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Exploring herbs and their compounds for potential drugs is a significant research focus due to the incurable nature of Sjögren's syndrome (SS), a prevalent chronic inflammatory autoimmune disease. Dendrobium officinale polysaccharide (DOP) has demonstrated diverse biological effects, particularly in immunomodulation. Nonetheless, limited research has been conducted on DOP concerning the treatment of SS. This research aims to examine the impacts of DOP on experimental SS (ESS) mice and its possible mechanisms. An ESS animal model was established using the immune induction method. Besides the control group, ESS mice were randomly assigned to the model (distilled water), the HCQ (60 mg/kg), the DOP (43 mg/kg), the DOP (130 mg/kg), and the DOP (390 mg/kg) groups. Drugs were treated for three weeks. The findings indicated that DOP enhanced saliva production of ESS mice and diminished lymphocyte infiltration and foci in the submandibular gland (SMG). DOP also significantly downregulated the mRNA content of proinflammatory factors (TNF-α, IL-1β, and IL-17) and the expression of genes and proteins of apoptotic factors (Bax and Caspase-3). Furthermore, DOP downregulated the BAFF and BAFF receptor (BAFFR) as well as Fas and Fas ligand (Fas-L) expressions in the SMG. Our study demonstrates that DOP may reduce inflammation and apoptosis by inhibiting BAFF/BAFFR and Fas/Fas-L signaling, thus producing therapeutic effects in ESS mice. [ABSTRACT FROM AUTHOR]

The herbicide acetochlor is widely used and detected in the environment and biota, and has been suspected to disrupt the thyroid endocrine system, but underlying mechanisms have not yet been clarified. In the present study, zebrafish larvae (7 days post-fertilization) were exposed to a series concentration of acetochlor (0, 1, 3, 10, 30, 100 and 300 µg l−1) within a 14-day window until 21 days post-fertilization. Thyroid hormones and mRNA expression profiles of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were analyzed. Exposure to the positive control, 3,5,3′-triiodothyronine (T3), altered the mRNA expression, suggesting that the HPT axis in the critical window of zebrafish responded to chemical exposure and could be used to evaluate the effects of chemicals on the thyroid endocrine system. The mRNA expressions of genes involved in thyroid hormone synthesis ( tshβ, slc5 a5 and tpo) were upregulated significantly with acetochlor treatment, which might be responsible for the increased thyroxine concentrations. The downregulation of genes related to thyroid hormone metabolism ( dio1 and ugt1 ab) and transport ( ttr) in zebrafish larvae exposed to acetochlor might further explain the increased thyroxine levels and decreased T3 levels. The mRNA expression of the thyroid hormone receptor ( trα) was also upregulated upon acetochlor exposure. Results suggested that acetochlor altered mRNA expression of the HPT axis-related genes and changed the whole body thyroid hormone levels in zebrafish larvae. It demonstrated that acetochlor could cause endocrine disruption of the thyroid system by simulating the biological activity of T3. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Vacuolar proteinase A (Pep4p) is required for the post-translational precursor maturation of vacuolar proteinases in Saccharomyces cerevisiae, and important for protein turnover after oxidative damage. The presence of proteinase A in brewing yeast leads to the decline of beer foam stability, thus the deletion or inhibition of Pep4p is generally used. However, the influence of Pep4p deletion on cell metabolism in Saccharomyces cerevisiae is still unclear. Herein, we report the identification of differentially down-regulated metabolic proteins in the absence of Pep4p by a comparative proteomics approach. 2D-PAGE (two-dimensional polyacrylamide gel electrophoresis) presented that the number of significantly up-regulated spots (the Pep4p-deficient species versus the wild type) was 183, whereas the down-regulated spots numbered 111. Among them, 35 identified proteins were differentially down-regulated more than 10-fold in the Pep4p-deficient compared to the wild-type species. The data revealed that Pep4p was required for the synthesis and maturation of several glycolytic enzymes and stress proteins, including Eno2p, Fba1p, Pdc1p, Tpi1p, Ssa1, Hsp82p, and Trr1p. The transcription and post-translational modifications of glycolytic enzymes like Eno2p and Fba1p were sensitive to the absence of Pep4p; whereas the depletion of the pep4 gene had a negative impact on mitochondrial and other physiological functions. The finding of this study provides a systematic understanding that Pep4p may serve as a regulating factor for cell physiology and metabolic processes in S. cerevisiae under a nitrogen stress environment. [ABSTRACT FROM AUTHOR]

Objective: To construct a predictive model for Psoriatic Arthritis (PsA) based on clinical and ultrasonic characteristics in patients with plaque psoriasis (PsP)., Patients and Methods: Demographic, clinical, and ultrasound data were collected from patients with PsP and PsA between May 2019 and December 2022., Results: A total of 212 patients with PsP and 123 with PsA in the training cohort, whereas the validation cohort comprised 91 patients with PsP and 49 with PsA. The multivariate logistic regression identified nail psoriasis (odds ratio [OR] 1.88, 95% CI: 1.07-3.29), synovitis (OR 18.23, 95% CI: 4.04-82.33), enthesitis (OR 3.71, 95% CI: 1.05-13.14), and bone erosion (OR 11.39, 95% CI: 3.05-42.63) as effective predictors for PsA. The area under the curve was 0.750 (95% CI, 0.691-0.806) and 0.804 (95% CI, 0.723-0.886) for the training and validation cohorts, respectively. The Hosmer-Lemeshow goodness-of-fit test showed good consistency for both the training cohort (p  =  0.970) and the validation cohort (p  =  0.967). Calibration curves also indicated good calibration for both cohorts. The DCA revealed that the predictive model had good clinical utility., Conclusions: We have developed a quantitative, intuitive, and convenient predictive model based on nail psoriasis, synovitis, enthesitis, and bone erosion to assess the risk of PsA in patients with plaque psoriasis., (© 2024 Deutsche Dermatologische Gesellschaft (DDG).)

Background: As one of the most effective biologic treatments for psoriasis, the short-term effectiveness of ustekinumab has yet to be studied extensively., Objective: The purpose of this study was to evaluate the short-term effectiveness and potential factors within four weeks after the first-dose ustekinumab treatment based on real-world data., Methods: The study enrolled 98 patients with moderate-to-severe psoriasis, given ustekinumab 45 mg at week 0, week 4, and then every 12 weeks. Based on clinical data collected at baseline and week 4, we investigated the short-term effectiveness of ustekinumab after the first dose and potential factors associated with the treatment. For evaluation, we collected demographic information, body data, medical history, laboratory examination results, Psoriasis Area and Severity Index (PASI), body surface area (BSA), and dermatology life quality index (DLQI). Response rates were calculated based on the number of patients that achieved a 75/90/100% reduction in PASI (PASI 75/90/100), and the primary treatment goal was to achieve PASI 75., Results: The response rates for PASI 75/90/100 at week 4 were 30.5%, 18.9%, and 16.8%, respectively. For PASI 75, the response rate was higher in patients without metabolic syndrome (MS) (without MS vs. with MS: 36.9% vs. 5.9%, p  = 0.013); the serum triglyceride (TG) level was significantly lower in patients achieving PASI 75 (expressed as mean ± standard deviation, achieved vs. unachieved: 1.82 ± 1.79 vs. 3.59 ± 8.89, p  = 0.010). For PASI 100, the response rates were higher in female patients (female vs. male: 26.3% vs. 10.5%, p  = 0.044) and patients with a family history of psoriasis (with family history vs. without family history: 44.4% vs. 13.9%, p  = 0.042). In addition, the possibility of achieving PASI 75/90/100 went up along with the serum high-density lipoprotein cholesterol (HDL-C) level (expressed as adjusted odds ratio < 95% confidence interval>: PASI 75: 28.484 < 2.035-248.419>, p  = 0.011; PASI 90: 28.226 < 2.828-281.729>, p  = 0.004; PASI 100: 12.175 < 1.876-79.028>, p  = 0.009)., Conclusion: In this study, nearly one-third of patients achieved PASI 75 after only the first-dose ustekinumab treatment. Sex, family history of psoriasis, MS, serum TG level might affect the short-term effectiveness, and serum HDL-C level may be a potential factor. The possibility of achieving treatment goals (PASI 75/90/100) at week 4 increased along with serum HDL-C levels.