Aims/Introduction
The present meta‐analysis was carried out to assess the association between exposure to the level of atmospheric particulate matter 2.5 (PM2.5; fine particulate matter with ...aerodynamic diameter less than 2.5 μm) and type 2 diabetes mellitus or gestational diabetes mellitus (GDM).
Materials and Methods
We searched the Medline, EMBASE, Cochrane and Web of Science databases to obtain articles according to the responding literature search strategies. Among a total of 279 identified articles, 55 were reviewed in depth, of which 10 articles (11 cohort studies) satisfied the inclusion criteria. Only cohort studies that disclosed the association between PM2.5 and type 2 diabetes mellitus or GDM were included in this article. A fixed‐effects model was selected if P > 0.1 and I2 < 50%; otherwise, a random‐effects model would be used to calculate the total effect value. Subgroup analysis was further carried out according to the types of diabetes mellitus (type 2 diabetes mellitus and GDM). The relative risk was used to estimate the association between PM2.5 and diabetes mellitus.
Results
The positive associations between PM2.5 and the incidence of type 2 diabetes mellitus were found in the long‐term exposure period (relative risk 1.25, 95% confidence interval 1.10–1.43), which showed that with every 10‐μg/m3 increase in PM2.5, the risk of type 2 diabetes mellitus would increase by 25% in the long‐term exposure. Although the significant associations were not identified between maternal exposure to PM2.5 and GDM in the first trimester, the second trimester and the entire pregnancy periods, we could conclude that maternal exposure to PM2.5 in the entire pregnancy period would be more likely to lead to developing GDM (relative risk 1.162, 95% confidence interval 0.806–1.675) than the other two periods.
Conclusions
Long‐term exposure to PM2.5 would be more likely to lead to developing type 2 diabetes mellitus, but more studies would be required to confirm the association between PM2.5 and GDM. It might be a wise to take effective measures to reduce PM2.5 exposure in vulnerable populations, especially for pregnant women.
Forest plot of Meta‐analysis in the associations between long terms expose to PM2.5 and type 2 diabetes mellitus (RR: risk ratios; 95% CI: 95% confidence intervals; I‐V: Inverse variance; D+L: DerSimonian‐Laired).
This analysis systematically reviewed the efficacy of evidence‐based care on diabetic foot ulcers. A computerised literature search was conducted for randomised controlled studies (RCTs) of ...evidence‐based care interventions for the treatment of diabetic foot ulcers using the PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM) and Wanfang databases from the date of inception of each database to June 2023. The articles were independently screened, data were extracted by two researchers, and the quality of each study was assessed using the Cochrane bias assessment tool. Meta‐analysis of the data was performed using RevMan 5.4 software. Twenty‐five RCTs with a total of 2272 patients were included. Meta‐analysis showed that, compared with other care methods, evidence‐based care significantly improved the treatment efficacy of diabetic foot ulcers (odds ratio: 3.91, 95% confidence interval CI: 2.76 to 5.53, p < 0.001) and significantly reduced their fasting plasma glucose (mean difference MD: −1.10, 95% CI: −1.24 to −0.96, p < 0.001), 2‐h postprandial glucose (2hPG) (MD: −1.69, 95% CI: −2.07 to −1.31, p < 0.001) and glycated haemoglobin (HbA1c) (MD: −0.71, 95% CI: −0.94 to −0.48, p < 0.001). Evidence‐based care intervention is effective at reducing FPG, 2hPG and HbA1c levels and improving treatment efficacy in patients with diabetic foot ulcers.
This study aimed to investigate the relationship between hypertension and Alzheimer's disease (AD) and demonstrate the key role of stroke in this relationship using mediating Mendelian randomization. ...AD, a neurodegenerative disease characterized by memory loss, cognitive impairment, and behavioral abnormalities, severely affects the quality of life of patients. Hypertension is an important risk factor for AD. However, the precise mechanism underlying this relationship is unclear. To investigate the relationship between hypertension and AD, we used a mediated Mendelian randomization method and screened for mediating variables between hypertension and AD by setting instrumental variables. The results of the mediated analysis showed that stroke, as a mediating variable, plays an important role in the causal relationship between hypertension and AD. Specifically, the mediated indirect effect value for stroke obtained using multivariate mediated MR analysis was 54.9%. This implies that approximately 55% of the risk of AD owing to hypertension can be attributed to stroke. The results suggest that the increased risk of AD owing to hypertension is mediated through stroke. The finding not only sheds light on the relationship between hypertension and AD but also indicates novel methods for the prevention and treatment of AD. By identifying the critical role of stroke in the link between hypertension and AD, this study provides insights into potential interventions that could mitigate the impact of hypertension on AD. This could help develop personalized treatments and help improve the quality of life of patients with AD who suffer from hypertension.
Amyotrophic lateral sclerosis (ALS) coexisting with chorea is very rare.
We present the case of a 48-year-old man with ALS and chorea; the diagnostic certainty was high based on clinical examination ...results. Combining the data from literature, we analyzed the characteristics of patients with ALS and chorea. We found that ALS coexisting with chorea is very rare, but is often hereditary with a genetic mutation. Most patients with ALS and chorea are caused by abnormal amplification of a CAG sequence in the HTT gene, and these patients have a mild course of disease. The FUS, VCP, and SETX genes also have low mutation frequencies in patients with ALS and chorea.
The abnormal amplification of a CAG sequence in the HTT gene in ALS with chorea has an obvious familial genetic tendency, and most patients have a mild disease course.
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•15a-c are mitochondria-targeted cytotoxic agents emitting fluorescence.•15b has the pronounced mitochondria-mediated cytotoxicity to breast cancer cells.•15b moderately inhibits ...TrxR2 in cells.•Instability of 15c affects its cytotoxicity and cell uptake amount.
Targeting specific mitochondrial alterations to kill cancer cells without affecting their normal counterparts emerges as a feasible strategy. Coumarin derivatives have demonstrated the potential anti-breast cancer activities. By coupling coumarin-3-carboxamide derivatives with mitochondria carrier triphenylphosphonium, mitocoumarins 15a-c were produced and tested as the anti-breast cancer fluorescence agents. Among them, 15b as the amide-based drug potently suppressed the cell growth in MCF-7, MDA-231, SK-BR-3 breast cancer cells with the IC50 values from 3.0 to 4.1 μM, including the lower cytotoxicity to normal MCF-10A cells with the IC50 value around 45.30 ± 2.45 μM. In mechanistic study for 15b in MDA-MB-231 cells, it could localize in mitochondria to elicit ROS burst and collapse Δψm. Besides, it could deplete GSH by an irreversible alkylation process and moderately inhibit mitochondrial thioredoxin reductase TrxR2, thus leading to aggravate cellular oxidative stress. This study reported 15b might be useful for the further development into a mitochondria-targeted anti-triple negative breast cancer drug.
Glioblastomas (GBMs), are the most common intrinsic brain tumors in adults and are almost universally fatal. Despite the progresses made in surgery, chemotherapy, and radiation over the past decades, ...the prognosis of patients with GBM remained poor and the average survival time of patients suffering from GBM was still short. Discovering robust gene signatures toward better understanding of the complex molecular mechanisms leading to GBM is an important prerequisite to the identification of novel and more effective therapeutic strategies. Herein, a comprehensive study of genome-scale mRNA expression data by combining GBM and normal tissue samples from 48 studies was performed. The 147 robust gene signatures were identified to be significantly differential expression between GBM and normal samples, among which 100 (68%) genes were reported to be closely associated with GBM in previous publications. Moreover, function annotation analysis based on these 147 robust DEGs showed certain deregulated gene expression programs (e.g., cell cycle, immune response and p53 signaling pathway) were associated with GBM development, and PPI network analysis revealed three novel hub genes (RFC4, ZWINT and TYMS) play important role in GBM development. Furthermore, survival analysis based on the TCGA GBM data demonstrated 38 robust DEGs significantly affect the prognosis of GBM in OS (p < 0.05). These findings provided new insights into molecular mechanisms underlying GBM and suggested the 38 robust DEGs could be potential targets for the diagnosis and treatment.
There is increasing evidence that the types of immune cells are associated with various neurodegenerative diseases. However, it is currently unclear whether these associations reflect causal ...relationships.
To elucidate the causal relationship between immune cells and neurodegenerative diseases, we conducted a two-sample Mendelian randomization (MR) analysis.
The exposure and outcome GWAS data used in this study were obtained from an open-access database (https://gwas.mrcieu.ac.uk/), the study employed two-sample MR analysis to assess the causal relationship between 731 immune cell features and four neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). All immune cell data was obtained from Multiple MR methods were used to minimize bias and obtain reliable estimates of the causal relationship between the variables of interest and the outcomes. Instrumental variable selection criteria were restricted to ensure the accuracy and effectiveness of the causal relationship between species of immune cells and the risk of these neurodegenerative diseases.
The study identified potential causal relationships between various immune cells and different neurodegenerative diseases. Specifically, we found that 8 different types of immune cells have potential causal relationships with AD, 1 type of immune cells has potential causal relationships with PD, 6 different types of immune cells have potential causal relationships with ALS, and 6 different types of immune cells have potential causal relationships with MS.
Our study, through genetic means, demonstrates close causal associations between the specific types of immune cells and AD, PD, ALS and MS, providing useful guidance for future clinical researches.
Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system. Currently, the pathological mechanisms of MS are not fully understood, but research has ...suggested that iron metabolism disorder may be associated with the onset and clinical manifestations of MS.
The study utilized publicly available databases and bioinformatics techniques for gene expression data analysis, including differential expression analysis, weighted correlation network analysis, gene enrichment analysis, and construction of logistic regression models. Subsequently, Mendelian randomization was used to assess the causal relationship between different iron metabolism markers and MS.
This study identified IREB2, LAMP2, ISCU, ATP6V1G1, ATP13A2, and SKP1 as genes associated with multiple sclerosis (MS) and iron metabolism, establishing their multi-gene diagnostic value for MS with an AUC of 0.83. Additionally, Mendelian randomization analysis revealed a potential causal relationship between transferrin saturation and MS (p=2.22E-02; OR 95%CI=0.86 (0.75, 0.98)), as well as serum transferrin and MS (p=2.18E-04; OR 95%CI=1.22 (1.10, 1.36)).
This study comprehensively explored the relationship between iron metabolism and MS through integrated bioinformatics analysis and Mendelian randomization methods. The findings provide important insights for further research into the role of iron metabolism disorder in the pathogenesis of MS and offer crucial theoretical support for the treatment of MS.
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