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      Oral zero-valent-molybdenum nanodots for inflammatory bowel disease therapy

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          Abstract

          Inflammatory bowel disease (IBD) affects millions of people each year. The overproduction of reactive oxygen species (ROS) plays a critical role in the progress of IBD and will be a potential therapeutic target. Here, we synthesize a kind of oral zero-valent-molybdenum nanodots (ZVMNs) for the treatment of IBD by scavenging ROS. These ultrasmall ZVMNs can successfully pass through the gastric acid and then be absorbed by the intestine. It has been verified that ZVMNs can down-regulate the quantity of ROS and reduce colitis in a mouse IBD model without distinct side effects. In addition, RNA sequencing reveals a further mechanism that the ZVMNs can protect colon tissues from oxidative stress by inhibiting the nuclear factor κB signaling pathway and reducing the production of excessive pro-inflammatory factors. Together, the ZVMNs will offer a promising alternative treatment option for patients suffering from IBD.

          Abstract

          Abstract

          Oral zero-valent-molybdenum nanodots were developed for the treatment of inflammatory bowel disease by scavenging reactive oxygen.

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          The global burden of IBD: from 2015 to 2025.

          Over 1 million residents in the USA and 2.5 million in Europe are estimated to have IBD, with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients. The majority of patients are diagnosed early in life and the incidence continues to rise; therefore, the effect of IBD on health-care systems will rise exponentially. Moreover, IBD has emerged in newly industrialized countries in Asia, South America and Middle East and has evolved into a global disease with rising prevalence in every continent. Understanding the worldwide epidemiological patterns of IBD will prepare us to manage the burden of IBD over time. The goal of this article is to establish the current epidemiology of IBD in the Western world, contrast it with the increase in IBD in newly industrialized countries and forecast the global effects of IBD in 2025.
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            The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

            Summary Background The burden of inflammatory bowel disease (IBD) is rising globally, with substantial variation in levels and trends of disease in different countries and regions. Understanding these geographical differences is crucial for formulating effective strategies for preventing and treating IBD. We report the prevalence, mortality, and overall burden of IBD in 195 countries and territories between 1990 and 2017, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods We modelled mortality due to IBD using a standard Cause of Death Ensemble model including data mainly from vital registrations. To estimate the non-fatal burden, we used data presented in primary studies, hospital discharges, and claims data, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to ensure consistency between measures. Mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were estimated. All of the estimates were reported as numbers and rates per 100 000 population, with 95% uncertainty intervals (UI). Findings In 2017, there were 6·8 million (95% UI 6·4–7·3) cases of IBD globally. The age-standardised prevalence rate increased from 79·5 (75·9–83·5) per 100 000 population in 1990 to 84·3 (79·2–89·9) per 100 000 population in 2017. The age-standardised death rate decreased from 0·61 (0·55–0·69) per 100 000 population in 1990 to 0·51 (0·42–0·54) per 100 000 population in 2017. At the GBD regional level, the highest age-standardised prevalence rate in 2017 occurred in high-income North America (422·0 [398·7–446·1] per 100 000) and the lowest age-standardised prevalence rates were observed in the Caribbean (6·7 [6·3–7·2] per 100 000 population). High Socio-demographic Index (SDI) locations had the highest age-standardised prevalence rate, while low SDI regions had the lowest age-standardised prevalence rate. At the national level, the USA had the highest age-standardised prevalence rate (464·5 [438·6–490·9] per 100 000 population), followed by the UK (449·6 [420·6–481·6] per 100 000). Vanuatu had the highest age-standardised death rate in 2017 (1·8 [0·8–3·2] per 100 000 population) and Singapore had the lowest (0·08 [0·06–0·14] per 100 000 population). The total YLDs attributed to IBD almost doubled over the study period, from 0·56 million (0·39–0·77) in 1990 to 1·02 million (0·71–1·38) in 2017. The age-standardised rate of DALYs decreased from 26·5 (21·0–33·0) per 100 000 population in 1990 to 23·2 (19·1–27·8) per 100 000 population in 2017. Interpretation The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease. Funding Bill & Melinda Gates Foundation.
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              Gut microbiota and IBD: causation or correlation?

              A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. The purpose of this Review is to summarize current associations between IBD and dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host–microbial relationships relevant to human disease and amenable to therapeutic interventions.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: VisualizationRole: Writing - original draftRole: Writing - review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing - original draft
                Role: InvestigationRole: Resources
                Role: Investigation
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing
                Role: ConceptualizationRole: InvestigationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: SupervisionRole: ValidationRole: Writing - review & editing
                Role: Formal analysisRole: MethodologyRole: Software
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Validation
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing
                Journal
                Sci Adv
                Sci Adv
                sciadv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                September 2022
                16 September 2022
                : 8
                : 37
                : eabp9882
                Affiliations
                [ 1 ]Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
                [ 2 ]Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
                [ 3 ]Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
                [ 4 ]Department of Surgery, Medical Center on Aging of Ruijin Hospital, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
                [ 5 ]Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-5927-7181
                https://orcid.org/0000-0002-4086-5928
                https://orcid.org/0000-0003-2156-6233
                https://orcid.org/0000-0001-8332-4710
                https://orcid.org/0000-0001-5533-5711
                https://orcid.org/0000-0001-6679-5414
                Article
                abp9882
                10.1126/sciadv.abp9882
                9481133
                36112678
                e869173e-d7c8-40a9-b46c-59dce4215cf3
                Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 10 March 2022
                : 29 July 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 82102190
                Funded by: Shanghai Science and Technology Commission;
                Award ID: 20JC1410100
                Funded by: Shanghai Science and Technology Commission;
                Award ID: 22ZR1439600
                Funded by: Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support;
                Award ID: 20191805
                Funded by: Foundation of National Facility for Translational Medicine (Shanghai);
                Award ID: TMSK-2021-122
                Funded by: Fellowship of China Postdoctoral Science Foundation;
                Award ID: 2020M681326
                Categories
                Research Article
                Biomedicine and Life Sciences
                SciAdv r-articles
                Health and Medicine
                Materials Science
                Health and Medicine
                Custom metadata
                Mjoy Azul

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