Arsenic trioxide alleviates atherosclerosis by inhibiting CD36-induced endocytosis and TLR4/NF-κB-induced inflammation in macrophage and ApoE-/- mice.

BACKGROUND: Inflammation and lipid accumulation are key events in atherosclerosis progression. Despite arsenic trioxide's (ATO) toxicity, at appropriate doses, it is a useful treatment for various diseases treatment. ATO prevents vascular restenosis; however, its effects on atherosclerotic plaque development and instability remain unclear. METHODS: ApoE-/- mice were fed high-fat diet for 4 months, and starting at the third month, ATO was intravenously administered every other day. Atherosclerotic lesion size, histological characteristics, and related protein and lipid profiles were assessed using samples from the aorta, carotid artery, and serum. The anti-inflammatory and anti-pyroptosis effects of ATO were investigated by stimulating RAW264.7 and THP-1 cell lines with oxidized low-density lipoprotein (ox-LDL) or lipopolysaccharide (LPS). RESULTS: ATO reduced atherosclerotic lesion formation and plasma lipid levels in ApoE-/- mice. In the serum and aortic plaques, ATO reduced the levels of pro-inflammatory factors, including interleukin (IL) 6 and tumor necrosis factor α, but increased IL-10 levels. Mechanistically, ATO promoted the CD36-mediated internalization of ox-LDL in a peroxisome proliferator-activated receptor γ-dependent manner. Furthermore, ATO downregulated Toll-like receptor 4 (TLR4) expression in plaques and macrophages and inhibited p65 nuclear translocation and IκBα degradation. ATO reduced macrophage pyroptosis by downregulating NLR family pyrin domain-containing 3 (NLRP3) expression and caspase 1 activation. CONCLUSION: ATO has potential atheroprotective effects, especially in macrophages. The mechanisms were inhibition of CD36-mediated foam cell formation and suppression of inflammatory responses and pyroptosis mediated by TLR4/nuclear factor κB and NLRP3 activation. Our findings provide evidence supporting the potential atheroprotective value of ATO.

The association between ambient temperature and semen quality in a Northern Peninsular Province, China.

BACKGROUND: Extreme ambient temperature has been linked to decline in males' semen quality. Although the temperature-semen quality association has been examined in certain cities of South China, how the effect size of the extreme temperature may lag over critical windows in spermatogenesis and whether the strength of association may vary in North China have yet been adequately explored. OBJECTIVES: To quantify the association between air temperature and semen quality, and identify critical exposure windows in a Northern Peninsular Province, China. MATERIALS AND METHODS: Data on semen quality in 2014-2019 were collected from the Human Sperm Bank of Institute of Women, Children and Reproductive Health, Shandong University, China. Daily meteorological data (0.01°×0.01°) were assigned to each subject's residential address. The linear mixed-effect model combined with the distributed lag nonlinear model was used to estimate the effect of ambient temperature over critical spermatogenesis windows. RESULTS: The temperature-semen quality association was inverted V-shaped, with the maximum lag being 0-45 days before ejaculation and the threshold being 9.2°C. Progressively and total motile sperm number, and total sperm number declined more substantially than other semen quality parameters. Semen quality was more sensitive to cold exposure during the epididymal storage period than the sperm motility development period. By contrast, semen quality was insensitive to heat exposure during both critical spermatogenesis windows. Impairment of certain semen quality parameters was more obvious for males with higher educational attainment and those aged over 35 years. DISCUSSION AND CONCLUSION: Exposure to non-optimal temperature is associated with decreased semen quality in North China, with the epididymal storage and sperm motility development periods more sensitive to cold exposure than heat. Older males and those with higher educations may need particular awareness.

Association Between Hydrological Conditions and Dengue Fever Incidence in Coastal Southeastern China From 2013 to 2019.

Importance: Dengue fever is a climate-sensitive infectious disease. However, its association with local hydrological conditions and the role of city development remain unclear. Objective: To quantify the association between hydrological conditions and dengue fever incidence in China and to explore the modification role of city development in this association. Design, Setting, and Participants: This cross-sectional study collected data between January 1, 2013, and December 31, 2019, from 54 cities in 4 coastal provinces in southeast China. The Standardized Precipitation Evapotranspiration Index (SPEI) was calculated from ambient temperature and precipitation, with SPEI thresholds of 2 for extreme wet conditions and -2 for extreme dry conditions. The SPEI-dengue fever incidence association was examined over a 6-month lag, and the modification roles of 5 city development dimensions were assessed. Data were analyzed in May 2022. Exposures: City-level monthly temperature, precipitation, SPEI, and annual city development indicators from 2013 to 2019. Main Outcomes and Measures: The primary outcome was city-level monthly dengue fever incidence. Spatiotemporal bayesian hierarchal models were used to examine the SPEI-dengue fever incidence association over a 6-month lag period. An interaction term between SPEI and each city development indicator was added into the model to assess the modification role of city development. Results: Included in the analysis were 70 006 dengue fever cases reported in 54 cities in 4 provinces in China from 2013 to 2019. Overall, a U-shaped cumulative curve was observed, with wet and dry conditions both associated with increased dengue fever risk. The relative risk [RR] peaked at a 1-month lag for extreme wet conditions (1.27; 95% credible interval [CrI], 1.05-1.53) and at a 6-month lag for extreme dry conditions (1.63; 95% CrI, 1.29-2.05). The RRs of extreme wet and dry conditions were greater in areas with limited economic development, health care resources, and income per capita. Extreme dry conditions were higher and prolonged in areas with more green space per capita (RR, 1.84; 95% CrI, 1.37-2.46). Highly urbanized areas had a higher risk of dengue fever after extreme wet conditions (RR, 1.80; 95% CrI, 1.26-2.56), while less urbanized areas had the highest risk of dengue fever in extreme dry conditions (RR, 1.70; 95% CrI, 1.11-2.60). Conclusions and Relevance: Results of this study showed that extreme hydrological conditions were associated with increased dengue fever incidence within a 6-month lag period, with different dimensions of city development playing various modification roles in this association. These findings may help in developing climate change adaptation strategies and public health interventions against dengue fever.

Association of acetaldehyde dehydrogenase 2 rs671 polymorphism with the occurrence and progression of atrial fibrillation.

Background: Acetaldehyde dehydrogenase 2 (ALDH2) is an essential enzyme in alcohol metabolism, playing a vital function in resisting oxidative stress. Lots of gene variants have been associated with atrial fibrillation (AF), among which the association between ALDH2 rs671 polymorphism and AF is variable. This study aimed to investigate the relationship between ALDH2 rs671 polymorphism and AF occurrence or progression and AF recurrence after catheter ablation. Methods: A total of 924 subjects were enrolled in the study. The ALDH2 genotypes are composed of wild-type homozygotes (ALDH2*1/*1), heterozygotes (ALDH2*1/*2), and mutant homozygotes (ALDH2*2/*2), in which the genotypes ALDH2*1/*2 and ALDH2*2/*2 are combined into the ALDH2*2. Univariate and multivariate logistic regression analyses were performed to investigate the association between ALDH2*2 and AF occurrence and progression. COX regression analysis was used to explore the association of ALDH2*2 with AF recurrence after catheter ablation. Results: The prevalence of AF differed significantly between the ALDH2*2 group (102/251) and ALDH2*1/*1 group (330/673) (P = 0.023). For AF occurrence, in the univariate analysis, alcohol consumption was a risk factors (OR: 1.503, P = 0.003), whereas ALDH2*2 was a protective factor (OR: 0.712, P = 0.023). In the multivariate analysis, alcohol consumption (P = 0.156) and ALDH2*2 (P = 0.096) were no longer independent factors. ALDH2*2 with non-drinking was associated with a decreased AF occurrence (OR: 0.65, P = 0.021), whereas ALDH2*2 with drinking was not (P = 0.365). For AF progression, multivariate analysis revealed ALDH2*2 could promote persistent AF in female AF patients (OR: 2.643, P = 0.008). Cox regression analysis suggested that ALDH2*2 (P = 0.752) was not a risk factor for AF recurrence after catheter ablation during a median 6 months follow-up. Conclusion: While ALDH2*2 was not directly related to AF, ALDH2*2 with non-drinking was associated with a decreased incidence of AF. ALDH2*2 may accelerate AF progression in female patients, increasing the likelihood of developing persistent AF. Therefore, individuals with ALDH2*2 should refrain from consuming alcohol to decrease the onset and progression of AF.

Tannic acid induces dentin biomineralization by crosslinking and surface modification.

It is currently known that crosslinking agents can effectively improve the mechanical properties of dentin by crosslinking type I collagen. However, few scholars have focused on the influence of crosslinking agents on the collagen-mineral interface after crosslinking. Analysis of the Fourier transform infrared spectroscopy (FTIR) results showed that hydrogen bonding occurs between the tannic acid (TA) molecule and the collagen. The crosslinking degree of TA to collagen reached a maximum 41.28 ± 1.52. This study used TA crosslinked collagen fibers to successfully induce dentin biomineralization, and the complete remineralization was achieved within 4 days. The crosslinking effect of TA can improve the mechanical properties and anti-enzyme properties of dentin. The elastic modulus (mean and standard deviation) and hardness values of the remineralized dentin pretreated with TA reached 19.1 ± 1.12 GPa and 0.68 ± 0.06 GPa, respectively, which were close to those of healthy dentin measurements, but significantly higher than those of dentin without crosslinking (8.91 ± 1.82 GPa and 0.16 ± 0.01 GPa). The interface energy between the surface of collagen fibers and minerals decreased from 10.59 mJ m-2 to 4.19 mJ m-2 with the influence of TA. The current work reveals the importance of tannic acid crosslinking for dentin remineralization while providing profound insights into the interfacial control of biomolecules in collagen mineralization.

Polydopamine Promotes Dentin Remineralization via Interfacial Control.

Biomineralization has intrigued researchers for decades. Although mineralization of type I collagen has been universally investigated, this process remains a great challenge due to the lack of mechanistic understanding of the roles of biomolecules. In our study, dentine was successfully repaired using the biomolecule polydopamine (PDA), and the remineralized dentine exhibited mechanical properties comparable to those of natural dentine. Detailed analyses of the collagen mineralization process facilitated by PDA showed that PDA can promote intrafibrillar mineralization with a decreased heterogeneous nucleation barrier for hydroxyapatite (HAP) by reducing the interfacial energy between collagen fibrils and amorphous calcium phosphate (ACP), resulting in the conversion of an increasing amount of nanoprecursors into collagen fibrils. The present work highlights the importance of interfacial control in dentine remineralization and provides profound insight into the regulatory effect of biomolecules in collagen mineralization as well as the clinical application of dentine restoration.

Fabrication of collagen membranes with different intrafibrillar mineralization degree as a potential use for GBR.

The process of biomineralization in dentin and bone tissue repair has been extensively studied. In vitro, biomineralization can be stimulated via a polymer-induced liquid precursor (PILP) process. Guided bone regeneration using a barrier membrane and bone substitute materials is widely used in implantology in cases where there is insufficient bone volume. Herein, we applied a homologous PILP processes to fabricate collagen films with a varying degree of mineralization and tested their performance. The results showed that the prepared biomineralized membranes are biocompatible, have a high stress strength and can promote MC3T3-e1 cell proliferation. This indicated that the membranes can be potentially applied in guided bone regeneration, with membranes containing a higher degree of mineralization achieving the best results.

MicroRNA 182 promotes T helper 1 cell by repressing hypoxia induced factor 1 alpha in experimental autoimmune encephalomyelitis.

MicroRNA 182 is important for the clonal expansion of CD4+ T cells (Th) following IL-2 stimulation and is a potential therapeutic target for autoimmune diseases. In the present study, we investigated the role of microRNA 182 in the differentiation of pro-inflammatory CD4+ T helper cell by overexpressing or silencing microRNA 182 expression both in in vivo and in vitro settings. We report that in the studied Chinese cohort, microRNA 182 is upregulated in patients with relapse and remitting multiple sclerosis (RRMS) and this upregulation is associated with increased IFN-γ producing CD4+ Th1 cells in the circulation. In the murine experimental autoimmune encephalomyelitis (EAE) model, global microRNA 182 overexpression exacerbates clinical symptoms and results in augmented CD4+ IFN-γ+ Th1 and CD4+ IL-17+ Th17 differentiation in vivo. Addition of microRNA 182 mimics in vitro represses both the protein expression and transcriptional activity of hypoxia induced factor 1α (HIF-1α) but increases the level of IFN-γ transcripts in sorted murine CD4+ T cells. Together, our results provide evidence that microRNA 182 may be one of the transitional hubs contribution to regulate Th cells expansion in response to self-antigens and differentiation of antigen specific Th cells during the progression of autoimmune inflammations.