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Metadherin-driven promotion of cancer stem cell phenotypes and its effect on immunity in hepatocellular carcinoma

World Journal of Gastroenterology 2024年第20期30卷 2624-2628页

作者： Nevena Todorović Amedeo Amedei Department of experimental and Clinical medicine University of FlorenceFlorence 50134Italy Clinic for Infectious and Tropical Diseases University Clinical Centre of SerbiaBelgrade 11000Serbia

In this editorial we provide commentary on the article published by Wang et al,featured in the recent issue of the World Journal of Gastroenterology in *** focus on the metadherin(MTDH),also known as astrocyte elevated gene-1 or lysine rich CEACAM1,and its effects on cancer stem cells(CSCs)and immunity in hepatocellular carcinoma(HCC).HCC is the most common primary liver cancer and one of the leading causes of cancer-related deaths *** HCC cases develop in the context of liver *** the pivotal mechanisms of carcinogenesis are gene mutations,dysregulation of diverse signaling pathways,epigenetic alterations,hepatitis B virus-induced hepatocarcinogenesis,chronic inflammation,impact of tumor microenvironment,oxidative *** the years,extensive research has been conducted on the MTDH role in various tumor pathologies,such as lung,breast,ovarian,gastric,hepatocellular,colorectal,renal carcinoma,neuroblastoma,melanoma,and ***,its involvement in tumor development processes including transformation,apoptosis evasion,angiogenesis,invasion,and metastasis via multiple signaling *** has been demonstrated that knockdown or knockout of MTDH disrupt tumor development and *** addition,numerous reports have been carried out regarding the MTDH influence on HCC,demonstrating its role as a predictor of poor prognosis,aggressive tumor phenotypes prone to metastasis and recurrence,and exhibiting significant potential for therapy ***,more studies finely investigated the influence of MTDH on *** CSCs are a small subpopulation of tumor cells that sharing traits with normal stem cells like self-renewal and differentiation abilities,alongside a high plasticity that alters their *** their presumed role in tumor initiation,they can drive also disease relapse,metastasis,and resistance to chemo and radiotherapy.

关键词： Hepatocellular carcinoma Metadherin Astrocyte elevated gene-1 Lysine rich

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Role of doxycycline in the treatment of dengue infection: An open-label, randomized, controlled, pilot trial

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Asian Pacific Journal of Tropical medicine 2024年第4期17卷 160-165页

作者： Banothu Vinod Kumar Kajal Kamboj Ashok Kumar Pannu Ashok Kumar Yadav Mandip Bhatia Atul Saroch Department of Internal medicine PGIMER ChandigarhIndia Department of experimental medicine&Biotechnology PGIMER ChandigarhIndia

Objective:To measure the effect of doxycycline on inflammatory marker[IL-6,TNF-α,ferritin and C reactive protein(CRP)]levels in patients with dengue ***:A single-centre,open-label,parallel-group randomized controlled trial was done in PGIMER Chandigarh from June 2021 to October *** were randomized using a simple randomization process into two groups:the doxycycline treatment group(n=35)and the control group(n=34).Patients in the treatment group were given oral doxycycline 100 mg twice daily for five days along with standard treatment,whereas patients in the control group received only standard *** objective was to measure the effect of doxycycline on inflammatory markers in dengue ***:On comparative analysis at day 5,there was a statistically significant reduction in the median values of ferritin and CRP in cases compared to the control group(ferritin:P=0.006 and CRP:P=0.006).No significant reduction was noted in the levels of IL-6 and TNF-α.Conclusions:Doxycycline treatment led to a reduction of inflammatory markers in dengue infection.

关键词： Dengue Cytokine Doxycycline Serum ferritin C reactive protein

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Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA centre for experimental medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom centre for experimental medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

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Clinical profile and risk factors of Strongyloides stercoralis infection

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Asian Pacific Journal of Tropical medicine 2024年第1期17卷 43-44页

作者： Rupak Chatterjee Alisha Acharya Subhoroop Ghosh Shatavisa Mukherjee Tapashi Ghosh Nandini Chatterjee Netai Pramanik Department of Tropical medicine School of Tropical MedicineKolkataWest BengalIndia Department of Microbiology School of Tropical MedicineKolkataWest BengalIndia Eastern Regional centre National One Health Program for Prevention and Control of ZoonosesSchool of Tropical Medicine KolkataWest BengalIndia Department of Clinical&experimental Pharmacology School of Tropical MedicineKolkataWest BengalIndia Department of medicine IPGMER-SSKM HospitalKolkataWest BengalIndia

Strongyloides(S.)stercoralis,endemic in tropical and subtropical countries,is a soil-transmitted geohelminth human parasite belonging to a group of nematodes called *** is one of the most overlooked parasitic infections enlisted among the WHO"neglected tropical diseases"[1].*** mainly infects humans but can also be found naturally in domestic dogs,cats,and some primates.

关键词： tropical subtropical listed

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Targeting PKM2 signaling cascade with salvianic acid A normalizes tumor blood vessels to facilitate chemotherapeutic drug delivery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2077-2096页

作者： Cheng Qian Yueke Zhou Teng Zhang Guanglu Dong Mengyao Song Yu Tang Zhonghong Wei Suyun Yu Qiuhong Shen Wenxing Chen Jaesung P.Choi Juming Yan Chongjin Zhong Li Wan Jia Li Aiyun Wang Yin Lu Yang Zhao Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China School of medicine&Holistic Integrative medicine Nanjing University of Chinese MedicineNanjing 210023China centre for Inflammation Faculty of ScienceCentenary InstituteSchool of Life SciencesUniversity of Technology SydneySydney NSW 2050Australia Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Experimental Demonstration Center for Basic Medicine EducationXuzhou Laboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004China Department of General Surgery Jiangsu Province Hospital of Chinese MedicineAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China Macquarie Medical School Faculty of MedicineHuman Health SciencesMacquarie UniversitySydney NSW 2109Australia

Aberrant tumor blood vessels are prone to propel the malignant progression of tumors,and targeting abnormal metabolism of tumor endothelial cells emerges as a promising option to achieve vascular normalization and antagonize tumor ***,we demonstrated that salvianic acid A(SAA)played a pivotal role in contributing to vascular normalization in the tumor-bearing mice,thereby improving delivery and effectiveness of the chemotherapeutic *** was capable of inhibiting glycolysis and strengthening endothelial junctions in the human umbilical vein endothelial cells(HUVECs)exposed to ***,SAA was inclined to directly bind to the glycolytic enzyme PKM2,leading to a dramatic decrease in endothelial *** importantly,SAA improved the endothelial integrity via activating theβ-Catenin/Claudin-5 signaling axis in a PKM2-dependent *** findings suggest that SAA may serve as a potent agent for inducing tumor vascular normalization.

关键词： Salvianic acid A Tumor vascular normalization PKM2 β-Catenin Claudin-5 Endothelial glycolysis Tight junctions Doxorubicin

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Confinement effect on CO_(2)and CH_(4)permeability in shale

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Energy Geoscience 2024年第1期5卷 256-263页

作者： Vikram Vishal Tuli Bakshi Computational and experimental Geomechanics Laboratory Department of Earth SciencesIndian Institute of Technology BombayMumbai400076India National centre of Excellence in Carbon Capture and Utilization Indian Institute of Technology BombayMumbai400076India

Gas flow in shales follows a number of physical mechanisms that include Knudsen diffusion,Darcy flow,and adsorption in the matrix and micro *** aim of the study is to resolve the interplay of gas transport in these media at increased effective stress as well as net pore *** this research,we investigated the nature of gas transport in the matrix of shale by sending He,CH_(4)and CO_(2)gases through a transient upstream pressure pulse decay instrument.A series of experiments were conducted at constant pore pressures and a gradually increasing confining *** same study was done in three different scenarios,injecting He,CO_(2)and CH_(4).At a constant pore pressure,gas permeability appears to decrease with an increasing confining pressure and effective *** increasing effective stress,the slip factor also decreases along with the *** decrease in slip could be attributed to prestressing,that is likely to create new *** the three purged gases,permeability of shale to CH_(4)is the highest,and that to CO_(2)is the lowest owing to its high *** permeability of CH_(4)against He,could be attributed to the dual transport mechanism.

关键词： Energy Porous media Gas transport Effective stress

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The interplay of drug therapeutics and immune responses to SARS-CoV-2

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Cellular & Molecular Immunology 2024年第2期21卷 197-200页

作者： Valeria Fumagalli Matteo Iannacone Division of Immunology Transplantationand Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly experimental Imaging centre IRCCS San Raffaele Scientific InstituteMilanItaly

The SARS-CoV-2 pandemic has necessitated rapid therapeutic and preventative *** vaccines form the frontline of defense,antiviral treatments such as nirmatrelvir have emerged as vital adjunctive measures,particularly for those unable or unwilling to be *** review delves into the potential influence of nirmatrelvir on enduring *** parallel,the potential of drug repurposing is explored,with bisphosphonates being examined for their possible effects against COVID-19 due to their immunomodulatory *** importance of rigorous clinical trials and careful interpretation of preliminary data is emphasized.

关键词： SARS-CoV-2 Nirmatrelvir Bisphosphonates Adaptive immunity Drug repurposing

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Physics-embedded machine learning search for Sm-doped PMN-PT piezoelectric ceramics with high performance

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Chinese Physics B 2024年第8期33卷 81-88页

作者：辛睿王亚祺房泽郑凤基高雯付大石史国庆刘建一张永成 College of Physics Center for Marine Observation and CommunicationsNational Demonstration Center for Experimental Applied Physics EducationQingdao UniversityQingdao 266071China centre for Theoretical and Computational Physics College of PhysicsQingdao UniversityQingdao 266071China

Pb(Mg_(1/3)Nb_(2/3))O_(3)–PbTiO_(3)(PMN-PT)piezoelectric ceramics have excellent piezoelectric properties and are used in a wide range of *** the solid solution ratios of PMN/PT and different concentrations of elemental doping are the main methods to modulate their piezoelectric *** combination of these controllable conditions leads to an exponential increase of possible compositions in ceramics,which makes it not easy to extend the sample data by additional experimental or theoretical *** this paper,a physics-embedded machine learning method is proposed to overcome the difficulties in obtaining piezoelectric coefficients and Curie temperatures of Sm-doped PMN-PT ceramics with different *** contrast to all-data-driven model,physics-embedded machine learning is able to learn nonlinear variation rules based on small datasets through potential correlation between ferroelectric *** on the model outputs,the positions of morphotropic phase boundary(MPB)with different Sm doping amounts are *** also find the components with the best piezoelectric property and comprehensive ***,we set up a database according to the obtained results,through which we can quickly find the optimal components of Sm-doped PMN-PT ceramics according to our specific needs.

关键词： Pb(Mg_(1/3)Nb_(2/3))O_(3)–PbTiO_(3)(PMN-PT)ceramic physics-embedded machine learning piezoelectric coefficient Curie temperature

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Ganoderma lucidum:a comprehensive review of phytochemistry,efficacy,safety and clinical study

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Food Science and Human Wellness 2024年第2期13卷 568-596页

作者： Sijia Wu Siyuan Zhang Bo Peng Dechao Tan Mingyue Wu Jinchao Wei Yitao Wang Hua Luo Macao centre for Research and Development in Chinese medicine State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China College of Pharmacy Guangxi Medical UniversityNanning 530021China Guangxi University of Chinese medicine Nanning 530001China

Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that *** has various clinical therapeutic *** experimental studies have confirmed that *** has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so *** the deepening of research,more than 300 compounds have been isolated from *** is an increasing population of ***-based products,and its international development is ***,*** has drawn much attention to its chemical composition,therapeutic effect,clinical value,and *** paper provides a comprehensive review of these aspects to enhance the global promotion of ***.

关键词： Ganoderma lucidum Phytochemistry Efficacy Safety Clinical study

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Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian centre for experimental Therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner Thoracic Surgery Research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of Thoracic Surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： Pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

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