RESUMO
The increasing attention towards diabetic cardiomyopathy as a distinctive complication of diabetes mellitus has highlighted the need for standardized diagnostic criteria and targeted treatment approaches in clinical practice. Ongoing research is gradually unravelling the pathogenesis of diabetic cardiomyopathy, with a particular emphasis on investigating various post-translational modifications. These modifications dynamically regulate protein function in response to changes in the internal and external environment, and their disturbance of homeostasis holds significant relevance for the development of chronic ailments. This review provides a comprehensive overview of the common post-translational modifications involved in the initiation and progression of diabetic cardiomyopathy, including O-GlcNAcylation, phosphorylation, methylation, acetylation and ubiquitination. Additionally, the review discusses drug development strategies for targeting key post-translational modification targets, such as agonists, inhibitors and PROTAC (proteolysis targeting chimaera) technology that targets E3 ubiquitin ligases.
Assuntos
Diabetes Mellitus , Cardiomiopatias Diabéticas , Humanos , Cardiomiopatias Diabéticas/genética , Processamento de Proteína Pós-Traducional , Ubiquitinação , Fosforilação , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Park dust is a carrier of heavy metal pollutants and could potentially harm the health of urban residents. The concentrations of 10 heavy metal(loid)s (HMs) in park dust from the Mianyang urban area were analysed via X-ray fluorescence spectrometry. Based on ArcGIS spatial analysis, Spearman correlation analysis, spatial autocorrelation analysis, and the positive matrix factorization (PMF) model, the spatial distribution and sources of HMs in park dust were studied. The average contents of Zn, Co, Cu, Cr, Pb, and Ba in park dust were 185.0, 33.7, 38.7, 178.7, 51.0, and 662.1 mg/kg, respectively, which are higher than the reference values. The 10 HMs exhibited obvious spatial distribution and local spatial agglomeration patterns. High concentrations of As and Pb were primarily concentrated in the eastern part of the Mianyang urban area. High concentrations of Zn, Cr, and Cu were largely distributed in parks near the Changjiang River and Fujiang River. A high concentration of Co was concentrated in the northern region. The high-value areas of Mn, Ba, V, and Ni occurred far from the city centre and were located in the southwestern region. We found that Pb and As primarily originated from mixed traffic and natural sources; Zn, Cr, and Cu mainly originated from industrial activities; Co largely originated from building sources; and Ba, Ni, Mn, and V were mostly derived from natural sources. Mixed, industrial, building, and natural sources accounted for 24.5%, 24.8%, 24.7%, and 26.0%, respectively, of the HM sources. Co, Cu, Cr, and Zn in the Mianyang urban area were obviously influenced by human activities and should receive close attention.
Assuntos
Poluentes Ambientais , Metais Pesados , Humanos , Chumbo , China , PoeiraRESUMO
The massive growth of various microorganisms on the orthodontic bracket can form plaques and cause diseases. A novel amine-terminated hyperbranched zirconium-polysiloxane (HPZP) antimicrobial coating was developed for an orthodontic stainless steel tank (SST). After synthesizing HPZP and HPZP-Ag coatings, their structures were characterized by nuclear magnetic resonance spectroscopy, scanning electron microscopy, thickness measurement, contact angle detection, mechanical stability testing, and corrosion testing. The cell toxicity of the two coatings to human gingival fibroblasts (hGFs) and human oral keratinocytes (hOKs) was detected by cell counting kit eight assays, and SST, HPZP@SST, and HPZP-Ag@SST were cocultured with Staphylococcus aureus, Escherichia coli, and Streptococcus mutans for 24 hr to detect the antibacterial properties of the coatings, respectively. The results show that the coatings are about 10 µm, and the water contact angle of HPZP coating is significantly higher than that of HPZP-Ag coating (P < 0.01). Both coatings can be uniformly and densely distributed on SST and have good mechanical stability and corrosion resistance. The cell counting test showed that HPZP coating and HPZP-Ag coating were less toxic to cells compared with SST, and the toxicity of HPZP-Ag coating was greater than that of HPZP coating, with the cell survival rate greater than 80% after 72 hr cocultured with hGFs and hOKs. The antibacterial test showed that the number of bacteria on the surface of different materials was ranked from small to large: HPZP@SST < HPZP-Ag@SST < SST and 800 µg/mL HPZP@SST showed a better bactericidal ability than 400 µg/mL after cocultured with S. aureus, E. coli, and S. mutans, respectively (all P < 0.05). The results showed that HPZP coating had a better effect than HPZP-Ag coating, with effective antibacterial and biocompatible properties, which had the potential to be applied in orthodontic process management.
Assuntos
Antibacterianos , Materiais Revestidos Biocompatíveis , Braquetes Ortodônticos , Siloxanas , Aço Inoxidável , Zircônio , Aço Inoxidável/química , Aço Inoxidável/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Braquetes Ortodônticos/microbiologia , Zircônio/química , Zircônio/farmacologia , Siloxanas/química , Siloxanas/farmacologia , Fibroblastos/efeitos dos fármacos , Teste de Materiais , Aminas/química , Aminas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície , Escherichia coli/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Gengiva/citologia , Gengiva/efeitos dos fármacosRESUMO
The environmental pollution caused by mineral exploitation and energy consumption poses a serious threat to ecological security and human health, particularly in resource-based cities. To address this issue, a comprehensive investigation was conducted on potentially toxic elements (PTEs) in road dust from different seasons to assess the environmental risks and influencing factors faced by Datong City. Multivariate statistical analysis and absolute principal component score were employed for source identification and quantitative allocation. The geo-accumulation index and improved Nemerow index were utilized to evaluate the pollution levels of PTEs. Monte Carlo simulation was employed to assess the ecological-health risks associated with PTEs content and source orientation. Furthermore, geo-detector and random forest analysis were conducted to examine the key environmental variables and driving factors contributing to the spatiotemporal variation in PTEs content. In all PTEs, Cd, Hg, and Zn exhibited higher levels of content, with an average content/background value of 3.65 to 4.91, 2.53 to 3.34, and 2.15 to 2.89 times, respectively. Seasonal disparities were evident in PTEs contents, with average levels generally showing a pattern of spring (winter) > summer (autumn). PTEs in fine road dust (FRD) were primarily influenced by traffic, natural factors, coal-related industrial activities, and metallurgical activities, contributing 14.9-33.9 %, 41.4-47.5 %, 4.4-8.3 %, and 14.2-29.4 % to the total contents, respectively. The overall pollution and ecological risk of PTEs were categorized as moderate and high, respectively, with the winter season exhibiting the most severe conditions, primarily driven by Hg emissions from coal-related industries. Non-carcinogenic risk of PTEs for adults was within the safe limit, yet children still faced a probability of 4.1 %-16.4 % of unacceptable risks, particularly in summer. Carcinogenic risks were evident across all demographics, with children at the highest risk, mainly due to Cr and smelting industrial sources. Geo-detector and random forest model indicated that spatial disparities in prioritized control elements (Cr and Hg) were primarily influenced by particulate matter (PM10) and anthropogenic activities (industrial and socio-economic factors); variations in particulate matter (PM10 and PM2.5) and meteorological factors (wind speed and precipitation) were the primary controllers of seasonal disparities of Cr and Hg.