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Abstract
Purpose
Oxidative stress and mitochondrial dysfunction are potential contributors to the compromised
tissue regeneration capacity of alveolar bone in diabetic patients. Berberine, an
active plant alkaloid, exhibits multiple pharmacological effects including antioxidation,
blood glucose- and blood lipid-lowering properties. However, it remains uncertain
whether berberine can improve impaired osteogenesis in type 2 diabetes mellitus (T2DM),
and its poor solubility and oral bioavailability also constrain its applications in
bone regeneration. Thus, our study aimed to probe the effects of berberine on bone
marrow stem cells (BMSCs) in a diabetic microenvironment, with a greater emphasis
on developing a suitable nano-delivery system for berberine and assessing its capability
to repair diabetic alveolar bone defects.
Methods
Firstly, BMSCs were exposed to berberine within a high glucose and palmitate (HG+PA)
environment. Reactive oxygen species levels, mitochondrial membrane potential, ATP
generation, cell apoptosis, and osteogenic potential were subsequently assessed. Next,
we explored the regulatory mechanism of autophagy flux in the positive effects of
berberine. Furthermore, a nanocarrier based on emulsion electrospinning for sustained
local delivery of berberine (Ber@SF/PCL) was established. We assessed its capacity
to enhance bone healing in the alveolar bone defect of T2DM rats through micro-computed
tomography and histology analysis.
Results
Berberine treatment could inhibit reactive oxygen species overproduction, mitochondrial
dysfunction, apoptosis, and improve osteogenesis differentiation by restoring autophagy
flux under HG+PA conditions. Notably, Ber@SF/PCL electrospun nanofibrous membrane
with excellent physicochemical properties and good biological safety had the potential
to promote alveolar bone remodeling in T2DM rats.
Conclusion
Our study shed new lights into the protective role of berberine on BMSCs under T2DM
microenvironment. Furthermore, berberine-loaded composite electrospun membrane may
serve as a promising approach for regenerating alveolar bone in diabetic patients.
Summary Background Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. Findings In 2021, there were 529 million (95% uncertainty interval [UI] 500–564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8–6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7–9·9]) and, at the regional level, in Oceania (12·3% [11·5–13·0]). Nationally, Qatar had the world's highest age-specific prevalence of diabetes, at 76·1% (73·1–79·5) in individuals aged 75–79 years. Total diabetes prevalence—especially among older adults—primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1–96·8) of diabetes cases and 95·4% (94·9–95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5–71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5–30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22–1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1–17·6) in north Africa and the Middle East and 11·3% (10·8–11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%. Interpretation Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers. Funding Bill & Melinda Gates Foundation.
We aimed to consolidate all epidemiologic data about severe periodontitis (SP) and, subsequently, to generate internally consistent prevalence and incidence estimates for all countries, 20 age groups, and both sexes for 1990 and 2010. The systematic search of the literature yielded 6,394 unique citations. After screening titles and abstracts, we excluded 5,881 citations as clearly not relevant to this systematic review, leaving 513 for full-text review. A further 441 publications were excluded following the validity assessment. A total of 72 studies, including 291,170 individuals aged 15 yr or older in 37 countries, were included in the metaregression based on modeling resources of the Global Burden of Disease 2010 Study. SP was the sixth-most prevalent condition in the world. Between 1990 and 2010, the global age-standardized prevalence of SP was static at 11.2% (95% uncertainty interval: 10.4%-11.9% in 1990 and 10.5%-12.0% in 2010). The age-standardized incidence of SP in 2010 was 701 cases per 100,000 person-years (95% uncertainty interval: 599-823), a nonsignificant increase from the 1990 incidence of SP. Prevalence increased gradually with age, showing a steep increase between the third and fourth decades of life that was driven by a peak in incidence at around 38 yr of age. There were considerable variations in prevalence and incidence between regions and countries. Policy makers need to be aware of a predictable increasing burden of SP due to the growing world population associated with an increasing life expectancy and a significant decrease in the prevalence of total tooth loss throughout the world from 1990 to 2010.
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