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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 100-105页

作者： Vahideh Abbasnia Mohsen Foadoddini Delaram Eslimi Esfahani Mohammad Reza Khazdair Shahrbanoo Oryan Department of biology Payame Noor UniversityTehranIran Cardiovascular Diseases Research center Birjand University of Medical SciencesBirjandIran Department of Animal Sciences Faculty of Biological SciencesKharazmi UniversityTehranIran

Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized ***:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of *** 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological ***,total and differential white blood cell counts were ***:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic *** addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of ***-induced lung pathological changes were significantly improved by treatment with rosmarinic ***:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.

关键词： Rosmarinic acid Asthma Ovalbumin Tracheal responsiveness Inflammation White blood cell

Seeing is believing: observation of migrasomes

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Biophysics Reports 2024年第2期10卷 67-81页

作者： Yuwei Huang Li Yu School of Basic Medical Sciences Translational Medicine Institute Xi'an Jiaotong University State Key Laboratory of Membrane biology Tsinghua University-Peking University Joint Center for Life SciencesBeijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University

Migrasomes are a novel type of cell organelle that form on the retraction fibers at the rear of migrating cells. In recent years, numerous studies have unveiled the mechanisms of migrasome formation and have highlighted significant roles of migrasomes in both physiological and pathological *** upon the strategies outlined in published works and our own research experiences, we have compiled a comprehensive set of protocols for observing migrasomes. These step-by-step instructions encompass various aspects such as cell culture, labeling, imaging, in vitro reconstitution, and statistical analysis. We believe that these protocols serve as a valuable resource for researchers exploring migrasome biology.

关键词： Migrasome Labeling Imaging In vitro reconstitution

CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer

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Genes & Diseases 2024年第4期11卷 381-399页

作者： Ming Shao Qingfei Pan Haiyan Tan Jing Wu Ha Won Lee Andrew D.Huber William C.Wright Ji-Hoon Cho Jiyang Yu Junmin Peng Taosheng Chen Department of Chemical biology and Therapeutics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Computational biology St.Jude Children's Research HospitalMemphisTN 38105USA center for Proteomics and Metabolomics St.Jude Children's Research HospitalMemphisTN 38105USA Department of Structural biology St.Jude Children's Research HospitalMemphisTN 38105USA Department of Developmental Neurobiology St.Jude Children's Research HospitalMemphisTN 38105USA

CYP3A5 is a cytochrome P450(CYP)enzyme that metabolizes drugs and contributes to drug resistance in ***,it remains unclear whether CYP3A5 directly influences cancer *** this report,we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal ***-omics analysis showed that CYP3A5 knockdown re-sults in a decrease in various glucose-related metabolites through its effect on glucose trans-port.A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP,a negative regulator of ***,CYP3A5-generated reactive oxygen species were proved to be responsible for atten-uating the AKT-4EBP1-TXNIP signaling ***3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic *** together,our results,for the first time,reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

关键词： cell migration CYP3A5 Glucose metabolism GLUT1 Pancreatic cancer TXNIP

RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key Laboratory of Molecular biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China Institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China Clinical Research center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been ***,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

The wheat sucrose synthase gene TaSus1 is a determinant of grain number per spike

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The Crop Journal 2024年第1期12卷 295-300页

作者： Liping Shen Lili Zhang Changbin Yin Xiaowan Xu Yangyang Liu Kuocheng Shen He Wu Zhiwen Sun Ke Wang Zhonghu He Xueyong Zhang Chenyang Hao Jian Hou Aoyue Bi Xuebo Zhao Daxing Xu Botao Ye Xuchang Yu Ziying Wang Danni Liu Yuanfeng Hao Fei Lu Zifeng Guo Key Laboratory of Plant Molecular Physiology Institute of BotanyChinese Academy of SciencesBeijing 100093China China National Botanical Garden Beijing 100093China State Key Laboratory of Plant cell and Chromosome Engineering Institute of Genetics and Developmental BiologyInnovative Academy of Seed DesignChinese Academy of SciencesBeijing 100101China Institute of Crop Sciences Chinese Academy of Agricultural Sciences(CAAS)Beijing 100081China University of Chinese Academy of Sciences Beijing 100049China International Maize and Wheat Improvement center(CIMMYT)China Office c/o CAASBeijing 100081China CAS-JIC Centre of Excellence for Plant and Microbial Science(CEPAMS) Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Some haplotypes of the sucrose synthase gene TaSus1 are associated with thousand-grain weight(TGW)in wheat(Triticum aestivum L.).However,no mutations have been identified within the gene to test this *** effects of TaSus1 on grain number per spike(GNS)also are largely *** previous genome-wide association study identified TaSus-A1 as a candidate gene controlling fertile spikelet number per spike(FSN).In the present study,we generated two independent mutants for the three TaSus1 homoeologs by CRISPR/Cas9-mediated genome *** triple mutants displayed lower FSN,GNS,grain number per spikelet(GNST),and TGW than wild-type *** 306 hexaploid wheat accessions,two single-nucleotide polymorphisms in TaSus-A1 contributed differently to *** of the two alleles into a wheat genetic background confirmed their *** alleles differed in geographical distribution among the accessions.

关键词： Domestication selection Fertile spikelet number per spike(FSN) Geographical differentiation Grain number per spike(GNS) TaSus1

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How plants sense and respond to osmotic stress

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Journal of Integrative Plant biology 2024年第3期66卷 394-423页

作者： Bo Yu Dai-Yin Chao Yang Zhao Shanghai center for Plant Stress biology CAS Center for Excellence in Molecular Plant SciencesThe Chinese Academy of SciencesShanghai 200032China Key Laboratory of Plant Carbon Capture The Chinese Academy of SciencesShanghai 200032China National Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologyThe Chinese Academy of SciencesShanghai 200032China University of Chinese Academy of Sciences Beijing 100049China

Drought is one of the most serious abiotic stresses to land *** sense and respond to drought stress to survive under water *** have studied how plants sense drought stress,or osmotic stress caused by drought,ever since Charles Darwin,and gradually obtained clues about osmotic stress sensing and signaling in *** stress is a physical stimulus that triggers many physiological changes at the cellular level,including changes in turgor,cell wall stiffness and integrity,membrane tension,and cell fluid volume,and plants may sense some of these stimuli and trigger downstream *** this review,we emphasized water potential and movements in organisms,compared putative signal inputs in cell wall-containing and cell wall-free organisms,prospected how plants sense changes in turgor,membrane tension,and cell fluid volume under osmotic stress according to advances in plants,animals,yeasts,and bacteria,summarized multilevel biochemical and physiological signal outputs,such as plasma membrane nanodomain formation,membrane water permeability,root hydrotropism,root halotropism,Casparian strip and suberin lamellae,and finally proposed a hypothesis that osmotic stress responses are likely to be a cocktail of signaling mediated by multiple *** also discussed the core scientific questions,provided perspective about the future directions in this field,and highlighted the importance of robust and smart root systems and efficient source-sink allocations for generating future high-yield stress-resistant crops and plants.

关键词： cell volume drought membrane tension osmotic stress turgor

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The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways

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Neural Regeneration Research 2024年第1期19卷 205-211页

作者： Sen Zeng Honglan Yang Binghao Wang Yongzhi Xie Ke Xu Lei Liu Wanqian Cao Xionghao Liu Beisha Tang Mujun Liu Ruxu Zhang Department of Neurology The Third Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Radiology The Third Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Health Management center The Third Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina center for Medical Genetics&Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina National Clinical Research center for Geriatric Disorders Central South UniversityChangshaHunan ProvinceChina Department of cell biology School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina

Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical *** aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment *** cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor ***-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem *** proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like ***2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem *** r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor *** findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stag

关键词： antisense oligonucleotides cell cycle arrest Charcot-Marie-Tooth disease 2Z induced pluripotent stem cells MAPK/ERK PI3K/Akt proliferation spinal muscular atrophy-like

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Elevated peripheral levels of receptor-interacting protein kinase 1(RIPK1)and IL-8 as biomarkers of human amyotrophic lateral sclerosis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 271-278页

作者： Jun Wei Min Li Zhi Ye Xinqian Hu Xiaoyan He Jia Wang Gaofeng Chen Chengyu Zou Daichao Xu Hongbing Zhang Junying Yuan Yunhong Zha Institute of Neural Regeneration and Repair and Department of Neurology The First College of Clinical Medical ScienceYichang Central HospitalCollege of Basic Medical ScienceChina Three Gorges UniversityHubei Province Clinical Medical Research Center for Rare Diseases of Nervous SystemYichang 443000China Interdisciplinary Research center on biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai Key Laboratory of Aging StudiesShanghai 201210China State Key Laboratory of Common Mechanism Research for Major Diseases Haihe Laboratory of Cell EcosystemDepartment of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Amyotrophic lateral sclerosis(ALS)is a devastating fatal neurodegenerative disease with no ***-interacting protein kinase 1(RIPK1)has been proposed to mediate pathogenesis of *** has been identified as an old drug that can also inhibit RIPK1 *** conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS ***1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor ***-hundred-sixty-two ALS participants dosed daily with primidone(62.5 mg)completed 24-week follow-up.A significant reduction was showed in serum levels of RIPK1 and IL-8,which were significantly higher in ALS patients than that of healthy controls(P<0.0001).Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms(P<0.05).Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS *** primidone may provide a promising therapeutic strategy for *** effect of primidone for the treatment of other inflammatory diseases may also be considered,since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome(CRS).(ChiCTR2200060149).

关键词： RIPK1 diseases Serum

Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 568-580页

作者： Hao ZHANG Xinshu WANG Bo HU Peicheng LI Yierfan ABUDUAINI Hongmei ZHAO Ayinaer JIEENSIHAN Xishuang CHEN Shiyu WANG Nuojin GUO Jian YUAN Yunhui LI Lei LI Yuntong YANG Zhongmin LIU Zhaosheng TANG Hua WANG Department of Endocrinology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Research center for Translational Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Cardiology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Biochemistry and Molecular biology School of MedicineTongji UniversityShanghai 200331China Shanghai Institute of Stem cell Research and Clinical Translation Shanghai East HospitalShanghai 200120China Ji’an Hospital Shanghai East HospitalJi’an 343000China

diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA *** umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)***-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains *** this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with *** glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were *** that interacted with IGF1R were determined through coimmunoprecipitation *** expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot ***-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of *** identification of the morphology and phenotype of HUcMSC was performed by way of oil red“O”staining and Alizarin red *** rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and ***1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown *** cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin *** infusion ameliorated abnormalities and preserved kidney structure and function in DM *** expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased sign

关键词： Insulin-like growth factor 1 receptor(IGF1R) Checkpoint kinase 2(CHK2) Protein 53(p53) diabetes mellitus Human umbilical cord mesenchymal stem cell(HUcMSC) DNA damage repair

SETD2 in cancer: functions, molecular mechanisms, and therapeutic regimens

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Cancer biology & Medicine 2024年第9期21卷 725-730页

作者： Yawen Weng Jing Xue Ningning Niu State Key Laboratory of Systems Medicine for Cancer Stem Cell Research Center Ren Ji Hospital Shanghai Cancer InstituteShanghai Jiao Tong University School of Medicine

In recent years, the histone methyltransferase SET domain containing 2 (SETD2) has garnered significant attention for its involvement in carcinogenesis. Herein we aim to summarize the research advances regarding SETD2 in tumors,elucidate the role in global epigenetic regulation, highlight potential therapeutic regimens for patients with SETD2 deficiency, and outline future research directions.

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