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The anti-neoplastic effects of metformin modulate the acquired phenotype of fbroblast cells in the breast cancer-normal fbroblast co-culture system

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Oncology Research 2024年第3期32卷 477-487页

作者： SAMANEH MOSTAFAVI ZUHAIR MOHAMMAD HASSAN department of immunology Faculty of Medical SciencesTarbiat Modares UniversityTehranIran

Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation,growth,and therapy *** hallmarks of cancer fibroblast interactions,consisting of caveolin 1(Cav1)and mono-carboxylate ransporter 4(MCT4)(metabolic coupling markers),along with IL-6,TGFB,and lactate secretion,are considered robust biomarkers predicting recurrence and *** order to promote a novel phenotype in normal fibroblasts,we predicted that breast cancer cells could be able to cause loss of Cavl and increase of MCT4,as well as elevate IL 6 and TGF in nearby nomal *** created a co culture model using breast cancer(4T1)and normal fibroblast(NIH3T3)cell lines cultured under specific experimental conditions in order to directly test our ***,we show that long-term co-culture of breast cancer cells and normal fibroblasts promotes loss of Cavl and gain of MCT4 in adjacent fibroblasts and increase lactate *** results were validated using the monoculture of each group separately as a *** this system,we show that me tformin inhibits IL-6 and TGFB secretion and re expresses Cavl in both ***,MCT4 and lactate stayed high after treatment with *** conclusion,our work shows that co-culture with breast cancer cells may cause signifcant alterations in the phenotype and secretion of normal ***,however,may change this state and affect fibroblasts'acquired ***,mitochondrial inhibition by metformin after 8 days of treatment,signi ficantly hinders tumor growth in mouse model of breast cancer.

关键词： Caveolin 1 Lactic acid Metformin NIH 3T3 cells Neoplasms

Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

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World Journal of Gastroenterology 2024年第5期30卷 471-484页

作者： Hui Hua Qian-Qian Zhao Miriam Nkesichi Kalagbor Guo-Zhi Yu Man Liu Zheng-Rui Bian Bei-Bei Zhang Qian Yu Yin-Hai Xu Ren-Xian Tang Kui-Yang Zheng Chao Yan Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogenic Biology and ImmunologyNational Demonstration Center for Experimental Basic Medical Science EducationLaboratory of Infection and ImmunityXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina department of Laboratory Medicine The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221002Jiangsu ProvinceChina

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment *** adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been *** To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing *** A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC *** sacrifice,the liver and the serum were collected from each *** hepatobiliary injuries,hepatic inflammation and fibrosis were *** targets of let-7a-5p and downstream molecule NF-κB were detected using Western *** rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 *** reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary ***,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic *** Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

关键词： Primary sclerosing cholangitis Recombinant adeno-associated virus 8 Let-7a-5p Therapeutic effects Inflammation

Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang department of experimental Surgery The Second Affiliated Hospital of Air Force Medical University department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-prolifera

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3049-3067页

作者： Jianming Yang Yawen Xiao Ningning Zhao Geng Pei Yan Sun Xinyu Sun Kaiyuan Yu Chunhui Miao Ran Liu Junqiang Lv Hongyu Chu Lu Zhou Bangmao Wang Zhi Yao Quan Wang Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Institute of ImmunologyState Key Laboratory of Experimental Hematologythe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsDepartment of ImmunologySchool of Basic Medical SciencesTianjin Institute of Urologythe Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Cellular and Molecular ImmunologyTianjin Medical UniversityTianjin 300070China department of Pathology Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center of Cancer/Key Laboratory of Cancer Prevention and TherapyTianjin/Tianjin’s Clinical Research Center of CancerTianjin 30060China department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300070China

The mucosal barrier is crucial for intestinal homeostasis,and goblet cells are essential for maintaining the mucosal barrier *** proviral integration site for Moloney murine leukemia virus-1(PIM1)kinase regulates multiple cellular functions,but its role in intestinal homeostasis during colitis is ***,we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models,in the presence of intestinal *** PIM1 leads to decreased goblet cells,thus impairing resistance to colitis and colitis-associated colorectal cancer(CAC)in ***,PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling ***,PIM1 interacts with histone deacetylase 2(HDAC2)and downregulates its level via phosphorylation,thereby altering the epigenetic profiles of Wnt signaling pathway ***,these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis,which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

关键词： PIM1 HDAC2 Goblet cell Gut microbiota Intestinal homeostasis Epigenetic modification Ulcerative colitis CAC

Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19

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Journal of Intensive Medicine 2024年第3期4卷 326-340页

作者： Jean-Marc Cavaillon Benjamin G.Chousterman Tomasz Skirecki Institut Pasteur ParisFrance department of Anesthesia and Critical Care Lariboisière University HospitalDMU ParabolAPHP NordParisFrance Inserm U942 University of ParisParisFrance department of Translational immunology and experimental Intensive Care Centre of Postgraduate Medical EducationWarsawPoland

Acute infections cause local and systemic disorders which can lead in the most severe forms to multi-organ failure and eventually to death. The host response to infection encompasses a large spectrum of reactions with a concomitant activation of the so-called inflammatory response aimed at fighting the infectious agent and removing damaged tissues or cells, and the anti-inflammatory response aimed at controlling inflammation and initiating the healing process. Fine-tuning at the local and systemic levels is key to preventing local and remote injury due to immune system activation. Thus, during bacterial sepsis and Coronavirus disease 2019 (COVID-19), concomitant systemic and compartmentalized pro-inflammatory and compensatory anti-inflammatory responses are occurring. Immune cells (e.g., macrophages, neutrophils, natural killer cells, and T-lymphocytes), as well as endothelial cells, differ from one compartment to another and contribute to specific organ responses to sterile and microbial insult. Furthermore, tissue-specific microbiota influences the local and systemic response. A better understanding of the tissue-specific immune status, the organ immunity crosstalk, and the role of specific mediators during sepsis and COVID-19 can foster the development of more accurate biomarkers for better diagnosis and prognosis and help to define appropriate host-targeted treatments and vaccines in the context of precision medicine.

关键词： Acute respiratory distress syndrome Bone marrow Cytokines Lungs Mucosa Vaccines

Skull and vertebral bone marrow in central nervous system inflammation

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Fundamental Research 2024年第2期4卷 246-250页

作者： Honglei Ren Qiang Liu department of Neurology Tianjin Neurological InstituteTianjin Institute of ImmunologyState Key Laboratory of Experimental HematologyInternational Joint Laboratory of Ocular DiseasesMinistry of EducationHaihe Laboratory of Cell EcosystemTianjin Medical University General HospitalTianjin 300052China

Emerging evidence has highlighted the capacity of hematogenous cells in skull and vertebral bone marrow to enter the meningeal borders via ossified vascular channels and maintain immune homeostasis in the central nervous system(CNS).CNS-adjacent skull and vertebral bone marrow comprises hematopoietic niches that can sense CNS injury and supply specialized immune cells to fine-tune inflammatory ***,we review recent advances in our understanding of skull and vertebral bone marrow-derived immune cells in homeostasis and inflammatory CNS ***,we discuss the implications for future development of therapies to mitigate CNS inflammation and its detrimental sequelae in neurological disorders.

关键词： Central nervous system Bone marrow Hematopoiesis Immune cells Neuroinflammation Stroke Multiple sclerosis

A cup of coffee for a brain long life

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Neural Regeneration Research 2024年第1期19卷 158-159页

作者： Chiara Porro Antonia Cianciulli Maria Antonietta Panaro department of Clinical and experimental Medicine University of FoggiaFoggiaItaly(Porro C)Department of BiosciencesBiotechnologies and EnvironmentUniversity of BariBariItaly

Coffee is one of the world's favorite and most popular beverages,the third most popular beverage after water and *** many people,it is an indispensable habit before going to work and a socialization tool for the rest of the *** general,the average consum ption varies from 2 to6 cups per *** are the health implications?Given this consum ption,the benefits are actually greater than the *** is the conclusion of a careful study published in the New England Journal of Medicine(van Dam et al.,2020).

关键词： favorite conclusion life

Fetal lung growth predicts the risk for early-life respiratory infections and childhood asthma

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World Journal of Pediatrics 2024年第5期20卷 481-495页

作者： Dimitra E.Zazara Olympia Giannou Steven Schepanski Mirja Pagenkemper Anastasios D.Giannou Maike Pincus Ioannis Belios Stefan Bonn Ania C.Muntau Kurt Hecher Anke Diemert Petra Clara Arck Division for experimental Feto-Maternal Medicine Department of Obstetrics and Fetal MedicineUniversity Medical Center Hamburg-Eppendorf(UKE)Martinistraße 5220251HamburgGermany University Children’s Hospital UKEHamburgGermany Computer Engineering and Informatics department Polytechnic SchoolUniversity of PatrasPatrasGreece Institute of Developmental Neurophysiology Center for Molecular Neurobiology Hamburg(ZMNH)UKEHamburgGermany department of Obstetrics and Fetal Medicine UKEHamburgGermany department of General Visceral and Thoracic SurgeryUKEHamburgGermany Section of Molecular immunology and Gastroenterology Ⅰ.Department of MedicineUKEHamburgGermany Pediatrics and Pediatric Pneumology Practice BerlinGermany Institute of Medical Systems Biology ZMNHUKEHamburgGermany Hamburg Center for Translational immunology UKEHamburgGermany

Background Early-life respiratory infections and asthma are major health burdens during *** predicting an increased risk for early-life respiratory diseases are ***,we identified the predictive value of ultrasound-monitored fetal lung growth for the risk of early-life respiratory infections and *** Fetal lung size was serially assessed at standardized time points by transabdominal ultrasound in pregnant women participating in a pregnancy *** between fetal lung growth and respiratory infections in infancy or early-onset asthma at five years were ***-learning models relying on extreme gradient boosting regressor or classifier algorithms were developed to predict respiratory infection or asthma risk based on fetal lung *** model development and validation,study participants were randomly divided into a training and a testing group,respectively,by the employed *** Enhanced fetal lung growth throughout pregnancy predicted a lower early-life respiratory infection *** sex was associated with a higher risk for respiratory infections in *** lung growth could also predict the risk of asthma at five years of *** designed three machine-learning models to predict the risk and number of infections in infancy as well as the risk of early-onset *** models’R2 values were 0.92,0.90 and 0.93,respectively,underscoring a high accuracy and agreement between the actual and predicted *** variables included known risk factors and novel predictors,such as ultrasound-monitored fetal lung *** Sonographic monitoring of fetal lung growth allows to predict the risk for early-life respiratory infections and asthma.

关键词： Asthma Child risk Early-life respiratory infections Prenatal lung development Sexual dimorphism

Current and future trends in whole genome sequencing in cancer

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Cancer Biology & Medicine 2024年第1期21卷 16-20页

作者： Yuki Katsuya department of experimental Therapeutics National Cancer Center Hospital5-1-1 TsukijiChuo-kuTokyo 104-0045Japan

Cancer remains a formidable global health challenge affecting millions of lives *** decades,conventional cancer treatments used a one-size-fits-all approach,overlooking the intricate genetic variations that drive *** emergence of cancer genomics has ushered in a new era of personalized and targeted cancer *** Human Genome Project,which was launched in 1990 and completed in 2003。

关键词： cancer Cancer annually