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Amyloid-beta and tau protein beyond Alzheimer's disease

Neural Regeneration Research 2024年第6期19卷 1262-1276页

作者： Morteza Abyadeh Vivek Gupta Joao A.Paulo Arezoo Gohari Mahmoudabad Sina Shadfar Shahab Mirshahvaladi Veer Gupta Christine T.O.Nguyen David I.Finkelstein Yuyi You Paul A.Haynes Ghasem H.Salekdeh Stuart L.Graham Mehdi Mirzaei ProGene Technologies Pty Ltd. 2. Department of Clinical medicine Faculty of Medicine Health and Human Sciences Macquarie Medical School Macquarie University Department of Cell Biology Harvard Medical School School of medicine Deakin University Department of Optometry and Vision Sciences School of Health Sciences Faculty of Medicine Dentistry and Health Sciences University of Melbourne The Florey Institute of Neuroscience and Mental health The University of Melbourne School of Natural Sciences Macquarie University

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer’s disease pathogenesis and are considered the main pathological hallmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, posttranslational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.

关键词： amyloid-beta cancer cardiovascular diseases diabetes neurodegeneration Tau traumatic brain injury

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Advances in clinical applications of bioceramics in the new regenerative medicine era

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World Journal of Clinical Cases 2024年第11期12卷 1863-1869页

作者： Noha Elshazly Fayza Eid Nasr Ayat Hamdy Safa Saied Mohamed Elshazly Tissue Engineering Laboratory Faculty of DentistryAlexandria UniversityAlexandria 21526Egypt Department of Biochemistry Faculty of ScienceAlexandria UniversityAlexandria 21526Egypt Public Dental Clinic Central Administration of DentistryMinistry of Health and PopulationAlexandria 21554Egypt Department of Surgery Faculty of Veterinary MedicineAlexandria 21526Egypt

In this editorial,we comment on the hard and soft tissue applications of different ceramic-based scaffolds prepared by different mechanisms such as 3D printing,sol-gel,and *** new concept of regenerative medicine relies on biomaterials that can trigger in situ tissue regeneration and stem cell recruitment at the defect site.A large percentage of these biomaterials is ceramic-based as they provide the essential requirements of biomaterial principles such as tailored multisize porosity,antibacterial properties,and angiogenic *** these previously mentioned properties put bioceramics on top of the hierarchy of biomaterials utilized to stimulate tissue regeneration in soft and hard tissue *** clinical applications registered the use of these materials in triggering soft tissue regeneration in healthy and diabetic patients such as bioactive glass *** results were promising and opened new frontiers for utilizing these materials on a larger *** same results were mentioned when using different forms and formulas of bioceramics in hard defect *** bioceramics were used in combination with other polymers and biological scaffolds to improve their regenerative and mechanical *** this progress will enable a larger scale of patients to receive such services with ease and decrease the financial burden on the government.

关键词： Regenerative medicine Bioceramics Chronic wounds Bone defects Clinical applications

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A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis

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International Journal of Oral Science 2024年第2期16卷 265-279页

作者： Alfredo Torres M.Angélica Michea Ákos Végvári Marion Arce Valentina Pérez Marcela Alcota Alicia Morales Rolando Vernal Mauricio Budini Roman A.Zubarev Fermín E.González Laboratory of Experimental Immunology&Cancer Faculty of DentistryUniversity of ChileSantiagoChile Department of Conservative dentistry Faculty of DentistryUniversity of ChileSantiagoChile Division of Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden Periodontal Biology Laboratory Faculty of DentistryUniversidad de ChileSantiagoChile Laboratory of Cellular and Molecular Pathology Institute for Research in Dental SciencesFaculty of DentistryUniversity of ChileSantiagoChile

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases,yet its association with progressive periodontitis remains *** investigate the involvement and significance of ferroptosis in periodontitis progression,we assessed sixteen periodontitis-diagnosed *** progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid(GCF)collection was performed for further *** metrics,proteomic data,in silico methods,and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with *** western blot analyses validated key ***,a single-cell RNA sequencing(scRNA-seq)dataset(GSE164241)for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis *** progression was identified as occurring at a faster rate than traditionally *** samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic *** addition,specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins,including SNCA,CA1,HBB,SLC4A1,and ANK1 was strongly associated with the clinical progression status of ***,we found specific proteins-drivers or suppressors-associated with ferroptosis(SNCA,FTH1,HSPB1,CD44,and GCLC),revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of ***,the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to *** analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients,which offer new insights into the molecular mechanisms of progressive periodontal *** findings may le

关键词： finding progression faster

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Evaluating implicit gender bias at Canadian otolaryngology meetings through use of professional title

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 12-17页

作者： Kylen Van Osch Agnieszka Dzioba Khadija Ahmed Andrew MacDonald Jamila Skinner Harley Williams Julie E.Strychowsky M.Elise Graham Department of Otolaryngology-Head&Neck Surgery Schulich School of Medicine&DentistryWestern UniversityLondonOntarioCanada Department of Otolaryngology London Health Sciences Centre Children's HospitalLondonOntarioCanada faculty of medicine Schulich School of Medicine&DentistryWestern UniversityLondonOntarioCanada

Objectives:Increasing numbers of women enter medical school *** number of female physicians in leadership positions has been much slower to *** are also well‐documented differences in the treatment of women as compared to men in professional *** presenters are less likely to be introduced by their professional title(“Doctor”)for grand rounds and conferences,especially with a man performing the *** study reviewed the Canadian Society of Otolaryngology–Head and Neck Surgery(CSOHNS)meetings from 2017 to 2020 to determine the proportion of presenters introduced by their professional title and whether this varied by ***:Recordings from CSOHNS meetings were reviewed and coded for introducer and presenter demographics,including leadership positions and ***‐squared tests of proportion and multivariate logistic regression was used to compare genders and identify factors associated with professional versus unprofessional forms of ***:No significant association was found between professional title use and introducer or presenter *** presenters were introduced with professional title 69.6%of the time,while male presenters were introduced with professional title 67.6%of the time(P=0.69).Residents were introduced with a professional title with the most frequency(75.8%),while attending staff were introduced with a professional title with the least frequency(63.0%)(P=0.02).Conclusions:The lack of gender bias in speaker introductions at recent CSOHNS meetings demonstrates progress in achieving gender equity in *** efforts should continue to define additional forms of unconscious bias that may be contributing to gender inequity in leadership positions.

关键词： attitude of health personnel gender identity Otolaryngology women

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Protective effects of cyclosporine and its analog NIM-811 in a murine model of hepatic ischemia-reperfusion injury

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Liver Research 2024年第1期8卷 46-53页

作者： Joshua Hefler Rena Pawlick Braulio A.Marfil-Garza Aducio Thiesen Nerea Cuesta-Gomez Sanaz Hatami Darren H.Freed Constantine Karvellas David L.Bigam A.M.James Shapiro Department of Surgery Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada Department of medicine Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada CHRISTUS-LatAm Hub Excellence&Innovation Center MonterreyMexico Alberta Diabetes Institute University of AlbertaEdmontonABCanada Clinical Islet Transplant Program University of AlbertaEdmontonABCanada Department of Laboratory medicine&Pathology Faculty of Medicine&DentistryUniversity of AlbertaEdmontonABCanada

Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of *** hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or ***(CsA),which is a well-known immunosuppressive agent that inhibits calcineurin,has the additional effect of inhibiting the mito-chondrial permeability transition pore(mPTP),thereby,preventing mitochondrial swelling and ***-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the *** this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine *** and methods:Before ischemic insult,the mice were administered with intraperitoneal normal saline(control);CsA at 2.5,10,or 25 mg/kg;or NIM-811 at 10 mg/***,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after *** alanine transaminase(ALT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory ***:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels(P<0.001,0.007,and 0.031,respectively).Moreover,the liver tissue showed reduced histological injury scores after treatment with CsA at 2.5,10,and 25 mg/kg and NIM-811(P=0.041,<0.001,0.003,and 0.043,respectively)and significant decrease in apoptosis after treatment with CsA at all doses(P=0.012,0.007,and<0.001,respectively).Levels of the pro-inflammatory cyto-kines,particularly interleukin(IL)-1β,IL-2,IL-4,IL-10,and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA(25 mg/kg)than those in the control ***

关键词： Cyclosporine(CsA) Cyclosporine analogue Liver surgery Ischemia-reperfusion injury(IRI) Animal model NIM-811

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Inhibition of Ehrlich ascites carcinoma growth by melatonin:Studies with micro-CT

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Oncology Research 2024年第1期32卷 175-185页

作者： SEHER YILMAZ ZÜLEYHA DOĞANYIĞIT MERT OCAK EVRIM SUNA ARIKAN SÖYLEMEZ ASLI OKAN OFLAMAZ SÜMEYYE UÇAR ŞÜKRÜATEŞ AMMAD AHMAD FAROOQI Department of Anatomy Faculty of MedicineYozgat Bozok UniversityYozgatTurkey Department of Mechanical and Aerospace Engineering Case Western Reserve UniversityClevelandOhioUSA Department of Histology and Embriology Faculty of MedicineYozgat Bozok UniversityYozgatTurkey Department of Anatomy Faculty of DentistryAnkara UniversityAnkaraTurkey Department of Medical Biology Faculty of MedicineAfyonkarahisar Health Sciences UniversityAfyonTurkey Department of Anatomy Faculty of MedicineErciyes UniversityKayseriTurkey Department of Molecular Oncology Institute of Biomedical and Genetic Engineering(IBGE)IslamabadPakistan

Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling *** has many benefits,such as organizing circadian rhythms and acting as a powerful *** aimed to show the antitumor effects of melatonin in both in vivo and in vitro models through the mammalian target of rapamycin(mTOR)signaling pathway and the Argyrophilic Nucleolar Regulatory Region(AgNOR),using the Microcomputed Tomography(Micro CT).Ehrlich ascites carcinoma(EAC)cells were administered into the mice by subcutaneous *** with solid tumors were injected intraperitoneally with 50 and 100 mg/kg melatonin for 14 *** measurements for the taken tumors were made with micro-CT imaging,immunohistochemistry(IHC),real-time polymerase chain reaction(PCR)and ***,the tumor tissue volume in the Tumor+100 mg/kg melatonin group was significantly lower than that in the other groups in the data obtained from micro-CT *** the IHC analysis,the groups treated with Tumor+100 mg/kg melatonin were compared when the mTOR signaling pathway and factor 8(F8)expression were compared with the control *** was determined that there was a significant decrease(p<0.05).Significant differences were found in the total AgNOR area/nuclear area(TAA/NA)ratio in the treatment groups(p<0.05).Furthermore,there were significant differences between the amount of mTOR mRNA for the phosphatidylinositol 3-kinase(PI3K),AKT Serine/Threonine Kinase(PKB/AKT)genes(p<0.05).Cell apoptosis was evaluated with Annexin V in an in vitro study with different doses of melatonin;It was observed that 100µg/mL melatonin dose caused an increase in the apoptotic cell *** this study,we have reported anti-tumor effects of melatonin in cell culture studies as well as in mice *** characterization of the melatonin-mediated cancer inhibitory effects will be valuable in advanc

关键词： Signaling pathway Apoptosis Real-time PCR AgNOR

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Neural plasticity in Parkinson's disease: a neuroimaging perspective

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Neural Regeneration Research 2024年第6期19卷 1203-1205页

作者： Christina Andica Koji Kamagata Department of Radiology Juntendo University Graduate School of Medicine faculty of health Data Science Juntendo University

Parkinson’s disease(PD) is a progressive neurodegenerative disorder characterized primarily by classical motor signs of bradykinesia,rigidity,tremors,and postural instability usually manifesti ng unilate rally or at least *** disease involves a loss of dopaminergic neurons projecting from the substantia nigra pars compacta to the dorsal striatum,

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Targeting oral-gut microbial transmission in diabetic coronary heart disease: unveiling key pathogenic mechanisms

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Science China Life Sciences 2024年第10期67卷 2287-2288页

作者： Ismail Cimen Aab Cardiovascular Research Institute Department of MedicineUniversity of Rochester School of Medicine and Dentistry

Diabetes significantly exacerbates the occurrence and adverse prognosis of coronary heart disease(CHD), emphasizing the importance of focusing on the prevention and management of diabetesrelated complications. This study identifies and verifies for the first time a distinctive oral-gut microbiota profile in patients with diabetic coronary heart disease(DCHD), marked by an increased abundance of oral Fusobacterium nucleatum and gut Lactobacillus.

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The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

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Genes & Diseases 2024年第1期11卷 321-334页

作者： Md Rakibul Alam Md Mizanur Rahman Zhiguo Li Department of Toxicology and Cancer Biology College of MedicineUniversity of KentuckyLexingtonKY 40506USA Department of medicine(Nephrology) Faculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6E2H7Canada

Exosomes are small membrane vesicles containing microRNA,RNA,DNA fragments,and proteins that are transferred from donor cells to recipient *** cells release exo-somes to reprogram the factors associated with the tumor microenvironment(TME)causing tu-mor metastasis and immune *** evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1(PD-L1)that binds with re-ceptor program death protein 1(PD-1)and promote tumor progression by escaping immune ***,some FDA-approved monoclonal antibodies are clinicallyused for cancer treatment by blocking PD-1/PD-L1 *** notable treatment outcomes,some pa-tients show poor drug *** PD-L1 plays a vital role in lowering the treatment response,showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the ef-fect of cell surface *** enhance therapeutic response,inhibition of exosomal PD-L1 is *** signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion ***-mune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine,nifedipine,lercanidipine,diltiazem,and verapamil were also reported to suppress cellular PD-L1 ***,to enhance the PD-1/PD-L1 blockage therapy response,the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic *** this review,we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient's drug response rate.

关键词： Calcium signaling CD8^(+)T cells Exosomal PD-L1 Exosomes biogenesis Immunosuppression Immunotherapy

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Bilateral adrenal histoplasmosis in a Malaysian tertiary hospital:Report of four cases

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Asian Pacific Journal of Tropical medicine 2024年第2期17卷 91-94页

作者： Kang WH Norasyikin Abdul Wahab Department of medicine Faculty of Medicine and Health SciencesUniversity Tunku Abdul RahmanMalaysia Department of medicine Pusat Perubatan Universiti KebangsaanMalaysia

Rationale:Adrenal histoplasmosis can present as bilateral adrenal enlargement with constitutional symptoms and/or adrenal *** these patients are initially investigated as secondary adrenal metastases before eventually their diagnosis established by histopathological examination of the adrenal *** concerns:We report 4 cases of patients aged 55-78 who presented with hypocortisolism and bilateral adrenal ***:Bilateral adrenal ***:Three patients received antifungal treatment for at least one year while 1 patient passed away before the initiation of antifungal ***:Two patients’adrenal function recovered not requiring any steroid replacement,while 1 patient still requires long-term steroid ***:Adrenal histoplasmosis should be excluded in patients from endemic areas presenting with bilateral adrenal masses and adrenal *** patients have an exposure to bird droppings,bat guano or soil contaminated with histoplasmosis *** examination of biopsied adrenal tissues is still the gold standard investigation as serology and molecular diagnostic methods are still not widely available in most centers in Malaysia.

关键词： Adrenal histoplasmosis Histoplasmosis Bilateral adrenal masses

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