Environmental triggers of autoimmunity: The association between bisphenol analogues and systemic lupus erythematosus.

The aim of this research was to examine the correlation between the exposure to bisphenol analogues (BPs), such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and the risk of developing systemic lupus erythematosus (SLE). Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was utilized to measure the levels of BPA, BPF, and BPS in the urine of 168 female participants diagnosed with SLE and 175 female participants who were deemed healthy controls. Logistic regression models were utilized to assess the connections between levels of bisphenol and the risk of SLE. The findings indicated that levels of BPA and BPF in the urine of individuals with SLE were markedly elevated compared to those in the control group. Higher exposure to BPA and BPF exhibited positive dose-response relationships with increased SLE risk. No significant associations were identified between BPS and the risk of SLE. These findings suggest exposure to BPA and BPF may be implicated as novel environmental triggers in the development of autoimmunity such as SLE. The significantly increased levels of these bisphenol analogues detected in SLE patients versus healthy controls, along with the associations between higher exposures and elevated SLE risk, which offers crucial hints for comprehending how endocrine-disrupting substances contribute to the genesis of autoimmune illnesses. Further research using robust longitudinal assessments of bisphenol analogue exposures is warranted to corroborate these epidemiological findings. Overall, this study highlights potential environmental risk factors for SLE while calling for additional investigation into the impact of bisphenol exposures on autoimmunity development.

No causal association between pneumoconiosis and three inflammatory immune diseases: a Mendelian randomization study.

Objectives: To investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout. Methods: The random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs). Results: There was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94-1.10, p = 0.74; OR = 1.00, 95% CI: 0.999-1.000, p = 0.50; OR = 1.00, 95% CI: 1.000-1.001, p = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96-1.07, p = 0.66; OR = 1.00, 95% CI: 1.00-1.00, p = 0.68; OR = 1.00, 95% CI: 1.00-1.00, p = 0.20]. Conclusion: Our study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.

Metabolomic profiles, polygenic risk scores and risk of rheumatoid arthritis: a population-based cohort study in the UK Biobank.

OBJECTIVE: To investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA). METHODS: 143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants in the UK Biobank. The Cox regression model was used to assess the associations between these metabolic biomarkers and RA risk, and genetic correlation and Mendelian randomisation analyses were performed to reveal their causal relationships. Subsequently, a metabolic risk score (MRS) comprised of the weighted sum of 17 clinically validated metabolic markers was constructed. A PRS was derived by assigning weights to genetic variants that exhibited significant associations with RA at a genome-wide level. RESULTS: A total of 620 incident RA cases were recorded during a median follow-up time of 8.2 years. We determined that 30 metabolic biomarkers were potentially associated with RA, while no further significant causal associations were found. Individuals in the top decile of MRS had an increased risk of RA (HR 3.52, 95% CI: 2.80 to 4.43) compared with those below the median of MRS. Further, significant gradient associations between MRS and RA risk were observed across genetic risk strata. Specifically, compared with the low genetic risk and favourable MRS group, the risk of incident RA in the high genetic risk and unfavourable MRS group has almost elevated by fivefold (HR 6.10, 95% CI: 4.06 to 9.14). CONCLUSION: Our findings suggested the metabolic profiles comprising multiple metabolic biomarkers contribute to capturing an elevated risk of RA, and the integration of genome-wide PRSs further improved risk stratification.

Investigation of Workability and Mechanical Properties of PVA Fiber-Reinforced Phosphogypsum-Based Composite Materials.

To address the poor characteristics of low strength and poor toughness in phosphogypsum-based construction material, this study investigates the influence of different diameters, lengths, and dosages of polyvinyl alcohol (abbreviated as PVA) fibers on the workability and mechanical properties of phosphogypsum-based construction material. The results show that as the length and dosage of PVA fibers increase, the flowability of the slurry gradually decreases, and the setting time also shortens. With an increase in the diameter of PVA fibers, the rate of decrease in flowability slows down, and the rate of shortening of setting time also gradually slows down. Moreover, the inclusion of PVA fibers significantly improves the mechanical strength of the specimens. When PVA fibers with a diameter of 15 µm, length of 12 mm, and dosage of 1.6% are used, the phosphogypsum-based construction material reinforced with PVA fibers exhibits optimal performance. Under this mixing ratio, the strength values of the specimens for flexural strength, bending strength, compressive strength, and tensile strength are 10.07 MPa, 10.73 MPa, 13.25 MPa, and 2.89 MPa, respectively. Compared to the control group, the strength enhancements are 273.00%, 164.29%, 15.32%, and 99.31%, respectively. SEM scanning of the microstructure provides a preliminary explanation for the mechanism of how PVA fibers affect the workability and mechanical properties of phosphogypsum-based construction material. The findings of this study can provide a reference for the research and application of fiber-reinforced phosphogypsum-based construction material.

Endocrine-disrupting chemicals and autoimmune diseases.

Endocrine-disrupting chemicals (EDCs) widely exist in people's production and life which have great potential to damage human and animal health. Over the past few decades, growing attention has been paid to the impact of EDCs on human health, as well as immune system. So far, researchers have proved that EDCs (such as bisphenol A (BPA), phthalate, tetrachlorodibenzodioxin (TCDD), etc.) affect human immune function and promotes the occurrence and development of autoimmune diseases (ADs). Therefore, in order to better understand how EDCs affect ADs, we summarized the current knowledge about the impact of EDCs on ADs, and elaborated the potential mechanism of the impact of EDCs on ADs in this review.

Suicide and suicidality in people exposed to pesticides: A systematic review and meta-analysis.

Exposure to pesticides has been proposed to be a positive association in suicide and suicidality. Many studies have explored this topic, but have reported inconsistent findings. We carried out a systematic review and meta-analysis of the now existing evidence on the association between pesticide exposure and the risk of suicide and suicidality. We searched PubMed, EMBASE and Web of Science databases for studies published up to February 1, 2023. For studies that provided detailed data, we applied quantitative meta-analysis to calculate Odds ratio (OR) with 95% Confidence Intervals (CIs) to evaluate the results. Heterogeneity among the included studies was assessed using Cochran's Q test, I2 statistic and tau-squared (τ2). Publication bias was evaluated by funnel plots, Egger's test, and Begg's test. In addition, subgroup analyses according to pesticides category and geographical area were performed. 2906 studies were initially identified, and 20 studies were eventually included. Fifteen of the studies were on suicide deaths and suicide attempts, and five were on suicidal ideation. Pesticide exposure was positively related to suicide deaths and suicide attempts (pooled OR = 1.31; 95%CI: 1.04-1.64, p < 0.001) and suicidal ideation (pooled OR = 2.43; 95%CI: 1.51-3.91, p = 0.015). In the subgroup analysis, mixed pesticide type (pooled OR = 1.55; 95%CI: 1.39-1.74) increased the risk of suicide deaths and suicide attempts. The results of the analysis by geographic area showed that the risk of suicide deaths and suicide attempts with pesticide exposure was 2.27 (95%CI = 1.36-3.78), and 1.33 (95%CI = 1.14-1.56) in Asia and Europe, respectively. The risk of suicidal ideation caused by pesticide exposure in Asia and America were 2.19 (95%CI = 1.08-4.42) and 2.99 (95%CI = 1.76-5.06). In conclusion, pesticide exposure may increase the risk of suicide and suicidality based on the current evidence.

Intestinal fungi and systemic autoimmune diseases.

Nearly 20 years of studies have shown that fungi and the human immune system (non-specific immunity and specific immunity) and bacterial--fungal interactions maintain a balance that can't lead to diseases. Fungi--microorganism that lives in human intestine--may play an important role in human health and disease. Population studies and animal models in some diseases have found the changes in the diversity and composition of fungi. The dysregulation of the fungi can disrupt the normal "running" of the immune system and bacteria, which triggers the development of inflammatory diseases. The latest studies of fungi in inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and type 1 diabetes mellitus were summarized. This review considers how the healthy host protect against the potential harm of intestinal fungi through the immune system and how fungal dysregulation alters host immunity.

Essential Trace Element Status in Systemic Lupus Erythematosus: a Meta-analysis Based on Case-Control Studies.

The homeostasis of trace elements is essential to regulate different aspects of the immune system and might play important roles in systemic lupus erythematosus (SLE). However, epidemiological evidences that compared the level of essential trace elements in SLE patients and healthy controls (HCs) did not reach a consensus. This was the first meta-analysis to comprehensively assess the level of zinc (Zn), copper (Cu), iron (Fe), and selenium (Se) in SLE and HCs. PubMed, Embase, and Web of Science were systematically searched until April 2022 to find relevant literatures. The PRISMA statement 2020 was followed to make sure the quality of reporting a meta-analysis. The outcomes were assessed by pooled standardized mean difference (SMD) and 95% confidence intervals (CIs). Finally, eleven articles with 1262 subjects were included in the meta-analysis. Significantly lower levels of Zn (SMD = -0.709; 95% CI: -1.173, -0.245; P = 0.003) and Fe (SMD = -1.783; 95% CI: -2.756, -0.809; P = 0.000) were found in SLE compared with HCs. Higher levels of Cu (SMD = 0.808; 95% CI: 0.234, 1.382; P = 0.006) were found in SLE patients. In addition, compared with HCs, Fe and Zn were lower in SLE patients in Asia and Cu was higher in SLE patients in Europe. However, no significant difference was observed in the level of Se (SMD = -0.251; 95% CI: -1.087, 0.586; P = 0.557). Above all, SLE patients exhibited lower Zn and Fe and increased Cu concentrations compared with HCs. Further studies are warranted to investigate the mechanism of Zn, Cu, and Fe in SLE patients.

Altered gut fungi in systemic lupus erythematosus - A pilot study.

Objective: Gut fungi, as symbiosis with the human gastrointestinal tract, may regulate physiology via multiple interactions with host cells. The plausible role of fungi in systemic lupus erythematosus (SLE) is far from clear and need to be explored. Methods: A total of 64 subjects were recruited, including SLE, rheumatoid arthritis (RA), undifferentiated connective tissue diseases (UCTDs) patients and healthy controls (HCs). Fecal samples of subjects were collected. Gut fungi and bacteria were detected by ITS sequencing and 16S rRNA gene sequencing, respectively. Alpha and beta diversities of microbiota were analyzed. Linear discriminant analysis effect size analysis was performed to identify abundance of microbiota in different groups. The correlation network between bacterial and fungal microbiota was analyzed based on Spearman correlation. Results: Gut fungal diversity and community composition exhibited significant shifts in SLE compared with UCTDs, RA and HCs. Compared with HCs, the alpha and beta diversities of fungal microbiota decreased in SLE patients. According to principal coordinates analysis results, the constitution of fungal microbiota from SLE, RA, UCTDs patients and HCs exhibited distinct differences with a clear separation between fungal microbiota. There was dysbiosis in the compositions of fungal and bacterial microbiota in the SLE patients, compared to HCs. Pezizales, Cantharellales and Pseudaleuria were enriched in SLE compared with HCs, RA and UCTDs. There was a complex relationship network between bacterial and fungal microbiota, especially Candida which was related to a variety of bacteria. Conclusion: This study presents a pilot analysis of fungal microbiota with diversity and composition in SLE, and identifies several gut fungi with different abundance patterns taxa among SLE, RA, UCTDs and HCs. Furthermore, the gut bacterial-fungal association network in SLE patients was altered compared with HCs.

Ambient air pollutants increase the risk of immunoglobulin E-mediated allergic diseases: a systematic review and meta-analysis.

Immunoglobulin E (IgE)-mediated allergic diseases, including eczema, atopic dermatitis (AD), and allergic rhinitis (AR), have increased prevalence in recent decades. Recent studies have proved that environmental pollution might have correlations with IgE-mediated allergic diseases, but existing research findings were controversial. Thus, we performed a comprehensive meta-analysis from published observational studies to evaluate the risk of long-term and short-term exposure to air pollutants on eczema, AD, and AR in the population (per 10-µg/m3 increase in PM2.5 and PM10; per 1-ppb increase in SO2, NO2, CO, and O3). PubMed, Embase, and Web of Science were searched to identify qualified literatures. The Cochran Q test was used to assess heterogeneity and quantified with the I2 statistic. Pooled effects and the 95% confidence intervals (CIs) were used to evaluate outcome effects. A total of 55 articles were included in the study. The results showed that long-term and short-term exposure to PM10 increased the risk of eczema (PM10, RRlong = 1.583, 95% CI: 1.328, 1.888; RRshort = 1.006, 95% CI: 1.003-1.008) and short-term exposure to NO2 (RRshort = 1.009, 95% CI: 1.008-1.011) was associated with eczema. Short-term exposure to SO2 (RRshort: 1.008, 95% CI: 1.001-1.015) was associated with the risk of AD. For AR, PM2.5 (RRlong = 1.058, 95% CI: 1.014-1.222) was harmful in the long term, and short-term exposure to PM10 (RRshort: 1.028, 95% CI: 1.008-1.049) and NO2 (RRshort: 1.018, 95% CI: 1.007-1.029) were risk factors. The findings indicated that exposure to air pollutants might increase the risk of IgE-mediated allergic diseases. Further studies are warranted to illustrate the potential mechanism for air pollutants and allergic diseases.

Rosmarinic Acid Combined with Adriamycin Induces Apoptosis by Triggering Mitochondria-Mediated Signaling Pathway in HepG2 and Bel-7402 Cells.

BACKGROUND Hepatic carcinoma is the third leading cause of cancer-related deaths. This study aimed to evaluate the anti-tumor effects of rosmarinic acid (RosA) combined with Adriamycin (ADM) on proliferation and apoptosis of hepatic carcinoma cell lines. MATERIAL AND METHODS Human HepG2 and Bel-7402 cells were treated with RosA and ADM and divided into HepG2 or Bel-7402, 25 µg/ml, 50 µg/m, and 100 µg/ml RosA+0.4 µg/ml ADM groups, respectively. The Cell Counting Kit-8 (CCK-8) assay was used to evaluate cell viability. Immunohistochemistry assay was used to examine B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) expression. Cell cycle analysis was used to detect cell cycle distribution. Flow cytometry and terminal deoxynucleotidyl transferase-mediated d-UTP nick-end labeling (TUNEL) assay were utilized to evaluate apoptosis. RESULTS RosA combined with ADM damaged cell morphology and decreased cell viability, and significantly decreased S-phase cell numbers compared to the HepG2 or Bel-7402 group (p<0.05). Apoptosis rates in the RosA combined with ADM group were significantly increased compared to the HepG2 or Bel-7402 group (p<0.05). TUNEL assay showed that RosA combined with ADM significantly induced DNA damage (TUNEL-positive staining) in the HepG2 and Bel-7402 groups (p<0.05). RosA combined with ADM significantly reduced Bcl-2 expression in HepG2 or Bel-7402 cells (p<0.05). RosA combined with ADM significantly increased Bax expression in HepG2 and Bel-7402 cells (p<0.05). Cell viability, apoptosis, cell cycle, and Bcl-2 and Bax expression were changed with increased concentrations of RosA. CONCLUSIONS RosA combined with ADM damaged tumor cell morphologies, decreased cell viability, and induced apoptosis of HepG2 and Bel-7402 by triggering the mitochondria-mediated signaling pathway.