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PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification

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

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Adverse effects of exposure to fine particles and ultrafine particles in the environment on different organs of organisms

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Journal of Environmental Sciences 2024年第1期135卷 449-473页

作者： Jianwei Zhang Zhao Chen Dan Shan Yang Wu Yue Zhao Chen Li Yue Shu Xiaoyu Linghu Baiqi Wang Department of Occupational and Environmental Health School of Public HealthTianjin Medical UniversityTianjin 300070China Department of medical Tianjin Stomatological HospitalSchool of MedicineNankai UniversityTianjin 300041China tianjin Key Laboratory of Environment Nutrition and Public HealthTianjin 300070China National Demonstration center for Experimental Preventive Medicine Education(tianjin medical University) Tianjin 300070China

Particulate pollution is a global risk factor that seriously threatens human *** particles(FPs)and ultrafine particles(UFPs)have small particle diameters and large specific surface areas,which can easily adsorb metals,microorganisms and other *** and UFPs can enter the human body in multiple ways and can be easily and quickly absorbed by the cells,tissues and *** the body,the particles can induce oxidative stress,inflammatory response and apoptosis,furthermore causing great adverse *** studies mainly take the population as the research object to study the distribution of diseases and health conditions in a specific population and to focus on the identification of influencing ***,the mechanism by which a substance harms the health of organisms is mainly demonstrated through toxicological *** epidemiological studies with toxicological studies will provide a more systematic and comprehensive understanding of the impact of PM on the health of *** this review,the sources,compositions,and morphologies of FPs and UFPs are briefly introduced in the first *** effects and action mechanisms of exposure to FPs and UFPs on the heart,lungs,brain,liver,spleen,kidneys,pancreas,gastrointestinal tract,joints and reproductive system are systematically *** addition,challenges are further pointed out at the end of the *** work provides useful theoretical guidance and a strong experimental foundation for investigating and preventing the adverse effects of FPs and UFPs on human health.

关键词： Fine particles Ultrafine particles Organs Adverse effect

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Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer’s Disease Mouse Model

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Research 2024年第1期2023卷 81-95页

作者： Fangxuan Chu Ruxin Tan Xin Wang Xiaoqing Zhou Ren Ma Xiaoxu Ma Ying Li Ruixu Liu Chunlan Zhang Xu Liu Tao Yin Zhipeng Liu Institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China tianjin Institutes of Health Science Tianjin301600China Neuroscience center Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing100730China

The neuropathological features of Alzheimer’s disease include amyloid *** emerging evidence suggests that Piezo1,a mechanosensitive cation channel,plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure,but the importance of Piezo1-mediated mechanotransduction in brain functions is less ***,apart from mechanical stimulation,Piezo1 channels are strongly modulated by *** assume that Piezo1 may play a role in converting mechanical and electrical signals,which could induce the phagocytosis and degradation of Aβ,and the combined effect of mechanical and electrical stimulation is superior to single mechanical ***,we design a transcranial magneto-acoustic stimulation(TMAS)system,based on transcranial ultrasound stimulation(TUS)within a magnetic field that combines a magnetoacoustic coupling effect electric field and the mechanical force of ultrasound,and applied it to test the above hypothesis in 5xFAD *** tests,in vivo electrophysiological recordings,Golgi–Cox staining,enzyme-linked immunosorbent assay,immunofluorescence,immunohistochemistry,real-time quantitative PCR,Western blotting,RNA sequencing,and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1.

关键词： stimulation Alzheimer Piezo1

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Reduction of the oxidative damage to H_(2)O_(2)-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside

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Food Science and Human Wellness 2024年第4期13卷 1864-1876页

作者： Meijing Zhang Gaoshuai Zhang Xiangxing Meng Xinxin Wang Jiao Xie Shaoshu Wang Biao Wang Jilite Wang Suwen Liu Qun Huang Xu Yang Jing Li Hao Wang State Key Laboratory of Food Nutrition and Safety Tianjin University of Science and Technology(TUST)Tianjin 300457China Key Laboratory of Environmental Pollution Monitoring and Disease Control Ministry of EducationGuizhou Medical UniversityGuiyang 550025China College of Chemical Engineering and Materials Science Tianjin University of Science and Technology(TUST)Tianjin 300457China Department of Agriculture Hetao CollegeBayannur 015000China College of Food Science&Technology Hebei Normal University of Science and TechnologyQinhuangdao 066004China National center of Supervision and inspection for Processed Food Quality Tianjin Institute for Food Safety Inspection TechnologyTianjin 300457China

Hyperoside and quercetin are similar in molecular *** this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network *** the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis *** findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial *** addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)*** was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the *** the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling ***,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 *** stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant ***,quercetin had a better antioxidant than hyperoside.

关键词： Hyperoside Quercetin HepG2 cell Oxidative damage Nrf2 signalling pathway

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Application of artificial hibernation technology in acute brain injury

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Neural Regeneration Research 2024年第9期19卷 1940-1946页

作者： Xiaoni Wang Shulian Chen Xiaoyu Wang Zhen Song Ziqi Wang Xiaofei Niu Xiaochu Chen Xuyi Chen Graduate School of tianjin University of Traditional Chinese Medicine TianjinChina Characteristic medical center of People’s Armed Police Forces TianjinChina

Controlling intracranial pressure,nerve cell regeneration,and microenvironment regulation are the key issues in reducing mortality and disability in acute brain *** is currently a lack of effective treatment *** has the characteristics of low temperature,low metabolism,and hibernation rhythm,as well as protective effects on the nervous,cardiovascular,and motor *** hibernation technology is a new technology that can effectively treat acute brain injury by altering the body’s metabolism,lowering the body’s core temperature,and allowing the body to enter a state similar to *** review introduces artificial hibernation technology,including mild hypothermia treatment technology,central nervous system regulation technology,and artificial hibernation-inducer *** summarizing the relevant research on artificial hibernation technology in acute brain injury,the research results show that artificial hibernation technology has neuroprotective,anti-inflammatory,and oxidative stress-resistance effects,indicating that it has therapeutic significance in acute brain ***,artificial hibernation technology can alleviate the damage of ischemic stroke,traumatic brain injury,cerebral hemorrhage,cerebral infarction,and other diseases,providing new strategies for treating acute brain ***,artificial hibernation technology is currently in its infancy and has some complications,such as electrolyte imbalance and coagulation disorders,which limit its *** research is needed for its clinical application.

关键词： cute brain injury artificial hibernation hypothermia low metabolism mild hypothermia

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An engineered DNA aptamer-based PROTAC for precise therapy of p53-R175H hotspot mutant-driven cancer

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Science Bulletin 2024年第13期69卷 2122-2135页

作者： Lingping Kong Fanlu Meng Ping Zhou Ruixin Ge Xiaoshan Geng Zhihao Yang Guo Li Linlin Zhang Jing Wang Jinfeng Ma Cheng Dong Jun Zhou Sijin Wu Diansheng Zhong Songbo Xie Department of medical Oncology Tianjin Medical University General HospitalTianjin 300052China center for Cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongCollege of Life SciencesShandong Normal UniversityJinan 250014China The Province and Ministry Co-sponsored Collaborative Innovation center for medical Epigenetics Key Laboratory of Immune Microenvironment and Disease(Ministry of Education)School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Lung Cancer InstituteTianjin Medical University General HospitalTianjin 300052China Haihe Laboratory of Cell Ecosystem State Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesNankai UniversityTianjin 300071China Wisdom Lake Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215028China Department of Ophthalmology Tianjin Medical University General HospitalLaboratory of Molecular OphthalmologyTianjin Key Laboratory of Ocular TraumaTianjin Medical UniversityTianjin 300052China

Targeting oncogenic mutant p53 represents an attractive strategy for cancer treatment due to the high frequency of gain-of-function mutations and ectopic expression in various cancer *** extensive efforts,the absence of a druggable active site for small molecules has rendered these mutants therapeutically *** we develop a selective and effective proteolysis-targeting chimera(PROTAC)for p53-R175H,a common hotspot mutant with dominant-negative and oncogenic *** a novel iterative molecular docking-guided post-SELEX(systematic evolution of ligands by exponential enrichment)approach,we rationally engineer a high-performance DNA aptamer with improved affinity and specificity for *** this resulting aptamer as a binder for PROTACs,we successfully developed a selective p53-R175H degrader,named ***53m induces the ubiquitin–protea some-dependent degradation of p53-R175H while sparing wildtype ***,dp53m demonstrates significant antitumor efficacy in p53-R175H-driven cancer cells both in vitro and in vivo,without ***,dp53m significantly and synergistically improves the sensitivity of these cells to cisplatin,a commonly used chemotherapy *** findings provide evidence of the potential therapeutic value of dp53m in p53-R175H-driven cancers.

关键词： P53 Aptamer PROTAC Cancer Drug resistance

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Changes in muscle strength and risk of cardiovascular disease among middle-aged and older adults in China:Evidence from a prospective cohort study

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Chinese medical Journal 2024年第11期137卷 1343-1350页

作者： Ze Yang Jiemin Wei Hongbo Liu Honglu Zhang Ruifang Liu Naijun Tang Xueli Yang Department of Occupational and Environmental Health School of Public HealthTianjin Medical UniversityTianjin 300070China tianjin Key Laboratory of Environment Nutrition and Public HealthTianjin Medical UniversityTianjin 300070China center for International Collaborative Research on Environment Nutrition and Public HealthTianjin 300070China

Background:Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases(CVDs)***,the association between muscle strength changes based on repeated measurements and CVD incidence remains ***:The study used data from the China Health and Retirement Longitudinal Study in 2011(Wave 1),2013(Wave 2),2015(Wave 3),and 2018(Wave 4).Low muscle strength was defined as handgrip strength<28 kg for men or<18 kg for women,or chair-rising time≥12 *** on changes in muscle strength from Waves 1 to 2,participants were categorized into four groups of Normal-Normal,Low-Normal,Normal-Low,and *** events,including heart disease and stroke,were recorded using a self-reported questionnaire during Waves 3 and 4 *** proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable *** ratios(HRs)and 95%confidence intervals(95%CIs)were estimated with the Normal-Normal group as the ***:A total of 1164 CVD cases were identified among 6608 *** to participants with sustained normal muscle strength,the CVD risks increased progressively across groups of the Low-Normal(HR=1.20,95%CI:1.01-1.43),the Normal-Low(HR=1.35,95%CI:1.14-1.60),and the Low-Low(HR=1.76,95%CI:1.49-2.07).Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and *** analyses showed that the significant associations between CVD and muscle strength changes were consistent across age,sex,and body mass index(BMI)***:The study found that muscle strength changes were associated with CVD *** suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.

关键词： Muscle strength Cardiovascular disease Prospective cohort study Aging Body mass index Sarcopenia

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Treatment of hemolymphangioma by robotic surgery: A case report

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 596-600页

作者： Tian-Ning Li Yan-Hong Liu Jia Zhao Hong Mu Lei Cao Department of Clinical Lab Tianjin First Central HospitalTianjin 300000China Nankai University Tianjin Union Medical CenterTianjin 300000China tianjin medical University Tianjin First Center HospitalTianjin 300000China

BACKGROUND Hemolymphangioma of the jejunum is rare and lacks clinical specificity,and can manifest as gastrointestinal bleeding,abdominal pain,and intestinal *** tomography,magnetic resonance imaging,and other examinations show certain characteristics of the disease,but lack *** capsule endoscopy and enteroscopy make up for this deficiency,the diagnosis also still re-quires *** SUMMARY A male patient was admitted to the hospital due to abdominal distension and abdominal pain,but a specific diagnosis by computed tomography examination was not *** resection of the small intestine was performed by robotic surgery,and postoperative pathological biopsy confirmed the diagnosis of *** recurrence in the follow-up examination was *** Robotic surgery is an effective way to treat hemolymphangioma through minima-lly invasive techniques under the concept of rapid rehabilitation.

关键词： Hemolymphangioma Enteroscopy Robotic surgery Rehabilitation Case report

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Interaction between adolescent sleep rhythms and gender in an obese population

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World Journal of Clinical Cases 2024年第1期12卷 86-94页

作者： Nan-Nan Wu Guo-Li Yan Hong-Yu Zhang Ling Sun Min Hou Guang-Ming Xu Department of Laboratory Medicine Tianjin Chest HospitalTianjin 300222China Mental Health center of tianjin medical University Tianjin Anding HospitalTianjin 300222China Department of Child and Adolescent Psychology Mental Health Center of Tianjin Medical UniversityTianjin 300222China

BACKGROUND The obesity rate of adolescents is gradually increasing,which seriously affects their mental health,and sleep plays an important role in adolescent *** To investigate the relationship between sleep rhythm and obesity among adolescents and further explores the interactive effect of sleep rhythm and gender on adolescent obesity,providing a theoretical basis for developing interventions for adolescent *** Research data source tianjin Mental Health Promotion Program for *** April to June 2022,this study selected 14201 students from 13 middle schools in a certain district of tianjin as the research subject using the convenient cluster sampling *** these students,13374 accepted and completed the survey,with an effective rate of 94.2%.The demographic data and basic information of adolescents,such as height and weight,were collected through a general situation *** sleep rhythm of adolescents was evaluated using the reduced version of the morningness-eveningness *** A total of 13374 participants(6629 females,accounting for 49.56%;the average age is 15.21±1.433 years)were *** them,the survey showed that 2942 adolescent were obesity,accounting for 22%and 2104 adolescent were overweight,accounting for 15.7%.Among them,1692 male adolescents are obese,with an obesity rate of 25.1%,higher than 18.9%of female *** is a statistically significant difference between the three groups(χ2=231.522,P<0.000).The obesity group has the smallest age(14.94±1.442 years),and there is a statistical difference in age among the three groups(F=69.996,P<0.000).Obesity rates are higher among individuals who are not-only-child,have residential experience within six months,have family economic poverty,and have evening-type sleep(P<0.05).Logistic regression analysis shows a correlation between sleep rhythm and adolescent ***-type sleep rhythm can increase the risk of obesity in male adoles

关键词： Adolescent Obesity Sleep rhythm Gender Interaction

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Epigenetics:Mechanisms,potential roles,and therapeutic strategies in cancer progression

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Genes & Diseases 2024年第5期11卷 300-314页

作者： Dong Wang Yan Zhang Qingbo Li Yu Li Wen Li Ao Zhang Jingxuan Xu Jingyan Meng Lin Tang Shuhua Lyu Graduate School Tianjin University of Traditional Chinese MedicineTianjin 301617China College of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pathology Tianjin Union Medical CenterTianjin 300121China

Mutations or abnormal expression of oncogenes and tumor suppressor genes are known to cause *** studies have shown that epigenetic modifications are key drivers of cancer development and ***,the mechanistic role of epigenetic dysregulation in the tumor microenvironment is not fully ***,we reviewed the role of epigenetic modifications of cancer cells and non-cancer cells in the tumor microenvironment and recent research advances in cancer epigenetic *** addition,we discussed the great potential of epigenetic combination therapies in the clinical treatment of ***,there are still some challenges in the field of cancer epigenetics,such as epigenetic tumor heterogeneity,epigenetic drug heterogeneity,and crosstalk between epigenetics,proteomics,metabolomics,and other omics,which may be the focus and difficulty of cancer treatment in the *** conclusion,epigenetic modifications in the tumor microenvironment are essential for future epigenetic drug development and the comprehensive treatment of *** combination therapy may be a novel strategy for the future clinical treatment of cancer.

关键词： Cancer Epigenetics Gene expression Heterogeneity Tumor microenvironment

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