Increased risk of adverse gestational outcomes in pregnant women with primary Sjögren's syndrome.

OBJECTIVES: This study aimed to identify risk factors contributing to diverse pregnancy outcomes in primary Sjögren's syndrome (pSS) cases. METHODS: A retrospective analysis was conducted on pregnant individuals with pSS, who received outpatient or inpatient care across multiple hospitals in Anhui Province, China, from January 2015 to December 2022. RESULTS: This study included 164 pregnant women with pSS and 328 control subjects, with no statistically significant difference in average age between the two groups. Analysis of pregnancy outcomes revealed that, compared with the control group, pregnant women in the pSS group were more likely to experience miscarriages, both spontaneous (12.80% vs 1.52%, p<0.001) and therapeutic (6.10% vs 0.91%, p<0.05). The proportion of placental abnormalities detected during prenatal ultrasound in women from the pSS group was higher (14.63% vs 6.40%, p<0.05). In the analysis of pregnancy outcomes for live-born neonates, a higher incidence of congenital heart abnormalities was observed in the pSS group (27.34% vs 12.03%, p<0.05). While there were no significant differences between the pSS pregnancies in terms of both normal and adverse pregnancy outcomes, a comparison of fetal survival and fetal loss in pSS pregnancies revealed a greater use of prophylactic anticoagulant therapy in the fetal survival group. Notably, the application of low molecular weight heparin (LMWH) emerged as an independent protective factor for fetal survival. CONCLUSIONS: Compared with non-autoimmune controls, pregnancy in women with pSS presents more challenges. Importantly, we observed that the use of LMWH as anticoagulant therapy is an independent protective measure for fetal survival.

Pirfenidone Attenuates the EMT Process and the Secretion of VEGF in TGF-ß2-Induced ARPE-19 Cells via Inhibiting the Activation of the NF-κB/Snail Signaling Pathway.

Aim: Pirfenidone (PFD), an antifibrotic drug, has various beneficial functions such as antioxidant, antifibrotic, and anti-inflammatory effects. This study aimed to explore the molecular mechanisms underlying how PFD modulates retinal pigment epithelial (RPE) cells involved in neovascularization and subretinal fibrosis. Methods: ARPE-19 cell lines were treated with transforming growth factor-beta 2 (TGF-ß2) alone or in combination with PFD. RPE cell viability, as a consequence of PFD use, was determined by the CCK-8 assay. Cell migration was assessed by the wound closure assay and quantified by the Image J software. Protein expression of the following markers was measured by the western blot analysis: an epithelial cell marker and E-cadherin; mesenchymal cell markers, fibronectin, matrix metalloprotein-9 (MMP-9), and alpha-smooth muscle actin (α-SMA); a fibrotic marker and connective tissue growth factor (CTGF); an angiogenesis marker and vascular endothelial growth factor (VEGF); NF-κB/Snail. The mRNA levels of fibronectin and α-SMA were determined by quantitative real-time PCR. VEGF was quantitatively measured by the enzyme-linked immunosorbent assay. Results: The cell viability assay revealed that PFD had no significant cytotoxic effect on RPE cells at concentrations of less than 1 mg/mL. The cell scratch assay showed that TGF-ß2 stimulation significantly improved the migration of RPE cells and that PFD attenuated this effect. PFD significantly inhibited the TGF-ß2-induced protein expression of E-cadherin and increased the TGF-ß2-induced protein expression of fibronectin, MMP-9, α-SMA, CTGF, and VEGF in ARPE-19 cells. The mRNA expression of fibronectin and α-SMA was inhibited by PFD in TGF-ß2-inducedARPE-19 cells. Additionally, the increased intracellular and supernatant expression of VEGF protein was suppressed by PFD. Mechanistically, RPE cells treated with PFD + TGF-ß2 exhibited a decrease in phosphorylation of the NF-κB P65 subunit and activation of Snail, compared with the RPE cells treated with TGF-ß2 alone. Conclusion: PFD ameliorated TGF-ß2-induced neovascularization and fibrosis by suppressing the NF-κB/Snail signaling pathway. Therefore, PFD may be a potential drug in the treatment of age-related macular degeneration.

AGTR1 blocker attenuates activation of Tenon's capsule fibroblasts after glaucoma filtration surgery via the NF-κB signaling pathway.

Activation of Tenon's capsule fibroblasts limits the success rate of glaucoma filtration surgery (GFS), the most efficacious therapy for patients with glaucoma. Angiotensin type 1 receptor (AGTR1) is involved in tissues remodeling and fibrogenesis. However, whether AGTR1 is involved in the progress of fibrogenesis after GFS is not fully elucidated. The aim of this study was to investigate the role of an AGTR1 in scar formation after GFS and the potential anti-fibrosis effect of AGTR1 blocker. AGTR1 expression level was increased in subconjunctival tissues in a rat model of GFS and transforming growth factor-beta 2 (TGF-ß2)-induced human Tenon's capsule fibroblasts (HTFs). AGTR1 blocker treatment suppressed TGF-ß2-induced HTF migration and α-smooth muscle actin (α-SMA) and fibronectin (FN) expression. AGTR1 blocker treatment also attenuated collagen deposition and α-SMA and FN expression in subconjunctival tissues of the rat model after GFS. Moreover, AGTR1 blocker decreased TGF-ß2-induced P65 phosphorylation, P65 nuclear translocation, and nuclear factor kappa B (NF-κB) luciferase activity. Additionally, BAY 11-7082 (an NF-κB inhibitor) significantly suppressed HTF fibrosis. In conclusion, our results indicate that AGTR1 is involved in scar formation after GFS. The AGTR1 blocker attenuates subconjunctival fibrosis after GFS by inhibiting the NF-κB signaling pathway. These findings indicate that targeting AGTR1 is a potential approach to attenuate fibrosis after GFS.