Osteoporosis is a bone disorder with remarkable changes in bone biologic material and consequent bone structural distraction, affecting millions of people around the world from different ethnic groups. Bone fragility is the worse outcome of the disease, which needs long term therapy and medical management, especially in the elderly. Many involved genes including environmental factors have been introduced as the disease risk factors so far, of which genes should be considered as effective early diagnosis biomarkers, especially for the individuals from high-risk families. In this review, a number of important criteria involved in osteoporosis are addressed and discussed.

No abstract

The brain in Alzheimer's disease is under increased oxidative stress, and this may have a role in the pathogenesis and neural death in this disorder. It has been verified that numerous signaling pathways involved in neurodegenerative disorders are activated in response to reactive oxygen species (ROS). EUK134, a synthetic salen-manganese antioxidant complex, has been found to possess many interesting pharmacological activities awaiting exploration. The present study is to characterize the role of Notch signaling in apoptotic cell death of SK-N-MC cells. The cells were treated with hydrogen peroxide (H2O2) or menadione to induce oxidative stress. The free-radical scavenging capabilities of EUK134 were studied through the MTT assay, glutathione peroxidase (GPx) enzyme activity assay, and glutathione (GSH) Levels. The extents of lipid peroxidation, protein carbonyl formation, and intracellular ROS levels, as markers of oxidative stress, were also studied. Our results showed that H2O2/menadione reduced GSH levels and GPx activity. However, EUK134 protected cells against ROS-induced cell death by down-regulation of lipid peroxidation and protein carbonyl formation as well as restoration of antioxidant enzymes activity. ROS induced apoptosis and increased NICD and HES1 expression. Inhibition of NICD production proved that Notch signaling is involved in apoptosis through p53 activation. Moreover, H2O2/menadione led to Numb protein down-regulation which upon EUK134 pretreatment, its level increased and subsequently prevented Notch pathway activation. We indicated that EUK134 can be a promising candidate in designing natural-based drugs for ROS-induced neurodegenerative diseases. Collectively, ROS activated Notch signaling in SK-N-MC cells leading to cell apoptosis.

Oral pemphigus vulgaris (PV) is a rare blistering disorder of the skin and mucous membranes in the mouth. Inflammasome serves as a molecular platform that mediates the autoactivation of caspase-1, which cleaves the pro-forms of IL-1β and IL-18 to active forms. Therefore, the main aim of this study was to evaluate the messenger RNA (mRNA) levels of NOD-like receptor-related protein (NLRP)1, NLRP3, and IPAF in the PBMCs of PV patients to determine their effect in PV pathogenesis. This study was designed as a cross-sectional study. We studied mRNA levels of three types of inflammasomes including NLRP1, NLRP3, and IPAF in 43 oral PV patients and 40 healthy controls by real-time PCR technique. Results were analyzed by SPSS software package version 18. Here, we showed that the mRNA levels of NLRP1 and IPAF in patients with active PV remarkably increased compared to those in healthy controls. However, the mRNA level of NLRP3 in PBMC of PV patients was similar to that of the control group. We showed important and emerging relationship of NLRP1 and IPAF mRNAs with PV disease progression. We hypothesize that NLRP1 and IPAF with cytokine activity of IL-1β are involved in the inflammation in PV patients.

No abstract