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Lkb1 orchestrates γδ T-cell metabolic and functional fitness to control IL-17-mediated autoimmune hepatitis

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Cellular & Molecular Immunology 2024年第6期21卷 546-560页

作者： Zhiqiang Xiao Shanshan Wang Liang Luo Wenkai Lv Peiran Feng Yadong Sun Quanli Yang Jun He Guangchao Cao Zhinan Yin Meixiang Yang Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment Zhuhai Institute of Translational MedicineZhuhai People’s Hospital Affiliated with Jinan UniversityJinan UniversityZhuhai519000China The Biomedical Translational Research Institute School of MedicineJinan UniversityGuangzhou510632China Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction The Fifth Affiliated Hospital(Heyuan Shenhe People’s Hospital)Jinan UniversityHeyuan517000China Key Laboratory of Ministry of Education for Viral Pathogenesis&Infection Prevention and Control(jinan University).Guangzhou Key Laboratory for Germ-Free Animals and Microbiota Application.Institute of Laboratory Animal Science School of MedicineJinan UniversityGuangzhou510632China

γδT cells play a crucial role in immune surveillance and serve as a bridge between innate and adaptive ***,the metabolic requirements and regulation ofγδT-cell development and function remain poorly *** this study,we investigated the role of liver kinase B1(Lkb1),a serine/threonine kinase that links cellular metabolism with cell growth and proliferation,inγδT-cell *** findings demonstrate that Lkb1 is not only involved in regulatingγδT lineage commitment but also plays a critical role inγδT-cell effector ***,T-cell-specific deletion of Lkb1 resulted in impaired thymocyte development and distinct alterations inγδT-cell subsets in both the thymus and peripheral lymphoid ***,loss of Lkb1 inhibited the commitment of Vγ1 and Vγ4γδT cells,promoted the maturation of IL-17-producing Vγ6γδT cells,and led to the occurrence of fatal autoimmune hepatitis(AIH).Notably,clearance ofγδT cells or blockade of IL-17 significantly attenuated ***,Lkb1 deficiency disrupted metabolic homeostasis and AMPK activity,accompanied by increased mTORC1 activation,thereby causing overactivation ofγδT cells and enhanced ***,activation of AMPK or suppression of mTORC1 signaling effectively inhibited IL-17 levels and attenuated AIH in Lkb1-deficient *** findings highlight the pivotal role of Lkb1 in maintaining the homeostasis ofγδT cells and preventing IL-17-mediated autoimmune diseases,providing new insights into the metabolic programs governing the subset determination and functional differentiation of thymicγδT cells.

关键词： Lkb1 γδT cell Autoimmune hepatitis IL-17 Metabolic quiescence

Astragaloside Ⅳ Improves Angiogenesis and Promotes Wound Healing in Diabetic Rats via the Activation of the SUMOylation Pathway

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Biomedical and Environmental Sciences 2021年第2期34卷 124-129页

作者： WANG Bao Shen MA Xiao Fang ZHANG Chun Yan LI Yan Xia LIU Xiao Zhi HU Chang Qing Department of Cardiovascular Surgery The No.1 Central Hospital of Baoding CityBaoding 071000HebeiChina Central Laboratory The Fifth Central Hospital of TianjinTianjin 300450China Tianjin Key Laboratory of Epigenetics for Organ Development in Preterm Infants The Fifth Central Hospital of TianjinTianjin 300450China Department of Pharmacy Tianjin Binhai New Area Hospital of Traditional Chinese MedicineTianjin 300450China The fifth Orthopaedics Department The No.1 Central Hospital of Baoding CityBaoding 071000HebeiChina

Radix astragali is the dried root of the legume Mongolian Astragalus or Astragalus membranaceus~([1]). Modern research has found that the main active ingredients in astragalus are astragalus polysaccharides, astragaloside, and astragalus isoflavones. Astragaloside IV(AS-IV) has been used internationally as a standard for evaluating the quality of astragalus medicinal materials.

关键词： Radix Wound dried

Ipsilateral synchronous papillary and clear renal cell carcinoma:A case report and review of literature

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World Journal of Clinical Cases 2022年第16期10卷 5428-5434页

作者： Jing Yin Mo Zheng Department of Pathology The Fifth Central Hospital of TianjinBinhai New AreaTianjin 300450China

BACKGROUND There is limited information on ipsilateral synchronous papillary renal cell carcinoma(PRCC)and clear cell renal cell carcinoma(CCRCC).Therefore,these rare tumors are often misdiagnosed preoperatively as a single tumor with intrarenal metastasis or some other *** management and long-term overall survival might be affected because the prognosis of the two tumors *** SUMMARY We describe a case of ipsilateral synchronous PRCC and CCRCC with two histological variants in a 72-year-old man,whose mass was found incidentally,with no other chief complaints and vital signs were *** ultrasound revealed a hypoechoic lobular mass with a volume of 7.8 cm×4.8 cm×2.8 cm in the middle to lower pole of the left kidney.A subsequent contrast-enhanced computed tomography scan showed a single endophytic mass of 7.5 cm in *** patient underwent laparoscopic left radical nephrectomy.A final diagnosis of ipsilateral synchronous PRCC and CCRCC was confirmed by pathological *** was no recurrence or metastasis after 25 mo *** We report a case of ipsilateral synchronous PRCC and CCRCC,and review related literature to estimate the prevalence of similar *** above descriptions may be expected to help understand the disease,and improve diagnosis in the future.

关键词： Clear cell renal cell carcinoma Papillary renal cell carcinoma Ipsilateral tumor Synchronous tumor Kidney Case report

Dl-3-n butylphthalide attenuates brain injury caused by cortical infarction accompanied by cranial venous drainage disturbance

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Stroke & Vascular Neurology 2022年第3期7卷 222-236页

作者： Kangping Song Xiuli Zeng Xiaomei Xie Rongxuan Zhu Jianye Liang Guobing Chen Li’an Huang Department of Neurology Jinan University First Affiliated HospitalGuangzhouChina Medical Imaging Center Jinan University First Affiliated HospitalGuangzhouChina Institute of Geriatric Immunology Medical college of Jinan UniversityGuangzhouChina

Background Cerebral venous disorder may have a harmful effect on ischaemic stroke;however,the underlying mechanism remains to be *** Dl-3-n butylphthalide is a multitarget agent for antiischaemic stroke,its neuroprotective role in brain ischaemia accompanied by brain venous disturbance remains *** this study,we induced cerebral venous disturbance by the occlusion of bilateral external jugular veins(EJVs)to explore the potential mechanism of the adverse effects of cerebrovenous disorders in cerebral infarction and explore the protective effect of Dl-3-n butylphthalide on cerebral infarction accompanied through cerebral venous *** Cerebral venous disturbance was induced in Sprague-Dawley rats through the permanent occlusion of bilateral EJVs,and cerebral ischaemic stroke was induced through the permanent occlusion of the right cortical branches of the middle cerebral artery.2,3,5-triphenyltetrazolium chloride staining,MRI,Evans blue extravasation and behavioural test were performed to evaluate infarction volume,cerebral blood flow(CBF),blood-brain barrier(BBB)integrity and neurological *** staining and western blot analysis were performed to detect loss of neuron,endothelial cells,pericytes and tight *** Bilateral EJVs occlusion did not cause cerebral infarction;however,it increased the infarction volume compared with the simple middle cerebral artery occlusion(MCAO)group,accompanied by severe neuron loss,worse neurological function,lower CBF,increased EJVs pressure,exacerbated Evans blue extravasation and brain oedema,as well as attenuated ***-3-n butylphthalide displayed a neuroprotective effect in rats with MCAO accompanied by EJVs occlusion by reducing neuron loss,accelerating CBF restoration,promoting angiogenesis and relieving BBB *** Bilateral EJVs occlusion did not significantly affect normal rats but aggravated brain damage in the case of ischaemic ***

关键词： protective infarction disturbance

Vitreous amyloidosis caused by a Lys55Asn variant in transthyretin: A case report

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World Journal of Clinical Cases 2022年第32期10卷 12000-12006页

作者： Yue Tan Yuan Tao Yan-Juan Sheng Chen-Ming Zhang Department of Ophthalmology The Jinan Second People’s HospitalJinan 250000Shandong ProvinceChina

BACKGROUND Amyloidosis is caused by misfolding of proteins and is characterized by formation of extracellular aggregates of insoluble *** primary effects in the eye include sharp deterioration of visual acuity as a result of vitreous *** to the local and systemic distribution characteristics of amyloid deposits and their fibrin components,amyloidosis can be classified as primary,secondary or ***,we report a typical case of vitreous amyloidosis in hereditary transthyretin amyloidosis(hATTR)to improve ophthalmologists’understanding of the disease and reduce misdiagnosis and *** SUMMARY The patient was a 49-year-old man who complained of progressive visual decline in both eyes over a 2-mo *** systemic diseases such as diabetes or hypertension were reported,and no obvious family history of disease was *** patient’s visual acuity was HM/10 cm in the right eye and 0.06 in the left *** had a transparent cornea in both eyes,with a normal anterior depth,clear aqueous humor,no obvious iris abnormalities,round pupils of approximately 3 mm in diameter,normal direct and indirect light reflexes,and normal intraocular *** various examinations,the patient was diagnosed with binocular vitreous amyloidosis secondary to hATTR associated with a Lys55Asn variant in *** binocular visual acuity recovered to 1.0 after binocular *** Vitreous amyloidosis is rare in the clinic and gene testing can assist the diagnosis accurately and effectively.

关键词： Vitreous amyloidosis Transthyretin Lys55Asn variant Vitrectomy Case report

Mechanical thrombectomy for acute occlusion of the posterior inferior cerebellar artery: A case report

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World Journal of Clinical Cases 2021年第10期9卷 2268-2273页

作者： Hong-Bo Zhang Pian Wang Yan Wang Jiang-Hong Wang Zheng Li Rong Li Department of Neurology Chengdu Fifth People's HospitalChengdu 611130Sichuan ProvinceChina

BACKGROUND Mechanical thrombectomy(MT)has been demonstrated to be useful for the treatment of ischemic stroke in patients with large vessel ***,recanalization by MT is not recommended for distal vessels such as second-order branches of the middle cerebral artery and posterior inferior cerebellar artery(PICA).Because of the small size and tortuosity of these arteries,the risks of using the available endovascular devices outweigh the benefits of ***,MT appears to be effective in patients with primary distal vessel occlusion in eloquent areas,those with a high National Institutes of Health Stroke Scale score,and those ineligible for recombinant tissue plasminogen activator ***,we report the use of MT for treating acute occlusion of the PICA using a directaspiration first-pass technique(ADAPT).CASE SUMMARY In this case,the patient received acute occlusion of the PICA with ADAPT when right internal carotid artery stenting was *** With the introduction of advanced endovascular devices,MT may now be a feasible treatment for acute occlusion of the PICA.

关键词： Posterior inferior cerebellar artery Mechanical thrombectomy Ischemic stroke Carotid artery stent Neurovascular interventions Case report

New Insight into Microvascular Perfusion by Analyzing Pipe Flow in a Cylindrical Elastic Shell

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Journal of Biomedical Science and Engineering 2018年第9期11卷 247-253页

作者： Yanchun Hu Anming Hu Shenju Song Yanxia Hu Department of Orthopaedics The Fifth People’s Hospital Jinan China Shandong Experimental High School Jinan China Department of Nursing The Fifth People’s Hospital Jinan China Department of Infectious Diseases Center for Disease Control and Prevention Jinan China

Background: Microvascular perfusion, a kind of regional perfusion, plays important roles in delivering oxygen and nutrients, and regulating blood pressure and responses to inflammation. Aim: The aim of this research is to analyze the characteristics of microvascular perfusion by conducting pipe flow in a circular elastic tube. Methods: A model was established with circular elastic tube to mimic microvascular perfusion. The velocity of pressure waves was calculated according to the time that the liquid took to spilt over. What’s more, the characteristics and significance of microvascular flow and arteriovenous anastomoses (AVAs) were analyzed. Results: It took the liquid about 0.1 second to spill over from the model, and the velocity of pressure waves is greater than 100 m/s in the elastic pipe. A mechanical switch structure and the corresponding mechanism were proposed for microvascular perfusion in AVAs. Conclusion: Microvascular perfusion maintains a considerable constancy of hemodynamics in different tissues, when ventricular contraction changes perfusion pressure to meet metabolic demands appropriately. This theory will help us to gain a new perspective in microvascular flow.

关键词： Microvascular Perfusion Hypertension Cylindrical Elastic Shell Fluid Flow

HLA-mismatched allogeneic adoptive immune therapy in severely immunosuppressed AIDS patients

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Signal Transduction and Targeted Therapy 2021年第6期6卷 1780-1787页

作者： Ruonan Xu Ji-Yuan Zhang Bo Tu Zhe Xu Hui-Huang Huang Lei Huang Yan-Mei Jiao Tao Yang Chao Zhang En-Qiang Qin Tian-Jun Jiang Yun-Bo Xie Yuan-Yuan Li Lei Jin Chun-Bao Zhou Ming Shi Mei Guo Hui-Sheng Ai Linqi Zhang Fu-Sheng Wang Treatment and Research Center for Infectious Diseases The Fifth Medical CenterPLA General HospitalBeijingChina Department of Hematology and Transplantation The Fifth Medical CenterPLA General HospitalBeijingChina Comprehensive AIDS Research Center School of MedicineTsinghua UniversityBeijingChina

Severely immunosuppressed AIDS patients with recurrent opportunistic infections(Ols)represent an unmet medical need even in the era of antiretroviral therapy(ART).Here we report the development of a human leukocyte antigen(HLA)-mismatched allogeneic adaptive immune therapy(AAIT)for severely immunosuppressed AIDS *** severely immunosuppressed AIDS patients with severe Ols were enrolled in this single-arm *** donors received subcutaneous recombinant granulocyte-colony-stimulating factor twice daily for 4-5 days to stimulate *** blood mononuclear cells were collected from these donors via leukapheresis and transfused into the coupled ***,immunological,and virological parameters were monitored during a 12-month follow-up *** found AAIT combined with ART was safe and well-tolerated at the examined doses and transfusion regimen in all 12 *** in clinical symptoms were evident throughout the study *** patients exhibited a steady increase of peripheral CD4^(+)T cells from a median 10.5 to 207.5 cells/μ*** increase in peripheral CD8^(+)T-cell count from a median 416.5 to 1206.5 cells/μl was found in the first 90 days since initiation of *** addition,their inflammatory cytokine levels and HIV RNA viral load decreased.A short-term microchimerism with donor cells was *** were no adverse events associated with graft-versus-host disease throughout the study ***,AAIT treatment was safe,and might help severely immunosuppressed AIDS patients to achieve a better immune restoration.A further clinical trial with control is necessary to confirm the efficacy of AAIT medication.

关键词： patients doses transfusion

EHMT2 (G9a) activation in mantle cell lymphoma and its associated DNA methylation and gene expression

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Cancer Biology & Medicine 2022年第6期19卷 836-849页

作者： Jun Wang Hui Xu Shuang Ge Chaoshuai Xue Hailing Li Xiaotong Jing Ke Liang Xiaoying Zhang Cuijuan Zhang International License institute of Pathology and Pathophysiology Shandong University School of MedicineJinan 250012China Department of Pathology Qianfoshan HospitalJinan 250300China Department of Pathology Qilu Hospital of Shandong UniversityJinan 250012China

Objective:The function of euchromatic histone-lysine N-methyltransferase 2(EHMT2)has been studied in several cancers;however,little is known about its role in mantle cell lymphoma(MCL).Thus,this study aimed to characterize the significance and function of EHMT2 in ***:EHMT2 expression in MCL and reactive hyperplasia(RH)were investigated by ***-wide analysis of DNA methylation was performed on EHMT2+MCL *** function of EHMT2 was determined by CCK&flow cytometry,and western blot *** expression profile analysis was performed before and after EHMT2 knockdown to search for EHMT2-regulated ***-immunoprecipitation(Co-IP)experiments were conducted to identify the proteins interacting with ***:EHMT2 was expressed in 68.57%(24/35)of MCLs but not in any ***-wide analysis of DNA methylation on EHMT2+MCLs revealed that multiple members of the HOX,FOX,PAX,SOX,and CDX families were hypermethylated or hypomethylated in EHMT2+***0I294,a EHMT2 inhibitor,inhibited MCL cell growth and stalled cells in the G1 ***,BIX01294 downregulated the expressions of cell cycle proteins,cyclin DI,CDK4,and P21,but upregulated the expressions of apoptosis-related proteins,Bax and ***-IP experiments revealed that EHMT2 interacted with UHRF1,HDAC1,and HDAC2 but not with *** EHMT2 knockdown,multiple genes were regulated,including CD5 and CCND1,mostly enriched in the Tec kinase signaling *** addition,several genes(e.g.,MARCH 1,CCDC50,HIP1,and WNT3)were aberrantly methylated in EHMT2+***:For the first time,we determined the significance of EHMT2 in MCL and identified potential EHMT2-regulated genes.

关键词： DNA methylation mantle cell lymphoma epigenetic biomarker EHMT2 gene expression