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Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： Antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly department of biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

Role of copper chelating agents: between old applications and new perspectives in neuroscience

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Neural Regeneration Research 2025年第3期20卷 751-762页

作者： Rosalba Leuci Leonardo Brunetti Vincenzo Tufarelli Marco Cerini Marco Paparella Nikola Puvača Luca Piemontese department of Pharmacy-Pharmaceutical Science University of Bari Aldo MoroBariItaly department of Precision and Regenerative Medicine and Jonian Area(DiMePRe-J) Section of Veterinary Science and Animal ProductionUniversity of Bari Aldo MoroBariItaly department of Engineering Management in biotechnology Faculty of Economics and Engineering Management in Novi SadUniversity Business Academy in Novi SadNovi SadSerbia

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

关键词： agriculture Alzheimer's disease chelators copper feed supplements multi-target

Late effects of the treatment of childhood cancer

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World Journal of Clinical Cases 2025年第7期13卷 6-12页

作者： Jelena Roganovic department of Pediatric Oncology and Hematology Children's Hospital ZagrebZagreb 10000Croatia Faculty of biotechnology and Drug Development University of RijekaRijeka 51000Croatia

Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being ***,the therapies responsible for this survival can also produce adverse physical and psychological long-term outcomes,referred to as late effects,which appear months to years after the completion of cancer *** has shown that 60%to 90%of childhood cancer survivors(CCSs)develop one or more chronic health conditions,and 20%to 80%of survivors experience severe or life-threatening complications during ***,understanding the late side effects of such treatments is important to improve the health and quality of life of the growing population of CCSs.

关键词： Survivorship Cancer Children Treatment Late effects

Variations in quantifying patient reported outcome measures to estimate treatment effect

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World Journal of Methodology 2025年第2期15卷 44-53页

作者： Sathish Muthu Srujun Vadranapu department of Orthopaedics Orthopaedic Research GroupCoimbatore 641045Tamil NaduIndia department of Orthopaedics Government Medical CollegeKarur 639004Tamil NaduIndia department of biotechnology Karpagam Academy of Higher EducationCoimbatore 641021Tamil NaduIndia department of Orthopaedics Royal Care Super Speciality HospitalCoimbatore 641062Tamil NaduIndia

In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical *** guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment *** any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real *** structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each *** mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given *** are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their *** article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.

关键词： Patient-reported outcome measures Treatment effect Minimal clinical important difference Patient-accepted symptom state Minimum detectable change Orthopedics

Gut virome:New key players in the pathogenesis of inflammatory bowel disease

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World Journal of Methodology 2025年第2期15卷 27-43页

作者： Helal F Hetta Rehab Ahmed Yasmin N Ramadan Hayam Fathy Mohammed Khorshid Mohamed M Mabrouk Mai Hashem department of Medical Microbiology and Immunology Faculty of MedicineAssiut UniversityAssiut 71515Egypt Division of Microbiology Immunology and BiotechnologyFaculty of pharmacyUniversity of TabukTabuk 71491Saudi Arabia Division of Microbiology Immunology and BiotechnologyDepartment of Natural Products and Alternative MedicineFaculty of PharmacyUniversity of TabukTabuk 71491Saudi Arabia department of Internal Medicine Division HepatogastroenterologyAssiut UniversityAssiut 71515Egypt department of Clinical Research Egyptian Developers of Gastroenterology and Endoscopy FoundationCairo 11936Egypt department of Internal Medicine Faculty of Medicine.Tanta UniversityTanta 31527Egypt department of Tropical Medicine Gastroenterology and HepatologyAssiut University HospitalAssiut 71515Egypt

Inflammatory bowel disease(IBD)is a chronic inflammatory illness of the *** the mechanism underlying the pathogenesis of IBD is not fully under-stood,it is believed that a complex combination of host immunological response,environmental exposure,particularly the gut microbiota,and genetic suscept-ibility represents the major *** gut virome is a group of viruses found in great frequency in the gastrointestinal tract of *** gut virome varies greatly among individuals and is influenced by factors including lifestyle,diet,health and disease conditions,geography,and *** majority of research has focused on the significance of gut bacteria in the progression of IBD,although viral populations represent an important component of the *** conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.

关键词： Inflammatory bowel disease Pathogenesis Gut virome Bacteriophage Eukaryotic viruses

Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan Su Yiming Zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

Crimean-Congo hemorrhagic fever:Pathogenesis,transmission and public health challenges

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World Journal of Virology 2025年第1期14卷 63-72页

作者： Sita Kumari Karanam Kandra Nagvishnu Praveen Kumar Uppala Sandhya Edhi Srinivasa Rao Varri department of Pharmaceutical biotechnology Maharajah’s College of PharmacyVizianagaram 535002Andhra PradeshIndia department of Pharmacology Santhiram Medical College and General HospitalNandyal 518501Andhra PradeshIndia department of Pharmacology Santhiram Medical College and General HospitalNandyal 518501Andhra PradeshIndia Department of Pharmaceutical AnalysisMaharajah's College of PharmacyVizianagaram 535002Andhra PradeshIndia

The dangerous Crimean-Congo hemorrhagic fever virus(CCHFV),an encapsulated negative-sense RNA virus of the family Nairoviridae,is transmitted from person to person via *** a case fatality rate between 10%to 40%,the most common ways that the disease may spread to humans are via tick bites or coming into touch with infected animals'blood or ***,the transfer of bodily fluids between individuals is another potential route of *** is a wide range of symptoms experienced by patients throughout each stage,from myalgia and fever to extreme bruising and excess *** management measures include minimising the spread of ticks from one species to another and from people to animals via the use of protective clothing,repellents,and proper animal *** order to prevent the spread of illness,healthcare workers must adhere to stringent *** the lack of an authorised vaccine,the main components of treatment now consist of preventative measures and supportive care,which may include the antiviral medicine *** still don't know very much about the virus's mechanisms,even though advances in molecular virology and animal models have improved our understanding of the pathogenesis of CCHFV.A critical need for vaccination that is both safe and effective,as well as for quick diagnosis and efficient treatments to lessen the disease's impact in areas where it is most *** steps towards lowering Crimean-Congo hemorrhagic fever mortality and morbidity rates were to anticipatethe future availability of immunoglobulin products.

关键词： Crimean-congo haemorrhagic fever Tick-borne illness Immunoglobulins Viral hemorrhagic fever Antiviral therapy

Enzymatic Enantioselective Synthesis of (R)-2-Trimethylsilyl-2-hydroxyl-propionitrile by Defatted Apple Seed Meal

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Chinese Journal of Chemistry 2003年第10期21卷 1360-1363页

作者：李宁宗敏华王菊芳刘晨吴虹 biotechnology department

The enantioselective synthesis of ( R ) 2 trimethylsilyl 2 hydroxyl propionitrile by ( R ) oxynitrilase contained in defatted apple seed meal in a biphasic system was successfully performed. The influences of some factors on the reaction were investigated systematically. Diisopropyl ether was found to be the best for this reaction among all the organic solvents examined. The optimal concentration of defatted apple seed meal, aqueous phase content, concentrations of acetyltrimethylsilane and acetone cyano^hydrin, buffer pH, reaction temperature were 4% ( W/V ), 23% ( V/V ), 20 mmol·L -1 , 40 mmol·L -1 , pH=5 0 and 40 ℃, respectively, under which the initial reaction rate, substrate conversion and product enantiomeric excess were 9 4 mmol·L -1 ·h -1 , 99% and >99%, respectively.

关键词： asymmetric synthesis,ketone cyanohydrin ( R ) oxynitrilase ( R ) 2 trimethylsilyl 2 hydroxyl propionitrile

Voices that matter:The impact of patient-reported outcome measures on clinical decision-making

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World Journal of Methodology 2025年第2期15卷 54-61页

作者： Naveen Jeyaraman Madhan Jeyaraman Swaminathan Ramasubramanian Sangeetha Balaji Sathish Muthu department of Orthopaedics ACS Medical College and HospitalDr MGR Educational and Research InstituteChennaiTN 600077India department of Research Methods Orthopaedic Research GroupCoimbatoreTN 641045India department of Orthopaedics Government Medical CollegeOmandurar Government EstateChennaiTN 600002India department of biotechnology Faculty of EngineeringKarpagam Academy of Higher EducationCoimbatoreTN 641021India department of Orthopaedics Government Medical CollegeKarurTN 639004India

The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific *** encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of *** integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments *** deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment ***,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health ***,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and *** these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of *** paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.

关键词： Patient-reported outcome measures Clinical decision-making Patient-centered care Healthcare technology Data management Policy development