Methotrexate (MTX), a cytotoxic chemotherapeutic agent, is considered an effective drug in the treatment of psoriasis. The aim of this study was to find out whether the effect of MTX treatment in psoriasis is due to oxidative stress-induced apoptosis. Psoriasis vulgaris patients (58 in number) were recruited for this study. Healthy volunteers (45 in number) served as control. Samples of psoriatic patients were collected and analyzed for total reactive oxygen species (ROS), malondialdehyde (MDA) levels, nitrite, nitrate levels and the activities of antioxidants like superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) and also the protein expression of caspase-3, before (Day 0) and after (at the end of 6 and 12 weeks) MTX treatment. Our results show a significant increase in tissue ROS and plasma MDA after MTX treatment when compared with before MTX treatment in psoriasis patients (p < 0.001). The levels of serum nitrite and nitrate were decreased significantly after MTX treatment (p < 0.001). The activities of plasma SOD, TAS and serum CAT levels were decreased, but not significantly after 12 weeks of treatment. The expression of caspase-3 was increased after MTX treatment. In conclusion, MTX induce apoptosis through oxidative stress by reducing NO and increasing caspase-3 levels. MTX-induced apoptosis may account for the beneficial effect of MTX treatment in psoriasis patients, which is characterized by acanthosis.
This study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE.
Background:Yoga is a science practiced in India over thousands of years. It produces constituent physiological changes and has sound scientific basis.Aim:Since exam stress modifies lipid profile and hematological parameters, we conducted an investigation on the effect of sudarshan kriya (SK and P) program on these parameters.Materials and Methods:Blood samples of 43 engineering students were collected at four intervals namely baseline (BL), exam stress (ES), three and six weeks practice of SK and P during exam stress. Lipid profile and hematological parameters were measured at all four intervals.Results:ES elevated total cholesterol (TC), triglycerides (TGL) and very low density lipoprotein (VLDL) levels. Hematological parameters affected by ES included neutrophil, lymphocytes, platelet count, packed cell volume (PCV) and mean cell volume (MCV). Three and six weeks practice of SK and P reduced the elevated lipid profile, hematological parameters and improved lymphocyte levels.Conclusion:Our study indicates that SK and P practice has the potential to overcome ES by improving lipid profile and hematological parameters.
Psoriasis is a chronic inflammatory skin disease characterized by hyper proliferation of keratinocytes. Recent data show that the epidermis thickening in psoriasis may be related to imbalance of homeostasis caused by abnormal apoptotic process. Maintenance of keratinocyte apoptotic process is very important in psoriasis. Methotrexate (MTX) has been used for many years to restore the normal skin in psoriasis condition. However, the exact mechanism of MTX in psoriasis condition is poorly understood. The aim of this study was to examine the role of MTX on keratinocyte apoptosis pathway in psoriasis patients. A total of 58 psoriasis vulgaris patients were recruited for this study. Nonlesional skin biopsies served as control. Skin biopsies of psoriatic patients were collected and analyzed for cytosolic, mitochondria and total cytochrome c by ELISA. Expression of caspase-9, NFκBp65, pAkt1 by western blot, real-time PCR and immunohistochemical analysis of c-FLIP protein was analyzed in nonlesional and lesional skin biopsies before (day 0) and after (at the end of 6 and 12 weeks) MTX treatment. After MTX treatment, a significant increase in cytochrome c was observed when compared with before MTX treatment in psoriasis patients (p < 0.001). Protein and gene expression of cleaved caspase-9 were significantly increased after MTX treatment, whereas the expression of Bcl-xL, c-FLIP, NFκBp65, pAkt1 significantly downregulated after MTX treatment. In conclusion, these results showed that intrinsic apoptotic pathway induced by MTX eventually adds the beneficial therapeutic role of MTX in psoriasis by controlling the acanthosis.
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