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Hydrogel loaded with bone marrow stromal cell-derived exosomes promotes bone regeneration by inhibiting inflammatory responses and angiogenesis

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World Journal of Stem Cells 2024年第5期16卷 499-511页

作者： Shuai Zhang Chuan Lu Sheng Zheng Guang Hong Division for International Collaborative and Innovative dentistry Tohoku University Graduate School of DentistrySendai 980-8575MiyagiJapan school of Stomatology Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina

BACKGROUND Bone healing is a complex process involving early inflammatory immune regu-lation,angiogenesis,osteogenic differentiation,and biomineralization.Fracture repair poses challenges for orthopedic surgeons,necessitating the search for efficient healing methods.AIM To investigate the underlying mechanism by which hydrogel-loaded exosomes derived from bone marrow mesenchymal stem cells(BMSCs)facilitate the process of fracture healing.METHODS Hydrogels and loaded BMSC-derived exosome(BMSC-exo)gels were charac-terized to validate their properties.In vitro evaluations were conducted to assess the impact of hydrogels on various stages of the healing process.Hydrogels could recruit macrophages and inhibit inflammatory responses,enhance of human umbilical vein endothelial cell angiogenesis,and promote the osteogenic differen-tiation of primary cranial osteoblasts.Furthermore,the effect of hydrogel on fracture healing was confirmed using a mouse fracture model.RESULTS The hydrogel effectively attenuated the inflammatory response during the initial repair stage and subsequently facilitated vascular migration,promoted the formation of large vessels,and enabled functional vascularization during bone repair.These effects were further validated in fracture models.CONCLUSION We successfully fabricated a hydrogel loaded with BMSC-exo that modulates macrophage polarization and angiogenesis to influence bone regeneration.

关键词： Hydrogel Bone marrow mesenchymal stem cells Macrophage polarization Angiogenesis Bone regeneration

Genetics in medical school curriculum:A look at the University of Rochester school of Medicine and dentistry

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第1期9卷 10-15页

作者： Deanne M. ROBINSON Chin-To FONG Department of Pediatrics University of Rochester School of Medicine and DentistryRochesterNY 14642USA

Genetics is assuming an increasingly important role in medicine. As a result,the teaching of genetics should also be increased proportionally to ensure that future physicians will be able to take advantage of the new genetic technology,and to understand the associated ethical,legal and social issues. At the University of Rochester school of Medicine and dentistry,we have been able to incorporate genetic education into a four-year medical curriculum in a fully integrated fashion. This model may serve as a template for other medical curriculum still in development.

关键词：遗传学高等教育医学教学课程改革罗彻斯特大学

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

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International Journal of Oral Science 2024年第1期16卷 85-96页

作者： Qingling Huang Yi Xiao Ting Lan Youguang Lu Li Huang Dali Zheng Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina Fujian Key Laboratory of Oral Diseases School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Preventive dentistry School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of dentistry The First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

关键词： WNT squamous tumorigenesis

Drug-induced mucosal alterations observed during esophagogastroduodenoscopy

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World Journal of Gastroenterology 2024年第16期30卷 2220-2232页

作者： Masaya Iwamuro Seiji Kawano Motoyuki Otsuka Department of Gastroenterology and Hepatology Okayama University Graduate School of MedicineDentistryand Pharmaceutical SciencesOkayama 700-8558Japan

Several features of drug-induced mucosal alterations have been observed in the upper gastrointestinal tract,i.e.,the esophagus,stomach,and duodenum.These include pill-induced esophagitis,desquamative esophagitis,worsening of gastroesophageal reflux,chemotherapy-induced esophagitis,proton pump inhibitor-induced gastric mucosal changes,medication-induced gastric erosions and ulcers,pseudomelanosis of the stomach,olmesartan-related gastric mucosal inflammation,lanthanum deposition in the stomach,zinc acetate hydrate tabletinduced gastric ulcer,immune-related adverse event gastritis,olmesartan-associated sprue-like enteropathy,pseudomelanosis of the duodenum,and lanthanum deposition in the duodenum.For endoscopists,acquiring accurate knowledge regarding these diverse drug-induced mucosal alterations is crucial not only for the correct diagnosis of these lesions but also for differential diag-nosis of other conditions.This minireview aims to provide essential information on druginduced mucosal alterations observed on esophagogastroduodenoscopy,along with representative endoscopic images.

关键词： Diagnosis Esophagogastroduodenoscopy Non-neoplastic lesions Esophageal lesions Gastric lesions Duodenal lesions

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 annually.The number of female physicians in leadership positions has been much slower to equalize.There are also well‐documented differences in the treatment of women as compared to men in professional settings.Female presenters are less likely to be introduced by their professional title(“Doctor”)for grand rounds and conferences,especially with a man performing the introduction.This 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 gender.Methods:Recordings from CSOHNS meetings were reviewed and coded for introducer and presenter demographics,including leadership positions and gender.Chi‐squared tests of proportion and multivariate logistic regression was used to compare genders and identify factors associated with professional versus unprofessional forms of address.Results:No significant association was found between professional title use and introducer or presenter gender.Female 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 medicine.Research 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

Using microglia-derived extracellular vesicles to capture diversity of microglial activation phenotypes following neurological injury

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Neural Regeneration Research 2024年第8期19卷 1633-1634页

作者： Austyn D.Roseborough Nikita Ollen-Bittle Shawn NWhitehead Vulnerable Brain Laboratory Department of Anatomy&Cell BiologySchulich School of Medicine&DentistryLondonOHCanada

Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perf... 详细信息

关键词： neurological cytes activation

Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn D.Roseborough Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead Department of Anatomy and Cell Biology Western UniversityLondonONCanada Schulich school of Medicine and dentistry Western UniversityLondonONCanada Deparment of Clinical Neurological Sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

Visible light cross-linking and bioactive peptides loaded integrated hydrogel with sequential release to accelerate wound healing complicated by bacterial infection

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Nano Research 2024年第3期17卷 1737-1747页

作者： Guiyan Wang Ning Yuan Jun Zhang Man Qin Suwei Dong Yuguang Wang Department of Pediatric dentistry Peking University School and Hospital of StomatologyBeijing 100081China State Key Laboratory of Natural and Biomimetic Drugs Chemical Biology Centerand School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Prosthodontics Peking University School and Hospital of StomatologyBeijing 100081China

The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge.The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected wounds.Here,a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is developed.The antibacterial peptide that consists of 11 residues(CM11,WKLFKKILKVL)is loaded onto acrylate-modified gelatin through charge interactions.A vascular endothelial growth factor mimetic peptide KLT(KLTWQELYQLKYKGI)with a GCG(Gly-Cys-Gly)modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene reaction.In this reaction,the acrylate gelatin undergoes cross-linkage within seconds.Based on the physical/chemical double crosslinking strategy,the bioactive peptides achieve sustained and sequential release.The results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus(MRSA)growth through the rapid release of CM11 peptides at early stage;it forms obvious growth inhibition zones against pathogenic bacterial strains.Moreover,cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT peptides.In a mouse skin wound infected with self-luminous MRSA,the CM11/KLT-functionalized hydrogels enhance wound healing,with rapidly bacterial infection reduction,lower expression of inflammatory factors,and neovascularization promotion.These results suggest that the rationally designed,sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.

关键词： antimicrobial peptide vascular endothelial growth factor(VEGF)mimetic peptide sequential release visible-light crosslinking hydrogel wound therapy

Amyloid-beta and tau protein beyond Alzheimer's disease

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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