Correction: A Novel Synthesized Sulfonamido-Based Gallate-JEZ-C as Potential Therapeutic Agents for Osteoarthritis.

[This corrects the article DOI: 10.1371/journal.pone.0125930.].

A Novel Synthesized Sulfonamido-Based Gallate-JEZ-C as Potential Therapeutic Agents for Osteoarthritis.

Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on osteoarthritis (OA). However, GA has much weaker anti-oxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel compound named JEZ-C and analyzed its anti-arthritis and chondro-protective effects. Comparison of JEZ-C with its sources i.e. GA and Sulfamethoxazole (SMZ) was also performed. Results showed that JEZ-C could effectively inhibit the IL-1-mediated induction of MMP-1 and MMP-13 and could induce the expression of TIMP-1, which demonstrated its ability to reduce the progression of OA. JEZ-C can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Meanwhile, expression of the collagen I gene was effectively downregulated, revealing the inhibition of chondrocytes dedifferentiation by JEZ-C. Hypertrophy that may lead to chondrocyte ossification was also undetectable in JEZ-C groups. The recommended dose of JEZ-C ranges from 6.25×10-7 µg/ml to 6.25×10-5 µg/ml, among which the most profound response was observed with 6.25×10-6 µg/ml. In contrast, its source products of GA and SMZ have a weak effect not only in the inhibition of OA but also in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed JEZ-C as a promising novel agent in the treatment of chondral and osteochondral lesions.

A novel synthesized sulfonamido-based gallic acid--LDQN-C: effects on chondrocytes growth and phenotype maintenance.

Chondrocyte based therapy is promising to treat symptomatic chondral and osteochondral lesions. Growth factors to accelerate the proliferation and retain the phenotype of chondrocytes in vitro are imperative. However, the high cost and rapid degradation of growth factors limited their further application. Therefore, it is significant to find substitutes that can preserve chondrocytes phenotype and ensure sufficient cells for cytotherapy. Antioxidant and anti-inflammatory agents or their derivatives that have effect on arthritis may be an alternative. In this study, we synthesized sulfonamido-based gallate - LDQN-C and investigated its effect on rat articular chondrocytes through examination of the cell proliferation, morphology, viability, glycosaminoglycans (GAGs) synthesis and cartilage specific gene expression. Results showed that LDQN-C could enhance secretion and synthesis of cartilage extracellular matrix (ECM) by up-regulating expression levels of aggrecan, collagen II and Sox9 genes compared to the GA treated group and control group. Expression of collagen type II was effectively up-regulated while collagen I was down-regulated, which demonstrated that the inhibition of chondrocytes dedifferentiation by LDQN-C. Range of 1.36×10(-9)M to 1.36×10(-7)M is recommended dose of LDQN-C, among which the most profound response was observed with 1.36×10(-8)M. GA at concentration of 0.125µg/mL was compared. This study might provide a basis for the development of a novel agent for the treatment of articular cartilage defect.

Tumor necrosis factor and interleukin-6 gene polymorphisms and endometriosis risk in Asians: a systematic review and meta-analysis.

A relationship between endometriosis and tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) gene polymorphisms has been raised for Asians. However, this topic is controversial. This study was a meta-analysis to explore whether TNF-α/IL-6 gene polymorphisms were associated with a risk of endometriosis in Asians. By searching PubMed, HuGENet, and China National Knowledge Infrastructure (CNKI) databases, 17 studies were identified and included (3372 cases and 4008 controls). The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between TNF-α/IL-6 gene polymorphisms and endometriosis risk. An association of TNF-α gene -1031T/C polymorphism with endometriosis was found (TT + TC vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 37.1%, P = 0.20; TT vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 43.0%, P = 0.173; TC vs. CC: OR 0.49, 95% CI 0.29-0.83, I(2) = 10.6%, P = 0.327). In addition, TNF-α-238A/G and IL-6 -174C/G gene polymorphisms were also likely to be associated with endometriosis in Asians. For the TNF-α-238A/G gene polymorphism, the OR was 1.577 (95% CI: 1.01-2.48). For the IL-6 -174C/G gene polymorphism, the OR was 1.554 (95% CI: 1.04-2.31). No associations were detected between the TNF-α-308A/G and IL-6 -634C/G polymorphisms and susceptibility to endometriosis. Our results indicate that the TNF-α gene -1031T/C polymorphism can reduce the risk of endometriosis, but for Asians, TNF-α-238A/G and IL-6 -174C/G gene polymorphisms may be a risk factor for endometriosis. No association was found for the TNF-α-308A/G and IL-6 -634C/G gene polymorphisms.

MDM2 SNP309 polymorphism is associated with lung cancer risk in women: A meta-analysis using METAGEN.

Lung cancer is the most common diagnosed malignancy and the leading cause of cancer-related mortality worldwide. Murine double minute 2 (MDM2) SNP309 polymorphisms have been reported to influence the risk of lung cancer. However, the published studies together with four subsequent meta-analyses have yielded contradictory results. To examine this inconsistency, we conducted a meta-analysis of 6,696 lung cancer cases and 7,972 controls from eight published case-control studies using METAGEN. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with STATA software and used to assess the strength of the association. In the overall analysis, a significant association between MDM2 SNP309 polymorphism and lung cancer risk was observed (OR, 1.143; 95% CI, 1.047-1.247). Moreover, stratified by ethnicity, a significant association was found in Asians (OR, 1.260; 95% CI, 1.111-1.429), but not in Europeans. Subgroup analysis of gender, histology and smoking status suggested that the MDM2 SNP309 genotype was associated with increased lung cancer risk in women (OR, 1.282; 95% CI, 1.062-1.548) and never smokers (OR, 1.328; 95% CI, 1.119-1.575). No statistically significant association was observed in males and ever smoking population, and no association was found in subgroup analysis based on histology. In conclusion, the association between MDM2 SNP309 and lung cancer was statistically significant, particularly in Asians, women and never smoking population.