Recent Advancements in Apoptosis-Based Therapeutic Approaches for Cancer Targeting

Apoptosis, known as programmed cell death, has been considered a potent target for the pharmacy industry. The scientific community has actively participated to research which evaluate active molecules for possible inhibition or induction of apoptosis. Nanocarriers especially for cancer targeting are widely found through literature; they mainly based on inorganic, lipid or polymer nanoparticles which incorporate anticancer drugs. Another important and innovative category of anticancer agents is that of microRNAs. In this chapter, a discussion about the most recent applications of apoptosis-based agents mainly focusing on cancer target is done

Procyanidins are potent inhibitors of LOX-1: a new player in the French Paradox

Lectin-like oxidized LDL receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL (oxLDL) and plays multiple roles in the development of cardiovascular diseases. We screened more than 400 foodstuff extracts for identifying materials that inhibit oxLDL binding to LOX-1. Results showed that 52 extracts inhibited LOX-1 by more than 70% in cell-free assays. Subsequent cell-based assays revealed that a variety of foodstuffs known to be rich in procyanidins such as grape seed extracts and apple polyphenols, potently inhibited oxLDL uptake in Chinese hamster ovary (CHO) cells expressing LOX-1. Indeed, purified procyanidins significantly inhibited oxLDL binding to LOX-1 while other ingredients of apple polyphenols did not. Moreover, chronic administration of oligomeric procyanidins suppressed lipid accumulation in vascular wall in hypertensive rats fed with high fat diet. These results suggest that procyanidins are LOX-1 inhibitors and LOX-1 inhibition might be a possible underlying mechanism of the well-known vascular protective effects of red wine, the French Paradox

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

BACKGROUND: Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. DISCUSSION: A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. SUMMARY: A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons

Modelling of Effect of Inflow Turbulence on Large Eddy Simulation of Bluff Body Flows

A random flow generation (RFG) algorithm for a previously established large eddy simulation (LES) code is successfully incorporated into a finite element fluid flow solver to generate the required inflow/initial turbulence boundary conditions for the LES computations of viscous incompressible turbulent flow over a nominally twodimensional circular cylinder at Reynolds number of 140,000. The effect of generated turbulent inflow boundary conditions on the near wake flow and the shear layer and on the prediction of integral flow parameters is studied based on long time average results. No-slip velocity boundary function is used but wall effects are taken into consideration with a near wall modelling methodology based on van Driest Damping approach. The numerical results obtained from simulations are compared with each other and with the experimental data for different turbulent inflow boundary conditions to assess the functionality of the RFG algorithm for the present LES code and hence its influence on the vortex shedding mechanism and the resulting flow field predictions

CT features of small bowel obstruction sur to mesodiverticular band

Meckel’s diverticulum is the most common congenital anomaly of the small intestine. Common complications related to a Meckel’s diverticulum include hemorrhage, intestinal obstruction, and inflammation. Small bowel obstruction due to mesodiverticular band of Meckel’s diverticulum is a rare complication. Herein, we report a case of small bowel obstruction occurring due to mesodiverticular band of a Meckel’s diverticulum. The important aspect of our case is clear demonstration of the mesodiverticular band adjacent to the Meckel’s diverticulum on pre-operative computed tomography (CT)