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Alternative splicing and related RNA binding proteins in human health and disease

Signal Transduction and Targeted Therapy 2024年第3期9卷 839-871页

作者： Yining Tao Qi Zhang Haoyu Wang Xiyu Yang Haoran Mu department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of Medicine200000 ShanghaiChina Shanghai Bone tumor Institution 200000 ShanghaiChina department of Biochemistry and Molecular Cell biology Shanghai Key Laboratory for Tumor Microenvironment and InflammationShanghai Jiao Tong University School of Medicine200000 ShanghaiChina

Alternative splicing(AS)serves as a pivotal mechanism in transcriptional regulation,engendering transcript diversity,and modifications in protein structure and *** varying tissues,developmental stages,or under specific conditions,AS gives rise to distinct splice *** implies that these isoforms possess unique temporal and spatial roles,thereby associating AS with standard biological activities and *** these,AS-related RNA-binding proteins(RBPs)play an instrumental role in regulating alternative splicing *** physiological conditions,the diversity of proteins mediated by AS influences the structure,function,interaction,and localization of proteins,thereby participating in the differentiation and development of an array of tissues and *** pathological conditions,alterations in AS are linked with various diseases,particularly *** changes can lead to modifications in gene splicing patterns,culminating in changes or loss of protein *** instance,in cancer,abnormalities in AS and RBPs may result in aberrant expression of cancer-associated genes,thereby promoting the onset and progression of *** and RBPs are also associated with numerous neurodegenerative diseases and autoimmune ***,the study of AS across different tissues holds significant *** review provides a detailed account of the recent advancements in the study of alternative splicing and AS-related RNA-binding proteins in tissue development and diseases,which aids in deepening the understanding of gene expression complexity and offers new insights and methodologies for precision medicine.

关键词： organs alterations thereby

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Cancer-associated fibroblasts express CD1d and activate invariant natural killer T cells under cellular stress

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Cellular & Molecular Immunology 2024年第1期21卷 91-94页

作者： Shengduo Pei Jonas Sjölund Yueyun Pan Kristian Pietras Mikael C.I.Karlsson department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholmSweden Division of Translational Cancer Research Department of Laboratory MedicineLund University Cancer CentreLund UniversityLundSweden

Invariant natural killer T(iNKT)cells are part of the family of unconventional T cells,and they recognize glycolipid antigens presented on the MHC class I like molecule CD1^([1]).In humans there are five CD1 molecules named CD1a to CD1e,whereas mice use only CD1d for lipid ***,iNKT cells can elicit both cytotoxicity similarly to conventional CD8 T cells and secrete cytokines that influence the adaptive immune response including providing direct T cell help to B cells^([2]).In the context of tumors,they can use both release of granzyme B and use Fas-mediated mechanisms for killing of tumor *** iNKT cells use a restricted TCR repertoire and CD1 molecules are non-heterogenous the risk of graft vs host disease is limited and thus these T cells have been an attractive option for off the shelf immunotherapy to treat cancer^([3]).

关键词： killer CD1d Cancer

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Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery:A systematic review and meta-analysis

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 893-906页

作者： Yao Zhou Xiao-Lei Zhang Hong-Xia Ni Tian-Jing Shao Ping Wang department of Operating Room Affiliated Tumor Hospital of Nantong University&Nantong Tumor HospitalNantong 226361Jiangsu ProvinceChina department of Gastrointestinal Surgery The Affiliated Tumor Hospital of Nantong University&Nantong Tumor HospitalNantong 226361Jiangsu ProvinceChina

BACKGROUND Colorectal cancer is a major global health challenge that predominantly affects older *** management,despite advancements,requires careful consideration of preoperative patient status for optimal *** To summarize existing evidence on the association of frailty with short-term postoperative outcomes in patients undergoing colorectal cancer *** A literature search was conducted using PubMed,EMBASE and Scopus databases for observational studies in adult patients aged≥18 years undergoing planned or elective colorectal surgery for primary carcinoma and/or secondary *** studies that conducted frailty assessment using recognized frailty assess-ment tools and had a comparator group,comprising nonfrail patients,were *** effect sizes were reported as weighted mean difference or relative risk(RR)with 95%confidence intervals(CIs).RESULTS A total of 24 studies were *** with nonfrail patients,frailty was associated with an increased risk of mortality at 30 d(RR:1.99,95%CI:1.47-2.69),at 90 d(RR:4.76,95%CI:1.56-14.6)and at 1 year(RR:5.73,95%CI:2.74-12.0)of follow *** patients had an increased risk of any complications(RR:1.81,95%CI:1.57-2.10)as well as major complications(Clavien-Dindo classification grade≥III)(RR:2.87,95%CI:1.65-4.99)compared with the control *** risk of reoperation(RR:1.18,95%CI:1.07-1.31),readmission(RR:1.70,95%CI:1.36-2.12),need for blood transfusion(RR:1.67,95%CI:1.52-1.85),wound complications(RR:1.49,95%CI:1.11-1.99),delirium(RR:4.60,95%CI:2.31-9.16),risk of prolonged hospitalization(RR:2.09,95%CI:1.22-3.60)and discharge to a skilled nursing facility or rehabilitation center(RR:3.19,95%CI:2.0-5.08)was all higher in frail *** Frailty in colorectal cancer surgery patients was associated with more complications,longer hospital stays,higher reoperation risk,and increased *** frailty assessment appears crucial for tailored surgical managem

关键词： Frailty Frail adults Colorectal surgery Colorectal cancer Complications Mortality Survival Slinical outcomes Meta-analysis

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Angiogenesis in diseases:A half-century excursion from the initial therapeutic concept to current clinical benefits

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Chinese Medical Journal 2024年第6期137卷 636-637页

作者： Yihai Cao department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholm 17177Sweden

Except a few tissues such as the cornea and cartilage that are avascular,blood vessels constitute a significant proportion of tissue masses in virtually all *** physiological conditions,the adult vasculature remains quiescent to retain tissue and organ homeostatic *** few or too many blood vessels are associated with the onset and progression of many *** response to injuries,most tissues undergo repair by switching on angiogenesis,a key process of new blood vessel formation.^([1])Similarly,angiogenesis is often active in pathological tissues,including tumors and ischemic tissues to aggravate disease progression.

关键词： injuries organs diseases

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5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

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Oncology Research 2024年第6期32卷 1047-1061页

作者： KIMBERLY FENECH ISAAC MICALLEF BYRON BARON Centre for Molecular Medicine and Biobanking University of MaltaMsidaMSD 2080Malta department of tumor Genetics and biology Graduate School of Medical SciencesFaculty of Life SciencesKumamoto UniversityKumamoto860-8556Japan

Background:Colorectal cancer(CRC)is one of the most frequently diagnosed *** many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many *** study looked into the effect of 5-FU dose escalation on EMT and protein methylation in *** and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of *** motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion *** was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized *** blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation ***:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of *** 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental *** was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell ***,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU ***:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU

关键词： Chemoresistance Epithelial-to-mesenchymal transition Protein methylation Protein methyltransferases

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Enhancing competency of clinical research nurses:A comprehensive training and evaluation framework

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World Journal of Clinical Cases 2024年第7期12卷 1378-1381页

作者： Yang-Xi Liu Yi Xu tumor Interventional department Taizhou Municipal HospitalTaizhou 318099Zhejiang ProvinceChina

The Sun et al's training program for clinical research nurses(CRNs)in the World Journal of Clinical Cases is a comprehensive and scientific *** includes structured frameworks for CRN training,aiming to improve CRN *** program emphasizes practical abilities,updates training content,and improves evaluation *** cultivation of CRN talents focuses on enhancing the training system,establishing a multifaceted evaluation framework,and continuously refining the training *** feedback and evalua-tion are essential to improve CRNs'competency in practical settings.

关键词： Clinical research nurse Framework Nurse Operations Practice Structure

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Observation of therapeutic effect of lamp irradiation combined with purple gromwell oil gauze on alleviating intestinal colic in patients

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1749-1755页

作者： Bi-Zhi Cen Yin-Song Chen Li-Ping Li Jing-Wen Wu Yan-Fen Xie department of tumor Center Foshan Hospital of Traditional Chinese MedicineFoshan 528000Guangdong ProvinceChina

BACKGROUND Intestinal colic is a common complication in patients who have undergone radical surgery for colorectal *** Chinese medicine has advantages,including safety and stability,for the treatment of intestinal *** irra-diation for abdominal ironing has been applied in the treatment of many gas-trointestinal *** gromwell oil has the effects of clearing heat,cooling blood,reducing swelling,and relieving *** The general effective rate in the observation group was 95.00%,which was significantly higher than that in the control group(86.67%,P0.05).After 1,2,3,and 4 d of treatment,the duration of symptoms in both groups were decreased,and the duration in the observation group was significantly lower than that in the control group(96.54±9.57 vs 110.45±11.23,87.26±12.07 vs 104.44±11.68,80.45±16.21 vs 99.44±14.95,73.18±15.58 vs 92.17±14.20;P0.05).CONCLUSION The use of lamp irradiation combined with purple gromwell oil gauze in patients with intestinal colic after radical surgery for colorectal cancer can reduce symptom duration,alleviate intestinal colic,and improve treatment efficacy,and this approach is *** is worth promoting the use of this treatment in clinical practice.

关键词： Lamp irradiation Purple gromwell oil gauze Intestinal colic Radical surgery for colorectal cancer Therapeutic effect

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Knockdown of circular RNA (CircRNA)_001896 inhibits cervical cancer proliferation and stemness in vivo and in vitro

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BIOCELL 2024年第4期48卷 571-580页

作者： JIA SHAO CAN ZHANG YAONAN TANG AIQIN HE WEIPEI ZHU department of Obstetrics and Gynecology The Second Affiliated Hospital of Soochow UniversitySuzhou215004China department of Gynecology Oncology Affiliated Tumor Hospital of Nantong UniversityNantong226361China

Objective:Previous studies indicated that aberrant circular RNA(circRNA)expression affects gene expression regulatory networks,leading to the aberrant activation of tumor pathways and promoting tumor cell ***,the expression,clinical signiﬁcance,and effects on cell propagation,invasion,and dissemination of circRNA_001896 in cervical cancer(CC)tissues remain ***:The Gene Expression Omnibus(GEO)datasets(GSE113696 and GSE102686)were used to examine differential circRNA expression in CC and adjacent *** expression of circRNA_001896 was detected in 72 CC patients usingﬂuorescence quantitative *** analysis with clinical pathological features was performed through COX multivariate and univariate *** effect of circRNA_001896 downregulation on CC cell propagation was examined using the cell counting kit-8(CCK-8)test,clonogenic,3D sphere formation,and in vivo tumorigenesis ***:Intersection of the GSE113696 and GSE102686 datasets revealed an increased expression of four circRNAs,including circRNA_001896,in CC *** quantitative PCR conﬁrmed circRNA_001896 as a circular *** expression of circRNA_001896 was considerably associated with lymph node metastasis,International Federation of Gynecologists and Obstetricians(FIGO)stage,tumor diameter,and survival period in CC *** hazards model(COX)univariate and multivariate analyses revealed that circRNA_001896 expressions are a distinct risk factor affecting CC patients’*** functional experiments showed that downregulating circRNA_001896 substantially suppressed CC cell growth,colony formation,and 3D sphere-forming *** vivo,tumorigenesis analysis in nude mice demonstrated that downregulating circRNA_001896 remarkably reduced the in vivo proliferation capacity of CC ***:CircRNA_001896 is highly expressed in CC tissues and is substantially related to lymph node metastasis,FIGO stage,tumor size,and surviva

关键词： Uterine cervical neoplasms RNA Circular Cell proliferation Cancer stem cells

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Revolutionizing tumor immunotherapy:unleashing the power of progenitor exhausted T cells

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Cancer biology & Medicine 2024年第6期21卷 499-512页

作者： Zhang Fang Xinyi Ding Hao Huang Hongwei Jiang Jingting Jiang Xiao Zheng department of tumor Biological Treatment The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China Jiangsu Engineering Research Center for tumor Immunotherapy The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China Institute for Cell Therapy of Soochow University The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China

In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.

关键词： Progenitor exhausted CD8^(+)T cells TCF-1 immunotherapy tumor microenvironment cellular crosstalk

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Exploring treatment options in cancer: tumor treatment strategies

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3337-3380页

作者： Beilei Liu Hongyu Zhou Licheng Tan Kin To Hugo Siu Xin-Yuan Guan department of Clinical Oncology The University of Hong Kong-Shenzhen HospitalShenzhenChina department of Clinical Oncology The University of Hong KongHong KongChina state Key Laboratory for Liver Research The University of Hong KongHong KongChina Advanced Energy Science and Technology Guangdong Laboratory HuizhouChina MOE Key Laboratory of tumor Molecular biology Jinan UniversityGuangzhouChina

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical and psychological ***,the landscape of tumor treatment has undergone a comprehensive and remarkable *** as fervently pursued modalities are small molecule targeted agents,antibody-drug conjugates(ADCs),cell-based therapies,and gene *** cutting-edge treatment modalities not only afford personalized and precise tumor targeting,but also provide patients with enhanced therapeutic comfort and the potential to impede disease ***,it is acknowledged that these therapeutic strategies still harbour untapped potential for further *** a comprehensive understanding of the merits and limitations of these treatment modalities holds the promise of offering novel perspectives for clinical practice and foundational research *** this review,we discussed the different treatment modalities,including small molecule targeted drugs,peptide drugs,antibody drugs,cell therapy,and gene *** will provide a detailed explanation of each method,addressing their status of development,clinical challenges,and potential *** aim is to assist clinicians and researchers in gaining a deeper understanding of these diverse treatment options,enabling them to carry out effective treatment and advance their research more effciently.

关键词： drugs treatment holds

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