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Identification of potential immune-related mechanisms related to the development of multiple myeloma

Chinese Medical Journal 2024年第13期137卷 1603-1613页

作者： Yaomei Wang Wenli Zhang Tiandong Li Mengmeng Liu Mengya Gao Xinqing Li Yufei Chen Yongping Song Wei Li Chunyan Du Fang Wang Lina Liu department of Hematology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China The Academy of Medical science College of MedicalZhengzhou UniversityZhengzhouHenan 450052China College of Public Health Zhengzhou UniversityZhengzhouHenan 450000China department of Research and Foreign Affairs The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China department of clinical Medicine Zhengzhou UniversityZhengzhouHenan 450052China department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Laboratory animal Center School of Medical SciencesZhengzhou UniversityZhengzhouHenan 450052China

Background:Although significant advances have been made in the treatment of multiple myeloma(MM),leading to unprecedented response and survival rates among patients,the majority eventually relapse,and a cure remains *** situation is closely related to an incomplete understanding of the immune microenvironment,especially monocytes/macrophages in patients with treatment-naïve *** aim of this study was to provide insight into the immune microenvironment,especially monocytes/macrophages,in patients with treatment-naïve ***:This study used the single-cell RNA sequencing(scRNA-seq)data of both patients with MM and heathy donors to identify immune cells,including natural killer(NK)cells,T cells,dendritic cells(DCs),and monocytes/*** data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM ***:A significant difference was observed between the bone marrow(BM)immune cells of the healthy controls and treatment-naïve MM patients through *** is noteworthy that,through an scRNA-seq data analysis,this study found that interferon(IFN)-induced NK/T cells,terminally differentiated effector memory(TEMRA)cells,T-helper cells characterized by expression of IFN-stimulated genes(ISG^(+)Th cells),IFN-responding exhausted T cells,mannose receptor C-type 1(MRC1)^(+)DCs,IFN-responding DCs,MHCII^(+)DCs,and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve ***,transcriptomic data of monocytes/macrophages demonstrated that"don’t eat me"-related genes and IFN-induced genes increase in treatment-naïve MM ***,scRNA-seq,transcriptomic data,and flow cytometry also showed an increased proportion of CD16^(+)monocytes/macrophages and expression level of ***-cell communication analysis indicated that monocytes/macrophages,whose related important signaling pathways include migration i

关键词： Multiple myeloma Monocytes/macrophages Single-cell RNA sequencing Immune cell Microenvironment Bone marrow Molecular characterization

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Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy(CAR–T)cell immunotherapy

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Oncology Research 2024年第9期32卷 1479-1516页

作者： ZHENGYI WANG LIANG ZHOU XIAOYING WU department of Institute of Laboratory animal sciences Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduChina Ministry of Education and Training Chengdu Second People’s HospitalChengduChina

Chimeric antigen receptor T-cesll therapy(CAR–T)has achieved groundbreaking advancements in clinical application,ushering in a new era for innovative cancer ***,the challenges associated with implementing this novel targeted cell therapy are increasingly *** in the clinical management of solid tumors,obstacles such as the immunosuppressive effects of the tumor microenvironment,limited local tumor infiltration capability of CAR–T cells,heterogeneity of tumor targeting antigens,uncertainties surrounding CAR–T quality,control,and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor *** factors have significantly impeded the widespread adoption and utilization of this therapeutic *** this paper,we comprehensively analyze recent preclinical and clinical reports on CAR–T therapy while summarizing crucial factors influencing its ***,we aim to identify existing solution strategies and explore their current research *** this review article,our objective is to broaden perspectives for further exploration into CAR–T therapy strategies and their clinical applications.

关键词： Chimeric antigen receptor T-cell therapy(CAR-T) Tumor targeting therapy Influencing factor Solution strategies

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The generation and use of animal models of osteosarcoma in cancer research

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Genes & Diseases 2024年第2期11卷 664-674页

作者： Feifei Pu Haoyu Guo Deyao Shi Fengxia Chen Yizhong Peng Xin Huang Jianxiang Liu Zhicai Zhang Zengwu Shao department of Orthopedics Wuhan Hospital of Traditional Chinese and Western Medicine (Wuhan No.1 Hospital)Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of Radiation and Medical Oncology Zhongnan HospitalWuhan UniversityWuhanHubei 430071China Hubei Cancer clinical Study Center Zhongnan HospitalWuhan UniversityWuhanHubei 430071China

Osteosarcoma is the most common malignant bone tumor affecting children and ***,the most common treatment is surgery combined with neoadjuvant *** the survival rate of patients with osteosarcoma has improved in recent years,it remains poor when the tumor(s)progress and distant metastases ***,better animal models that more accurately replicate the natural progression of the disease are needed to develop improved prognostic and diagnostic markers,as well as targeted therapies for both primary and metastatic *** present review described animal models currently being used in research investigating osteosarcoma,and their characteristics,advantages,and *** models may help elucidate the pathogenic mechanism(s)of osteosarcoma and provide evidence to support and develop clinical treatment strategies.

关键词： animal model Cancer Osteosarcoma Pathogenic mechanism Translational research

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Hypoxia in the pulmonary vein increases pulmonary vascular resistance independently of oxygen in the pulmonary artery

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animal Models and Experimental Medicine 2024年第2期7卷 156-165页

作者： Sigridur Olga Magnusdottir Carsten Simonsen Dan Stieper Karbing Bodil Steen Rasmussen Benedict Kjaergaard Biomedical Research Laboratory Aalborg University HospitalAalborgDenmark department of clinical Medicine Aalborg UniversityAalborgDenmark department of Cardiothoracic Surgery Aalborg University HospitalAalborgDenmark department of Health science and Technology Aalborg UniversityAalborgDenmark department of Anesthesia and Intensive Care Aalborg University HospitalAalborgDenmark

Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical *** is not fully elucidated where in the circulation the regulation of resistance takes *** is often referred to as if it is in the arteries,but we hypothesized that it is in the venous side of the pulmonary ***:In an open thorax model,pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary *** the same time the lungs were ventilated with extreme variations of inspired air from 5%to 100%oxygen,making it possible to make combinations of high and low oxygen content through the pulmonary circulation.A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood *** different combinations of oxygenation,pulmonary vascular resistance(PVR)was ***:With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein,PVR was *** more extreme hypoxia PVR suddenly *** with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary ***:The impact of hypoxia occurs from the alveolar level and forward with the blood *** experiments indicated that the regulation of PVR is mediated from the venous side.

关键词： animal models cardiopulmonary support Hypoxic pulmonary vasoconstriction pulmonary circulation

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Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

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Neural Regeneration Research 2024年第7期19卷 1541-1547页

作者： Xingyong Chen Nannan Yao Yanguang Mao Dongyun Xiao Yiyi Huang Xu Zhang Yinzhou Wang department of Neurology Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityFuzhouFujian ProvinceChina department of Neurology Cangzhou Central HospitalCangzhouHebei ProvinceChina Fujian Academy of Medical science FuzhouFujian ProvinceChina Key Testing Laboratory of Fujian Province FuzhouFujian ProvinceChina

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain ***,the potential links between them following ischemic stroke remain largely *** present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin ***,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia *** r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and *** ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,*** addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/***,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

关键词： blood-brain barrier CYP1B1 oxidative stress oxygen glucose deprivation/reoxygenation tight junction vascular endothelial cells Wnt/β-catenin pathway β-catenin

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Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

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Journal of animal science and Biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok Kwon Dae-Jin Jung Dae-Hyun Kim Jun-Koo Yi Jae-Jung Ha Ji-Hyun Lee Seong-Beom Lee Woo-Jae Son Soo-Young Yum Won-Wu Lee Goo Jang Laboratory of Theriogenology and Biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio Co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea Comparative Medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been considered as powerful tool in agricultural ***,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising ***,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in *** this point of view,electroporation in embryos has been risen as an *** First,editing efficiency of our electroporation methods were tested for *** of mutation on embryo was confirmed by T7E1 *** first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,*** case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for ***,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep *** recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double *** surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both *** These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively ***,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

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Clinicopathological Description of a Chronic Lymphocytic Leukemia in a Dog

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Open Journal of Veterinary Medicine 2024年第7期14卷 155-162页

作者： Maria Clara Boni Raffi Giovanna Valverde Magalhães Barbosa Alana Carolina Capais Rodrigues Sheila Canevese Rahal John P. Kastelic Luíz Guilherme Dercore Benevenuto Iolanda Simões Braga Beatriz Poloni Batista Felipe César Da Silva Brasileiro Fernanda Barthelson Carvalho de Moura Priscylla Tatiana Chalfun Guimarães Okamoto Regina Kiomi Takahira Alessandra Melchert Noeme Sousa Rocha department of Veterinary Clinics School of Veterinary Medicine and Animal Science So Paulo State UniversityUNESP Botucatu SP Brazil Independent Veterinary Practitioner department of Veterinary Surgery and animal Reproduction School of Veterinary Medicine and Animal Science So Paulo State UniversityUNESP Botucatu SP Brazil Faculty of Veterinary Medicine University of Calgary Calgary Canada

Hematopoietic tumors are associated with diagnostic and therapeutic challenges and a poor prognosis. Furthermore, their pathophysiology in dogs is not well understood. Chronic lymphocytic leukemia has been rarely reported in golden retrievers, perhaps due to difficulties in diagnosis and care. An 8-year-old spayed female golden retriever was referred to our hospital with a 2-month history of fatigue, weakness, and selective appetite. The dog was diagnosed with chronic lymphocytic leukemia based on blood smear evaluation. Despite treatment, the dog deteriorated and the owners opted for euthanasia. Histopathological examination revealed atypical lymphocytes in the spleen, extramedullary hematopoiesis in the spleen and liver, bone marrow depletion, moderate neutrophilic myocarditis, and acute renal tubular necrosis. In an immunohistochemical panel, cells in the spleen and bone marrow were positive for anti-CD20, anti-CD45, anti-CD3, anti-IBA-1, anti-Ki67, anti-MUM-1, and anti-PAX-5. In conclusion, the leukemia diagnosis was confirmed through reactive histiocytosis, marked extramedullary hematopoiesis, and other clinical and laboratory findings. Herein, we report a case of chronic lymphocytic leukemia in a female dog with clinical, laboratory, and necroscopy findings.

关键词： Canine Cancer Neoplasia Therapeutics

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Expanding the horizons of targeted protein degradation:A non-small molecule perspective

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2402-2427页

作者： Xiaowei Huang Fengbo Wu Jing Ye Lian Wang Xiaoyun Wang Xiang Li Gu He department of Pharmacy and department of Dermatology&Venerology West China HospitalSichuan UniversityChengdu 610041China department of Urology West China HospitalSichuan UniversityChengdu 610041China Laboratory of Dermatology Clinical Institute of Inflammation and ImmunologyFrontiers Science Center for Disease-Related Molecular Network and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Targeted protein degradation(TPD)represented by proteolysis targeting chimeras(PROTACs)marks a significant stride in drug discovery.A plethora of innovative technologies inspired by PROTAC have not only revolutionized the landscape of TPD but have the potential to unlock functionalities beyond ***-small-molecule-based approaches play an irreplaceable role in this field.A wide variety of agents spanning a broad chemical spectrum,including peptides,nucleic acids,antibodies,and even vaccines,which not only prove instrumental in overcoming the constraints of conventional small molecule entities but also provided rapidly renewing *** we summarize the burgeoning non-small molecule technological platforms inspired by PROTACs,including three major trajectories,to provide insights for the design strategies based on novel paradigms.

关键词： Targeted protein degradation Proteolysis targeting chimera Endocytosis Autophagy Proximity-inducing modality Post-translational modification

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Experimental and computational study of annealed nickel sulfide quantum dots for catalytic and antibacterial activity

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Nano Materials science 2024年第3期6卷 355-364页

作者： Muhammad Ikram Sawaira Moeen Ali Haider Anwar Ul-Hamid Haya Alhummiany Hamoud H.Somaily Souraya Goumri-Said Mohammed Benali Kanoun Solar Cell Applications Research Lab Department of PhysicsGovernment College University LahoreLahore54000PunjabPakistan department of clinical sciences Faculty of Veterinary and Animal SciencesMuhammad Nawaz ShareefUniversity of Agriculture66000MultanPunjabPakistan Core Research Facilities King Fahd University of Petroleum&MineralsDhahran31261Saudi Arabia department of Physics Faculty of ScienceUniversity of JeddahP.O.Box 13151Jeddah21493Saudi Arabia department of Physics Faculty of ScienceKing Khalid UniversityP.O.Box 9004AbhaSaudi Arabia Physics department College of Science and General StudiesAlfaisal UniversityP.O.Box 50927Riyadh11533Saudi Arabia department of Mathematics and sciences College of Humanities and SciencesPrince Sultan UniversityP.O.Box 66833Riyadh11586Saudi Arabia

This research investigates the hydrothermal synthesis and annealing duration effects on nickel sulfide(NiS_(2) quantum dots(QDs)for catalytic decolorization of methylene blue(MB)dye and antimicrobial *** size increased with longer annealing,reducing catalytic ***–vis,XRD,TEM,and FTIR analyses probed optical structural,morphological,and vibrational *** confirmed NiS2's anorthic structure,with crystallite size growing from 6.53 to 7.81 nm during extended ***–Vis exhibited a bathochromic shift,reflecting reduced band gap energy(Eg)in NiS_(2).TEM revealed NiS_(2)QD formation,with agglomerated QD average size increasing from 7.13 to 9.65 nm with prolonged *** NiS_(2) showed significant MB decolorization(89.85%)in acidic *** NiS_(2) QDs demonstrated notable antibacterial activity,yielding a 6.15mm inhibition zone against Escherichia coli(***)compared to ***-principles computation supported a robust interaction between MB and NiS_(2),evidenced by obtained adsorption *** study highlights the nuanced relationship between annealing duration,structural changes,and functional properties in NiS_(2)QDs,emphasizing their potential applications in catalysis and antibacterial interventions.

关键词： NiS_(2) antibacterial quantum dots dye degradation DFT

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Lonicera Japonica Caulis Ameliorates LPS and TNF-α-Induced HT-29 Cell Injury by Inhibiting the MAPK/ERK/JNK/p38 Pathway

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Biomedical and Environmental sciences 2024年第7期37卷 805-810页

作者： Hanxiu Lu Wei Yan Xiao Yuan Yongbo Kang Zhongjian Liu Qiang Guo Faculty of Life science and Technology Kunming University of Science and TechnologyKunming 650031YunnanChina School of medicine Kunming University of Science and TechnologyKunming 650031YunnanChina department of Gastroenterology The First People’s Hospital of Yunnan ProvinceKunming 650032YunnanChina department of Gastroenterology The First People’s Hospital of Yuxi CityYuxi 653100YunnanChina Institute of Basic and clinical Medicine The First People’s Hospital of Yunnan ProvinceKunming 650032YunnanChina

Inflammatory bowel disease(IBD)is characterized by chronic inflammation of the intestinal tract,and shows a high rate of *** have accumulated extensive experience in the treatment of IBD,with biologics and small molecule drugs having greatly expanded the therapeutic scope of IBD in recent ***,such treatments involve a high price and a single target of drug action.

关键词： drugs treatment p38

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