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DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of Cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

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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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Stepping up after spinal cord injury:negotiating an obstacle during walking

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Neural Regeneration Research 2025年第7期20卷 1919-1929页

作者： Alain Frigon Charly G.Lecomte Department of Pharmacology-Physiology Faculty of Medicine and Health SciencesUniversitéde SherbrookeCentre de recherche du Centre Hospitalier Universitaire de SherbrookeSherbrookeQCCanada

Every day walking consists of frequent voluntary modifications in the gait pattern to negotiate *** spinal cord injury,stepping over an obstacle becomes *** over an obstacle requires sensorimotor transformations in several structures of the brain,including the parietal cortex,premotor cortex,and motor *** information and planning are transformed into motor commands,which are sent from the motor cortex to spinal neuronal circuits to alter limb trajectory,coordinate the limbs,and maintain *** spinal cord injury,bidirectional communication between the brain and spinal cord is disrupted and animals,including humans,fail to voluntarily modify limb trajectory to step over an ***,in this review,we discuss the neuromechanical control of stepping over an obstacle,why it fails after spinal cord injury,and how it recovers to a certain extent.

关键词： biomechanics locomotion neurophysiology obstacle negotiation spinal cord injury

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Significance of balloon aortic valvuloplasty as palliative procedure for symptom benefit in patients with severe aortic stenosis

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Journal of Geriatric Cardiology 2024年第3期21卷 374-378页

作者： Jovica Banovic Vladimir Djuric Vojislav Vuksinovic Sasa Loncar Department of Internal medicine/Prijedor Republic of SrpskaBosnia and Herzegovina University Clinical centre of Republic of Srpska Cardiology ClinicBanja LukaRepublic of SrpskaBosnia and Herzegovina

Aortic stenosis(AS)stands out as the most prevalent individual valvular defect *** onset and progression of AS mirror an active process akin to atherosclerosis,and the traditional triad of symptoms includes chest pain,breathlessness,and loss of *** takes a significant downturn when symptoms manifest,with mortality reaching approximately 50%-85% within the subsequent 5 years after symptom onset.

关键词： balloon stenosis mortality

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Identifying behavioral determinants and stage of readiness for performing knee massage among individuals with knee osteoarthritis:An observational study

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Journal of Integrative medicine 2024年第1期22卷 54-63页

作者： Donya Nemati Niki Munk Navin Kaushal College of Nursing the Ohio State UniversityColumbusOH 43210USA Department of Health Sciences School of Health&Human SciencesIndiana UniversityIndianapolisIN 46202USA National centre for Naturopathic medicine Southern Cross UniversityLismoreNew South Wales 2480Australia Australian Research centre in Complementary and Integrative medicine(ARCCIM) Massage&Myotherapy Australia Fellow and Visiting Faculty of HealthUniversity of Technology SydneyNew South Wales 2007Australia

Objective Patients who experience knee osteoarthritis or chronic knee pain can alleviate their symptoms by performing self-knee *** the readiness and types of determinants needed to facilitate self-knee massage is needed to design effective,theory-informed *** primary objective of this study was to apply the transtheoretical model of behavior change to identify how factors,which include the type of knee condition and pain level,predict an individual’s readiness to adopt self-knee *** secondary objective employed the capability,opportunity and motivation-behavior(COM-B)model to identify relevant determinants that are predictive of an individual’s readiness to undertake self-knee *** An observational study design was used to recruit individuals with knee osteoarthritis(n=270)and chronic knee pain(n=130).Participants completed an online survey that assessed the transtheoretical model of behavior change stages,COM-B determinants(capability,opportunity and motivation),along with self-administered massage *** analysis of covariance and structural equation modeling were used to test the primary and secondary objective,*** Participants who had knee osteoarthritis scored higher on the action stage compared to those with chronic pain(P=0.003),and those who experienced greater level of pain scored higher in the contemplation(P<0.001)and action phases(P<0.001)of performing knee massage compared to those with milder *** COM-B structural equation model revealed self-administered knee massage to be predicted by capability(β=0.31,P=0.004)and motivation(β=0.29,P<0.001),but not opportunity(β=–0.10,P=0.39).Pain level predicted motivation(β=0.27,P<0.001),but not capability(β=0.09,P=0.07)or opportunity(β=0.01,P=0.83).Tests for mediating effects found that determinants of COM-B(motivation and capability)mediate between pain level and self-administered massage behavior(β=0.10,P=0.002).Conclusion Cl

关键词： Osteoarthritis Massage Self-management Transtheoretical model of behavior change Behavioral model

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Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma

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Oncology Research 2024年第7期32卷 1163-1172页

作者： LISANNE K.A.NEIJENHUIS LEUTA L.NAUMANN SONIA A.M.FERKEL SAMUEL J.S.RUBIN STEPHAN ROGALLA Division of Gastroenterology and Hepatology Department of MedicineSchool of MedicineStanford UniversityStanford94305USA Department of Surgery Leiden University Medical CenterLeiden2333 ZAThe Netherlands centre for Human Drug Research Leiden2333 CLThe Netherlands Department of General VisceralVascular and Thoracic SurgeryCharite University Medicine BerlinBerlin10117Germany

Background:Osteosarcoma is the most common malignant primary bone *** prognosis for patients with disseminated disease remains very poor despite recent advancements in ***,current treatment regimens bear a signiﬁcant risk of serious side ***,there is an unmet clinical need for effective therapies with improved safety proﬁ*** is an antibacterial agent that has been shown to induce cell death in different types of cancer cell ***:In this study,we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma.K7M2 murine osteosarcoma cells were injected,both intramuscular and intraperitoneal,into 60 BALB/c mice on day *** were then randomized to receive treatment with taurolidine 2%(800 mg/kg),taurolidine 1%(400 mg/kg),or NaCl 0.9%control for seven days by intravenous or intraperitoneal ***:After 35 days,mice were euthanized,and the tumors were harvested for *** mice were excluded from the analysis due to *** weight was signiﬁcantly lower in the 2%taurolidine intraperitoneal treatment group from day 9 to 21,consistent with elevated mortality in this *** tumor weight was signiﬁcantly lower in the 1%(p=0.003)and 2%(p=0.006)intraperitoneal taurolidine treatment groups compared to the *** antineoplastic effects were observed on intramuscular tumors or for intravenous administration of *** were no signiﬁcant differences in microvessel density or mitotic rate between treatment *** body weight and elevated mortality in the 2%taurolidine intraperitoneal group suggest that the lower 1%dose is ***:In conclusion,there is no evidence of antiangiogenic activity,and the antitumor effects of taurolidine on osteosarcoma observed in this study are ***,its toxic proﬁle grants further *** these observations,further research is necessary to

关键词： Osteosarcoma Taurolidine Cancer treatment Chemotherapy Murine models

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Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way Yin Ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan Yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)*** study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of ***,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and *** presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual *** potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

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Orchard Sports Injury and Illness Classification System (OSIICS) Version 15

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Journal of Sport and Health Science 2024年第4期13卷 599-604页

作者： John W.Orchard Ebonie Rio Kay M.Crossley Jessica J.Orchard Margo Mountjoy School of Public Health University of SydneySydneyNSW 2006Australia La Trobe Sport and Exercise medicine Research centre La Trobe UniversityMelbourneVIC 3083Australia Department of Family medicine McMaster UniversityHamilton L8S 4L8Canada

Background:Sports medicine(injury and illnesses)requires distinct coding systems because the International Classification of Diseases is insuf-ficient for sports medicine *** Orchard Sports Injury and Illness Classification System(OSIICS)is one of two sports medicine coding systems recommended by the International Olympic *** updates of coding systems are ***:For Version 15,updates for mental health conditions in athletes,sports cardiology,concussion sub-types,infectious diseases,and skin and eye conditions were considered particularly ***:Recommended codes were added from a recent International Olympic Committee consensus statement on mental health conditions in *** landmark sports cardiology papers were used to update a more comprehensive list of sports cardiology *** union protocols on head injury assessment were used to create additional concussion ***:It is planned that OSIICS Version 15 will be translated into multiple new languages in a timely fashion to facilitate international *** large number of recently published sport-specific and discipline-specific consensus statements on athlete surveillance warrant regular updating of OSIICS.

关键词： Sports cardiology Dermatology Eye injuries Concussion Infectious diseases Sports injury classification

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Classical taxonomy,molecular phylogeny and genetic analysis of the genus Exitianus Ball,1929(Hemiptera:Cicadellidae:Deltocephalinae)from Egypt

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Zoological Systematics 2024年第2期49卷 143-157页

作者： Rabab M.El-Hady Ahmed F.El-Sayed Survey&Taxonomy Department Plant Protection Research InstituteAgriculture Research CentreGizaEgypt Microbial Genetics Department Biotechnology Research InstituteNational Research CentreGizaEgypt Egypt Center for Research and Regenerative medicine(ECRRM) CairoEgypt

Egyptian species of the leafhopper genus Exitianus Ball,1929,***(St?l,1855),***(Distant,1908),and *** Ross,1968 are ***,morphological descriptions,and a key for their identification are *** this study,we used molecular techniques to confirm morphological identification and detect phylogeny among the three Exitianus *** partial nucleotide sequences of the amplified products obtained were determined by Macrogen *** nucleotide sequences of 28S rDNA and COX genes of the EGY-ARC-9,EGY-ARC-4,and EGY-ARC-5 were determined by Macrogen Korea,blasted into BLAST at the National Center for Biotechnology Information website(NCBI)and compared with those deposited in the GenBank DNA *** results represented the homology percentage between the partial sequences of the 28S rRNA and COX genes from each species and related species obtained from GenBank DNA *** morphological identifications of the three Exitianus species were confirmed by molecular characterization and sequencing of 28S rDNA and COX genes and identified as ***,***,and ***,their sequences of 28srDNA and COX genes were deposited in GenBank with an accession number(LC670610,LC670607,and OQ196105)for 28srDNA gene and(LC775357,LC775358,and LC775359)for the COX gene.

关键词： Auchenorrhyncha Chaismini taxonomic 28S rDNA phylogenetic

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Bio-analysis of Saliva Using Paper Devices and Colorimetric Assays

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Journal of Analysis and Testing 2024年第1期8卷 114-132页

作者： Adhan Narasimhan Harshil Jain Kowshika Muniandy Raja Chinnappan Naresh Kumar Mani Microfluidics Sensors and Diagnostics(μSenD)LaboratoryCentre for MicrofluidicsBiomarkersPhotoceutics&Sensors(μBioPS)Department of BiotechnologyManipal Institute of TechnologyManipal Academy of Higher EducationManipalKarnataka 576104India College of medicine Alfaisal UniversityRiyadh 11533SaudiArabia Tissue/Organ Bioengineering&BioMEMS Lab Organ Transplant Centre of ExcellenceTransplant Research&Innovation DepartmentKing Faisal Specialist Hospital and Research CentreRiyadhSaudi Arabia

In light of the evolving nature of various diseases,time becomes a crucial factor in diagnosis and identifying the underlying causes.A point-of-care device provides a rapid diagnosis of a disease without using complex and advanced instruments,which are costly and difficult to transport.A paper-based device is a relatively frugal solution wherein the paper is used as a substratum in which the reactions are carried *** methods are non-invasive,and the sample collection is relatively *** is one such body fluid in which various biomarkers are present for numerous *** of saliva has attracted more attention recently due to its non-invasiveness and *** the discovery of clinical biomarkers from salivary analysis has the potential to revolutionize the healthcare sector by providing crucial information to monitor the health status of individuals and disease progression which enables personalized *** review provides the limitation of the traditional methods in clinical applications and highlights the significance of saliva as a non-invasive biological fluid that is a source of multiple biomarkers associated with various *** also provides insights into the different paper-based colorimetric microfluidic devices developed against salivary biomarkers in the past *** major challenges in the point-of-care application and the future prospects have been discussed as ***,we also emphasize the importance of this approach in dental disease diagnosis which is least explored and holds potential applications.

关键词： Paper-based assay Salivary analysis Non-invasive Point-of-care Body fluids Biomarkers Qualitative detection

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