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miR-125b reverses cisplatin resistance by regulating autophagy via targeting RORA/BNIP3L axis in lung adenocarcinoma

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Oncology Research 2024年第4期32卷 643-658页

作者： LEI LIU NA GUO XIANGLING LI QIAN XU RUILONG HE LIMIN CHENG CHUNYAN DANG XINYU BAI YIYING BAI XIN WANG QIANHUI CHEN LI ZHANG department of immunology Chengde Medical UniversityChengde067000China department of Pathology Chengde Medical UniversityChengde067000China department of Oncology The Affiliated Hospital of Chengde Medical UniversityChengde067000China department of Hepatobiliary Surgery The Affiliated Hospital of Chengde Medical UniversityChengde067000China

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the *** has been shown that microRNAs(miRNAs)play a significant role in tumor *** this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR *** decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival ***-125b decreased the A54./DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of *** addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in *** mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed *** on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.

关键词： Lung adenocarcinoma miRNAs Cisplatin Resistance Autophagy

Polio eradication surveillance in Sri Lanka,2019-2023

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Asian Pacific Journal of Tropical Medicine 2024年第6期17卷 268-272页

作者： M.A.Y.Fernando N.S.Madarasinghe C.Rangana N.Weerasinghe D.C.U.D.Weligamage J.I.Abeynayake department of medical Microbiology and immunology Faculty of MedicineUniversity of ColomboSri Lanka department of Virology Medical Research InstituteColombo 08Sri Lanka medical Research Institute Colombo 08Sri Lanka

Objective:To evaluate the polio laboratory surveillance carried out from January,2019 to May,2023 by the Polio Regional Reference Laboratory,Sri ***:This retrospective study analyzed all stool samples received under the acute flaccid paralysis(AFP)and immunodeficient vaccine-derived poliovirus(VDPV)surveillance at Polio Regional Reference Laboratory,Sri Lanka from January,2019 to May,*** results of the testing methodologies were extracted from the laboratory data system,i.e.,poliovirus virus isolation,intra-typic differentiation/VDPV real time reverse transcriptase polymerase chain reaction(ITD/VDPV rRTPCR)and sequencing,along with the data on timing of reporting results,stool adequacy and *** was analyzed using descriptive ***:A total of 214. stool samples from 164. cases were received for AFP surveillance from Sri Lanka(93.61%),Maldives(1.52%),and immunodeficient VDPV(4.86%)*** polioviruses(19/164.,1.15%)and non-polio enteroviruses(73/164.,4.4.%)were isolated,while Sabin-like 3 virus was detected in majority(12/19,63.15%)among the poliovirus *** polioviruses or circulating VDPVs were not detected among the *** all years of the study,the non-polio AFP detection rate was>1/100000 in children aged less than 15 years,whereas stool adequacy rate was>80%.All results were reported within 14.days of receipt,ensuring timely reporting as per global ***:The Polio Regional Reference Laboratory,Sri Lanka plays a vital role in maintaining the polio-free status in the country through its robust laboratory surveillance,while adhering to the surveillance ***-detection of wild polioviruses and circulating VDPV during the study period reinforces the polio-free status in the country.

关键词： Poliovirus Polio laboratory surveillance Regional reference laboratory Polio eradication

YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation

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Research 2024年第2期6卷 401-415页

作者： Jiadi Lv Xiaohan Liu Yabo Zhou Feiran Cheng Haoran Chen Shunshun Li Dianheng Wang Li Zhou Zhenfeng Wang Nannan Zhou Jie Chen Bo Huang department of immunology&State Key Laboratory of Common Mechanism Research for Major Diseases Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical College(PUMC)Beijing100005China department of Histology and Embryology Basic Medical CllegeChina Medical UniversityShenyangLiaoning 11122China department of immunology Basic Medical Cllege China Medical UniversityShenyangLiaoning 110122China department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China

Solid tumor cells live in a highly dynamic mechanical *** the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an ***,we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like ***,integrin?was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein(YAP).YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G(MAFG),allowing MAFG to transactivate the stemness genes NANOG,SOX2,and *** also restoredβ8 expression,thereby forming a closed mechanical ***,MAFG expression is correlated with worse *** findings provide mechanical insights into the regulation of tumor cell dedifferentiation,which has therapeutic implications for exploring innovative strategies to attack malignancies.

关键词： activation thereby MAF

Evaluation of urea breath test as a diagnostic tool for Helicobacter pylori infection in adult dyspeptic patients

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World Journal of Gastroenterology 2024年第17期30卷 2302-2307页

作者： Zeinab Nabil Ahmed Said Asmaa Mohamed El-Nasser department of medical Microbiology&immunology Faculty of Medicine for Girls Al-Azhar UniversityNasr City 11754CairoEgypt

In this editorial,we discuss the article in the World Journal of *** article conducts a meta-analysis of the diagnostic accuracy of the urea breath test(UBT),a non-invasive method for detecting Helicobacter pylori(***)infection in *** is based on radionuclide-labeled *** methods,both invasive and non-invasive,are available for diagnosing *** infection,inclu-ding endoscopy with biopsy,serology for immunoglobulin titers,stool antigen analysis,and *** guidelines recommend UBTs as the primary choice for diagnosing *** infection and for reexamining after eradication *** is used to be the first choice non-invasive test due to their high accuracy,specificity,rapid results,and ***,its performance remains unaffected by the distribution of *** in the stomach,allowing a high flow of patients to be *** its widespread use,the performance characteristics of UBT have been inconsistently described and remain incompletely *** are two UBTs available with Food and Drug Administration approval:The 13C and 14. *** tests are affordable and can provide real-time *** may prefer the 13C test because it is non-radioactive,compared to 14. which uses a radioactive isotope,especially in young children and pregnant *** there was heterogeneity among the studies regarding the diagnostic accuracy of both UBTs,13C-UBT consistently outperforms the *** makes the 13C-UBT the preferred diagnostic ***,the provided findings of the meta-analysis emphasize the significance of precise considerations when choosing urea dosage,assessment timing,and measurement techniques for both the 13C-UBT and 14.-UBT,to enhance diagnostic precision.

关键词： Helicobacter pylori Urea breath test Diagnosis Diagnostic test accuracy Meta-analysis

IGF2BPs as novel m^(6)A readers:Diverse roles in regulating cancer cell biological functions,hypoxia adaptation,metabolism,and immunosuppressive tumor microenvironment

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Genes & Diseases 2024年第2期11卷 890-920页

作者： Meiqi Duan Haiyang Liu Shasha Xu Zhi Yang Fusheng Zhang Guang Wang Yutian Wang Shan Zhao Xiaofeng Jiang department of General Surgery The Fourth Affiliated Hospital of China Medical UniversityShenyangLiaoning 110032China department of Gastroendoscopy The Fourth Affiliated Hospital of China Medical UniversityShenyangLiaoning 110032China department of Rheumatology and immunology The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110002China

m^(6)A methylation is the most frequent modification of mRNA in eukaryotes and plays a crucial role in cancer progression by regulating biological ***-like growth factor 2 mRNA-binding proteins(IGF2BP)are newly identified m^(6)A‘readers’.They belong to a family of RNA-binding proteins,which bind to the m^(6)A sites on different RNA sequences and stabilize them to promote cancer *** this review,we summarize the mechanisms by which different upstream factors regulate IGF2BP in *** current literature analyzed here reveals that the IGF2BP family proteins promote cancer cell proliferation,survival,and chemoresistance,inhibit apoptosis,and are also associated with cancer glycolysis,angiogenesis,and the immune response in the tumor ***,with the discovery of their role as‘readers’of m^(6)A and the characteristic re-expression of IGF2BPs in cancers,it is important to elucidate their mechanism of action in the immunosuppressive tumor *** also describe in detail the regulatory and interaction network of the IGF2BP family in downstream target RNAs and discuss their potential clinical applications as diagnostic and prognostic markers,as well as recent advances in IGF2BP biology and associated therapeutic value.

关键词： Cancer IGF2BP Immunosuppressive TME m^(6)A Molecular mechanism Therapy

Effects of serum inflammatory factors,health index and disease activity scores on ankylosing spondylitis patients with sleep disorder

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World Journal of Psychiatry 2024年第6期14卷 866-875页

作者： Hui Wang Jia-Ying Sun Yue Zhang department of Rheumatology and immunology The First Affiliated Hospital of Harbin Medical UniversityHarbin 150001Heilongjiang ProvinceChina

BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of *** To investigate the clinical significance of serum inflammatory factors,health index and disease activity scores in patients with AS complicated by sleep *** A total of 106 AS patients with comorbid sleep disorders were included in the *** patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical *** serum levels of inflammatory factors,including C-reactive protein,erythrocyte sedimentation rate,interleukin(IL)-6,tumour necrosis factor-αand IL-1β,were *** activity scores,such as the Bath AS functional index,Bath AS disease activity index,Bath AS metrology index and AS disease activity score,were *** health index was obtained through the Short Form-36 *** The study found significant associations amongst serum inflammatory factors,health index and disease activity scores in AS patients with comorbid sleep *** correlations were found between serum inflammatory factors and disease activity scores,indicating the influence of heightened systemic inflammation on disease severity and functional ***,negative correlations were found between disease activity scores and health index parameters,highlighting the effect of disease activity on various aspects of healthrelated quality of *** regression analysis further confirmed the predictive value of these factors on patient outcomes,underscoring their potential utility in risk assessment and *** The findings demonstrate the intricate interplay amongst disease activity,systemic inflammation and patientreported health outcomes in AS patients complicated by sleep *** results emphasise the need for comprehensive care strategies that address the diverse needs and challe

关键词： Inflammatory factors Disease activity scores Health index Ankylosing spondylitis Sleep disorders

PIM1-HDAC2 axis modulates intestinal homeostasis through epigenetic modification

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3049-3067页

作者： Jianming Yang Yawen Xiao Ningning Zhao Geng Pei Yan Sun Xinyu Sun Kaiyuan Yu Chunhui Miao Ran Liu Junqiang Lv Hongyu Chu Lu Zhou Bangmao Wang Zhi Yao Quan Wang Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Institute of ImmunologyState Key Laboratory of Experimental Hematologythe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsDepartment of ImmunologySchool of Basic Medical SciencesTianjin Institute of Urologythe Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Cellular and Molecular ImmunologyTianjin Medical UniversityTianjin 300070China department of Pathology Tianjin Medical University Cancer Institute and Hospital/National Clinical Research Center of Cancer/Key Laboratory of Cancer Prevention and TherapyTianjin/Tianjin’s Clinical Research Center of CancerTianjin 30060China department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300070China

The mucosal barrier is crucial for intestinal homeostasis,and goblet cells are essential for maintaining the mucosal barrier *** proviral integration site for Moloney murine leukemia virus-1(PIM1)kinase regulates multiple cellular functions,but its role in intestinal homeostasis during colitis is ***,we demonstrate that PIM1 is prominently elevated in the colonic epithelia of both ulcerative colitis patients and murine models,in the presence of intestinal *** PIM1 leads to decreased goblet cells,thus impairing resistance to colitis and colitis-associated colorectal cancer(CAC)in ***,PIM1 modulates goblet cell differentiation through the Wnt and Notch signaling ***,PIM1 interacts with histone deacetylase 2(HDAC2)and downregulates its level via phosphorylation,thereby altering the epigenetic profiles of Wnt signaling pathway ***,these findings investigate the unknown function of the PIM1-HDAC2 axis in goblet cell differentiation and ulcerative colitis/CAC pathogenesis,which points to the potential for PIM1-targeted therapies of ulcerative colitis and CAC.

关键词： PIM1 HDAC2 Goblet cell Gut microbiota Intestinal homeostasis Epigenetic modification Ulcerative colitis CAC

The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao department of immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou Institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier Research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life Sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate ***,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still *** used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil ***5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic *** addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type *** bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human ***,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in *** RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected *** these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrop

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang Xiaoguang Li Xinjie Bao 4.4.Doctor medical Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes