucleophilic cyclization of o-aminoaryl alkyne. The reaction results in chiral indoles containing all-carbon quaternary stereocenters under atmospheric conditions, with a wide range of substrates exhibiting good enantioselectivity(44 examples). Mechnism and DFT studies show that the stereocontrol is reasonably achieved through the collaborative control of a large silicon substituted chiral ligand and C-H···π, LP···π interactions between aryl rings of the carboxylate group and the substrate. Control experiments demonstrate that Rh-aryl bond formation via in situ nucleophilic cyclization is more critical for reaction efficiency than via C-H activation of the nucleophilic cyclization byproduct.

关键词： C(sp3)−H activation Desymmetrization Enantioselective Heteroarylation π Interactions

Liquid biopsy for gastric cancer:Techniques,applications,and future directions

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World Journal of Gastroenterology 2024年第12期30卷 1680-1705页

作者： Cristina Díaz del Arco M Jesús Fernández Aceñero Luis Ortega Medina department of Surgical pathology Health Research Institute of the Hospital Clínico San CarlosHospital Clínico San CarlosMadrid 28040Spain department of Legal Medicine Psychiatry and PathologyUniversidad Complutense de MadridMadrid 28040Spain

After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other ***,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or *** techniques are diverse,intricate,and *** must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential ***,the implementation of LB in clinical practice still faces several *** potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient *** the other hand,gastric cancer(GC)is a disease often diagnosed at advanced *** recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these *** application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these *** this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

关键词： Liquid biopsy Gastric cancer Circulating tumor cells Cell-free DNA Circulating tumor DNA Molecular

Upregulation of α-ENaC induces pancreatic β-cell dysfunction,ER stress,and SIRT2 degradation

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Journal of Biomedical research 2024年第3期38卷 241-255页

作者： Xue Zhang Dan Zhang Lei Huo Xin Zhou Jia Zhang Min Li Dongming Su Peng Sun Fang Chen Xiubin Liang department of pathophysiology Nanjing Medical UniversityNanjingJiangsu 211166China department of pathology Nanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjingJiangsu 210009China Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjingJiangsu 211166China department of pathology Nanjing Medical UniversityNanjingJiangsu 211166China

Islet beta cells(β-cells)produce insulin in response to high blood glucose levels,which is essential for preserving glucose ***-gated ion channels inβ-cells,including Na+,K+,and Ca2+channels,aid in the release of *** epithelial sodium channel alpha subunit(α-ENaC),a voltage-independent sodium ion channel,is also expressed in human pancreatic endocrine ***,there is no reported study on the function of ENaC in theβ-*** the current study,we found thatα-ENaC was expressed in human pancreatic glandule and pancreatic isletβ-*** the pancreas of db/db mice and high-fat diet-induced mice,and in mouse isletβ-cells(MIN6 cells)treated with palmitate,α-ENaC expression was ***α-ENaC was overexpressed in MIN6 cells,insulin content and glucose-induced insulin secretion were significantly *** the other hand,palmitate injured isletβ-cells and suppressed insulin synthesis and secretion,but increasedα-ENaC expression in MIN6 ***,α-ENaC knockout(Scnn1a−/−)in MIN6 cells attenuatedβ-cell disorder induced by ***,α-ENaC regulated the ubiquitylation and degradation of sirtuin 2 inβ-cells.α-ENaC also modulatedβ-cell function in correlation with the inositol-requiring enzyme 1 alpha/X-box binding protein 1(IRE1α/XBP1)and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein(PERK/CHOP)endoplasmic reticulum stress *** results suggest thatα-ENaC may play a novel role in insulin synthesis and secretion in theβ-cells,and the upregulation ofα-ENaC promotes isletβ-cell *** conclusion,α-ENaC may be a key regulator involved in isletβ-cell damage and a potential therapeutic target for type 2 diabetes mellitus.

关键词： α-ENaC pancreaticβ-cells type 2 diabetes mellitus endoplasmic reticulum stress sirtuin 2

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Anisotropic microtopography surface of chitosan scaffold regulating skin precursor-derived Schwann cells towards repair phenotype promotes neural regeneration

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Regenerative Biomaterials 2024年第3期3卷 68-81页

作者： Meng Cong Xia Wu Lingjie Zhu Guohao Gu Fei Ding Guicai Li Haiyan Shi Key Laboratory of Neuroregenration of jiangsu and Ministry of Education and Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China department of pathophysiology School of MedicineNantong UniversityNantong 226001China

For repairing peripheral nerve and spinal cord defects,biomaterial scaffoid-based cell-therapy was emerged as an effective strategy,requiring the positive response of seed cells to biomaterial substrate and environment *** work highlighted that the imposed surface properties of scaffold could provide important guidance cues to adhered cells for ***,the insufficiency of native Schwann cells and unclear cellular response mechanisms remained to be *** that,this study aimed to illuminate the micropatterned chitosan-film action on the rat skin precursor-derived Schwann cells(SKP-SCs).Chitosanfilm with different ridge/groove size was fabricated and applied for the SKP-SCs *** indicated that SKP-SCs cultured on 30μm size microgroove surface showed better oriented alignment *** SKP-sCs presented similar genic phenotype as repair Schwann cells,increasing expression of c-Jun,neural cell adhesion molecule,and neurotrophic receptor ***,SKP-SC-secretome was subjected to cytokine array GS67 assay,data indicated the regulation of paracrine phenotype,a panel of cytokines was verifed up-regulated at secreted level and gene expression level in induced *** up-regulated cytokines exhibit a series of promotive neural regeneration functions,including cell survival,cell migration,cell proliferation,angiogenesis,axon growth,and cellular organization *** bioinformatics ***,the effectively polarized SKP-SCs-sourced secretome,promoted the proliferation and migration capacity of the primarily cultured native rat Schwann cells,and augmented neurites growth of the cultured motoneurons,as well as boosted axonal regrowth of the axotomy-injured *** together,SKP-SCs obtained pro-neuroregeneration phenotype in adaptive response to the anisotropic topography surface of chitosan-film,displayed the oriented parallel growth,the transition towards repair Schwann cell genic phenot

关键词： anisotropic microtopography skin precursor-derived Schwann cells chitosan-flm neural regeneration phenotype regulation

Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2673-2682页

作者： Huang Chen Rui-Ying Jiang Zhan Hua Xiao-Wei Wang Xiao-Li Shi Ye Wang Qian-Qian Feng Jie Luo Wu Ning Yan-Fen Shi Da-Kui Zhang Bei Wang Jian-Zheng Jie Ding-Rong Zhong department of pathology China-Japan Friendship HospitalBeijing 100029China department of Gastrointestinal Surgery China-Japan Friendship HospitalBeijing 100029China department of Scientific research GeneisBeijing 100012China

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly *** To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in *** We enrolled 2271 Chinese CRC patients at the China-Japan Friendship *** proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain *** status was determined using an MSI detection *** analyses were conducted using SPSS software and logistic *** The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,*** mutations were more likely to occur in patients with moderate-to-high *** mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural *** MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous ***,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,*** dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II *** This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

关键词： Colorectal cancer Deficient mismatch repair Microsatellite instability Gene mutation Comprehensive analysis