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Repurposing disulfiram with CuET nanocrystals:Enhancing anti-pyroptotic effect through NLRP3 inflammasome inhibition for treating inflammatory bowel diseases

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2698-2715页

作者： Xueming Xu Yuanfeng Han Jiali Deng Shengfeng Wang Shijie Zhuo Kai Zhao Wenhu Zhou hematology and Department of Critical Care Medicine The Third Xiangya HospitalCentral South UniversityChangsha 410013China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China Hunan Chidren's Hospital Changsha 410007China Department of Pharmacy The Third Xiangya HospitalCentral South UniversityChangsha 410013China Key laboratory of Biological Nanotechnology of National Health Commission Changsha 410008China

Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing ***,disulfiram(DSF),a drug primarily used for alcohol addiction treatment,has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis,a form of programmed cell *** therapeutic activity of DSF can be further enhanced by the presence of Cu^(2+),although the underlying mechanism of this enhancement remains *** this study,we investigated the mechanistic basis of Cu^(2+)-induced enhancement and discovered that it is attributed to the formation of a novel copper ethylthiocarbamate(CuET)*** exhibited significantly stronger anti-pyroptotic activity compared to DSF and employed a distinct mechanism of ***,despite its potent activity,CuET suffered from poor solubility and limited permeability,as revealed by our druggability *** overcome these intrinsic limitations,we developed a scalable method to prepare CuET nanocrystals(CuET NCs)using a metal coordination-driven self-assembly *** studies demonstrated that CuET NCs exhibited a 6-fold improvement in ***,CuET NCs exhibited high biodistribution in the intestine,suggesting their potential application for the treatment of inflammatory bowel diseases(IBDs).To evaluate their therapeutic efficacy in vivo,we employed a murine model of DSS-induced colitis and observed that CuET NCs effectively attenuated inflammation and ameliorated colitis *** findings highlight the discovery of CuET as a potent anti-pyroptotic agent,and the development of CuET NCs represents a novel approach to enhance the druggability of CuET.

关键词： Drug repurposing Pyroptosis Nanoparticles Bioavailability Disulfiram DSS-induced colitis NLRP3 inflammasome CuET

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New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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Oncology Research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER Division of Oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for hematology and Oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers *** main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma *** therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second *** availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented ***,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk *** recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within *** review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy Gene expression Omics

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Navigating the labyrinth of long non-coding RNAs in colorectal cancer:From chemoresistance to autophagy

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3376-3381页

作者： Jia-Mei Yu Chong-Qi Sun Huan-Huan Xu Ya-Li Jiang Xing-Yu Jiang Si-Qi Ni Ting-Yu Zhao Ling-Xiang Liu Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina Department of hematology and Oncology Department of Geriatric Lung Cancer Research LaboratoryJiangsu Province Geriatric HospitalNanjing 210009Jiangsu ProvinceChina Central laboratory The Friendship Hospital of Ili Kazakh Autonomous PrefectureIli&Jiangsu Joint Institute of HealthYining 835000Xinjiang Uyghur Autonomous RegionChina

Long non-coding RNAs(lncRNAs),with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity,have been found to impact colorectal cancer(CRC)through various biological *** expression can regulate autophagy,which plays dual roles in the initiation and progression of cancers,including *** expression of lncRNAs is associated with the emergence of ***,it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating *** recent studies titled“Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506”and“Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription”revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC,*** this editorial,we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.

关键词： Long non-coding RNA Autophagy Chemoresistance Oxaliplatin Colorectal cancer

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Poly(A)-specific RNase(PARN)generates and regulates miR-125a-5p 3’-isoforms,displaying an altered expression in breast cancer

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1805-1807页

作者： Luisa Tomasello Shoshanah M.Holub Giovanni Nigita Rosario Distefano Carlo M.Croce Department of Cancer Biology and Genetics The Ohio State UniversityColumbusOHUSA Department of Internal Medicine Division of HematologyThe Ohio State UniversityColumbusOHUSA

Dear Editor,MicroRNAs(miRNAs)are small non-coding RNAs crucial for post-transcriptional gene regulation,processed from primary miRNA transcripts by Drosha and Dicer.1 Latest advancements in Next Generation Sequencing highlighted the existence of miRNA isoforms(isomiRs)resulting from alternative processing,RNA editing,or post-transcriptional modifications.

关键词： breast cancer advancement

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Predictive value of T cell receptor repertoire profiling for immunosuppressive therapy in severe aplastic anemia

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Genes & Diseases 2024年第1期11卷 95-98页

作者： Cunte Chen Yuling Zhang Dongpei Lu Zelong Zhang Jun Yang Xiaowei Chen Ming Zhou Wenjian Mo Caixia Wang Qinghua Cai Yumiao Li Ruiqing Zhou Shilin Xu Wei Zhou Tingfen Deng Shiyi Pan Yanli Xu Shunqing Wang Yuping Zhang Department of hematology Guangzhou First People's HospitalSouth China University of TechnologyGuangzhouGuangdong 510180China Guangzhou Junruikang Biotechnology Co. LtdGuangzhouGuangdong 510700China

Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).

关键词： anemia aplastic interferon

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A multicenter prospective study on the management of hepatoblastoma in children:a report from the Chinese Children's Cancer Group

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World Journal of Pediatrics 2024年第6期20卷 590-601页

作者： Meng-Jie Tang Xiao-Li Ma Xiang-Ling He Wei-Hua Pan Xiao-Hong Zhang Sha-Yi Jiang Ju Gao Fu Lie Wei Yao Song Gu Wei-Ling Zhang Qiang Zhao Shi-Hao Huang Yong-Jun Fang Wei Liu Hui-Zhong Niu Chun-Mei Wang Li-Rong Sun Hui Gao Yun-Peng Dai Shun-Gen Huang Zhi-Yong Zhong Xi-Ge Wang Zhong-Rong Li Liang-Chun Yang Ye-Ming Wu Huan-Min Wang Xin Sun Xiao-Jun Yuan Department of Pediatric hematology/Oncology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang RoadYangpu DistrictShanghai 200092China Medical Oncology Department Pediatric Oncology CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of hematology/Oncology Children's Medical CenterHunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 41005China Department of Pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of hematology/Oncology Guangzhou Women and Children's Medical CenterNational Children's Medical Center for South Central RegionGuangzhou 510623China Department of hematology Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200062China Department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041China Department of hematology/Oncology Qilu Children's Hospital of Shandong UniversityJinan 250022China Department of Pediatric Surgery Children's Hospital of Fudan UniversityShanghai 201102China Department of General Surgery Shanghai Children's Medical Center(National Children's Medical Center-Shanghai)Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Pediatrics Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of hematology/Oncology Children's Hospital of Nanjing Medical UniversityNanjing 210008China Department of hematology/Oncology Henan Children's HospitalZhengzhou 450018China Department of Pediatric General Surgery Hebei Children's Hospital of Hebei Medical UniversityShijiazhuang City 050031China Children's Hospital the First Affliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Paediatric

Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(CCCG)in *** A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was *** demographics,treatment protocols,and other related information were *** regression models and Kaplan-Meier curve methods were *** The 4-year event-free survival(EFS)and overall survival(OS)were 76.9 and 93.5%,*** 4-year EFS rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,*** 4-year 0S was 100%,97.3%,94.4%,and 86.8%,*** regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 *** with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 ***≥8 years,R+,and E+were independent risk factors for *** with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

关键词： Alpha-fetoprotein Hepatoblastoma Multicenter Prospective study Survival

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Infection in Multiple Myeloma: Microbiological Profile and Prognosis in Senegalese Patients

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Open Journal of Blood Diseases 2024年第2期14卷 47-58页

作者： Seynabou Fall El Hadj Daouda Niang Khadim Sarr Lolita Mariéme Camara-Tall Modou Moustapha Ciss Amy Thiam Aminata Dakono Awa Ndiaye Fatou Samba Diago Ndiaye Clinical hematology Department of Dalal Jamm Hospital Gudiawaye Dakar Sngal hematology Clinic Unit of Aristide Le Dantec Hospital Dakar Sngal

Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.

关键词： Multiple Myeloma Infections Tuberculosis Senegal

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The non-canonical poly(A)polymerase FAM46C promotes erythropoiesis

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Journal of Genetics and Genomics 2024年第6期51卷 594-607页

作者： Ke Yang Tiangi Zhu Jiaying Yin Qiaoli Zhangg Jing Li Hong Fan Gajing Han Weiyin Xu Nan Liu Xiang Lv Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China Liangzhu laboratory Zhejang UniversityHangzhouZhejang 311121China Institute of hematology Zhejiang UniversityHangzhouZhejiang 311121China The State Key laboratory for Complex Severeand Rare DiseasesHaihe Laboratory of Cell EcosystemDepartment of PathophysiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Medical Epigenetics Research Center Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

The post-transcriptional regulation of mRNA is a crucial component of gene *** disruption of this process has detrimental effects on the normal development and gives rise to various *** for novel post-transcriptional regulators and exploring their roles are essential for understanding development and *** a multimodal analysis of red blood cell trait genome-wide association studies(GWAS)and transcriptomes of erythropoiesis,we identify FAM46C,a non-canonical RNA poly(A)polymerase,as a necessary factor for proper red blood cell ***46C is highly expressed in the late stages of the erythroid lineage,and its developmental upregulation is controlled by an erythroidspecific *** demonstrate that FAM46C stabilizes mRNA and regulates erythroid differentiation in a polymerase activity-dependent ***,we identify transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C,which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox *** conclusion,our study unveils a unique role of FAM46C in positively regulating lysosome and mitochondria components,thereby promoting erythropoiesis.

关键词： FAM46C TENT5C Poly(A)polymerase Erythroblasts Post-transcriptional regulation Erythroid-specific enhancer

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Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

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Protein & Cell 2024年第5期15卷 315-330页

作者： Alkmini T.Anastasiadi Vasiliki-Zoi Arvaniti Krystalyn E.Hudson Anastasios G.Kriebardis Constantinos Stathopoulos Angelo D’Alessandro Steven L.Spitalnik Vassilis L.Tzounakas Department of Biochemistry School of MedicineUniversity of Patras26504 PatrasGreece Department of Pathology and Cell Biology Columbia University Irving Medical CenterNew York CityNY 10032USA laboratory of Reliability and Quality Control in laboratory hematology(HemQcR) Department of Biomedical SciencesSchool of Health&Caring SciencesUniversity of West Attica(UniWA)12243 EgaleoGreece Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus13001 AuroraCOUSA Present address:Institute for Fundamental Biomedical Research(IFBR) Biomedical Sciences Research Center“Alexander Fleming”Vari11527 AthensGreece

We need to talk about red blood *** cells are defined as cells containing distinct nuclei and other membranous ***,red blood cells(RBCs)lack a nucleus and organelles—perhaps to limit the generation of reactive oxygen species(Zhang et al.,2011)—and are filled with hemoglobin(Hb).This oxygen carrier is limited to the cytosol by the cell membrane and cytoskeleton,which maintain cellular integrity and deformability as RBCs pass through narrow capillaries(Gratzer,1994)to perform their primary function of gas exchange.

关键词： membranous maintain

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Parenteral iron therapy in children with iron deficiency anemia

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World Journal of Clinical Cases 2024年第13期12卷 2138-2142页

作者： Jelena Roganovic Department of Pediatric hematology and Oncology Children’s Hospital Zagreb10000 ZagrebCroatia Faculty of Biotechnology and Drug Development University of RijekaRijeka 51000Croatia

Iron deficiency anemia(IDA)continues to be a global public health *** iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral *** subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is *** numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very *** mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron *** this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.

关键词： Anemia Iron deficiency Intravenous iron Iron deficiency anemia Children

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