The phosphatidylinositol 3-kinase (PI3 K)/Akt/mammalian target of rapamycin (mTOR) signaling axis plays a central role in cell proliferation, growth and survival under physiological conditions. However, aberrant PI3 K/Akt/mTOR signaling has been implicated in many human cancers, including human triple negative breast cancer. Therefore, dual inhibitors of PI3 K/Akt and mTOR signaling could be valuable agents for treating breast cancer. The objective of this study was to investigate the effect of piperlongumine (PPLGM), a natural alkaloid on PI3 K/Akt/mTOR signaling, Akt mediated regulation of NF-kB and apoptosis evasion in human breast cancer cells. Using molecular docking studies, we found that PPLGM physically interacts with the conserved domain of PI3 K and mTOR kinases and the results were comparable with standard dual inhibitor PF04691502. Our results demonstrated that treatment of different human triple-negative breast cancer cells with PPLGM resulted in concentration- and time-dependent growth inhibition. The inhibition of cancer cell growth was associated with G1-phase cell cycle arrest and down-regulation of the NF-kB pathway leads to activation of the mitochondrial apoptotic pathway. It was also found that PPLGM significantly decreased the expression of p-Akt, p70S6K1, 4E-BP1, cyclin D1, Bcl-2, p53 and increased expression of Bax, cytochrome c in human triple-negative breast cancer cells. Although insulin treatment increased the phosphorylation of Akt (Ser473), p70S6K1, 4E-BP1, PPLGM abolished the insulin mediated phosphorylation, it clearly indicates that PPLGM acts through PI3 k/Akt/mTOR axis. Our results suggest that PPLGM may be an effective therapeutic agent for the treatment of human triple negative breast cancer.
Premature Ejaculation (PE) is a very common male sexual problem. Anxiety, stress, fear etc., are the main predisposing factors of PE. In Ayurveda, this condition can be correlated with Shukragata Vata. In the present study, fifty five patients with PE were grouped into two and were treated with Stambhanakaraka Yoga (n = 30) and Placebo (n = 20) for a duration of two months, with luke warm water as anupana. Psychological counseling was given to the patients in both the groups. After completion of treatment, Stambhanakaraka Yoga showed significant results against placebo in all parameters, namely Intravaginal Ejaculation Latency Time (IELT), voluntary control over ejaculation, patient and partner's satisfaction, performance anxiety.
ABSTARCTDiet, lifestyle and mental status are known to play pivotal roles in the occurrence of many chronic diseases. Constipation is one amongst them, which is the commonest complain and significant healthcare problem especially in elderly that increases with age and affect ones physical and mental wellbeing. It is the premonitory symptoms of many existing or forthcoming diseases. In the present study, the survey of elderly patients with constipation has been done to evaluate the patterns of dietary habits, life style and mental health along with their relationships with risk factors for constipation in Saurashtra region of Gujarat especially in the Jamnagar city. Data shows that the majority of the patients were male. Of all the respondents, stress, sedentary lifestyle, lack of exercise, and ruksha (dry), sheeta (cold) diets , bad eating habits like vishamashana (irregularity in time and quantity of meal), viruddhashana (incompatible diet) were found to be linked to constipation. The elders reporting constipation had tension, anxious mood, depressed mood, disturbed sleep and delayed onset of sleep.
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