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Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui Ling He Jing Wang Regenerative medicine Program Ottawa Hospital Research InstituteOttawaONCanada Department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada Department of Pediatrics and medicine Johns Hopkins Medical SchoolBaltimoreMDUSA Department of Cellular and Molecular medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available *** most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy ***,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological *** that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological *** molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted *** this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

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Neutrophils in the tumor microenvironment-when a company becomes a crowd

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Cellular & Molecular Immunology 2024年第4期21卷 313-314页

作者： Zvi G.Fridlender Zvi Granot faculty of medicine Hebrew University of JerusalemJerusalemIsrael Institute of Pulmonary medicine Hadassah-Hebrew University Medical Center91120 JerusalemIsrael Department of Developmental Biology and Cancer Research Institute for Medical Research Israel CanadaFaculty of MedicineHebrew University91120 JerusalemIsrael

Traditionally,neutrophils are perceived as terminally differentiated cells with defined functions and limited *** is commonly believed that circulating,marginating and tissue-infiltrating neutrophils belong to the same homogeneous population and are capable of switching between these *** research has stagnated since the early 1980s,maintaining a narrow and simplistic view of their capabilities.

关键词： narrow infiltrating differentiated

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Reliability of a computerized system for strabismus screening

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 126-130页

作者： Supaporn Tengtrisorn Alan Frederick Geater Department of Ophthalmology Faculty of MedicinePrince of Songkla UniversityHat-YaiSongkla 90110Thailand Epidemiology Unit Faculty of MedicinePrince of Songkla UniversityHat-YaiSongkla 90110Thailand

AIM:To evaluate the reliability of Photo-Hirschberg screening for global strabismus performed by non-specialized ***:Participants at three sites were *** person at each site was trained in visual acuity measurement and use of the computerized *** acuity was measured,and strabismus testing was performed using two flash *** data from the three primary observers were sent to an experienced assistant researcher,who was blinded to the primary results,for *** primary and re-evaluation results of the Photo-Hirschberg screenings using weighted kappa for agreement were ***:The study included 181 participants(88 males and 93 females)and the results for primary and re-evaluation screenings were *** participants with contrasting results presented with unclear corneal light *** and specificity were 100%[95%confidence interval(CI):29.0%-100%]and 99.4%(95%CI:96.6%-100%),respectively,based on the Agresti test of the primary evaluation,considering the re-evaluated classification as ***:The computerized system can be used for primary strabismus screening by non-specialized personnel,with 98.8%agreement with ***,it cannot be used as a substitute for professional examination.

关键词： strabismus screening computerized system Photo-Hirschberg screening

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Nrf2 as a potential target for the treatment of epilepsy

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Neural Regeneration Research 2024年第9期19卷 1865-1866页

作者： Prince Kumar Singh Tawfeeq Shekh-Ahmad Institute for Drug Research School of PharmacyFaculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael

Epilepsy is a prevalent chronic brain disorder that is characterized by a persistent predisposition to recurrently generate epileptic seizures and is often associated with cognitive and psychological *** affects approximately 65 million individuals,including both males and females of all ages worldwide,and poses a significant burden on patients,their families,and the health system(Vezzani et al.,2019).

关键词： epilepsy Nrf2

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B7 homolog 3 in pancreatic cancer

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World Journal of Gastroenterology 2024年第31期30卷 3654-3667页

作者： Dijana Perovic Marija Dusanovic Pjevic Vladimir Perovic Milka Grk Milica Rasic Maja Milickovic Tanja Mijovic Petar Rasic Institute of Human Genetics Faculty of MedicineUniversity of BelgradeBelgrade 11000Serbia Institute of Microbiology and Immunology Faculty of MedicineUniversity of BelgradeBelgrade 11000Serbia Department of Abdominal Surgery Mother and Child Health Care Institute of Serbia“Dr.Vukan Cupic”Belgrade 11000Serbia faculty of medicine University of BelgradeBelgrade 11000Serbia

Despite advances in cancer treatment,pancreatic cancer(PC)remains a disease with high mortality rates and poor survival *** B7 homolog 3(B7-H3)checkpoint molecule is overexpressed among many malignant tumors,including PC,with low or absent expression in healthy *** modulating various immunological and nonimmunological molecular mechanisms,B7-H3 may influence the progression of ***,the impact of B7-H3 on the survival of patients with PC remains a subject of ***,most available scientific data recognize this molecule as a suppressive factor to antitumor immunity in ***,it has been demonstrated that B7-H3 stimulates the migration,invasion,and metastasis of PC cells,and enhances resistance to *** preclinical models of PC,B7-H3-targeting monoclonal antibodies have exerted profound antitumor effects by increasing natural killer cell-mediated antibodydependent cellular cytotoxicity and delivering radioisotopes and cytotoxic drugs to the tumor ***,PC treatment with B7-H3-targeting antibody-drug conjugates and chimeric antigen receptor T cells is being tested in clinical *** review provides a comprehensive analysis of all PC-related studies in the context of B7-H3 and points to deficiencies in the current data that should be overcome by future research.

关键词： B7 homolog 3 Pancreatic cancer Prognosis Signaling pathways Immunotherapy

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Prognostic factors and clinical features of rhino-orbitalmucormycosis cases:an update for patient and visual survivals

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 916-923页

作者： Mustafa Aksoy Altan Atakan Ozcan Burak Ulas Department of Ophthalmology Cukurova University Faculty of MedicineSaricamAdana 01330Türkiye

AIM:To determine the frequency of patients’vision survival and prognostic factors and evaluate clinical features in rhino-orbital ***:Forty-three eyes of 43 patients followed up with orbital mucormycosis infections were included in the *** characteristics of the patients,symptoms at admission,ophthalmologic and non-ophthalmologic examination findings,clinical findings during follow-up,medical and surgical procedures,and complications were *** survival was determined by assessing the incidence of mortality,and vision survival was defined as achieving a final visual acuity of at least light ***:Twenty-seven(62.8%)patients were male,and 16(37.2%)were *** the underlying disease status of the patients was examined,it was observed that all patients had an underlying disease and diabetes constituted the majority(65.2%).Periorbital swelling(69.8%)and ophthalmoplegia(53.5%)were the most common symptoms and findings at the admission of patients with mucormycosis *** disease resulted in death in 22(51.2%)*** presence of fever and shorter duration of antifungal therapy were associated with lower patient *** surgery was not found to be associated with the survival of the *** eye,loss of pupillary light reflex,and development of central retinal artery occlusion were associated with lower vision ***:This study presents one of the most extensive patient series in the literature on rhino-orbital *** the patients’symptoms at the time of admission and the clinical findings during the infection process will increase awareness about the disease.

关键词： mucormycosis rhino-orbital-mucormycosis orbital apex syndrome retinal arterial occlusion

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Effects of high glucose and severe hypoxia on the biological behavior of mesenchymal stem cells at various passages

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World Journal of Stem Cells 2024年第4期16卷 434-443页

作者： Fatimah Almahasneh Ejlal Abu-El-Rub Ramada R Khasawneh Rawan Almazari Department of Basic Medical Sciences Faculty of MedicineYarmouk UniversityIrbid 21163Jordan

BACKGROUND Mesenchymal stem cells(MSCs)have been extensively studied for therapeutic potential,due to their regenerative and immunomodulatory *** passage and stress factors may affect the biological characteristics of MSCs,but the details of these effects have not been recognized *** To investigate the effects of stress factors(high glucose and severe hypoxia)on the biological characteristics of MSCs at different passages,in order to optimize the therapeutic applications of *** In this study,we investigated the impact of two stress conditions;severe hypoxia and high glucose on human adipose-tissue derived MSCs(hAD-MSCs)at passages 6(P6),P8,and ***,senescence and apoptosis were evaluated measuring WST-1,senescence-associated beta-galactosidase,and annexin V,*** Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control,while the extent of senescence did not change significantly under stress *** P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at *** cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage,while no change in apoptosis was *** the other hand,MSCs cultured under hypoxia showed decreased senescence,increased apoptosis and no significant change in proliferation when compared to the same conditions at *** These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages,and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.

关键词： Mesenchymal stem cells High glucose Hypoxia Stressful microenvironment Serial passage Senescence Apoptosis

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MicroRNA-329-3p inhibits the Wnt/β-catenin pathway and proliferation of osteosarcoma cells by targeting transcription factor 7-like 1

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Oncology Research 2024年第3期32卷 463-476页

作者： Hur SUN MASANORI KAWANO TATSUYA IWASAKI ICHRO ITONAGA YUTA KUBOTA HROSHI TSUMURA KAZUHRO TANAKA Department of Orthopaedic Surgery Faculty of MedicineOita UniversityOita879-5503Japan

An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding *** study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 *** growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of ***329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell ***,a clinical comparison study was performed using the TCGA ***,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo *** miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic *** expression of proteins that indicate apoptosis increased *** cell cycle was arrested in the G0/G1 phase,and the G1/S transition was *** introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt *** experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues *** 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in *** cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR *** these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcom

关键词： MiR-329-3p TCF7L1 Wnt/β-catenin pathway Osteosarcoma Proliferation

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Tri-modal death distribution towards personalized management of intraductal papillary neoplasm of the bile duct patients:Every story has its own conclusion

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 313-316页

作者： Vor Luvira Department of Surgery Faculty of MedicineKhon Kaen UniversityKhon KaenThailand

The concept of intraductal papillary neoplasm of the bile duct(IPNB)has gained recognition as a discrete entity[1,2],possessing many features including multiplicity[3,4],mucin production[3],slow progression[3,5],various morphology[6,7],easy sloughing and seeding[8],and having unique risk factors[2,9-11].We have previously proposed a morphologic classification[6]and a progression model of IPNB[12].

关键词： neoplasm bile conclusion

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Neoadjuvant treatment of pancreatic ductal adenocarcinoma:Whom,when and how

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1223-1230页

作者： Nebojsa Manojlovic Goran Savic Stevan Manojlovic Clinic for Gastroenterology and Hepatology Military Medical AcademyFaculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia Military Medical Academy Faculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia faculty of medicine University of BelgradeBelgrade 11000Serbia

Pancreatic ductal adenocarcinoma(PDAC),which is notorious for its aggressiveness and poor prognosis,remains an area of great unmet medical need,with a 5-year survival rate of 10%-the lowest of all solid *** diagnosis,only 20%of patients have resectable pancreatic cancer(RPC)or borderline RPC(BRPC)disease,while 80%of patients have unresectable tumours that are locally advanced pancreatic cancer(LAPC)or have distant *** 60%of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy(CHT)because of postoperative complications and early cancer *** important paradigm shift to achieve better outcomes has been the sequence of therapy,with neoadjuvant CHT preceding *** surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers:RPC,BRPC,and *** main goal of neoadjuvant treatment(NAT)is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT,reducing tumour volume before surgery to improve the rate of margin-negative resection(R0 resection,a microscopic margin-negative resection),reducing the rate of positive lymph node occurrence at surgery,providing early treatment of occult micrometastatic disease,and assessing tumour chemosensitivity and tolerance to treatment as potential surgical *** this editorial,we summarize evidence concerning NAT of PDAC,providing insights into future practice and study *** research is needed to establish predictive biomarkers,measures of therapeutic response,and multidisciplinary stra tegies to improve patient-centered outcomes.

关键词： Pancreatic adenocarcinoma Neoadjuvant treatment Chemotherapy Upfront surgery Radiotherapy Response evaluation

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