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The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

Neural Regeneration Research 2024年第4期19卷 800-806页

作者： Xinxin Wang Yushu Hu Renshi Xu medical college of Nanchang University department of Neurology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical College

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory ***,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the *** disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized *** TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral *** review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

关键词： amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress pathogenesis post-translational modification protein quality control system stress granules TAR DNA-binding protein 43(TDP-43)

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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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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU Yan-Lin LV Lin QIAN The first clinical medical college of Lanzhou University LanzhouGansuChina Geriatric Cardiovascular department and Gansu clinical Research Center for Geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is *** Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction *** Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association *** without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome *** dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the *** In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni ***,no significant relationships were observed between other iron and LV *** Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the *** We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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Knockdown of RCN1 contributes to the apoptosis of colorectal cancer via regulating IP3R1

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BIOCELL 2024年第5期48卷 835-845页

作者： XUAN SHI YUFEN WANG CHENYU LI WANGSHU FU XINYUE ZHANG AIXIA GONG department of Gastroenterology The First Affiliated Hospital of Dalian Medical UniversityDalianChina department of Gastroenterology The First Affiliated Hospital of Jinzhou Medical UniversityJinzhouChina The first clinical college Dalian Medical UniversityDalianChina

Background:The incidence of colorectal cancer(CRC)has been increasing in recent ***,the discovery of factors that can assist in alleviating CRC is urgently ***:To identify a potential factor involved in the development of CRC,we screened the upregulated genes in tumor tissues through four datasets from an online *** expression of reticulocalbin 1(RCN1),a Ca2+-binding protein,was upregulated in the four *** on loss-offunction experiments,the effect of RCN1 on cell viability was assessed by Cell Counting Kit-8(CCK-8)*** regulatory effect of RCN1 on apoptosis was evaluated through Annexin V-fluorescein 5-isothiocyanate(FITC)/propidium iodide(PI)staining assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)assay in RKO and SW480 *** of endoplasmic reticulum(ER)stress signaling pathways was confirmed by estimating the phosphorylation and expression of PRKR-like ER kinase(PERK),inositol-requiring kinase-1(IRE1),transcription factor 6(ACT6),and CCAAT/enhancer-binding protein-homologous protein(CHOP).The intracellular Ca2+homeostasis regulated by RCN1 was determined through the detection of Ca2+concentration and mitochondrial membrane potential(MMP)***,whether inositol 1,4,5-trisphosphate receptor type 1(IP3R1)was involved in the regulation of RCN1 in CRC was verified through the depletion of IP3R1 in RKO ***:Knockdown of RCN1 reduced cell viability and facilitated apoptosis in RKO and SW480 *** of PERK and IRE1,activation of ATF6,and upregulation of CHOP were induced by the absence of RCN1,suggesting that the unfolded protein response(UPR)was activated in CRC *** concentration of Ca2+in mitochondria was increased after RCN1 depletion,followed by reduction in the MMP and release of cytochrome c from mitochondria to the cytoplasm in RKO and SW480 ***,it was demonstrated that IP3R1 mediates the effect of RCN1 on apoptosis i

关键词： Reticulocalbin 1 Unfolded protein response IP3R1 Colorectal cancer

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Chronic infectious unilateral giant thyroid cyst related to diabetes mellitus:A case report

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World Journal of clinical Cases 2024年第8期12卷 1497-1503页

作者： Jiang-Bo Liu Shi-Lei Zhang Wen-Long Jiang Hai-Kuan Sun Hao-Chen Yang department of Thyroid and Breast Surgery The First Affiliated HospitalCollege of Clinical MedicineHenan University of Science and TechnologyLuoyang 471000Henan ProvinceChina clinical Medicine School The First Clinical CollegeChongqing Medical UniversityChongqing 400016China

BACKGROUND Patients rarely develop complicated infections in thyroid ***,we describe a patient with chronic infected unilateral giant thyroid cyst related to diabetes mellitus(DM).CASE SUMMARY A 66-year-old male was admitted due to an evident neck lump for 5 d after approximately 40 years of gradually progressive neck mass and 7 years of *** ultrasound and computed tomography scan showed a giant lump in the left thyroid gland *** was diagnosed with a large thyroid nodule complicated by tracheal dislocation and had surgical *** exploration revealed evident inflammatory edema and exudation between the left anterior neck muscles,the nodule and glandular ***,inflammatory lesions did not affect major neck ***,a left partial thyroidectomy was *** observation showed that the cystic thyroid mass consisted of extensive cystic wall calcification and was rich in massive rough sand-like calculi content and purulent *** pathology confirmed benign thyroid cyst with chronic *** The progression of this chronic infectious unilateral giant thyroid cyst may have been related to DM,and identifying blood vessels involvement can prevent serious complications during operation.

关键词： Thyroid nodule Infection Diabetes mellitus Surgery Case report

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A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

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Neural Regeneration Research 2024年第8期19卷 1828-1834页

作者： Yongjiang Zhang Shiyi Yin Run Song Xiaoyi Lai Mengmeng Shen Jiannan Wu Junqiang Yan Key Laboratory of Neuromolecular Biology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains ***-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains *** kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum *** is regulated by PERK and is a target of the unfolded protein *** is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh *** this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s *** used adeno-associated virus to knockdown PHB2 *** res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s *** rexpression of PHB2 inhibited these *** also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s *** found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted *** addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of *** findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

关键词： endoplasmic reticulum dopaminergic neuron microtubule-associated protein 1 light chain 3 mitophagy oxidative stress Parkin Parkinson’s disease PKR-like endoplasmic reticulum kinase reactive oxygen species prohibitin-2

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Circ_0053943 complexed with IGF2BP3 drives uveal melanoma progression via regulating N6-methyladenosine modification of Epidermal growth factor receptor

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Oncology Research 2024年第5期32卷 983-998页

作者： ANDI ZHAO YUE WANG ZIJIN WANG QING SHAO QI GONG HUI ZHU SHIYA SHEN HU LIU XUEJUAN CHEN department of Ophthalmology The First Affiliated Hospital with Nanjing Medical UniversityNanjing210029China The first clinical medical college Nanjing Medical UniversityNanjing211166China department of Ophthalmology Nanjing First HospitalNanjing Medical UniversityNanjing210006China

Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple ***,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain *** this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative ***_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo ***,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target *** sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional *** assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling ***,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.

关键词： Uveal melanoma Hsa_circ_0053943 IGF2BP3 EGFR MAPK/ERK signaling pathway

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Long Non-coding RNA PCED1B Antisense RNA 1 Promotes Cell Proliferation and Invasion in Hepatocellular Carcinoma by Regulating the MicroRNA-34a/CD44 Axis

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Current medical science 2024年第3期44卷 503-511页

作者： Jian-gang BI Qi LI Yu-sheng GUO Li-ping LIU Shi-yun BAO Ping XU department of Hepatobiliary and Pancreatic Surgery Shenzhen People's HospitalThe Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China department of Endocrinology Shenzhen People's HospitalThe Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020China

Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC *** interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down *** RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western *** cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion *** HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal *** PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC ***,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each ***,PCED1B-AS1 increased the expression level of CD44,which was targeted by *** cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite ***,PCED1B-AS1 suppressed the role of ***,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in *** PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.

关键词： long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1) hepatocellular carcinoma microRNA-34a(miR-34a) CD44 proliferation invasion

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Pathological mechanisms of amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第5期19卷 1036-1044页

作者： Yushu Hu Wenzhi Chen Caihui Wei Shishi Jiang Shu Li Xinxin Wang Renshi Xu department of clinical Medicine Nanchang UniversityNanchangJiangxi ProvinceChina department of Neurology Jiangxi Provincial People’s HospitalNanchangJiangxi ProvinceChina department of Neurology The First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of ***,the journey to understanding or treating amyotrophic lateral sclerosis is still a long *** to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic *** progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral ***,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral *** addition,we discuss current emerging strategies for the treatment of amyotrophic lateral *** the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.

关键词： amyotrophic lateral sclerosis cellular pathways disease mechanisms motor neuron neurodegenerative disease

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Meiotic nuclear divisions 1 suppresses the proliferation and invasion of pancreatic cancer cells via regulating H2A.X variant histone

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BIOCELL 2024年第1期48卷 111-122页

作者： DONGQIN WANG YAN SHI ZHIQIANG WANG JING ZHANG LUYAO WANG HONGYU MA SHUHUA SHI XIAOFU LIAN HUA HUANG XIAOJING WANG CHAOQUN LIAN Anhui Province Key Laboratory of clinical and Preclinical Research in Respiratory Disease Molecular Diagnosis CenterThe Department of Pulmonary Critical Care MedicineFirst Affiliated Hospital of Bengbu Medical CollegeBengbu233030China department of Genetics School of Life SciencesBengbu Medical CollegeBengbu233000China department of clinical Medicine Bengbu Medical CollegeBengbu233030China Research Center of clinical Laboratory science Bengbu Medical CollegeBengbu233030China

Introduction:Among all malignant tumors of the digestive system,pancreatic carcinoma exhibits the highest mortality ***,prevention and effective treatment are urgent issues that need to be ***:The study focused on meiotic nuclear divisions 1(MND1),integrating data from the Gene Expression Profiling Interactive Analysis(GEPIA)database with prognostic survival ***,experiments at cellular level were employed to demonstrate the effect of MND1 on the proliferation and migration of *** small-molecule inhibitor of MND1 was used to suppress the migration of PC cells by knocking down MND1 using small interfering RNA(siRNA)in Patu-8988 and Panc1 cell ***:The results of Cell Counting Kit-8 indicated that the suppression of MND1 resulted in a decrease in cell *** healing and Transwell assays revealed that MND1 knockdown reduced cell migration and *** cytometry revealed that inhibiting MND1 hindered the cell ***,MND1 could stimulate the proliferation,migration,and invasion of Patu-8988 and Panc1 cells by increasing the expression of ***,MND1 had a positive effect on H2AFX expression in PC *** MND1 expression suggests the low overall survival rate of individuals diagnosed with ***:These findings suggest that MND1 has the potential to be a gene with the ability to accurately diagnose and treat PC.

关键词： Pancreatic carcinoma MND1 H2AFX Cell cycle

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