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Osteoarthritis (OA) is a progressive joint disease. The etiology of OA is considered to be multifactorial. Currently, there is no definitive treatment for OA, and the existing treatments are not very effective. Hypercholesterolemia is considered a novel risk factor for the development of OA. Statins act as a competitive inhibitor of the β‐hydroxy β‐methylglutaryl‐CoA (HMG‐CoA) reductase and are widely used to manage hypercholesterolemia. Inhibition of HMG‐CoA reductase results in reduced synthesis of a metabolite named mevalonate, thereby reducing cholesterol biosynthesis in subsequent steps. By this mechanism, statins such as atorvastatin and simvastatin could potentially have a preventive impact on joint cartilage experiencing osteoarthritic deterioration by reducing serum cholesterol levels. Atorvastatin can protect cartilage degradation following interleukin‐1β‐stimulation. Atorvastatin stimulates the STAT1‐caspase‐3 signaling pathway that was shown to be responsible for its anti‐inflammatory effects on the knee joint. Simvastatin had chondroprotective effects on OA in vitro by reducing matrix metalloproteinases expression patterns. In this study, we tried to review the therapeutic effects of statins on OA.

Introduction and objectives In varicose veins, blood pressure increases in the veins of the lower extremities due to mechanical stimulation and function remodeling. The aim of this study is assessment of Signaling pathways associated with structural changes in varicose veins. Materials and methods This pilot study was performed on patients with varicose veins, which had undergone surgery. The healthy tissues from trauma patients or vascular bypass without underlying diseases were used for control samples. Hematoxylin-eosin, trichrome, and elastin staining were used for histopathological examination. The levels of MDA (malondialdehyde), total thiol, SOD (Superoxide dismutase) and NO (nitric oxide) level were measured using Elisa kits to evaluate the oxidative stress level. Gene expression levels of MMP2, MMP9, FOXO3a, APOE and p53 genes were determined using Real-time PCR. Results This study showed, the vascular Vein wall changes are visible in vascular collagen staining. Although these changes are observed in the structure of vascular wall collagen fibers, the accumulation of collagen and elastin was increased in the walls of varicose veins compared to the control group. The amount of nitric oxide and thiol were increased in the varicose group (P < 0.0001). The expression of metalloproteinase2 gene associated with extracellular matrix change was increased in varicose veins. However, the amount of metalloproteinase 9 was decreased in this group compared to control group. FOXO3a, APOE Genes were down-regulated in the varicose veins compared to control group, while p53 gene expression was significantly increased in the varicose group (P < 0.0001). Conclusion This study demonstrated changes in oxidative stress, morphological structure, and aging pathways in varicose when compared to non-varicose veins. The changes in oxidative stress may be associated with the variations in morphological structure and aging pathways which contribute to the pathogenesis of varicose veins.

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Most diabetic lower-limb amputations probably result from combinations of contributing causes rather than from unitary causes. Iron-induced damage might modulate the development of chronic diabetes complications. In this study, the relationship between tissue iron levels and polarization of macrophages in induction of angiogenesis was investigated in diabetic ulcer samples and the transitional zone of diabetic ulcers. Patients with diabetic ulcers who underwent amputation were included. The transitional zone of diabetic ulcers, from the same diabetic patients, was used as a control group. After tissue preparation, Perls Prussian blue staining and immunohistochemistry for CD11c, CD163, and CD68 markers were done. Vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), Tie2, and protein kinase B (also known as AKT) transcription of genes were measured by real-time polymerase chain reaction. For statistical analysis, we used independent samples t-test or its nonparametric equivalents, Mann–Whitney U test was used for quantitative variables, and chi-square (or Fisher's exact test) for qualitative variables. According to the results, the ratio of M2 to M1 macrophages was decreased in ulcers tissue compared to the transitional zone of diabetic ulcers. The expression of angiogenesis-related genes was increased due to hypoxia induction such as HIF and VEGF in ulcer tissue ( P < .0001), but the expression of vascular stability-related genes such as Tie2 was decreased ( P < .0001).In amputated diabetic ulcers, the polarization of macrophages is toward the classic type, but no connection was found in terms of tissue iron and help in the polarization of macrophages.