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Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1665-1674页

作者： Jie Xiong Shu Cheng Xiao Gao Shan-He Yu Yu-Ting Dai Xin-Yun Huang Hui-Juan Zhong Chao-Fu Wang Hong-Mei Yi Hao Zhang Wei-Guo Cao Rong Li Wei Tang Yan Zhao Peng-Peng Xu Li Wang Wei-Li Zhao Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Nuclear Medicine Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of pathology Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Otolaryngology Shanghai Rujin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Radiation Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Hematology Navy Medical Center of PLAShanghaiChina Pole de Recherches Sino-Francais en Science du Vivant et Genomique Laboratory of Molecular PathologyShanghaiChina

Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive *** explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase ll study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 *** complete response and overall response rate after induction treatment were 59%(95%Cl,43-79%)and 68%(95%Cl,47-84%),*** a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,63-95%),*** most frequently grade 3/4 adverse events were neutropenia(32%,n=7)and hypofibrinogenemia(18%,n=4),which were manageable and led to no discontinuation of *** proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-l correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab *** conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage *** lipid profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

关键词： killer metabolism lymphoma

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Atherosclerosis originating from childhood:Specific features

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Journal of Biomedical Research 2024年第3期38卷 233-240页

作者： Anastasia V.Poznyak Alexey A.Yakovlev MikhailА.Popov Elena B.Zhigmitova Vasily N.Sukhorukov Alexander N.Orekhov Institute for Atherosclerosis Research Moscow 121609Russia Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology Moscow 109240Russia Department of Cardiac Surgery Moscow Regional Research and Clinical InstituteMoscow 129110Russia laboratory of Angiopathology Institute of General Pathology and PathophysiologyMoscow 125315Russia

Atherosclerosis is extremely ***,it is considered a disease of older people,who most often experience problems with the heart and blood *** much attention from the scientific community has been paid to studying the association between aging and atherosclerosis,as well as its consequences,there is evidence that atherosclerosis occurs at an early *** may form both during intrauterine development and in *** plays an important role in childhood atherosclerosis,along with previous infectious diseases and excess weight of both the child and the *** the present review,we examined the development of atherosclerosis and the prerequisites in childhood.

关键词： atherosclerosis childhood pediatrics cardiovascular disease

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Development of a stable attenuated double-mutant of tobacco mosaic virus for cross-protection

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Journal of Integrative Agriculture 2024年第7期23卷 2318-2331页

作者： Xiaojie Xu Shaoyan Jiang Chunju Liu Xujie Sun Qing Zhu Xiuzhai Chen Pengchao Jiang Fenglong Wang Yanping Tian Xiangdong Li The Engineering Research Institute of Agriculture and Forestry Ludong UniversityYantai 264025China laboratory of Plant Virology Department of Plant PathologyCollege of Plant ProtectionShandong Agricultural UniversityTai’an 271018China Weifang Tobacco Corporation Weifang 261031China Linyi Tobacco Corporation Linyi 276000China Tobacco Research Institute Chinese Academy of Agricultural SciencesQingdao 266101China

Tobacco(Nicotiana tabacum)and tomato(Solanum lycopersicum)are two major economic crops in *** mosaic virus(TMV;genus Tobamovirus)is the most prevalent virus infecting both ***,some widely cultivated tobacco and tomato cultivars are susceptible to TMV and there is no effective strategy to control this ***-protection can be a safe and environmentally friendly strategy to prevent viral ***,stable attenuated TMV mutants are *** this study,we found that the substitutions in the replicase p126,arginine at position 196(R^(196))with aspartic acid(D),glutamic acid at position 614(E^(614))with glycine(G),serine at position 643(S^(643))with phenylalanine(F),or D at position 730(D^(730))with S,significantly reduced the virulence and replication of ***,only the mutation of S^(643) to F reduced the RNA silencing suppression activity of TMV p126.A double-mutant TMV-E614G-S643F induced no visible symptom and was genetically stable through six successive passages in tobacco ***,our results showed that TMV-E614G-S643F double-mutant could provide effective protection against the wild-type TMV infection in tobacco and tomato *** study reports a promising mild mutant for cross-protection to control TMV in tobacco and tomato plants.

关键词： cross-protection double-mutant p126 tobacco mosaic virus virulence

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Nature’s Pharmacy under Siege: Investigating Antibiotic Resistance Pattern in Endophytic Bacteria of Medicinal Plants

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Advances in Microbiology 2024年第4期14卷 183-208页

作者： Bonoshree Sarkar Afroza Sultana Nabila Nawar Binti Farhana Tasnim Chowdhury Sadia Afrin Mohammad Fahim Taibur Rahman Atiqur Rahman Infection Biology laboratory Department of Biochemistry and Molecular Biology University of Dhaka Dhaka Bangladesh Department of pathology University of Alabama at Birmingham Birmingham USA

Antibiotic resistance poses a significant global health threat, necessitating a thorough understanding of its prevalence in various ecological contexts. Medicinal plants, renowned for their therapeutic properties, host endophytic bacteria that produce bioactive compounds. Understanding antibiotic resistance dynamics in these bacteria is vital for human health and antibiotic efficacy preservation. In this study, we investigated antibiotic resistance profiles in endophytic bacteria from five medicinal plants: Thankuni, Neem, Aparajita, Joba, and Snake plant. We isolated and characterized 113 endophytic bacteria, with varying resistance patterns observed against multiple antibiotics. Notably, 53 strains were multidrug-resistant (MDR), with 14 exhibiting extensive drug resistance (XDR). Thankuni-associated bacteria displayed 44% MDR and 11% XDR, while Neem-associated bacteria showed higher resistance (60% MDR, 13% XDR). Aparajita-associated bacteria had lower resistance (22% MDR, 6% XDR), whereas Joba-associated bacteria exhibited substantial resistance (54% MDR, 14% XDR). Snake plant-associated bacteria showed 7% MDR and 4% XDR. Genus-specific distribution revealed Bacillus (47%), Staphylococcus (21%), and Klebsiella (11%) as major contributors to MDR. Our findings highlight diverse drug resistance patterns among plant-associated bacteria and underscore the complexity of antibiotic resistance dynamics in diverse plant environments. Identification of XDR strains emphasizes the severity of the antibiotic resistance problem, warranting further investigation into contributing factors.

关键词： Antibiotic Resistance Endophytic Bacteria Medicinal Plants Drug Resistance

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UBE2T mediates the stemness properties of breast cancer cells through the mTOR signaling pathway

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BIOCELL 2024年第6期48卷 959-970页

作者： JIAWEI YIN YONGSHENG WANG GUANGWEI WEI MINGXIN WEN Department of Traumatology The Second Hospital of Shandong UniversityJinan250033China Department of pathology Weifang People’s HospitalWeifang261000China Department of Human Anatomy Shandong University School of MedicineJinan250012China Department of Cell Biology and Key laboratory of Experimental Teratology Shandong University School of MedicineJinan250012China

Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft ***:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent ***,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and *** UBE2T exhibited the opposite ***2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of *** target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in ***:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.

关键词： UBE2T Breast cancer Breast cancer stem cell mTOR

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The lactylation index predicts the immune microenvironment and prognosis of pan-cancer patients

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BIOCELL 2024年第8期48卷 1223-1239页

作者： XUEJIA ZHAI JIE LIU JINWEI XIAO TAO ZHANG JUN WANG JIANJUN LI SHICANG YU Department of Oncology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing400038China Department of Stem Cell and Regenerative Medicine Institute of Pathology and Southwest Cancer CenterSouthwest HospitalThird Military Medical University(Army Medical University)Chongqing400038China Key laboratory of Cancer Immunopathology Ministry of EducationChongqing400038China International Joint Research Center for Precision Biotherapy Ministry of Science and TechnologyChongqing400038China Jin-feng laboratory Chongqing401329China

Background:Protein lactylation is a new way for the“metabolic waste”lactic acid to perform novel ***,our understanding of the contribution of protein lactylation to both tumor progression and therapeutic interventions remains *** construction of a scoring system for lactylation to predict the prognosis of pancancer patients and to evaluate the tumor immune microenvironment(TIME)would improve our understanding of the clinical significance of ***:Consensus clustering analysis of lactylation-related genes was used to cluster 177 pancreatic adenocarcinoma(PAAD)***,a scoring system was developed using the least absolute shrinkage and selection operator(LASSO)*** validation and external validation were both conducted to assess and confirm the predictive accuracy of the scoring ***,leucine rich repeat containing 1(LRRC1),a newly discovered lactylation-related gene,was analyzed in PAAD in ***:Utilizing the profiles of 332 lactylation-related genes,a total of 177 patients with PAAD were segregated into two distinct ***^(high) patients had a poorer prognosis than LacCluster^(low) *** the differential analysis between the LacCluster^(high) and LacCluster^(low) groups,we identified additional genes associated with *** genes were then integrated to construct the LacCluster-enhanced system,which enabled more accurate prognosis prediction for patients with ***,a lactylation index containing three genes(LacI-3)was constructed using LASSO *** was done to enhance the usability of the LacCluster-enhanced system in the *** to those in the LacI-3^(high) subgroup,patients in the LacI-3^(low) subgroup exhibited increased expression of immune checkpoint-related genes,more immune cell infiltration,lower tumor mutation burdens,and better prognoses,indicating a“hot tumor”***,knocking down the expression of LRRC1,

关键词： Pancreatic adenocarcinoma Pan-cancer Lactylation Prognosis Tumor immune microenvironment LRRC1

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Mitochondrial GRIM19 Loss Induces Liver Fibrosis through NLRP3/IL33 Activation via Reactive Oxygen Species/NF-κB Signaling

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Journal of Clinical and Translational Hepatology 2024年第6期12卷 539-550页

作者： Xiaohui Xu Jinmei Feng Xin Wang Xin Zeng Ying Luo Xinyu He Meihua Yang Tiewei Lv Zijuan Feng Liming Bao Li Zhao Daochao Huang Yi Huang Institute of Pediatrics Children’s Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Pediatric Metabolism and Inflammatory DiseasesChongqingChina Department of Cardiology Children’s Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Key Cardiovascular SpecialtyLaboratory of Children’s Important Organ Development and Diseases of Chongqing Municipal Health CommissionChongqingChina Department of laboratory Medicine Chongqing Western HospitalChongqingChina Key laboratory of Molecular Biology for Infectious Diseases Ministry of EducationInstitute for Viral HepatitisChongqing Medical UniversityChongqingChina Department of laboratory Medicine The Third People’s Hospital of ChengduChengduSichuanChina Departments of Neurology Epilepsy CenterBarnes-Jewish Hospital and Washington University School of MedicineSt.LouisMOUSA Department of Clinical pathology and laboratory Medicine Weill Cornell Medical College of Cornell UniversityNew YorkNYUSA Departments of Medicine(Oncology) Washington University School of MedicineSt.LouisMOUSA

Background and Aims:Hepatic fibrosis(HF)is a critical step in the progression of hepatocellular carcinoma(HCC).Gene associated with retinoid-IFN-induced mortality 19(GRIM19),an essential component of mitochondrial respiratory chain complex I,is frequently attenuated in various human cancers,including ***,we aimed to investigate the potential relationship and underlying mechanism between GRIM19 loss and HF ***:GRIM19 expression was evaluated in normal liver tissues,hepatitis,hepatic cirrhosis,and HCC using human liver disease spectrum tissue *** studied hepatocyte-specific GRIM19 knockout mice and clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein-9(Cas9)lentivirus-mediated GRIM19 gene-editing in murine hepatocyte AML12 cells in vitro and in *** performed flow cytometry,immunofluorescence,immunohistochemistry,western blotting,and pharmacological intervention to uncover the potential mechanisms underlying GRIM19 loss-induced ***:Mitochondrial GRIM19 was progressively downregulated in chronic liver disease tissues,including hepatitis,cirrhosis,and HCC ***-specific GRIM19 heterozygous deletion induced spontaneous hepatitis and subsequent liver fibrogenesis in *** addition,GRIM19 loss caused chronic liver injury through reactive oxygen species(ROS)-mediated oxidative stress,resulting in aberrant NF-κB activation via an IKK/IKB partner in ***-more,GRIM19 loss activated NLRP3-mediated IL33 signaling administration of the NLRP3 inhibitor MCC950 dramatically via the ROS/NF-κB pathway in *** alleviated GRIM19 loss-driven HF in ***:The mitochondrial GRIM19 loss facilitates liver fibrosis through NLRP3/IL33 activation via ROS/NF-κB signaling,providing potential therapeutic approaches for earlier HF prevention.

关键词： Liver fibrosis GRIM19 Reactive Oxygen Species NF-κB NLRP3 inflammasome IL33.

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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

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Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2748-2760页

作者： Hua-yang Fan Ming-da Zhao Hong-jie Jiang Zhen-wei Yu Yu-jiang Fan Xin-hua Liang Ya-ling Tang Yong Sun State Key laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041China National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China State Key laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Department of Oral pathology West China Hospital of StomatologySichuan UniversityChengdu 610041China

Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC *** analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC ***-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p ***-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC *** results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC ***,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC *** findings provide a new perspective for the development of OSCC treatments.

关键词： Oral squamous cell carcinoma CircRNA MiRNA sponge Antagomir MiRNA delivery Cisplatin-based nanoparticles Drug delivery systems Tumor elimination

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Elimination of methicillin‑resistant Staphylococcus aureus biofilms on titanium implants via photothermally‑triggered nitric oxide and immunotherapy for enhanced osseointegration

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Military Medical Research 2024年第2期11卷 157-179页

作者： Yong‑Lin Yu Jun‑Jie Wu Chuan‑Chuan Lin Xian Qin Franklin R.Tay Li Miao Bai‑Long Tao Yang Jiao Department of pathology Affiliated Hospital of Zunyi Medical UniversityZunyi 563003GuizhouChina laboratory Research Center the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Blood Transfusion Laboratory of Radiation Biologythe Second Affiliated HospitalArmy Military Medical UniversityChongqing 400037China Department of Reproductive Endocrinology Chongqing Health Center for Women and ChildrenChongqing 401147China The Graduate School Augusta UniversityAugustaGA 30912USA Department of Stomatology the Seventh Medical Center of PLA General HospitalBeijing 100700China

Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)*** is a need to explore more effective approaches for the treatment of MRSA biofilm ***:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@*** physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release *** synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid *** staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture *** staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in ***:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and

关键词： Polydopamine nanoparticles Methicillin-resistant Staphylococcus aureus Nitric oxide Osseointegration Osteo-immunomodulation Photothermal effect Titanium implants

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