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A double-network porous hydrogel based on high internal phase emulsions as a vehicle for potassium sucrose octasulfate delivery accelerates diabetic wound healing

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Regenerative Biomaterials 2024年第4期3卷 82-97页

作者： Zhiwei Wang Lingshun Sun Weixing Wang Zheng Wang Ge Shi Honglian Dai Aixi Yu department of Orthopedics Trauma and Microsurgery Zhongnan Hospital of Wuhan UniversityWuhan 430070China State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Biomedical Materials and Engineering Research Center of Hubei ProvinceWuhan University of TechnologyWuhan 430070China

Diabetic wounds are a difficult medical *** secretion of matrix metalloproteinase-9(MMP-9)in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular damage,which seriously hinders diabetic wound *** solve these issues,a double-network porous hydrogel composed of poly(methyl methacrylate-co-acrylamide)(p(MMA-co-AM))and polyvinyl alcohol(PVA)was constructed by the high internal phase emulsion(HIPE)technique for the delivery of potassium sucrose octasulfate(PSO),a drug that can inhibit MMPs,increase angiogenesis and improve *** hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies,high porosity,high specific surface area,excellent mechanical properties and suitable swelling ***,the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO *** addition,both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds,increasing growth factor secretion,improving vascularization,increasing collagen deposition and promoting ***,this study provided a reliable therapeutic strategy for diabetic wound healing,some theoretical basis and new insights for the rational design and preparation of wound hydrogel dressings with high porosity,high drug-loading performance and excellent mechanical properties.

关键词： high internal phase emulsions double-network porous hydrogel drug delivery diabetic wound healing sucrose octasulfate

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PICOTEES:a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants from Chinese children cohorts

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Journal of genetics and Genomics 2024年第2期51卷 243-251页

作者： Xinran Dong Yulan Lu Lanting Guo Chuan Li Qi Ni Bingbing Wu Huijun Wang Lin Yang Songyang Wu Qi Sun Hao Zheng Wenhao Zhou Shuang Wang center for Molecular Medicine Children's Hospital of Fudan UniversityShanghai 201102China Key Laboratory of Birth Defects Children's Hospital of Fudan UniversityShanghai 201102China department of Bioinformatics Hangzhou Nuowei Information Technology Co.LtdHangzhouZhejiang 310000China The Third Research Institute of the Ministry of Public Security Shanghai 200031China Xiamen Campus of Children's Hospital of Fudan University XiamenFujian 361006China Institutes for Systems genetics West China HospitalChengduSichuan 610041China Shanghai Putuo People's Hospital Tongji UniversityShanghai 200060China

The growth in biomedical data resources has raised potential privacy concerns and risks of genetic information leakage. For instance, exome sequencing aids clinical decisions by comparing data through web services, but it requires significant trust between users and providers. To alleviate privacy concerns, the most commonly used strategy is to anonymize sensitive data. Unfortunately, studies have shown that anonymization is insufficient to protect against reidentification attacks. Recently, privacy-preserving technologies have been applied to preserve application utility while protecting the privacy of biomedical data. We present the PICOTEES framework, a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants (https://***:3000/). PICOTEES enables privacy-preserving queries of the phenotype spectrum for a single variant by utilizing trusted execution environment technology, which can protect the privacy of the user's query information, backend models, and data, as well as the final results. We demonstrate the utility and performance of PICOTEES by exploring a bioinformatics dataset. The dataset is from a cohort containing 20,909 genetic testing patients with 3,152,508 variants from the Children's Hospital of Fudan University in China, dominated by the Chinese Han population (>99.9%). Our query results yield a large number of unreported diagnostic variants and previously reported pathogenicity.

关键词： Privacy protecti on Rare diseases in children Genetic testing Web system Trusted executi on envir onment

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Association analysis of genetic variants in critical patients with COVID-19 and validation in a Chinese population

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Virologica Sinica 2024年第2期39卷 347-350页

作者： Yi Yin Yi Zhang Lelin Sun Shuqiang Wang Yong Zeng Bo Gong Lulin Huang Yongquan He Zhenglin Yang center for Natural Products Research Chengdu Institute of BiologyChinese Academy of SciencesChengdu610213China Sichuan Provincial Key Laboratory for Human Disease Gene Study Center for Medical GeneticsDepartment of Laboratory MedicineSichuan Academy of Medical Sciences&Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026) Sichuan Academy of Medical Sciences&Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China University of Chinese Academy of Sciences Beijing100049China Infectious Disease department Sichuan Academy of Medical Sciences&Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China department of Ophthalmology Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China

Dear Editor,Genome-wide association studies(GWASs)have reported a genetic association between certain populations and the severity of *** severe patients,changes in the locus 3p21.31(including SLC6A20,LZTFL1,CCR9,FYCO1,CXCR6,and XCR1)are associated with COVID-19 hospitalization(Ellinghaus et al.,2020).Moreover,variations in 9p34.2 region(including genes related to the ABO blood grouping)can affect both susceptibility and severity of COVID-19;in particular,individuals with blood group A may have an increased risk of COVID-19 infection,while those with blood group O may have a protective effect(Ellinghaus et al.,2020;Shelton et al.,2021).

关键词： patients protective

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The emerging world of subcellular biological medicine:extracellular vesicles as novel biomarkers,targets,and therapeutics

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Neural Regeneration Research 2022年第5期17卷 1020-1022页

作者： Leon G.Coleman The University of North Carolina at Chapel Hill School of MedicineDepartment of PharmacologyBowles Center for Alcohol StudiesChapel HillNCUSA

The COVID-19 pandemic,with all its tragedy,has also ushered in a new era of biological *** global crisis has brought along with it an opportunity that had not been foreseen by many-it brought the therapeutic use of su... 详细信息

关键词： hered brought opportunity

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Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

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World Journal of Psychiatry 2024年第1期14卷 88-101页

作者： Zhong-Yu Huang Zi-Pan Lyu Hong-Gui Li Hua-Zhi You Xiang-Na Yang Cai-Hui Cha center for Medical Research on Innovation and Translation Institute of Clinical MedicineGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510000Guangdong ProvinceChina School of Biological Sciences Nanyang Technological UniversityNanyang Ave 639798Singapore department of Pediatrics First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina department of Nutrition First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina department of Pediatric Traditional Chinese Medicine Clinic Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina department of Psychology Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely *** presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for *** To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental *** A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy *** in plasma were set as exposures with ASD as the main *** causal relationships were estimated using the inverse variant weight(IVW)*** also performed leave-one-out sensitivity tests to validate the robustness of the *** on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and *** Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and *** Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and *** findings offer perspectives for the discovery of diagnos

关键词： Des-Arg(9)bradykinin Autism spectrum disorder Mendelian randomization Metabolite Enrichment analysis

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Rare dentin defects:Understanding the pathophysiological mechanisms of COLXVA1 mutations

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Genes & Diseases 2024年第5期11卷 1-5页

作者： Isaac Maximiliano Bugueno Tristan Rey Alexandra Jimenez-Armijo Marzena Kawczynski Naji Kharouf Marie-Cecile Maniere Yann Herault Agnes Bloch-Zupan Virginie HaushalterLaugel Institute of genetics and Molecular and Cellular Biology(IGBMC) CNRS-UMR7104INSERM U1258Universitede StrasbourgIllkirch 67400France Faculty of Dentistry Universitede StrasbourgStrasbourg 67000France Institute of Advanced studies(USIAS) Universitede StrasbourgStrasbourg 67045France Reference center for Rare Oral and Dental Diseases(CRMR-O-Rares) Oral Medicine and Surgery DepartmentHopitaux Universitaires de Strasbourg(HUS)Strasbourg 67000France Rare Diseases Health Network“TETE COU”&European Reference Network ERN CRANIO Strasbourg 67000France “Institut de Genetique Medicale d’Alsace” Laboratory of Genetic DiagnosticHopitaux Universitaires de Strasbourg(HUS)Strasbourg 67000France Biomaterials and Bioengineering Laboratory Inserm UMR_S 1121Strasbourg 67000France Orofacial Development and Regeneration Faculty of MedicineInstitute of Oral BiologyCentre of Dental MedicineUniversity of ZurichZurich 8032Switzerland

Dentin is a mineralized tissue with a chemical composition similar to bone but with a higher mineralized density and *** constitutes the central structure of the tooth between the internal pulp and external enamel toward the oral cavity or cementum toward the underlying *** dentin defects occur in a variety of rare genetic *** can manifest as“isolated”occurrences such as in dentinogenesis imperfecta(DI)or dentin dysplasia(DD)or can be associated with other symptoms in diseases such as osteogenesis imperfecta,Goldblatt syndrome,microcephalic osteodysplastic primordial dwarfism type Ⅱ,among others.

关键词： diseases den rigidity

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Unveiling DNA methylation in Alzheimer’s disease:a review of array-based human brain studies

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Neural Regeneration Research 2024年第11期19卷 2365-2376页

作者： Victoria Cunha Alves Eva Carro Joana Figueiro-Silva Neurodegenerative Diseases Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network center for Biomedical Research Neurodegenerative Diseases(CIBERNED)MadridSpain PhD Program in Neuroscience Autonoma de Madrid UniversityMadridSpain Neurotraumatology and Subarachnoid Hemorrhage Group Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research Into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain Institute of Medical genetics University of ZurichZurichSwitzerland department of Molecular Life Science University of ZurichZurichSwitzerland

The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA *** review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease *** examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease *** entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the ***,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal ***,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory *** complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation *** the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease *** research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.

关键词： Alzheimer’s disease ANK1 BIN1 DNA methylation epigenome-wide association studies HOXA3 MCF2L RHBDF2

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Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis

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World Journal of Gastroenterology 2016年第48期22卷 10482-10501页

作者： Sebastian Mueller department of Medicine and center for alcohol Research Salem Medical CenterUniversity of Heidelberg

Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a majorhealth problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis(SPH), which identifies an elevated sinusoidal pressure(SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequ-ence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts(SPH part?Ⅰ: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmH g and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures(SPH part?Ⅱ: perpetuation). It also defines the "point of no return" where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies.

关键词： liver stiffness Stretch force Sinusoidal pressure hypothesis liver cirrhosis Hepatic arterial buffer response biomechanics Arterialization Hepatic stellate cells Fibroblasts cellular and intercellular mechano-signaling

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Iron metabolism and arthritis: Exploring connections and therapeutic avenues

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中华医学杂志(英文版) 2024年第14期137卷 1651-1662页

作者： Zhuo Dachun Xiao Wenze Tang Yulong Jiang Shuai Geng Chengchun Xie Jiangnan Ma Xiaobei Zhang Qing Tang Kunhai Yu Yuexin Bai Lu Zou Hejian Liu Jing Wang Jiucun department of Rheumatology Shanghai Pudong Hospital Human Phenome Institute Zhangjiang Fudan International Innovation Center Fudan University Shanghai China State Key Laboratory of Genetic Engineering School of Life Science Fudan University Shanghai China department of Vascular Surgery Shanghai Pudong Hospital Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling Fudan University Pudong Medical Center Shanghai China department of Anthropology and Human genetics School of Life Sciences Ministry of Education Key Laboratory of Contemporary Anthropology Fudan University Shanghai China Division of Rheumatology Huashan Hospital State Key Laboratory of Genetic Engineering School of Life Science Fudan University Shanghai China Institute of Rheumatology Immunology and Allergy Allergy and Disease Research Center Fudan University Shanghai China Research Unit of Dissecting the Population genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058) Chinese Academy of Medical Sciences Beijing China

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

关键词： Iron metabolism Arthritis Inflammation Immunity Rheumatoid arthritis Psoriatic arthritis Gouty arthritis

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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García Victoria Moreno-Manzano Consuelo Guerri María Pascual department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

关键词： adolescence binge-like ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

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