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Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning Zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi Zhang Yu-Ying Tan Li Zhang Wen-Tao Jiang School of Medicine Nankai UniversityTianjin 300192China tianjin key Laboratory of Molecular Diagnosis and Treatment of Liver cancer Tianjin First Center HospitalTianjin 300192China Department of Liver Transplantation Tianjin First Center HospitalTianjin 300192China First Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion Tumor immune microenvironment Apoptosis

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Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

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Neural Regeneration Research 2025年第4期20卷 990-1008页

作者： Lan Zhang Jingge Wei Xilei Liu Dai Li Xiaoqi Pang Fanglian Chen Hailong Cao Ping Lei Haihe Laboratory of Cell Ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina Department of Urology Tianjin Medical University General HospitalTianjinChina tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent *** is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of *** microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive *** article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative *** article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial ***,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s *** findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

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Clinicopathologic and molecular characteristics of 44 patients with pure secretory breast carcinoma

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cancer Biology & Medicine 2019年第1期16卷 139-146页

作者： Lijuan Li Nan Wu Fangxuan Li Lingmei Li Lijuan Wei Juntian Liu Department of cancer prevention Center Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer Key Laboratory of Breast Cancer Prevention and Therapy Tianjin Medical UniversityMinistry of Education Department of Pathology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer Key Laboratory of Breast Cancer Prevention and Therapy Tianjin Medical UniversityMinistry of Education

Objective: Secretory breast carcinoma(SBC) is a rare type of breast malignancy, accounting for less than 0.02% of all infiltrating breast malignancies. The pure SBC, a type of SBC without another type of breast malignant neoplasm, is particularly rare. This study aimed to investigate the clinicopathologic and molecular features of pure ***: The main pathological parameters such as estrogen receptor(ER), progesterone receptor(PR), and human epithelial growth factor receptor 2(C-erbB-2) were detected by immunohistochemistry(IHC), and the clinicopathologic and prognostic difference were compared with invasive ductal carcinoma(IDC). Fluorescent in situ hybridization(FISH) and reverse transcription polymerase chain reaction(RT-PCR) was performed to identify the ETV6-NTRK3 rearrangement of ***: We found that the positivity rates of ER, PR, C-erbB-2, p53, and S-100 were 47.7%(21/44), 52.3%(23/44), 36.4%(16/44), 27.3%(12/44), and 95.5%(42/44), respectively, which were higher than those reported in previous studies. Special periodic acid-Schiff analysis was performed in 36 patients, and the value of the Ki-67 index ranged from 1% to 50%(mean value:10%). Interestingly, most patients with pure SBC harbored an ETV6-NTRK3 rearrangement with an 88.6%(39/44) expression rate. Compared with IDC, the tumor size of most patients with SBC was larger than 2 cm(P = 0.024). Ultrasound showed benign lesions, and the total misdiagnosis rate was higher(P = 0.020). Although the pathological classification was mostly triple-negative breast cancers(P = 0.036), there was less metastasis(P = 0.029), and the overall prognosis was better than that of the IDC ***: Although axillary lymph node metastasis, local recurrence, or distant metastasis may occur, SBC is also considered an indolent neoplasm with a good prognosis. Once diagnosed, surgical treatment should be performed as soon as possible,followed by appropriate adjuvant chemotherapy, irradiation, and endocrine the

关键词： Breast cancer pure secretory breast carcinoma clinicopathologic feature therapeutics and prognosis

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Progress of research in the application of ultrasound technology for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2823-2837页

作者： Qiuquan Cai Lianghui Meng Meina Quan Ling Wang Jing Ren Chenguang Zheng Jiajia Yang Dong Ming Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Innovation Center for Neurological Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Brain-Computer Interaction and Human-Machine Fusion Haihe Laboratory Tianjin UniversityTianjinChina tianjin key Laboratory of Brain Science and Neural Engineering Tianjin UniversityTianjinChina

Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive *** presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s *** use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent *** a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive *** article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound *** is placed on the benefits of introducing these treatment methods and their potential *** found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque *** believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.

关键词： Alzheimer’s disease blood-brain barrier drugs magnetic resonance imaging-guided focused ultrasound microbubbles scanning ultrasound ultrasound ultrasound stimulation

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Function of Slit/Robo signaling in breast cancer

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Frontiers of Medicine 2015年第4期9卷 431-436页

作者： Feng Gu Yongjie Ma Jiao Zhang Fengxia Qin Li Fu tianjin Medical University cancer Institute and Hospital National Clinical Research Center of CancerKey Laboratory of Breast Cancer Prevention and Therapy of the Ministry of Education key Laboratory of cancer prevention and therapy of tianjin Tianjin 300060China

Slit and Robo are considered tumor suppressors because they are frequently inactivated in various tumor tissue. These genes are closely correlated with CpG hypermethylation in their promoters. The Slit/Robo signaling pathway is reportedly involved in breast cancer development and metastasis. Overexpression of Slit/ Robo induces its tumor suppressive effects possibly by inactivating the β-catenin/LEF/TCF and PI3K/Akt signaling pathways or by altering β-catenin/E-cadherin-mediated cell-cell adhesion in breast cancer cells. Furthermore, loss of Slit proteins or their Robo receptors upregulates the CXCL12/CXCR4 signaling axis in human breast carcinoma. In addition, this pathway regulates the distant migration of breast cancer cells not only by mediating the phosphorylation of the downstream molecules of CXCL12/CXCR4 and srGAPs, such as PI3K/ Src, RAFTK/Pyk2, and CDC42, but also by regulating the activities of MAP kinases. This review includes recent studies on the functions of Slit/Robo signaling in breast cancer and its molecular mechanisms.

关键词： Slit/Robo hypermethylation β-catenin CXCL12/CXCR4 migration

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Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

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Neural Regeneration Research 2025年第8期20卷 2153-2168页

作者： Xinyu You Lin Niu Jiafeng Fu Shining Ge Jiangwei Shi Yanjun Zhang Pengwei Zhuang National key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Haihe Laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina First Teaching Hospital of tianjin University of Traditional Chinese Medicine TianjinChina National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina

Traumatic brain injury is a prevalent disorder of the central nervous *** addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are *** dysfunction is a significant consequence of traumatic brain *** the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous *** gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated *** comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut ***,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain *** review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effec

关键词： traumatic brain injury brain-gut-microbiome axis gut microbiota neuroimmune immunosuppression host defense vagal afferents bacterial infection dorsal root ganglia nociception neural circuitry

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Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis

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Frontiers of Medicine 2021年第5期15卷 649-656页

作者： Jingyue Zhang Yawen Song Qianqian Shi Li Fu tianjin Medical University cancer Institute and Hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Breast Cancer Prevention and TherapyTianjin Medical universityMinistry of EducationTianjin 300060China

Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism,which is manifested by increased endogenous fat mobilization,hypertriglyceridemia,and increased fatty acid *** acid synthase(FASN)is a key enzyme for the de novo synthesis of fatty acids,and monoacylglycerol esterase(MGLL)is an important metabolic enzyme that converts triglycerides into free fatty *** enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways,the most common of which is the PI3K–AKT signaling *** can also regulate the immune microenvironment,participate in epithelial–mesenchymal transition,and then regulate tumor invasion and *** literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and *** article introduces the structures and functions of FASN and MGLL,their relationship with abnormal lipid metabolism,and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.

关键词： FASN MGLL lipid metabolism tumor invasion metastasis

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Silencing of syndecan-binding protein enhances the inhibitory effect of tamoxifen and increases cellular sensitivity to estrogen

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cancer Biology & Medicine 2018年第1期15卷 29-38页

作者： Jun Zhang Xiaolong Qian Fangfang Liu Xiaojing Guo Feng Gu Li Fu department of breast cancer tianjin medical university cancer institute and hospital national clinical research center for cancerkey laboratory of cancer prevention and therapytianjintianjin's clinical research center for cancerkey laboratory of breast cancer prevention and therapy ministry of education Tianjin 300060 China

Objective:Tamoxifen is used as a complementary treatment for estrogen receptor(ER)-positive breast cancer(BCa),but many patients developed *** aim of this study was to examine the role of syndecan-binding protein(SDCBP)silencing in ER-positive BCa ***:In MCF-7/T47D cells,the effects of SDCBP silence/overexpression on cell proliferation and estrogenic response were *** proliferation was examined using the MTT assay and cell cycle regulators were examined by Western *** response was examined from a luciferase activity and evaluation of transcript levels of p S2 and progesterone receptor(PR)upon estrogen *** of ER-positive BCa were stained with ERα,PR,and SDCBP antibodies,and their expression correlations were ***:We found that SDCBP silencing inhibited the proliferation of ER-positive BCa cells and arrested a greater number of cells in the G1 phase of the cell cycle compared to tamoxifen alone,while SDCBP overexpression limited the anti-cancer effects of *** silencing and overexpression also enhanced and attenuated the estrogenic response,*** of SDCBP was negatively correlated with PR,ERα,and the PR/ERαratio in ER-positive BCa tissue ***:SDCBP may be involved in tamoxifen resistance in ER-positive *** treatment combined with SDCBP silencing may provide a novel treatment for endocrine therapy-resistant BCa.

关键词： Syndecan-binding protein(SDCBP) tamoxifen breast cancer endocrine-therapy resistance

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Artificial intelligence-based comprehensive analysis of immune-stemness-tumor budding profile to predict survival of patients with pancreatic adenocarcinoma

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cancer Biology & Medicine 2023年第3期20卷 196-217页

作者： Tianxing Zhou Quan Man Xueyang Li Yongjie Xie Xupeng Hou Hailong Wang Jingrui Yan Xueqing Wei Weiwei Bai Ziyun Liu Jing Liu Jihui Hao Department of Pancreatic cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Department of Hepatopancreatobiliary Surgery Tongliao City HospitalTongliao 028000China Department of Breast Oncoplastic Surgery Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerKey Laboratory of Breast Cancer Prevention and TherapyTianjin Medical UniversityMinistry of EducationTianjin 300060China Department of cancer Cell Biology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerKey Laboratory of Breast Cancer Prevention and TherapyTianjin Medical UniversityMinistry of EducationTianjin 300060China Department of Diagnostic and Therapeutic Ultrasonography Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerKey Laboratory of Breast Cancer Prevention and TherapyTianjin Medical UniversityMinistry of EducationTianjin 300060China

Objective:Pancreatic ductal adenocarcinoma(PDAC)is an aggressive ***8^(+)T cells,cancer stem cells(CSCs),and tumor budding(TB)have been significantly correlated with the outcome of patients with PDAC,but the correlations have been independently *** addition,no integrated immune-CSC-TB profile for predicting survival in patients with PDAC has been ***:Multiplexed immunofluorescence and artificial intelligence(AI)-based comprehensive analyses were used for quantification and spatial distribution analysis of CD8^(+)T cells,CD133^(+)CSCs,and *** vivo humanized patient-derived xenograft(PDX)models were *** analysis,calibration curve,time-dependent receiver operating characteristic curve,and decision curve analyses were performed using R ***:The established‘anti-/pro-tumor’models showed that the CD8^(+)T cell/TB,CD8^(+)T cell/CD133^(+)CSC,TB-adjacent CD8^(+)T cell,and CD133^(+)CSC-adjacent CD8^(+)T cell indices were positively associated with survival of patients with *** findings were validated using PDX-transplanted humanized mouse *** integrated nomogram-based immune-CSC-TB profile that included the CD8^(+)T cell/TB and CD8^(+)T cell/CD133^(+)CSC indices was established and shown to be superior to the tumor-nodemetastasis stage model in predicting survival of patients with ***:‘Anti-/pro-tumor’models and the spatial relationship among CD8^(+)T cells,CSCs,and TB within the tumor microenvironment were *** strategies to predict the prognosis of patients with PDAC were established using AI-based comprehensive analysis and machine learning *** nomogram-based immune-CSC-TB profile can provide accurate prognosis prediction for patients with PDAC.

关键词： Artificial intelligence CD8 CSCs tumor budding PDAC nomogram

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Crucial role of Anxa2 in cancer progression:highlights on its novel regulatory mechanism

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cancer Biology & Medicine 2019年第4期16卷 671-687页

作者： Tong Wang Zhiyong Wang Ruifang Niu Liang Wang Second Department of Breast Tumor Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Breast Cancer Prevention and TherapyMinistry of EducationKey Laboratory of Cancer Prevention and Therapy TianjinTianjin's Clinical Research Center for CancerTianjin 300060China Public Laboratory Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Breast Cancer Prevention and TherapyMinistry of EducationKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China Modern Distance Education College Nankai UniversityTianjin 300071China

Anxa2 is the most studied member of the calcium-mediated phospholipid-binding protein family annexins and is a biomarker in *** this review,we listed clinical findings and confirmed the value of Anxa2 in early diagnosis and prognostic prediction due to its overexpression and adverse effect on the outcome in most ***2 plays a pivotal role in cancer cell proliferation,migration,invasion,metastasis,and treatment *** understanding of its cancer-promoting function might make it an ideal target for cancer ***,we systematically summarized the mechanism of Anxa2 in regulating epithelialmesenchymal transition(EMT),cytoskeleton dynamicity,cell cycle,apoptosis,angiogenesis,and immunology by using various tumor *** data emphasize the potential of Anxa2 for targeted intervention in *** Anxa2 expression,neutralizing the cell surface Anxa2,or inhibiting its activation,such as through Tyr23 phosphorylation,could be considered based on the regulatory mechanism of Anxa2 in tumor progression.

关键词： Anxa2 cancer diagnosis prognosis metastasis treatment resistance

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