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Blood-brain barrier pathology in cerebral small vessel disease

Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan Department of Medical Imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

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Lymphatic vessel:origin,heterogeneity,biological functions,and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 442-478页

作者： Zhaoliang Hu Xushi Zhao Zhonghua Wu Bicheng Qu Minxian Yuan Yanan Xing Yongxi Song Zhenning Wang Department of surgical Oncology and General Surgery The First Hospital of China Medical UniversityKey Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors(China Medical University)Ministry of Education155 North Nanjing StreetHeping DistrictShenyang 110001China

Lymphatic vessels,comprising the secondary circulatory system in human body,play a multifaceted role in maintaining homeostasis among various tissues and *** are tasked with a serious of responsibilities,including the regulation of lymph absorption and transport,the orchestration of immune surveillance and *** vessel development undergoes a series of sophisticated regulatory signaling pathways governing heterogeneous-origin cell populations stepwise to assemble into the highly specialized lymphatic vessel ***,as defined by new lymphatic vessels sprouting from preexisting lymphatic vessels/embryonic veins,is the main developmental mechanism underlying the formation and expansion of lymphatic vessel networks in an ***,abnormal lymphangiogenesis could be observed in many pathological conditions and has a close relationship with the development and progression of various *** studies have revealed a set of lymphangiogenic factors and cascades that may serve as the potential targets for regulating abnormal lymphangiogenesis,to further modulate the progression of ***,an increasing number of clinical trials have demonstrated the promising interventions and showed the feasibility of currently available treatments for future clinical *** lymphangiogenic promoters or inhibitors not only directly regulates abnormal lymphangiogenesis,but improves the efficacy of diverse *** conclusion,we present a comprehensive overview of lymphatic vessel development and physiological functions,and describe the critical involvement of abnormal lymphangiogenesis in multiple ***,we summarize the targeting therapeutic values of abnormal lymphangiogenesis,providing novel perspectives for treatment strategy of multiple human diseases.

关键词： therapeutic origin specialized

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Quality assessment of surgery for colorectal cancer:Where do we stand?

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 982-987页

作者： Stefan Morarasu Cristian Livadaru Gabriel-Mihail Dimofte The Second Department of surgical Oncology Regional Institute of OncologyIasi 707483Romania

Quality assurance in surgery has been one of the most important topics of debate among colorectal surgeons in the past *** has produced new surgical standards that led in part to the impressive oncological outcomes we see in many units *** mesorectal excision,complete mesocolic excision(CME),and the Japanese D3 lymphadenectomy are now benchmark techniques embraced by many surgeons and widely recommended by surgical ***,there are still ongoing discrepancies in outcomes largely based on surgeon *** is one of the main reasons why many countries have shifted colorectal cancer surgery only to high volume *** markers of surgical quality is thus a perquisite to ensure that standards and oncological outcomes are met at an institutional *** the evolution of CME surgery,various quality markers have been described,mostly based on measurements on the surgical specimen and lymph node yield,while others have proposed radiological markers(*** stumps)measured on postoperative scans as part of the routine cancer *** is no ideal marker;however,taken together and assembled into a new score or set of criteria may become a future point of reference for reporting outcomes of colorectal cancer surgery in research studies and defining subspecialization requirements both at an individual and hospital level.

关键词： Colorectal cancer Colon surgery Arterial stump Complete mesocolic excision surgical quality

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Unveiling the culprit:the fusobacterium lineage that populates colorectal cancer

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2349-2350页

作者： Johannes Betge Matthias P.Ebert Department of Medicine Ⅱ Medical Faculty MannheimHeidelberg UniversityMannheimGermany Junior Clinical Cooperation Unit Translational Gastrointestinal Oncology and preclinical Models German Cancer Research Center(DKFZ)HeidelbergGermany DKFZ Hector Cancer Institute at University Medical Center MannheimGermany MMPU Microbiota Drug Metabolism and Cancer Therapy European Molecular Biology LaboratoryHeidelbergGermany

In a recent study published in Nature,Zepeda-Rivera et al.1 discovered that one distinct clade of Fusobacterium nucleatum animalis(Fna)dominates the colorectal cancer(CRC)tumor *** work unravels a more precise understanding of a major bacterial species associated with CRC progression,thereby establishing a new focus for future studies,which may aid to develop improved microbiome-based diagnostics and treatments(Fig.1).

关键词： colorectal al. cancer

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Enhancement of the Antigenotoxic and Antioxidant Actions of Eugenol from Spice Clove and the Stabilizer Gum Arabic on Colorectal Carcinogenesis

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Food and Nutrition Sciences 2024年第1期15卷 71-100页

作者： Nayanna de Oliveira Ramos Melo Lucas Gabriel da Costa Marques Humberto Maia Costa Neto Matheus De Sousa Silva Francisco Vagnaldo Fechine Jamacaru Bruno Coêlho Cavalcanti Antônio Adailson De Sousa Silva Conceição Aparecida Dornelas Postgraduate Program in Medical-surgical Sciences School of Medicine Federal University of Ceará Fortaleza Brazil School of Medicine Federal University of Ceará Fortaleza Brazil Nucleus of Research and Development of Medicines (NPDM) Laboratory of Pharmacology and Preclinical Research School of Medicine Federal University of Ceará Fortaleza Brazil Nucleus for Research and Development of Medicines (NPDM) National Laboratory of Experimental Oncology Federal University of Ceará Fortaleza Brazil Postgraduate Program in Pathology and Medical-surgical Sciences School of Medicine Federal University of Ceará Fortaleza Brazil

Spices are defined as any aromatic condiment of plant origin used to alter the flavor and aroma of foods. Besides flavor and aroma, many spices have antioxidant activity, mainly related to the presence in cloves of phenolic compounds, such as flavonoids, terpenoids and eugenol. In turn, the most common uses of gum arabic are in the form of powder for addition to soft drink syrups, cuisine and baked goods, specifically to stabilize the texture of products, increase the viscosity of liquids and promote the leavening of baked products (e.g., cakes). Both eugenol, extracted from cloves, and gum arabic, extracted from the hardened sap of two species of the Acacia tree, are dietary constituents routinely consumed virtually throughout the world. Both of them are also widely used medicinally to inhibit oxidative stress and genotoxicity. The prevention arm of the study included groups: Ia, IIa, IIIa, Iva, V, VI, VII, VIII. Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the same period and for an additional 9 weeks, the animals received either water, 10% GA, EUG, or 10% GA + EUG by gavage. The treatment arm of the study included groups Ib, IIb, IIIb e IVb, IX, X, XI, XII). Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the subsequent 9 weeks, the animals received either water, 10% GA, EUG or 10% GA + EUG by gavage. The novelty of this study is the investigation of their use alone and together for the prevention and treatment of experimental colorectal carcinogenesis induced by dimethylhydrazine. Our results show that the combined use of 10% gum arabic and eugenol was effective, with antioxidant action in the colon, as well as reducing oxidative stress in all colon segments and preventing and treating genotoxicity in all colon segments. Furthermore, their joint administration reduced the number of aberrant crypts and th

关键词： Eugenol Gum Arabic Carcinogenesis Oxidative Stress Genotoxicity

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Network pharmacology combined with molecular docking revealed the potential targets of Coridius chinensis in prostate cancer treatment

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World Journal of Clinical Cases 2024年第27期12卷 6094-6104页

作者： Mei Zhang Jing Ma Feng-Yin Zeng Xiao-Hui Hou School of preclinical Medicine Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina

BACKGROUND Prostate cancer(PCa)has high morbidity and mortality rates in elderly *** a history of thousands of years,traditional Chinese medicine derived from insects could be an important source for developing cancer-targeted drugs to prevent tumorigenesis,enhance therapeutic effects,and reduce the risk of recurrence and *** studies have shown that Coridius chinensis(Cc)has anticancer *** To elucidate the mechanism of action of Cc against PCa via network pharma-cology and molecular *** Potential targets for Cc and PCa were predicted using ChemDraw 19.0 software,the PharmMapper database and the GeneCards ***,the STRING database was used to construct the protein–protein interaction *** Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment and molecular docking analyses were subsequently conducted to identify the key targets,active ingredients and pathways *** GO and KEGG analyses indicated that the PI3K-Akt signalling pathway was the critical pathway(P valuestudies are *** We used network pharmacology to predict the bioactive components and important targets of Cc for the treatment of PCa,supporting the development of Cc as a natural anticancer agent.

关键词： Coridius chinensis Molecular docking Network pharmacology Prostate cancer Traditional Chinese medicine

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Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 436-457页

作者： Yao Rong Ming-Zheng Tang Song-Hua Liu Xiao-Feng Li Hui Cai First Clinical Medical College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Key laboratory of Molecular Diagnostics and Precision Medicine for surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina NHC Key laboratory of Diagnosis and Therapy of Gastrointestinal Tumor Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver ***,this mechanism of action has not been *** sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus *** identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were ***,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was *** Of 518 common DEGs were obtained by screening for functional *** hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”*** enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver ***,we selected 10 of the hub genes for in vitro expression validation in liver cancer *** Our study reveals a common pathogenesis of liver cancer and *** common pathways and key genes may provide new ideas for further mechanistic studies.

关键词： COVID-19 Liver cancer Differentially expressed genes Hub genes Pathogenesis

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Analysis of the potential biological value of pyruvate dehydrogenase E1 subunitβin human cancer

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 144-181页

作者： Yao Rong Song-Hua Liu Ming-Zheng Tang Zhi-Hang Wu Guo-Rong Ma Xiao-Feng Li Hui Cai First Clinical Medical College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Key laboratory of Molecular Diagnostics and Precision Medicine for surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina NHC Key laboratory of Diagnosis and Therapy of Gastrointestinal Tumor Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in ***,few studies have elucidated the role and mechanism of PDHB in different *** To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in *** vitro experiments were performed to examine the biological regulation of PDHB in liver *** Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas(TCGA)*** of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset *** regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer *** correlation between PDHB and receiver operating characteristic diagnostic curve,clinicopathological staging,somatic mutation,tumor mutation burden(TMB),microsatellite instability(MSI),DNA methylation,and drug susceptibility in pan-cancer was also *** algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment,as well as the co-expression analysis of PDHB and immune checkpoint(ICP)*** expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing,and the functional enrichment analysis of PDHB-related genes was *** study also validated the level of mRNA or protein expression of PDHB in several ***,in vitro experiments verified the regulatory effect of PDHB on the proliferation,migration,and invasion of liver *** PDHB was significantly and differently expressed in most *** was significantly associated with prognosis in patients with a wide range of cancers,including kidney renal clear cell carcinoma,kidney renal papillary cell carcinoma,breast invasive carcinom

关键词： Cuprotosis Pyruvate dehydrogenase E1 subunitβ Pan-cancer Prognosis Liver cancer

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A Heterozygous Phospholamban Variant(p.R14del)Leads to Left Ventricular Involvement and Heart Failure Phenotypes in Arrhythmogenic Right Ventricular Cardiomyopathy

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Phenomics 2024年第1期4卷 13-23页

作者： Han Mo Xiumeng Hua Mengni Bao Zhe Sun Xiao Chen Mengda Xu Jiangping Song Shenzhen Key laboratory of Cardiovascular Disease Fuwai Hospital Chinese Academy of Medical SciencesShenzhen 518057China State Key laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical College167A Beilishi RoadXi Cheng DistrictBeijing 100037China Beijing Key laboratory of preclinical Research and Evaluation for Cardiovascular Implant Materials Animal Experimental CentreFuwai HospitalNational Center for Cardiovascular DiseaseChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

This study aimed to determine the prevalence and clinical features of Arrhythmogenic Right Ventricular Cardiomyopathy(ARVC)caused by pathogenic mutations in the Phospholamban(PLN)*** study included 170 patients who had a confrmed diagnosis of ARVC and underwent PLN genetic screening using next-generation *** fndings of this study provide valuable insights into the association between PLN mutations and ARVC,which can aid in the development of more efective diagnostic and treatment strategies for ARVC *** of the patients evaluated,six had a rare pathogenic mutation in PLN with the same p.R14del *** screening revealed that heterozygous carriers of p.R14del exhibited a defnite ARVC *** clinical studies,individuals with the p.R14del mutation experienced a similar rate of malignant arrhythmia events as those with classic desmosome *** adjusting for covariates,individuals with PLN mutations had a two point one seven times greater likelihood of experiencing transplant-related risks compared to those who did not possess PLN mutations(95%CI 1.08–6.82,p=0.035).The accumulation of left ventricular fat and fbers is a pathological marker for ARVC patients with p.R14del *** a cohort of 170 Chinese ARVC patients,three point fve percent of probands had the PLN pathogenic variant(p.R14del)and all were *** data shows that PLN-related ARVC patients are at high risk for ventricular arrhythmias and heart failure,which requires clinical diferentiation from classic ***,carrying the p.R14del mutation can be an independent prognostic risk factor in ARVC patients.

关键词： Arrhythmogenic right ventricular cardiomyopathy Phospholamban Left ventricular involvement Heart failure Risk stratifcation

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Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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World Journal of Gastroenterology 2024年第25期30卷 3182-3184页

作者： Jeffrey A Lowell Michael J Farber Keith Sultan Department of Medicine Zucker School of Medicine at HofstraNorth Shore University Hospital-Long Island Jewish Medical CenterManhassetNY 11030United States preclinical studies New York Institute of Technology College of Osteopathic MedicineGlen HeadNY 11545United States Division of Gastroenterology Northwell HealthNorth Shore University Hospital and Long Island Jewish Medical CenterGreat NeckNY 10021United States

Inflammatory bowel disease(IBD)is entering a potentially new era of combined *** et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this *** importance of controlled trials should be stressed in establishing new treatment *** prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

关键词： Inflammatory bowel disease Biologics Immunomodulators Dual-therapy Combination therapy

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