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Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

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Neural Regeneration Research 2024年第9期19卷 2010-2018页

作者： Yan Wang Dai Li Lan Zhang Zhenyu Yin Zhaoli Han Xintong Ge Meimei Li Jing Zhao Shishuang Zhang Yan Zuo Xiangyang Xiong Han Gao Qiang Liu Fanglian Chen Ping Lei Department of Geriatrics Tianjin Medical University General HospitalTianjinChina tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina tianjin Neurological Institute Tianjin Medical University General HospitalTianjinChina

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain ***,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains *** this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of *** found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum ***,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured ***,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly *** findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum ***,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

关键词： apoptosis C/EBP homologous protein endoplasmic reticulum stress exosome inositol-requiring enzyme 1α microglia miR-124-3p neuron repetitive mild traumatic brain injury X-box binding protein 1

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Neoantigen cancer vaccines:a new star on the horizon

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Cancer Biology & Medicine 2024年第4期21卷 274-311页

作者： Xiaoling Li Jian You Liping Hong Weijiang Liu Peng Guo Xishan Hao Cell Biotechnology Laboratory Tianjin Cancer Hospital Airport HospitalTianjin 300308China National Clinical Research Center for Cancer Tianjin 300060China Haihe Laboratory of Synthetic Biology Tianjin 300090China Department of Thoracic Oncology Tianjin Cancer Hospital Airport HospitalTianjin 300308China Department of Thoracic Oncology Surgery Tianjin Medical University Cancer Institute&HospitalTianjin 300060China tianjin Medical University Cancer Institute&hospital Tianjin 300060China

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer *** of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal *** neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint *** made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of ***,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents *** review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

关键词： Immunotherapy neoantigen cancer vaccine solid tumors high-throughput sequencing bioinformatics PDOs AI HLA TCR

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Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2113-2122页

作者： Jun-Feng Wang Xiao-Xia Yang Jian Zhang Yan Zheng Fu-Qing Zhang Xiao-Feng Shi Yu-Liang Wang Department of Colorectal Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Neurology Tianjin First Center HospitalTianjin 300192China Prosthodontics Studio Tianjin Stomatological HospitalTianjin 300041China Department of Clinical Laboratory Medicine Tianjin Institute of UrologyThe Second Hospital of Tianjin Medical UniversityTianjin 300211China Department of Emergency Tianjin First Central HospitalTianjin 300192China

BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of *** mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain *** supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent *** Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and ***,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release *** was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+*** The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg ***,ADSC-based cell therapy could be a beneficial approach for p

关键词： Colorectal cancer COVID-19 Adipose-derived mesenchymal stem cells T helper cell Immunomodulation

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Symmetry of upper eyelid after unilateral blepharoptosis repair with minimally invasive conjoint fascial sheath suspension technique

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 53-60页

作者： Yianzhu Liu Wenli Chen Xia Chen tianjin Eye hospital Tianjin 300020China tianjin Key Lab of Ophthalmology and Visual Science Tianjin 300020China

AIM:To investigate the symmetry of upper eyelid in patients with unilateral mild and moderate blepharoptosis who underwent unilateral minimally invasive combined fascia sheath(CFS)***:A retrospective study of patients who underwent unilateral minimally invasive CFS suspension surgery between January 2018 and December *** criteria included unilateral mild and moderate ptosis,good levator muscle function(>9 mm)and follow-up of at least ***-and post-operative symmetry was graded subjectively for marginal reflex distance 1(MRD1),tarsal platform show(TPS)and eyebrow fat span(BFS).A t-test was used to evaluate MRD1,TPS and BFS asymmetry by calculating delta *** Bézier curve tool of the Image J software was used to extract the upper eyelid contours,where the symmetry was measured by the percentage of overlapping curvatures(POC).RESULTS:Totally 105 patients(105 eyelids)were included(mild group,n=84;moderate group,n=21).Postoperatively,all patients increased MRD1 and decreased TPS in the ptotic eye while maintaining unchanged *** asymmetric delta value for MRD1 was measured to be 1.48±0.86 preoperatively,and it decreased to 0.58±0.67 postoperatively in all cases(P=0.0004).In patients with mild ptosis,the asymmetry value of TPS fell significantly from 1.15±0.62 to 0.68±0.38(P=0.0187).The symmetry of the upper eyelid contour increased in all subgroups of patients,with a POC of 59.39%±13.45%preoperatively and POC of 78.29%±13.80%***:Minimally invasive CFS suspension is proved to be an effective means of improving the symmetry of unilateral ptosis in terms of MRD1(all subgroups),POC(all subgroups)and TPS(only mild group),whereas BFS is unaffected.

关键词： symmetry unilateral blepharoptosis minimally invasive combined fascia sheath suspension

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Human umbilical cord mesenchymal stem cells derivedexosomes on VEGF-A in hypoxic-induced mice retinal astrocytes and mice model of retinopathy of prematurity

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1238-1247页

作者： Xiao-Tian Zhang Bo-Wen Zhao Yuan-Long Zhang Song Chen tianjin Eye hospital Tianjin 300020China tianjin Key Lab of Ophthalmology and Visual Science Tianjin 300020China

AIM:To observe the effect of human umbilical cord mesenchymal stem cells(hUCMSCs)secretions on the relevant factors in mouse retinal astrocytes,and to investigate the effect of hUCMSCs on the expression of vascular endothelial growth factor-A(VEGF-A)and to observe the therapeutic effect on the mouse model of retinopathy of prematurity(ROP).METHODS:Cultured hUCMSCs and extracted exosomes from them and then retinal astrocytes were divided into control group and hypoxia *** assay,flow cytometry,reverse transcription-polymerase chain reaction(RT-PCR)and Western blot were used to detect related *** mechanisms by which hUCMSCs exosomes affect VEGF-A expression in hypoxia-induced mouse retinal astrocytes were *** last,the efficacy of exosomes of UCMSCs in a mouse ROP model was ***6 was used to comprehensively process data ***:The secretion was successfully extracted from the culture supernatant of hUCMSCs by gradient *** oxygen species(ROS)and hypoxia inducible factor-1α(HIF-1α)of mice retinal astrocytes under different hypoxia time and the expression level of VEGF-A protein and VEGF-A mRNA increased,and the ROP cell model was established after 6h of *** secretions of medium and high concentrations of hUCMSCs can reduce ROS and HIF-1α,the expression levels of VEGF-A protein and VEGF-A mRNA are statistically significant and concentration *** with the ROP cell model group,the expression of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signal pathway related factors in the hUCMSCs exocrine group is significantly *** intravitreal injection of the secretions of medium and high concentrations of hUCMSCs can reduce VEGF-A and HIF-1αin ROP model *** staining shows that the number of retinal neovascularization in ROP mice decreases with the increase of the dose of hUCMSCs ***:In a hypoxia induced

关键词： human umbilical cord mesenchymal stem cells retinal astrocytes retinopathy of prematurity vascular endothelial growth factor hypoxia inducible factor

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Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

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Journal of Geriatric Cardiology 2024年第4期21卷 443-457页

作者： Jing-Yue XU Zheng-Kai XUE Ya-Ru ZHANG Xing LIU Xue ZHANG Xi YANG Tong LIU Kang-Yin CHEN tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of Cardiologythe Second Hospital of Tianjin Medical UniversityTianjinChina

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this *** A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent *** Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + *** In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept c

关键词： remodeling cardiac inhibited

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Circ_0003855 involvement of esophageal cancer progression through miR-622/FLOT1

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Oncology Research 2024年第5期32卷 925-931页

作者： JINGJING TIAN XIBAO HU XINRONG ZHANG Department of Gastroenterology Tianjin Nankai HospitalTianjin300100China Department of Digestive Medicine First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin300100China

To confirm the relationship between Circ_0003855 and EC,we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC,and the expression levels of Circ_0003855,miR-622,and FLOT1 were *** results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells,while miR-622 was lowly expressed(p0.05).Synthesizing the results of these experiments above,we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells,and its mechanism is related to miR-622 and FLOT1.

关键词： Circ_0003855 miR-622 FLOT1 Esophageal cancer Cell proliferation

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Key role of interferon regulatory factor 1(IRF-1)in regulating liver disease:progress and outlook

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 451-470页

作者： Tao CHEN Shipeng LI Dewen DENG Weiye ZHANG Jianjun ZHANG Zhongyang SHEN First Central Clinical School Tianjin Medical UniversityTianjin 300192China Department of Organ Transplant Tianjin First Central HospitalTianjin 300192China Research Institute of Transplant Medicine Nankai UniversityTianjin 300192China Department of Hepatobiliary Surgery Henan Provincial People’s HospitalZhengzhou 450000China Key Laboratory of Organ Transplant Tianjin First Central HospitalTianjin 300192China

Interferon regulatory factor 1(IRF-1)is a member of the IRF *** is the first transcription factor to be identified that could bind to the interferon-stimulated response element(ISRE)on the target gene and displays crucial roles in the interferoninduced signals and ***-1,as an important medium,has all of the advantages of full cell cycle regulation,cell death signaling transduction,and reinforcing immune surveillance,which are well *** studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases,including but not limited to inhibiting the replication of the hepatitis virus(A/B/C/E),alleviating the progression of liver fibrosis,and aggravating hepatic ischemiareperfusion injury(HIRI).The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients,which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer;additionally,the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease(AFLD/NAFLD),cholangiocarcinoma suppression,and uncommon traits in other liver diseases that had previously received little ***,several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 *** this paper,we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.

关键词： Interferon regulatory factor(IRF-1) Hepatitis virus Liver fibrosis Hepatic ischemia-reperfusion injury(HIRI) Liver cancer

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Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 557-567页

作者： Sheng ZENG Shaoqiang XING Yifei ZHANG Haifeng WANG Qian LIU Department of Urology Tianjin First Central HospitalTianjin 300192China Department of Urology First Central Clinical CollegeTianjin Medical UniversityTianjin 300192China

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery,radiotherapy,and chemotherapy,with some promising *** aims to kill tumor cells by mobilizing or stimulating cytotoxic immune ***,the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high ***,nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens,activating targeted T cells,modulating the immunosuppressive tumor microenvironment,and improving the treatment *** Calmette-Gué;rin(BCG)is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis,which was first reported to have antitumor activity in *** therapy can activate the immune system by inducing various cytokines and chemokines,and its specific immune and inflammatory responses exert antitumor *** was first used during the 1970s as an intravesical treatment agent for bladder cancer,which effectively improved immune antitumor activity and prevented tumor *** recently,nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune *** this study,we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.

关键词： Bladder cancer Bacillus Calmette-Gué rin vaccine Nanocarrier Genetic engineering Immunotherapy

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A contradictory phenomenon of thicken pericardium and cardiac compression without inferior vena cava dilation:sign of IVC escape

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Journal of Geriatric Cardiology 2024年第5期21卷 583-587页

作者： Tie-Nan CHEN Shuang ZHAO Shuai QIAO Yong-Yong HAN Qing LIU Chang-Le LIU Guang-Ping LI Tong LIU Hua-Ying FU Department of Cardiovascular Surgery Second Hospital of Tianjin Medical UniversityTianjinChina Department of Cardiology Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular DiseaseTianjin Institute of Cardi-ologyThe Second Hospital of Tianjin Medical UniversityTianjinChina Department of Oncology Second Hospital of Tianjin Medical UniversityTianjinPeople's Republic of China

A 77-year-old female presented with shortness of breath and tightness of chest was *** past medical history included hypertension and she has been taking nifedipine *** years before,she was diagnosed with pericardial effusion(Figure 1)and had pericardiocentesis *** physical examination,her blood pressure was 151/100 mm-Hg and her pulse rate was 91 beats/min.

关键词： admitted cardiac thick

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