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Pan-immune-inflammation value as a prognostic biomarker for colon cancer and its variation by primary tumor location

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World Journal of Gastroenterology 2024年第33期30卷 3823-3836页

作者： Qian-Yu Wang Wen-Tao Zhong Yi Xiao Guo-Le Lin Jun-Yang Lu Lai Xu Guan-Nan Zhang Jun-Feng Du Bin Wu department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China medical department of General Surgery The First Medical CenterChinese PLA General HospitalBeijing 100853China

BACKGROUND A growing body of research indicates significant differences between left-sided colon cancers(LCC)and right-sided colon cancers(RCC).Pan-immune-inflammation value(PIV)is a systemic immune response marker that can predict the prognosis of patients with colon ***,the specific distinction between PIV of LCC and RCC remains *** To investigate the prognostic and clinical significance of PIV in LCC and RCC *** This multicenter retrospective cohort study included 1510 patients with colon cancer,comprising 801 with LCC and 709 with *** used generalized lifting regression analysis to evaluate the relative impact of PIV on disease-free survival(DFS)in these ***-Meier analysis,as well as univariate and multivariate analyses,were used to examine the risk factors for *** correlation between PIV and the clinical characteristics was statistically analyzed in these *** A total of 1510 patients{872 female patients(58%);median age 63 years[interquartile ranges(IQR):54-71];patients with LCC 801(53%);median follow-up 44.17 months(IQR 29.67-62.32)}were *** was significantly higher in patients with RCC[median(IQR):214.34(121.78-386.72)vs 175.87(111.92-286.84),P227.84)was associated with worse DFS in LCC[PIV-high:Adjusted hazard ratio(aHR)=2.39;95%confidence interval:1.70-3.38;P<0.001]but not in RCC(PIV-high:aHR=0.72;95%confidence interval:0.48-1.08;P=0.114).CONCLUSION These findings suggest that PIV may predict recurrence in patients with LCC but not RCC,underscoring the importance of tumor location when using PIV as a colon cancer biomarker.

关键词： Colon cancer Left-sided colon cancer Right-sided colon cancer Pan-immune-inflammation value Systemic inflammatory biomarkers Prognosis

The role of m^(6)A RNA methylation in autoimmune diseases: Novel therapeutic opportunities

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Genes & Diseases 2024年第1期11卷 252-267页

作者： Yunan Shan Wei Chen Yanbin Li The first clinical medical college Shandong University of Traditional Chinese MedicineJinanShandong 250013China department of Neurology The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qjanfoshan HospitalShandong Institute of NeuroimmunologyShandong Key Laboratory of Rheumatic Disease and Translational MedicineJinanShandong 250013China department of Gastroenterology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China

N6-methyladenosine m^(6)A modifications,as one of the most common forms of in-ternal RNA chemical modifications in eukaryotic cells,have gained increasing attention in recent *** m^(6)A RNA modifications exert various crucial roles in various biological pro-cesses,such as embryonic development,neurogenesis,circadian rhythms,and *** advances have highlighted that m^(6)A RNA modification plays an important role in im-mune response,especially in the initiation and progression of autoimmune *** this re-view,we summarized the regulatory mechanisms of m^(6)A methylation and its biological functions in the immune system and mainly focused on recent progress in research on the po-tential role of m^(6)A RNA methylation in the pathogenesis of autoimmune diseases,thus providing possible biomarkers and potential targets for the prevention and treatment of auto-immunediseases.

关键词： Adaptive immunity Autoimmune diseases Innate immunity Immune response m^(6)A RNA methylation

Hyperglycemia activates FGFR1 via TLR4/c-Src pathway to induce inflammatory cardiomyopathy in diabetes

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1693-1710页

作者： Xiong Chen Jinfu Qian Shiqi Liang Jianchang Qian Wu Luo Yujuan Shi Hong Zhu Xiang Hu Gaojun Wu Xiaokun Li Guang Liang department of Endocrinology the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China Chemical Biology Research Center School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China department of Wound Repair the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China department of Cardiology the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China School of Pharmaceutical sciences Hangzhou Medical CollegeHangzhou 311399China

Protein tyrosine kinases (RTKs) modulate a wide range of pathophysiological events in several non-malignant disorders, including diabetic complications. To find new targets driving the development of diabetic cardiomyopathy (DCM), we profiled an RTKs phosphorylation array in diabetic mouse hearts and identified increased phosphorylated fibroblast growth factor receptor 1 (p-FGFR1) levels in cardiomyocytes, indicating that FGFR1 may contribute to the pathogenesis of DCM. Using primary cardiomyocytes and H9C2 cell lines, we discovered that high-concentration glucose (HG) transactivates FGFR1 kinase domain through toll-like receptor 4 (TLR4) and c-Src, independent of FGF ligands. Knocking down the levels of either TLR4 or c-Src prevents HG-activated FGFR1 in cardiomyocytes. RNA-sequencing analysis indicates that the elevated FGFR1 activity induces pro-inflammatory responses via MAPKs–NFκB signaling pathway in HG-challenged cardiomyocytes, which further results in fibrosis and hypertrophy. We then generated cardiomyocyte-specific FGFR1 knockout mice and showed that a lack of FGFR1 in cardiomyocytes prevents diabetes-induced cardiac inflammation and preserves cardiac function in mice. Pharmacological inhibition of FGFR1 by a selective inhibitor, AZD4547, also prevents cardiac inflammation, fibrosis, and dysfunction in both type 1 and type 2 diabetic mice. These studies have identified FGFR1 as a new player in driving DCM and support further testing of FGFR1 inhibitors for possible cardioprotective benefits.

关键词： Diabetic cardiomyopathy Protein tyrosine kinases FGFR1 Cardiomyocytes Inflammatory responses Toll-like receptor4 c-Src NFkB

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

Immunomodulation of Proton-activated G Protein-coupled Receptors in Inflammation

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Current medical science 2024年第3期44卷 475-484页

作者： Min-shan LI Xiang-hong WANG Heng WANG department of Otolaryngology-Head and Neck Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Institute of Allergy and clinical Immunology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei clinical Research Center for Nasal Inflammatory Diseases Wuhan430030China

Proton-activated G protein-coupled receptors(GPCRs),initially discovered by Ludwig in 2003,are widely distributed in various *** receptors have been found to modulate the immune system in several inflammatory diseases,including inflammatory bowel disease,atopic dermatitis,and ***-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular *** detection triggers downstream signaling pathways within the cells,ultimately influencing the function of immune *** this review,we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.

关键词： proton-activated G protein-coupled receptors inflammation immunomodulation disease

TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway

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Current medical science 2024年第3期44卷 589-602页

作者： An-bang SUN Fang-hua LI Lin ZHU Xi-xi ZENG Min ZHU Qing-hua LEI Yan-hong LIAO department of Anatomy School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China department of Transfusion Medicine Wuhan Hospital of Traditional Chinese and Western MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China department of Nephrology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China department of Thoracic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China National Basic medical Teaching Demonstration Center Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Neurological Diseases of Ministry of Education Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney ***,the knockout of transient receptor potential channel 6(TRPC6)has shown promise in alleviating renal ***,the regulatory impact of TRPC6 on renal fibrosis remains *** In vivo,TRPC6 knockout(TRPC6−/−)mice and age-matched 129 SvEv(WT)mice underwent unilateral renal ischemia-reperfusion(uIR)injury surgery on the left renal pedicle or sham *** and serum were collected on days 7,14,21,and 28 after *** vitro,primary tubular epithelial cells(PTECs)were isolated from TRPC6−/−and WT mice,followed by treatment with transforming growth factorβ1(TGFβ1)for 72 *** anti-fibrotic effect of TRPC6−/−and the underlying mechanisms were assessed through hematoxylin-eosin staining,Masson staining,immunostaining,qRT-PCR,and Western *** Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ***6−/−alleviated renal fibrosis by reducing the expression of fibrotic markers(Col-1,α-SMA,and vimentin),as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in ***,we found that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase 3 beta(GSK3β)signaling pathway,a pivotal player in renal fibrosis,was down-regulated following TRPC6 *** These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3β*** TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

关键词： transient receptor potential channel 6 ischemia-reperfusion injury renal fibrosis renal tubular epithelial cells

Electrospun PCL/gelatin/arbutin nanofiber membranes as potent reactive oxygen species scavengers to accelerate cutaneous wound healing

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Regenerative Biomaterials 2024年第3期3卷 43-55页

作者： Mindong Du Shuhan Liu Nihan Lan Ruiming Liang Shengde Liang Maoqiang Lan Disen Feng Li Zheng Qingjun Wei Ke Ma department of Orthopaedics Trauma and Hand Surgery The First Affliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530521China Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration The First Affliated Hospital of Guangxi Medical UniversityGuangxi Medicar UniversityNanning530021China Guangxi Collaborative Innovation Center for Biomedicine The First Affliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China department of Plastic&Cosmetic Surgery.The first Affliated Hospital of Guangxi medical University Guangxi Medical UniversityNanning 530021China Pharmaceutical college Guangxi Medical UniversityNanning530021China

The presence of excessive reactive oxygen species(Ros)at a skin wound site is an important factor affecting wound *** scavenging,which regulates the ROS microenvironment,is essential for wound *** this study,we used novel electrospun PCL/gelatin/arbutin(PCL/G/A)nanofibrous membranes as wound dressings,with PCL/gelatin(PCL/G)as the backbone,and plantderived arbutin(hydroquinone-β-D-glucopyranoside,ARB)as an effective antioxidant that scavenges ROos and inhibits bacterial infection in *** loading of ARB increased the mechanical strength of the nanofibres,with a water vapour transmission rate of more than 2500g/(m^(2)×24h),and the water contact angle decreased,indicating that hydrophilicity and air permeability were significantly *** release and degradation experiments showed that the nanofibre membrane controlled the drug release and exhibited favourable *** experiments showed that the PCL/G/A nanofibre membranes were biocompatible,and DPPH and ABTS+radical scavenging experiments indicated that PCL/G/A could effectively scavenge ROS to reflect the antioxidant *** addition,haemostasis experiments showed that PCL/G/A had good haemostatic effects in vitro and in *** vivo animal wound closure and histological staining experiments demonstrated that PCL/G/A increased collagen deposition and remodelled epithelial tissue regeneration while showing good in vivo biocompatibility and *** conclusion,we successfully prepared a multifunctional wound dressing,PCL/G/A,for skin wound healing and investigated its potential role in wound healing,which is beneficial for the clinical translational application of phytomedicines.

关键词： arbutin nanofiber membranes wound dressing reactive oxygen species

Primary pulmonary meningioma and minute pulmonary meningothelial-like nodules: Rare pulmonary nodular lesions requiring more awareness in clinical practice

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World Journal of clinical Cases 2024年第11期12卷 1857-1862页

作者： Li-Dan Liu Ke-Xin Zhang Hai-Ning Zhang Yi-Wen Zheng Hong-Tao Xu department of Pathology The First Hospital and College of Basic Medical Sciences of China Medical UniversityShenyang 110001Liaoning ProvinceChina

In this editorial,we comment on an article by Ruan et al published in a recent issue of the World Journal of clinical *** meningothelial proliferative lesions,including primary pulmonary meningiomas,minute pulmonary meningothelial-like nodules,and metastatic pulmonary meningiomas are rare pulmonary *** lesions are difficult to differentiate from lung cancers based on clinical and imaging ***,we briefly introduce the clinical,imaging,and pathological characteristics of these lesions and discuss their pathogenesis to strengthen the current understanding of pulmonary meningothelial proliferative lesions in clinical diagnosis and therapy.

关键词： Pulmonary meningothelial proliferation Primary pulmonary meningioma Minute pulmonary meningothelial-like nodule Lung neoplasm Rare pulmonary nodular lesion

Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

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Neural Regeneration Research 2024年第11期19卷 2480-2487页

作者： Feibiao Dai Chengyun Hu Xue Li Zhetao Zhang Hongtao Wang Wanjun Zhou Jiawu Wang Qingtian Geng Yongfei Dong Chaoliang Tang Graduate School Wannan Medical CollegeWuhuAnhui ProvinceChina department of Anesthesiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Core Facility Center for medical sciences The First Affiliated Hospital of USTC(Anhui Provincial Hospital)HefeiAnhui ProvinceChina department of Pharmacy The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina department of Neurosurgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion *** calcium channels are involved in cerebral ischemia/reperfusion ***3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain ***,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains ***,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal *** results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal *** further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion ***3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion ***,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal *** the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion *** findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 *** from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

关键词： calcineurin Cav3.2 channel cerebral ischemia/reperfusion hippocampus hypoxia/reoxygenation inflammatory response nuclear factor of activated T cells 3 oxidative stress primary hippocampal neurons stroke