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Epigenetic regulation of the inflammatory response in stroke

Neural Regeneration research 2025年第11期20卷 3045-3062页

作者： Jingyi Liang Fei Yang Zixiao Li Qian Li School of Basic Medical Sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina laboratory for clinical Medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China national clinical research center for Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina national center for Healthcare Quality Management in Neurological diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain research BeijingChina research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering research center of Digital Healthcare for Neurological diseases BeijingChina Department of Biochemistry and Molecular biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing key laboratory of cancer Invasion and Metastasis research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment

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Revolutionizing breast cancer detection:Advances in fluorescent probe technology

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Nano research 2025年第1期18卷 653-674页

作者： Qian Gao Lin Tang Jun Zhan Yiyuan Xue Feng Luo state key laboratory of Oral diseases&national center for Stomatology&national clinical research center for Oral diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China Emergency Obstetrics and Gynecology West China Second University HospitalSichuan UniversityChengdu 610041China Department of Obstetrics and Gynecology West China Second University HospitalSichuan UniversityChengdu 610041China Department of Prosthodontics West China School of StomatologySichuan UniversityChengdu 610041China

With the increasing incidence of breast cancer globally,there is an urgent demand for enhanced diagnostic and therapeutic *** comprehensive review explores advancements in fluorescent probe technology for breast cancer imaging and early *** probes offer unparalleled sensitivity and specificity in detecting cancer biomarkers,enabling early diagnosis and delineation of tumor margins during *** categorize these probes into molecular,nano,ratiometric,the second near-infrared window(NIR-II),and multifunctional varieties,each with unique capabilities for targeting specific cancer *** review highlights recent innovations in probe design,emphasizing their applications in pathogenesis studies,drug development,precision medicine,and fluorescence-guided *** their promising clinical potential,challenges such as safety,biomarker targeting accuracy,system compatibility,and clinical translation *** these hurdles is crucial for the integration of fluorescent probes into standard cancer care,aiming to improve treatment outcomes and patient quality of life.

关键词： breast cancer fluorescent probes imaging early diagnosis biomarker

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu state key laboratory of Membrane biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation center for Human Brain Protection and national clinical research center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina state key laboratory of Stem Cell and Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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Portal Hypertension Refractory Ascites Caused by Secondary Hemochromatosis

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Journal of clinical and Translational Hepatology 2023年第4期11卷 987-990页

作者： Jun Tie Wen Yuan Jia Xiaoyuan Gou state key laboratory of cancer biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesXijing HospitalAir Force Medical UniversityXi’anShaanxiChina

We report a patient with refractory ascites because of portal hypertension caused by hemochromatosis secondary to *** our knowledge,this is the first well-documented case of this association.A 46-year-old male patient who was repeatedly infused with red blood cells for anemia secondary to osteopetrosis suffered from refractory *** serum-ascites albumin gradient was 29.9 g/*** computed tomography(CT)showed a large amount of ascites,hepatomegaly,and *** marrow biopsy showed a small bone marrow cavity with no hematopoietic tissue.A peripheral blood smear showed tear drop red blood cells and *** ferritin was 8,855.0 ng/***,we considered that the ascites resulted from portal hypertension caused by hemochromatosis secondary to *** simultaneously performed the transjungular intrahepatic portal-systemic shunt(TIPS)and obtained a transjungular liver *** portal pressure gradient before TIPS was 28 mmHg,and iron staining was strongly positive on liver biopsy,which confirmed our *** TIPS,both abdominal distention and ascites gradually resolved,and no recurrence as observed after the 12-month postoperative follow-up was *** case indicated that regular monitoring of iron load is important for patients with *** is safe and effective for portal hypertension complications due to osteopetrosis.

关键词： Refractory ascites Secondary hemochromatosis Osteopetrosis Transjugular intrahepatic portosystemic shunt Case report

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DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways

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cancer Communications 2018年第1期38卷 474-487页

作者： Feng Du Lina Sun Yi Chu Tingyu Li Chao Lei Xin Wang Mingzuo Jiang Yali Min Yuanyuan Lu Xiaodi Zhao Yongzhan Nie Daiming Fan state key laboratory of cancer biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical University127 Chang Le West RoadXi’an 710032China

Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in *** damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses;however,its critical role in GC remains poorly *** present study aimed to investigate the poten-tial relationship and the underlying mechanism between DDIT4 and GC ***:We used western blotting,real-time polymerase chain reaction,and immunohistochemical or immunoflu-orescence to determine DDIT4 expression in GC cells and ***-content screening,cell counting kit-8 assays,colony formation,and in vivo tumorigenesis assays were performed to evaluate cell *** cytometry was used to investigate cell apoptosis and cell cycle ***:DDIT4 was upregulated in GC cells and ***,downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle *** contrast,ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated *** analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation,and increased chemosensitivity upon DDIT4 ***:DDIT4 promotes GC proliferation and tumorigenesis,providing new insights into the role of DDIT4 in the tumorigenesis of human GC.

关键词： DNA damage-inducible transcript 4 Gastric cancer Proliferation Mitogen-activated protein kinase p53

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Bariatric surgery induces alterations in effective connectivity between the orbitofrontal cortex and limbic regions in obese patients

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Science China(Information Sciences) 2020年第7期63卷 49-59页

作者： Shijun DUAN Gang JI Guanya LI Yang HU Wenchao ZHANG Jia WANG Dardo TOMASI Nora D.VOLKOW Yongzhan NIE Guangbin CUI Gene-Jack WANG Yi ZHANG Department of Radiology Tangdu Hospital Fourth Military Medical University state key laboratory of cancer biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases Fourth Military Medical University center for Brain Imaging School of Life Science and Technology Xidian University laboratory of Neuroimaging National Institute on Alcohol Abuse and Alcoholism

Obese subjects show enhanced brain responses in motivation and reward neurocircuitry encompassing sensory and somatic integration-interception, motivation-reward(striatal), emotion, and memory processes, which attenuate frontal region activation during food cues. Bariatric surgery(BS) is the only reliable treatment for morbid obesity. Unfortunately, it is unknown how BS affects neurocircuitry after weight loss. We aimed to examine effects of BS on the basal activity of brain areas involved in reward and motivation processing, emotion, memory, and gut-brain interaction. We combined resting-state fMRI with amplitude of low-frequency fluctuation(ALFF) and Granger causality analysis(GCA) to assess interactions between regions within the frontal-mesolimbic circuitry in 16 obese subjects(OB) and 22 normal-weight(NW) *** OB group was studied at baseline and 1 month post BS. Comparisons between OB and NW, and preand post BS showed significant differences in ALFF in areas involved in drive(caudate, orbitofrontal cortex(OFC)), arousal(thalamus), and conditioning/memory(amygdala, hippocampus)(P < 0.05, FDR correction). GCA revealed that in the OB group, the OFC had greater connectivity to limbic regions(amygdala,hippocampus, and medial thalamus) and the caudate. Post BS, the connectivity of the OFC to limbic regions decreased, whereas the connectivity from the amygdala and hippocampus to the caudate and thalamus was enhanced, particularly in subjects with lower body mass index(BMI). OFC activation in the OB group was associated with BMI prior to surgery, and changes in OFC post surgery were associated with alterations in BMI. Overall, the functional connectivity of the OFC was significantly decreased. As it is important for salience attribution and connected to limbic brain regions involved with emotional reactivity and conditioning after BS, its significant association with BMI changes indicates the contribution of OFC changes to the improved control of eating behavi

关键词： fMRI Granger causality analysis obesity bariatric surgery frontal-mesolimbic

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Biological properties and clinical applications of berberine

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Frontiers of Medicine 2020年第5期14卷 564-582页

作者： Danyang Song Jianyu Hao Daiming Fan Department of Gastroenterology Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China state key laboratory of cancer biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'an 710032China

Berberine,an isoquinoline alkaloid isolated from the Chinese herb Coptis chinens is and other Berber is plants,has a wide range of pharmacological *** can be used to treat many diseases,such as cancer and digestive,metabolic,cardiovascular,and neurological *** has protective capacities in digestive *** can inhibit toxins and bacteria,including Helicobac terpylo riprotect the intestinal epithelial barrier from injury,and ameliorate liver *** also inhibits the proliferation of various types of cancer cells and impedes invasion and *** evidence has confirmed that berberine improves the efficacy and safety of *** addition,berberine regulates glycometabolism and lipid metabolism,improves energy expenditure,reduces body weight,and alleviates nonalcoholic fatty liver *** also improves cardiovascular hemodynamics,suppresses ischemic arrhythmias,attenuates the development of atherosclerosis,and reduces *** shows potent neuroprotective effects,including antioxidative,antiapoptotic,and ***,berberine exerts protective effects against other *** mechanisms of its functions have been extensively explored,but much remains to be *** article summarizes the main pharmacological actions of berberine and its mechanisms in cancer and digestive,metabolic,cardiovascular,and neurological diseases.

关键词： berberine Coptis chinensis pharmacological properties mechanism clinical applications

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS key laboratory of Translational research on Lung cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and cancer (IBMC) Chinese Academy of Sciences Department of clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractionclinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing key laboratory of Carcinogenesis and Translational research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal cancer center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University key laboratory of Carcinogenesis and cancer Invasion Ministry of Education state key laboratory of Holistic Integrative Management of Gastrointestinal cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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BTF3L4 Overexpression Mediates APAP-induced Liver Injury in Mouse and Cellular Models

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Journal of clinical and Translational Hepatology 2024年第3期12卷 245-256页

作者： Junchao Lin Aqiang Fan Zhujin Yifu Qibing Xie Liu Hong Wei Zhou state key laboratory of cancer biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesAir Force Military Medical UniversityXi’anShaanxiChina Department of digestive Surgery Xijing HospitalAir Force Military Medical UniversityXi’anShaanxiChina

Background and Aims:Acetaminophen(APAP)-induced liver injury(AILI)has an increasing incidence ***,the mechanisms contributing to such liver injury are largely unknown and no targeted therapy is currently *** study aimed to investigate the effect of BTF3L4 overexpression on apoptosis and inflammation regulation in vitro and in ***:We performed a proteomic analysis of the AILI model and found basic transcription factor 3 like 4(BTF3L4)was the only outlier transcription factor overexpressed in the AILI model in ***3L4 overexpression increased the degree of liver injury in the AILI ***:BTF3L4 exerts its pathogenic effect by inducing an inflammatory response and damaging mitochondrial *** BTF3L4 expression increases the degree of apoptosis,reactive oxygen species generation,and oxidative stress,which induces cell death and liver *** damage of mitochondrial function by BTF3L4 triggers a cascade of events,including reactive oxygen species accumulation and oxidative *** to the available AILI data,BTF3L4 expression is positively associated with inflammation and may be a potential biomarker of ***:Our results suggest that BTF3L4 is a pathogenic factor in AILI and may be a potential diagnostic maker for AILI.

关键词： BTF3L4 APAP-induced liver injury Apoptosis Mitochondrial morphology Inflammation

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