Current Pharmaceutical Design - Volume 19, Issue 15, 2013

Heme Oxygenase (HO) –1 and –2 exert antioxidant, cytoprotective and vascular actions in male diabetic rats. However, there is no information about the expression and functional significance of the renal HO system in diabetic females. The present study tested the hypothesis that the HO system is differentially regulated in the kidney of female Sprague Dawley diabetic rats, protecting it from nitrosative and glomerular fun Read More

Periodontal diseases are common inflammatory conditions of the supporting apparatus of the teeth which lead to early tooth loss. This review discusses the evidence for a role of reactive oxygen species in inducing periodontal tissue damage and focuses on recent evidence showing increased local and systemic alterations in the redox balance of periodontitis. An appraisal of the methods for analysis of oxidative stres Read More

Heme is the functional group of diverse hemoproteins and crucial for many cellular processes. However, heme is increasingly recognized as a culprit for a wide variety of pathologies, including sepsis, malaria, and kidney failure. Excess of free heme can be detrimental to tissues by mediating oxidative and inflammatory injury. Protective mechanisms against free heme are therefore pivotal for cellular survival. We po Read More

Reactive oxygen species (ROS) are regarded as hazardous by-products of mitochondrial respiration. In addition to the respiratory chain, specific ROS-generating systems have evolved. In particular, p66Shc is a mitochondrial redox protein that oxidizes cytochrome c to generate H2O2. Consistently, the deletion of p66Shc in cells and tissue results in reduced levels of ROS and oxidative stress. Taking advantage of the p66 Read More

Oxygen therapy is a life-sustaining treatment for patients with respiratory failure. However, prolonged exposure to high oxygen concentrations often results in hyperoxia-induced acute lung injury (HALI). At present, no effective therapeutic intervention can attenuate the development of HALI. In the present study, we investigated whether hydrogen sulfide (H2S) can confer lung protection in a mouse model of HALI. C57BL Read More

The benefits of multi-target action are well established in a variety of pathological models. Many dietary supplements and nutraceuticals may be useful to slow age-related cognitive declines and the risk of developing neurodegenerative disease. L-Carnosine and EGCG are natural compounds that have received particular attention because of their potential role in modulating oxidative stress associated with aging and chronic c Read More

Background: Recently, increasing attention has been given to neuroendocrine differentiation (NED) of Prostate Cancer and its diagnostic, prognostic and therapeutic potential. During multistep carcinogenesis, cytodifferentiation of malignant/premalignant cells into more mature or normal-like cells, has become an attractive modality of treatment and promises to be a less toxic and a more specific targeting strategy than conve Read More

Non-alcoholic fatty liver disease (NAFLD), an accumulation of intra-hepatic triglycerides that is often considered the hepatic manifestation of insulin resistance, is the most common cause of chronic liver disease in the Western countries with up to one third of the population affected. NAFLD is a spectrum of disturbances that encompasses various degrees of liver damage ranging from simple steatosis to non-alcoholic steatohepa Read More

Oxidative stress caused by supraphysiological production of reactive oxygen species (ROS), can cause cellular injury associated with protein and lipid oxidation, DNA damage, and mitochondrial dysfunction. The cellular responses triggered by oxidative stress include the altered regulation of signaling pathways that culminate in the regulation of cell survival or cell death pathways. Recent studies suggest that autophagy, a cell Read More

Heat shock protein 60kDa (Hsp60) is a chaperone classically believed to be involved in assisting the correct folding of other mitochondrial proteins. Hsp60 also plays a role in cytoprotection against cell stressors, displaying for example, antiapoptotic potential. Despite the plethora of studies devoted to the mechanism of Hsp60's function, especially in prokaryotes, fundamental issues still remain unexplored, including the defin Read More

Identification of imatinib mesylate as a potent inhibitor of the Abl kinase and the subsequent findings that this compound displays growth inhibitory and pro-apoptotic effects in Bcr-Abl+ cells, has deeply conditioned CML treatment. Unfortunately the initial striking efficacy of this drug has been overshadowed by the development of clinical resistance. A wide variety of molecular mechanisms can underlie such resistance mechani Read More

Carbon Monoxide (CO), long thought to be a simple environmental pollutant is now known to have a critical role in cellular functions ranging from vasodilation to circadian rhythms. In this review, we will begin with a discussion of the enzyme responsible for CO production: heme oxygenase. Because this review will focus on the effects of CO in the brain, we will transition to CO toxicology and determine if this simple diatomic Read More

Renal ischemia is the most common cause of acute kidney injury (AKI) still associated with high mortality rates of about 50% in the intensive care unit. Postischemic AKI is characterized by decreased glomerular filtration rate and high renal vascular resistance with endothelial activation and dysfunction, a process of critical importance that is followed by a reduction in microvascular blood flow mainly affecting the renal outer Read More

Novel penetrating cations were used for the design of mitochondria-targeted compounds and tested in model lipid membranes, in isolated mitochondria and in living human cells in culture. Rhodamine-19, berberine and palmatine were conjugated by aliphatic linkers with plastoquinone possessing antioxidant activity. These conjugates (SkQR1,SkQBerb, SkQPalm) and their analogs lacking plastoquinol moiety (C12R1,C10B Read More

Many disturbances in the normal function of endoplasmic reticulum (ER) cause accumulation of unfolded proteins in the lumen of ER, triggering an evolutionary conserved response, termed the unfolded protein response (UPR). The UPR is the mechanism enabling cells to cope with unfolded proteins, accumulated in ER lumen after the cell has been exposed to various unfavorable conditions. The UPR process has strong prosu Read More

Radiotherapy is one of the treatment options for locally or regionally advanced prostate cancer, but radioresistance of prostate cancer cells is a practical limitation of radiotherapy. The identification of molecular targets of radioresistance in prostate cancer is important to improve therapeutic intervention. The aim of this review is to give more biological insight into some well known processes involved in radioresistance of prost Read More

Diaryl ether family as one of the promising second generation HIV-1 non-nucleoside reverse transcriptase inhibitors has attracted considerable attention over the past few years, among which clinical candidate MK-4965 has been advanced into phase II clinical trials. The successful development of diaryl ether family provides valuable avenues in traditional medicinal chemistry, crystallography and computer-aided dr Read More

The antibody display technology (ADT) such as phage display (PD) has substantially improved the production of monoclonal antibodies (mAbs) and Ab fragments through bypassing several limitations associated with the traditional approach of hybridoma technology. In the current study, we capitalized on the PD technology to produce high affinity single chain variable fragment (scFv) against tumor necrosis factor-alpha (TNF- Read More