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Aim: Impaired apoptosis and proliferation resulted in autoreactive lymphocyte development and inflammation in Rheumatoid arthritis (RA). TP53, BAX, FOXO1, and RB1 are related genes in cell survival, proliferation, and inflammation which could be important in RA development and disease severity. Here we investigated their expression in peripheral blood mononuclear cells (PBMCs) from RA patients in comparison to healthy controls. Methods: Fifty healthy controls and 50 RA patients were selected. The quantitative real‐time polymerase chain reaction was used to assess the gene expression level in PBMCs. Results: The mRNA expression of TP53 (FC = 0.65, p =.000), BAX (FC = 0.76, p =.008), FOXO1 (FC = 0.59, p =.000) and RB1 (FC = 0.50, p =.000) were significantly reduced in RA PBMCs. TP53 expression was negatively correlated with miR‐16‐5p (p =.032) and FOXO1 expression was negatively correlated with miR‐335‐5p (p =.005) and miR‐34a‐5p (p =.014). A positive correlation was seen between TP53 expression and its downstream gene, BAX (p =.001). FOXO1 expression was also negatively correlated with disease activity, DAS28 (p =.021). Conclusion: All selected genes have downregulated expression in RA PBMCs which could be correlated with RA pathogenesis by regulating apoptosis, cell survival, inflammatory mediator production, and proliferation. Due to the correlation of miR‐16‐5p, miR‐34a‐5p, and miR‐335‐5p with TP53 and FOXO1 expression in RA PBMCs, they could be used as future therapeutic targets. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is characterized by immune dysfunctions and chronic inflammation that mainly affects diarthrodial joints. Genetics has long been surveyed in searching for the etiopathogenesis of the disease and partially clarified the conundrums within this context. Epigenetic alterations, such as DNA methylation, histone modifications, and noncoding RNAs, which have been considered to be involved in RA pathogenesis, likely explain the nongenetic risk factors. Epigenetic modifications may influence RA through fibroblast‐like synoviocytes (FLSs). It has been shown that FLSs play an essential role in the onset and exacerbation of RA, and therefore, they may illustrate some aspects of RA pathogenesis. These cells exhibit a unique DNA methylation profile in the early stage of the disease that changes with disease progression. Histone acetylation profile in RA FLSs is disrupted through the imbalance of histone acetyltransferases and histone deacetylase activity. Furthermore, dysregulation of microRNAs (miRNAs) is immense. Most of these miRNAs have shown an aberrant expression in FLSs that are involved in proliferation and cytokine production. Besides, dysregulation of long noncoding RNAs in FLSs has been revealed and attributed to RA pathogenesis. Further investigations are needed to get a better view of epigenetic alterations and their interactions. We also discuss the role of these epigenetic alterations in RA pathogenesis and their therapeutic potential. [ABSTRACT FROM AUTHOR]

Objectives: Impaired wound healing and skin dehydration are the mainstay of systemic sclerosis (SSc) cutaneous manifestations. Aquaporin‐3 (AQP3) has a pivotal role in skin hydration and wound healing. Epidermal growth factor receptor (EGFR) activation is impaired in SSc fibroblasts. It is unclear whether AQP3 downregulation or epidermal growth factor (EGF) signaling are the primary points of dysregulation in SSc patients. Methods: Skin punch biopsies were obtained from 10 SSc patients and 10 healthy subjects. The mRNA and/or protein expression levels of AQP3, EGFR/p‐EGFR, matrix metalloproteinase‐1/2/9 (MMP‐1/2/9), and tissue inhibitors of metalloproteinase‐1 (TIMP1) at baseline and after EGF and transforming growth factor‐β1 (TGF‐β1) treatment was evaluated in extracted fibroblasts using real‐time polymerase chain reaction and western blot analysis. Results: SSc fibroblasts expressed lower AQP3 and EGFR, compared with normal fibroblasts. Normal fibroblasts increased AQP3 expression in response to EGF whereas AQP3 expression had no change in EGF‐treated‐SSc fibroblasts. Likewise, EGFR was activated in response to EGF in the normal group but not SSc group. Baseline expression of MMP‐1/2/9 and TIMP1 was not different between SSc and controls. EGF treatment did not result in alteration of any MMPs expression in either of the groups. Combination treatment resulted in a significant upregulation of MMP‐1 in normal fibroblasts compared with SSc fibroblasts, while in SSc fibroblasts MMP‐9 expression was upregulated in response to treatment with TGF‐β1 only. Conclusion: Downregulation of AQP3 expression in SSc fibroblasts may be related to reduced EGFR expression and activation. TGF‐β1 (alone or in combination with EGF) only can upregulate AQP3 expression in SSc fibroblasts so, TGF‐β1 affect MMP‐1 and MMP‐9 just in SSc fibroblasts. [ABSTRACT FROM AUTHOR]

A magnetically separable graphitic carbon nitride nanocomposite (Fe3O4/g‐C3N4) as a catalyst for the three‐component condensation reactions of carbonyl compounds, amines and trimethylsilylcyanide was thoroughly investigated. The reaction of these three components was found to be efficient, economical and green and took place in the presence of a catalytic amount of the magnetically separable catalyst to yield the corresponding α‐aminonitriles in good to excellent yields. The prepared nanocomposite was characterized using scanning electron microscopy and energy‐dispersive X‐ray and Fourier transform infrared spectroscopies. The nanocomposite was also found to be reusable could be recovered easily and reused several times without distinct deterioration in its catalytic activity. [ABSTRACT FROM AUTHOR]