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Rheumatoid arthritis (RA) is an autoimmune disease that significantly impacts quality of life by disrupting CD4+ T cell immune homeostasis. The identification of a low-side-effect drug for RA treatment is urgently needed. Our previous study suggests that Trichinella spiralis paramyosin (Ts-Pmy) has immunomodulatory effects, but its potential effect on CD4+ T cell response in RA remains unclear. In this study, we used a murine model to investigate the role of rTs-Pmy in regulating CD4+ T cell differentiation in collagen-induced arthritis (CIA). Additionally, we assessed the impact of rTs-Pmy on CD4+ T cell differentiation towards the Th1 and Th17 phenotypes, which are associated with inflammatory responses in arthritis, using in vitro assays. The results demonstrated that rTs-Pmy administration reduced arthritis severity by inhibiting Th1 and Th17 response while enhancing Treg response. Prophylactic administration of Ts-Pmy showed superior efficacy on CIA compared to therapeutic administration. Furthermore, in vitro assays demonstrated that rTs-Pmy could inhibit the differentiation of CD4+ T cells into Th1 and Th17 while inducing the production of Tregs, suggesting a potential mechanism underlying its therapeutic effects. This study suggests that Ts-Pmy may ameliorate CIA by restoring the immune balance of CD4+ T cells and provides new insights into the mechanism through which helminth-derived proteins exert their effects on autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background: Trichinellosis is a serious food-borne parasitic zoonosis worldwide. In the effort to develop vaccine against Trichinella infection, we have identified Trichinella spiralis Heat shock protein 70 (Ts-Hsp70) elicits partial protective immunity against T. spiralis infection via activating dendritic cells (DCs) in our previous study. This study aims to investigate whether DCs were activated by Ts-Hsp70 through TLR2 and/or TLR4 pathways. Methods and findings: After blocking with anti-TLR2 and TLR4 antibodies, the binding of Ts-Hsp70 to DCs was significantly reduced. The reduced binding effects were also found in TLR2 and TLR4 knockout (TLR2-/- and TLR4-/-) DCs. The expression of TLR2 and TLR4 on DCs was upregulated after treatment with Ts-Hsp70 in vitro. These results suggest that Ts-Hsp70 is able to directly bind to TLR2 and TLR4 on the surface of mouse bone morrow-derived DCs. In addition, the expression of the co-stimulatory molecules (CD80, CD83) on Ts-Hsp70-induced DCs was reduced in TLR2-/- and TLR4-/- mice. More evidence showed that Ts-Hsp70 reduced its activation on TLR2/4 knockout DCs to subsequently activate the naïve T-cells. Furthermore, Ts-Hsp70 elicited protective immunity against T. spiralis infection was reduced in TLR2-/- and TLR4-/- mice correlating with the reduced humoral and cellular immune responses. Conclusion: This study demonstrates that Ts-Hsp70 activates DCs through TLR2 and TLR4, and TLR2 and TLR4 play important roles in Ts-Hsp70-induced DCs activation and immune responses. [ABSTRACT FROM AUTHOR]

Background: A few studies have examined the association between ambient temperature and preterm birth (PTB), and the results have been inconsistent. This study explored the association between ambient temperature and PTB in Shenzhen, China.Methods: Data of daily singleton PTB, air pollution and meteorological variables from 2005 to 2011 were collected in Shenzhen. A distributed lag non-linear model (DLNM) was used to investigate the association of the low and high temperatures (1st, 5th, 95th, and 99th percentiles) with PTB.Results: The median temperature was 24.5 °C and the 1st, 5th, 95th, and 99th percentiles of daily mean temperatures were 9, 12.5, 29.9 and 30.7 °C, respectively. The prevalence of singleton PTB was 5.61 % in Shenzhen. The association between temperature and PTB was not linear. There was an immediate positive association of low temperature (1st and 5th percentiles) and a negative association of high temperature (95th and 99th percentiles) with PTB. The effect of low temperature 9 °C (1st) on PTB on the current day was stronger than that of 12.5 °C (5th), with a relative risk (RR) of 1.54 (95 % CI: 1.36-1.75) and 1.49 (95 % CI: 1.35-1.63), respectively. The cumulative RR (up to 30 days) of 9 and 12.5 °C was 1.72 (95 % CI: 1.28-2.33) and 1.96 (95 % CI: 1.60-2.39), respectively. The cumulative effects (up to 30 days) of high temperature (95th and 99th percentiles) on PTB were 0.69 (95 % CI: 0.60-0.80) and 0.62 (95 % CI: 0.52-0.74), respectively. The cumulative effect (up to 30 days) of low temperatures on vaginal delivery PTB was lower than that of the cesarean section PTB with an RR of 1.58 (95 % CI: 1.12-2.22) and 1.93 (95 % CI: 1.21-3.08), respectively.Conclusions: This study suggests that low temperature might be a risk factor, while high temperature might be a protective factor of PTB in Shenzhen. [ABSTRACT FROM AUTHOR]

Background: Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. Methods and Findings: Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES) intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN), and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells) and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17) in the spleens, MLN and colon of treated mice. Conclusions: Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Escherichia coli O157:H7 is an important food-borne pathogen that can cause hemorrhagic colitis and hemolytic-uremic syndrome in humans. pO157_Sal, a novel conjugative plasmid is present in a Chinese O157:H7 outbreak strain Xuzhou21. Here we investigated the phenotypic and transcriptional differences between the wild type strain Xuzhou21 and the pO157_Sal cured mutant strain Xuzhou21m. RNA-Seq analysis found that all 52 ORFs encoded on pO157_Sal were transcribed. One hundred and sixty eight chromosomal and pO157 genes were differentially expressed (≥2 fold difference) between Xuzhou21 and Xuzhou21m. Sixty-seven and 101 genes were up-regulated and down-regulated respectively by pO157_Sal including genes related to stress response, adaption and virulence. The plasmid-cured mutant Xuzhou21m grew slower than wild type Xuzhou21 and pO157_Sal plasmid complemented strain Xuzhou21c in M9 medium under the condition of high NaCl or presence of sodium deoxycholate (NaDC), corroborating with the RNA-Seq data. Seven differentially expressed genes are associated with NaDC resistance, including the adenine-specific DNA-methyltransferase gene (dam), multidrug efflux system subunit gene mdtA, hyperosmotically inducible periplasmic protein gene osmY and oxidation-reduction related genes while two differentially expressed genes (osmY and pspD) are likely to be related to resistance to osmotic pressure. A number of differentially expressed genes were virulence associated including four genes encoding T3SS effectors from the chromosome and ehxD from pO157. Through complementation of Xuzhou21m with a plasmid construct carrying the pO157_Sal hha homolog we further showed that the pO157_Sal hha represses the expression of T3SS effectors. These findings demonstrated that the plasmid pO157_Sal affects the transcription of the chromosomal and pO157 plasmid genes and contributes to the enhanced ability to resist stress. We conclude that pO157_Sal plays an important role in regulating global gene expression and affects the virulence and adaptation of E. coli O157:H7. [ABSTRACT FROM AUTHOR]

Objectives: To explore the relationship between estradiol (E2) and the incidence of hyperuricemia (HUA) in adult women and to explore whether glucolipid metabolism disorders play a mediating role in mediating this relationship., Methods: A total of 2,941 participants aged 20-65 years were included in the National Health and Nutrition Examination Survey (NHANES) 2013-2016. Multivariate logistic regression analysis was performed to evaluate the correlations of E2 with HUA. Multivariate linear regression analysis was performed to evaluate the associations between E2 and triglyceride (TG), total cholesterol (TC), and the triglyceride-glucose index (TyG). The restricted cubic spline (RCS) model was used to further explore the association between E2 and HUA and between TG, TC, and TyG and HUA. Mediation analyses were performed to examine whether TC, TG, and TyG mediated the relationship between E2 and HUA., Results: After adjusting for covariates, logistic regression revealed that ln(E2) was significantly associated with HUA in the female subgroup ( p = 0.035) and that the incidence of HUA tended to increase with decreasing ln(E2) ( p for trend = 0.026). Linear regression showed that E2 was significantly associated with TC ( p = 0.032), TG ( p = 0.019), and TyG ( p = 0.048). The RCS model showed that ln(E2) was linearly correlated with the incidence of HUA ( p -overall = 0.0106, p -non-linear = 0.3030). TC and TyG were linearly correlated with HUA (TC: p -overall = 0.0039, p -non-linear = 0.4774; TyG: p -overall = 0.0082, p -non-linear = 0.0663), whereas TG was non-linearly correlated with HUA. Mediation analyses revealed that TC, TG, and TyG significantly mediated the relationship between ln(E2) and HUA (TC, indirect effect: -0.00148, 7.5%, p = 0.008; TG, indirect effect: -0.00062, 3.1%, p = 0.004; TyG, indirect effect: -0.00113, 5.6%, p = 0.016)., Conclusion: In conclusion, this study demonstrated that compared with women aged 20-45 years, women aged 45-55 years and 55-65 years had lower E2 levels and a greater incidence of HUA. E2 levels and the incidence of HUA were negatively associated in female individuals but not in male individuals. In addition, TC, TG, and TyG, which are markers of glucolipid metabolism, played a mediating role in the association between E2 and HUA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Qian, Cui, Li, Cheng and Gao.)