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The m^(6)A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

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Genes & Diseases 2024年第2期11卷 993-1008页

作者： Fangyi Yao Fangmin Zhong Junyao Jiang Ying Cheng Shuai Xu Jing Liu Jin Lin Jing Zhang Shuqi Li Meiyong Li Yanmei Xu Bo Huang Xiaozhong Wang Jiangxi Province Key laboratory of laboratory Medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Chronic myeloid leukemia(CML)is a common adult *** the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor *** N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological ***1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is *** this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase ***,KIAA1429 regulated the total level of RNA m^(6)A modification in the CML cells and promoted the malignant biological behaviors of CML cells,including proliferation,migration,and imatinib *** KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis,consequently inhibiting CML proliferation and drug efflux,ultimately increasing the sensitivity of CML cells to ***,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their ***,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell *** also inhibited the tumorigenesis of CML cells in *** combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to *** study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis to up-regulate RAB27B expression,thereby promoting CML *** exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

关键词： Chronic myeloid leukemia KIAA1429 N6-methyladenine RAB27B Rucaparib YTHDF1

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clinical applications of metagenomics next-generation sequencing in infectious diseases

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 471-484页

作者： Ying LIU Yongjun MA department of clinical laboratory Affiliated Jinhua HospitalZhejiang University School of MedicineJinhua 321000China

Infectious diseases are a great threat to human *** and accurate detection of pathogens is important in the diagnosis and treatment of infectious *** next-generation sequencing(mNGS)is an unbiased and comprehensive approach for detecting all RNA and DNA in a *** the development of sequencing and bioinformatics technologies,mNGS is moving from research to clinical application,which opens a new avenue for pathogen *** studies have revealed good potential for the clinical application of mNGS in infectious diseases,especially in difficult-to-detect,rare,and novel ***,there are several hurdles in the clinical application of mNGS,such as:(1)lack of universal workflow validation and quality assurance;(2)insensitivity to high-host background and low-biomass samples;and(3)lack of standardized instructions for mass data analysis and report ***,a complete understanding of this new technology will help promote the clinical application of mNGS to infectious *** review briefly introduces the history of next-generation sequencing,mainstream sequencing platforms,and mNGS workflow,and discusses the clinical applications of mNGS to infectious diseases and its advantages and disadvantages.

关键词： Metagenomics next-generation sequencing(mNGS) Infectious disease Cerebrospinal fluid(CSF) Oxford Nanopore Technologies(ONT) Microbiome

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Rapid and sensitive detection of urinary KIM-1 using fully printed photonic crystal microarrays

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Nano Research 2024年第5期17卷 4329-4337页

作者： Yang Liu Xuwei He Zewei Lian Qian Guo Jimei Chi Xiaoxue Lin Liyue Zhang Zheng Liu Yingyuan Liu Meng Su Keyu Wang Qiangguo Ao Qingli Cheng department of Nephrology The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China Chinese PLA Medical School Beijing 100853China Key laboratory of Green Printing CAS Research/Education Center for Excellence in Molecular SciencesBeijing Engineering Research Center of Nanomaterials for Green Printing TechnologyBeijing National Laboratory for Molecular Sciences(BNLMS)Institute of ChemistryChinese Academy of Sciences(ICCAS)Beijing 100190China department of Rheumatology and Immunology Peking University International HospitalBeijing 102206China department of clinical laboratory The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China

Urinary kidney injury molecule 1(uKIM-1)serves as a reliable marker for the early diagnosis of acute kidney injury(AKI).The rapid and facile detection of changes in uKIM-1 is essential for early AKI diagnosis,ultimately improving the prognosis of *** this study,we developed a fully printed photonic crystal-integrated microarray with photonic crystal-enhanced fluorescence properties,which can detect uKIM-1 levels at the *** confirmed its efficacy in the early diagnosis of AKI using clinical urine *** quantitative detection of uKIM-1 was achieved within 10 *** lowest limit of detection is 8.75 pg·mL^(-1) with an accuracy of 94.2%.The diagnostic efficacy was validated using 86 clinical urine samples,highlighting the high sensitivity and stability of the photonic crystal ***,a facile and reliable immunoassay was designed and prepared for the rapid quantitative detection of uKIM-1,which is crucial for the early identification and convenient detection of AKI in hospital or community ***,convenient,cost-effective,and long-term monitoring of changes in uKIM-1 levels can assist clinicians in making timely adjustments to treatment regimens,preventing the transition from AKI to chronic kidney disease(CKD),improving the quality of life of patients with AKI,and reducing healthcare *** highlights the advantages of utilizing urine samples as a noninvasive and easily accessible medium for early detection and monitoring of kidney-related conditions.

关键词： photonic crystal point-of-care testing urine kidney injury molecule-1(KIM-1) acute kidney injury

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Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice

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Biomedical and Environmental Sciences 2024年第1期37卷 19-30页

作者： MENG Li Ying TAO Wen Fu LI Jing ZHU Min ZHONG De Bin ZHOU Jing QIN Xue WEI Rong Guo department of clinical laboratory The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina department of clinical laboratory The Fifth Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina Jiangsu Key laboratory of Environmental Engineering Jiangsu Academy of Environmental SciencesNanjing 210000JiangsuChina

Objective The aim of this study was to assess the impact of bisphenol A(BPA)and its substitute,bisphenol F(BPF),on the colonic fecal community structure and function of *** We exposed 6–8-week-old male C57BL/6 mice to 5 mg/(kg∙day)and 50μg/(kg∙day)of BPA or BPF for 14 *** samples from the colon were analyzed using 16S rRNA *** Gut microbiome community richness and diversity,species composition,and function were significantly altered in mice exposed to BPA or *** change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and ***,pathways related to carbohydrate and amino acid metabolism showed substantial *** Mice exposed to different BP analogs exhibited distinct gut bacterial community richness,composition,and related metabolic *** the essential role of gut bacteria in maintaining intestinal homeostasis,our study highlights the intestinal toxicity of BPs in vertebrates.

关键词： Bisphenol A(BPA) Bisphenol F(BPF) 16S rRNA Microbiota

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Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1677-1692页

作者： Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu State Key laboratory of Natural Medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionDepartment of PhysiologySchool of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China department of clinical Pharmacology School of PharmacyNanjing Medical UniversityNanjing 211166China

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal *** identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is *** our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus *** enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory ***,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy ***,*** up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet *** espe-cially significant finding is that *** activates the AhR pathway,thereby promoting the expression of *** summary,our results strongly indicate that *** enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关键词： Chemotherapy Mucositis Eubacterium coprostanoligenes MUC2 AUF1

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Calculus bovis in hepatocellular carcinoma:Tumor molecular basis,Wnt/β-catenin pathway role,and protective mechanism

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World Journal of Gastroenterology 2024年第35期30卷 3959-3964页

作者： Khaled Mohamed Mohamed Koriem department of Medical Physiology Medical Research and Clinical Studies InstituteNational Research CentreGiza 12622Egypt

In this editorial,we comment on the recent article by Huang et *** editorial focuses specifically on the molecular mechanisms of hepatocellular carcinoma(HCC),mechanism of Wnt/β-catenin pathway in HCC,and protective mechanism of Calculus bovis(CB)in *** cancer is the fourth most common cause of cancer-related deaths *** most prevalent kind of primary liver cancer,HCC,is typically brought on by long-term viral infections(hepatitis B and C),non-alcoholic steatohepatitis,excessive alcohol consumption,and other conditions that can cause the liver to become chronically inflamed and *** is a wellknown traditional remedy in China and Japan and has been used extensively to treat a variety of diseases,such as high fever,convulsions,and *** in lipid metabolism,cholesterol metabolism,bile acid metabolism,alcohol metabolism,and xenobiotic detoxification lead to fatty liver disease and liver ***,which is a tricarboxylic acid cycle intermediate,is vital to energy production and mitochondrial *** is also thought to be a signaling molecule in metabolism and in the development and spread of liver *** Wnt/β-catenin pathway is made up of a group of proteins that are essential for both adult tissue homeostasis and embryonic *** is frequently caused by the dysregulation of the Wnt/β-catenin signaling *** HCC liver carcinogenesis,Wnt/β-catenin signaling is activated by the expression of downstream target *** between the liver and the gut exists via the portal vein,biliary tract,and systemic ***"gutliver axis"controls intestinal *** of the main factors contributing to the development,progression,and treatment resistance of HCC is the abnormal activation of the Wnt/β-Catenin signaling ***,understanding this pathway is essential to treating *** ingredients of CB,particularly oleanolic acid,ergosterol,and ursolic acid,have anti-p

关键词： Hepatocellular carcinoma MicroRNAs Wnt/β-catenin pathway Calculus bovis Apoptosis

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Evaluation of the value of combined detection of tumor markers CA724,carcinoembryonic antigen,CA242,and CA19-9 in gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1737-1744页

作者： Chong-Mei Zhou Shao-Hua Zhao department of clinical laboratory Henan Provincial People's HospitalZhengzhou 450003Henan ProvinceChina

BACKGROUND Gastric cancer is a global health concern that poses a significant threat to human *** To detecting serum changes in carcinoembryonic antigen(CEA),carbohydrate antigens(CA)724,CA242,and CA19-9 expression among patients with gastric *** Eighty patients diagnosed with gastric cancer between January 2020 and January 2023 were included in the observation group,while 80 patients with benign gastric diseases were included in the control *** groups were tested for tumor markers(CA724,CEA,CA242,and CA19-9].Tumor marker indicators(CA724,CEA,CA242,and CA19-9)were compared between the two groups,assessing positive rates of tumor markers across various stages in the observation ***,single and combined detection of various tumor markers were *** The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value observed for the combined detection of CA724,CEA,CA242,and CA19-9 were higher than those of CA724,CEA,CA242,and CA19-9 ***,the combined detection of CA724,CEA,CA242,and CA19-9 has a high diagnostic accuracy and could reduce the occurrence of missed or misdiagnosed cases,facilitating the early diagnosis and treatment of *** CA724,CEA,CA242,and CA19-9 serum levels in gastric cancer patients significantly surpassed those in non-gastric cancer patients(Pclinical promotion.

关键词： Biomarkers Serum Gastric cancer Diagnostic value

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Metadherin-driven promotion of cancer stem cell phenotypes and its effect on immunity in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第20期30卷 2624-2628页

作者： Nevena Todorović Amedeo Amedei department of Experimental and clinical Medicine University of FlorenceFlorence 50134Italy Clinic for Infectious and Tropical Diseases University Clinical Centre of SerbiaBelgrade 11000Serbia

In this editorial we provide commentary on the article published by Wang et al,featured in the recent issue of the World Journal of Gastroenterology in *** focus on the metadherin(MTDH),also known as astrocyte elevated gene-1 or lysine rich CEACAM1,and its effects on cancer stem cells(CSCs)and immunity in hepatocellular carcinoma(HCC).HCC is the most common primary liver cancer and one of the leading causes of cancer-related deaths *** HCC cases develop in the context of liver *** the pivotal mechanisms of carcinogenesis are gene mutations,dysregulation of diverse signaling pathways,epigenetic alterations,hepatitis B virus-induced hepatocarcinogenesis,chronic inflammation,impact of tumor microenvironment,oxidative *** the years,extensive research has been conducted on the MTDH role in various tumor pathologies,such as lung,breast,ovarian,gastric,hepatocellular,colorectal,renal carcinoma,neuroblastoma,melanoma,and ***,its involvement in tumor development processes including transformation,apoptosis evasion,angiogenesis,invasion,and metastasis via multiple signaling *** has been demonstrated that knockdown or knockout of MTDH disrupt tumor development and *** addition,numerous reports have been carried out regarding the MTDH influence on HCC,demonstrating its role as a predictor of poor prognosis,aggressive tumor phenotypes prone to metastasis and recurrence,and exhibiting significant potential for therapy ***,more studies finely investigated the influence of MTDH on *** CSCs are a small subpopulation of tumor cells that sharing traits with normal stem cells like self-renewal and differentiation abilities,alongside a high plasticity that alters their *** their presumed role in tumor initiation,they can drive also disease relapse,metastasis,and resistance to chemo and radiotherapy.

关键词： Hepatocellular carcinoma Metadherin Astrocyte elevated gene-1 Lysine rich

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Characterization of the CpsQ Regulon Reveals Its Role in the Transcription of Type Ⅵ Secretion System 2 Genes in Vibrio parahaemolyticus

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Biomedical and Environmental Sciences 2024年第4期37卷 436-439页

作者： LUO Xi LI Xue ZHANG Miao Miao HUANG Qing Lian ZHANG Yi Quan JI Shen Jie LU Ren Fei department of clinical laboratory Affiliated Nantong Hospital 3 of Nantong UniversityNantong Third People’s HospitalNantong 226006JiangsuChina department of clinical laboratory Qidong People’s HospitalQidong 226200JiangsuChina

Vibrio parahaemolyticus,a gram-negative halophilic bacterium that naturally inhabits coastal waters,causes gastroenteritis,skin infections,and septicemia in human beings[1].This bacterium produces multiple virulence factors,including thermostable direct hemolysin(TDH),TDH-related hemolysin(TRH),type Ⅲ secretion system 1(T3SS1),T3SS2,type Ⅵ secretion system 1(T6SS1),and T6SS2[1].Furthermore,Ⅴ.parahaemolyticus forms biofilms on the surface,which help it in adapting to unfavorable conditions[2].Mature biofilm formation requires special structures,including lateral and polar flagella,exopolysaccharide(EPS),and type Ⅳ pili[2].

关键词： coastal system T3SS

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High-throughput computational screening and in vitro evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione(C3),as a novel EGFR—HER2 dual inhibitor in gastric tumors

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Oncology Research 2024年第2期32卷 251-259页

作者： MESFER AL SHAHRANI REEM GAHTANI MOHAMMAD ABOHASSAN MOHAMMAD ALSHAHRANI YASSER ALRAEY AYED DERA MOHAMMAD RAJEH ASIRI PRASANNA RAJAGOPALAN department of clinical laboratory Sciences College of Applied Medical SciencesKing Khalid UniversityAbhaSaudi Arabia

Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation,adhesion,angiogenesis,and *** therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic ***,dual inhibition strategies are recommended to increase potency and reduce *** this study,we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase ***-based High-throughput Virtual Screening(D-HTVS)was used to screen the whole ChemBridge small molecular library against EGFR and *** atomistic molecular dynamic simulation was conducted to understand the dynamics and stability of the protein-ligand ***/HER2 kinase enzymes,KATOIII,and Snu-5 cells were used for in vitro *** atomistic Molecular Dynamics simulations followed by solvent-based Gibbs binding free energy calculation of top molecules,identified compound C3(5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione)to have a good affinity for both EGFR and *** predicted compound,C3,was promising with better binding energy,good binding pose,and optimum interactions with the EGFR and HER2 residues.C3 inhibited EGFR and HER2 kinases with IC50 values of 37.24 and 45.83 nM,*** GI50 values of C3 to inhibit KATOIII and Snu-5 cells were 84.76 and 48.26 nM,*** on these findings,we conclude that the identified compound C3 showed a conceivable dual inhibitory activity on EGFR/HER2 kinase,and therefore can be considered as a plausible lead-like molecule for treating gastric cancers with minimal side effects,though testing in higher models with pharmacokinetic approach is required.

关键词： Dual inhibitor Drug discovery EGFR/HER2 kinase Gastric cancer High-throughput screening

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