Recent Patents on Biomarkers (Discontinued) - Volume 3, Issue 1, 2013

Involvement of extracellular ATP in inflammatory processes originated in the 1970s when Dahlquist and Diamant reported its histamine releasing action from mast cells. Later a specific ATP receptor was found on these cells, identified as the P2X7 receptor (P2X7R). From these early observations the P2X7R has become increasingly considered as an important regulator of inflammation. Since then, its key role in inflammasome-activated maturation as well as in regulation of the release of several cytokines - including IL-1beta, IL-6, IL-18 and TNF-alpha - has been discovered and widely recognized. Therefore, antagonists of the P2X7 receptor are thought to have therapeutic potential as novel antiinflammatory therapies. The function of the P2X7R in inflammation and its potential role in diseases as well as patent background of its antagonists in the last five years will be reviewed and discussed.

Considerable evidence gained in the past decade has supported a better understanding and management of neurodegenerative diseases, in the face of the continuous increase of their prevalence in the world. Inflammation, mitochondrial dysfunction and oxidative stress are now recognized to be hallmarks of all neurological disorders. Along with therapies targeting these features, new therapeutic strategies are emerging, based on microRNA, vaccination, generation and graft of neurons, as well as therapies based on multifaceted drugs. Are also taken into account vectors designed to deliver large molecule pharmaceuticals or genes across the blood-brain barrier. Current treatments are mainly symptomatic, therefore it is hoped that therapies based on patents described in the present review will lead to really curative treatments.

The toxicity of heavy metal varied on the absorption, concentration, and determination of the toxicant at its site of action. The end product of toxicant reacts with the endogenous target molecule like receptors, enzymes, DNA, protein, or lipid and seriously alters the biological micro environment, resulting structural and functional changes due to toxic damage. Heavy metals intoxication leads to increased lipid peroxidation with alterations in antioxidant defenses. Vitamin E (α-tocopherol) is a fat soluble antioxidant that inhibits the production of reactive oxygen species formed when fat undergoes oxidation. Vitamin E is linked to regulate various diseases like cancer, atherosclerosis, hypertension, male infertility etc. This review discussed on significance of vitamin E (α-tocopherol) as a biomarker against metal toxicities including a modified methodology developed by author and his group to evaluate serum vitamin E concentration. Biomarkers can provide direct measures of actual effects of chemicals upon living organisms in the field, there by overcoming large areas of uncertainty implicit in normal risk assessment. It may be suggested that future studies should screen on individual exposed to heavy metal based on their antioxidant status in blood like serum vitamin E (α-tocopherol) level as a marker of oxidative or inflammatory risk. Researchers should confirm whether markers of oxidative risk are lowered, in addition to monitoring direct toxicity outcomes. The review also focuses on recent patent of α-tocopherol as biomarker.

Delayed or improper diagnosis of bacterial infection can result in sepsis, serious, and often deadly or inflammatory response. Thus, there is a need for a simple assay that can detect low levels of bacteria, which are faster and sensitive in order to provide data for establish treatment decisions in a clinically relevant time frame. Advances in materials research and molecular biology play an important role in understand and development the best way for bacterial diagnosis kits and methods to reach specific targets from the cellular metabolism such as particular enzymes. Recent changes in the diagnostic methods are using simple techniques especially focus to distinguish enzymatic reactions, dependent on substrate and biochemical allowing the bacteria presence detection by very fast reactions. This review highlights the state-ofart in patents of enzymatic biomarkers for early detection of bacteria based-on nanostructures chromogenic or fluorogenic.

Aspirin therapy is the cornerstone of therapy and is considered as the “gold standard” antiplatelet agent for primary and secondary prevention of cardiovascular events. Aspirin inhibits the COX-1 enzyme and therefore blocks platelet thromboxane A2 synthesis. Several recent studies have suggested that some patients may not get the full benefits of aspirin therapy. These findings raise the question that some patients may be resistant to aspirin's antiplatelet effects. There is no universally accepted definition of aspirin resistance (AR). The exact mechanisms leading to AR are not very well understood but are likely multi-factorial. Several point-of-care assays of platelet function have been developed in recent years to rapidly screen individuals on aspirin as anti-platelet therapy. The ideal test would be capable of distinguishing individuals at risk of ischemic and bleeding events and could be used to guide dose adjustments in therapy. Utility of currently available tests in identifying aspirin-resistant patients remains to be determined. No data exist to guide aspirin therapy on the basis of platelet function test results. This article includes what AR means, the mechanisms, and clinical relevance of AR including platelet activity, methods to identify aspirin resistance, management of AR and relevant patents.

Hepatocellular Carcinoma remains a major fatal disease that is resistant to most cytotoxic therapeutics owed to the aberrant activation of signalling cascades. Recent patents reveal a new family of drugs that has been studied for molecularly targeting these cascades; multi-kinase inhibitors, are nowadays considered as novel therapeutic approaches. Therefore in this study, we aimed at investigating the impact of Imatinib mesylate, a tyrosine kinase inhibitor, on Human Hepatoma (HuH-7) cellular behavior and specifically its effect on p53 tumor suppressor gene. HuH-7 cells were transfected with a reporter vector containing a specific enhancer element that is activated upon binding to intracellular p53; consequently downstream luciferase reporter gene is activated. Cells were treated with Imatinib and we looked for p53 induction upon drug stimulation. Additionally; viability, metabolism, proliferation and apoptosis were evaluated. Upon Imatinib treatment, p53 expression showed a significant increase represented in increased luminescence. Moreover; a decrease in cellular viability and metabolic activity along with a considerable inhibition of proliferation and a vast increase in Caspase 9 activity were observed when compared to untreated cells. This study suggests that the effects of Imatinib mesylate might be attributable to enhanced active p53 in HuH-7 cells with consequent reduction in cancer progression properties. The article also summarizes some recent relevant patents.

Osteoarthritis (OA) is a multifactorial disease that affects millions of people around the world and it is the most common joint disease. The purpose of this study was to examine the kinetics of the expression of some lysosomal molecules and cellular process involved in the ethiopathogenesis of OA within two experimental models; also we reviewed recent patents on lysosomal proteins and discuss its possible value as early OA biomarkers. Ultrastructural analysis of chondrocytes from the articular cartilage explants, which were induced to oxidative stress with H2O2 showed changes as: cellular shrinkage, nuclear condensation and large amount of vesicles, suggesting a cell death process. To determine the participation of lysosomes in the cell death process, we studied the expression of the lysosomal biomarkers, Cathepsin D and LIMP II using an Immunohistofluorescence procedure. Both proteins were up-regulated in the time course of the stress induction. Furthermore, Cathepsin D and TUNEL labels were found in the same chondrocytes suggesting that lysosomes have an important role in the chondrocytes death. Afterwards, the kinetic expression of Cathepsin D during the kinetics of OA pathogenesis in a rat model showed an up-regulation since 5 to 45 days after induction. Therefore our results strongly suggest a main role of lysosomal pathway in the chondrocytes death since the beginning of the degenerative process. Recent patents on lysosomal proteins have been published in several pathologies, different to cartilage disorders, opening the possibility that lysosomal molecules within the cartilage and the synovial fluid could be also useful as biomarkers for OA beginning and progression.