Activation of the STING-IRF3 pathway involved in psoriasis with diabetes mellitus.

Psoriasis and type 2 diabetes mellitus (T2DM) share similar inflammatory pathways in their pathogenesis. The stimulator of interferon genes (STING)-interferon regulatory factor 3 (IRF3) pathway has recently been shown to play an important role in immune and metabolic diseases. In this study, we investigated the activation of the STING-IRF3 pathway in human immortalized keratinocytes (HaCaT) cells treated with palmitic acid (PA) and imiquimod (IMQ). Additionally, we detected the STING-IRF3 pathway in diabetic mice with imiquimod (IMQ)-induced psoriasis and assessed the potential of STING inhibitor C-176. Furthermore, skin samples from patients with psoriasis and diabetes were collected for immunohistochemical analysis. The results indicated that the STING-IRF3 pathway was activated in HaCaT cells. Moreover, the STING pathway was also found to be induced in the skin tissue of diabetic mice with psoriasis; the inflammatory responses were ameliorated by treatment with C-176. In the skin tissue samples of patients with psoriasis and diabetes, immunohistochemistry showed that the expression levels of STING and phosphorylated IRF3 were also significantly increased. Thus, we conclude that the STING-IRF3 pathway is involved in the inflammatory response in the manifestation of psoriasis with T2DM. Inhibition of the activation of the STING pathway can ameliorate the development of psoriasis in diabetes and could be targeted for the development of therapeutic agents for these conditions.

The Research Progress of Exosomes in Osteoarthritis, With Particular Emphasis on the Therapeutic Effect.

Exosomes participate in many physiological and pathological processes by regulating cell-to-cell communication. This affects the etiology and development of diseases, such as osteoarthritis (OA). Although exosomes in the OA tissue microenvironment are involved in the progression of OA, exosomes derived from therapeutic cells represent a new therapeutic strategy for OA treatment. Recent studies have shown that exosomes participate in OA treatment by regulating the proliferation, apoptosis, inflammation, and extracellular matrix synthesis of chondrocytes. However, studies in this field are scant. This review summarizes the therapeutic properties of exosomes on chondrocytes in OA and their underlying molecular mechanisms. We also discuss the challenges and prospects of exosome-based OA treatment.

Impact of rli87 gene deletion on response of Listeria monocytogenes to environmental stress.

Listeria monocytogenes (LM) is a zoonotic pathogen that widely adapts to various environments. Recent studies have found that noncoding RNAs (ncRNAs) play regulatory roles in LM responses to environmental stress. To understand the role of ncRNA rli87 in the response regulation, a rli87 deletion strain LM-Δrli87 was constructed by homologous recombination and tested for stress responses to high temperature, low temperature, high osmotic pressure, alcohol, acidity, alkaline and oxidative environments, along with LM EGD-e strain (control). The results showed that compared with LM EGD-e, LM-Δrli87 grew faster (P < 0.05) at low temperature (30 °C), high temperature (42 °C), and in alkaline condition (pH = 9), similarly (P > 0.05) in acidic and high osmatic pressure (10% NaCl) conditions. When cultured in medium containing 3.8% ethanol, the growth was not significantly different between the two strains (P > 0.05). When cultured at pH 9, they had similar growth rates in the first 5 h (P > 0.05), but the rates were significantly different after 6 h (P < 0.05). The expression of rsbV, rsbW, hpt, clpP, and ctsR was upregulated in LM-∆rli87 compared with LM EGD-e at pH 9, indicating that the rli87 gene regulated the expression of the five genes in alkaline environment. Our results suggest that the rli87 gene has an important regulatory role in LM's response to temperature (30 and 42 °C), alkaline stresses.

Neointimal hyperplasia inhibition effect of angiotensin II type 1 receptor blockers in patients after coronary stent implantation: a meta-analysis.

BACKGROUND AND OBJECTIVE: It remains unclear whether angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) can inhibit neointimal hyperplasia after stent implantation in patients with coronary artery disease. The aim of this meta-analysis was therefore to evaluate the benefits of ARBs in patients after coronary stent implantation based on the currently available randomized controlled trials. METHODS: We conducted a pooled analysis of randomized controlled trials to compare outcomes after stent implantation in patients administered ARBs with those not administered ARBs. We searched Ovid/MEDLINE, EMBASE, and the ISI web of knowledge using the terms 'angiotensin receptor blocker,' 'renin angiotensin system inhibitor,' 'angiotensin receptor antagonist,' 'stent,' 'angiograph,' 'percutaneous coronary intervention (PCI),' and 'coronary artery disease.' Published meta-analyses, review articles, and editorials were reviewed for potential studies of interest. The inclusion criteria were randomized controlled trials published in English, with a follow-up period of 6 months, comparing the outcomes after coronary stent implantation with and without the administration of any kind of ARB, reporting at least one outcome of interest (restenosis rate and late lumen loss). Data abstraction included study design, patient characteristics, follow-up period, type of ARB, type of stent, restenosis rate, and late lumen loss. Fixed-effects models were used to calculate the pooled relative risk for the restenosis rate and the standardized mean difference for late lumen loss. RESULTS: Five studies were included, with a total number of 624 patients. Seventy-five of 314 patients in the ARB group were diagnosed with in-stent restenosis at the 6-month follow-up, compared with 87 of 310 patients in the control group (relative risk 0.85; 95% CI 0.65, 1.11; p = 0.23). Consistent with this, there was no significant difference in late lumen loss between the two groups (0.04 mm; 95% CI -0.15, 0.23; p = 0.66). CONCLUSION: There is no evident benefit with the use of an ARB in terms of inhibition of neointimal hyperplasia in patients after coronary stent implantation.