Bioscience hypotheses最新文献

Rosiglitazone is widely used to improve diabetes mellitus, but its adverse cardiovascular effect is recently recognized. The exact mechanism is still unknown. In this paper, we predict that rosiglitazone probably regulates the insulin gene expression, which cause complications in the long term use.

Traditional methods such as chemotherapy and radiation therapy offer only limited success in treating cancer. Part of the reason is related to our misunderstanding of what cancer is: it is not the cause but the consequence of a weakened living system. Localized cellular stress, caused by toxins, mutagens or radiation, coupled with a weakened systemic response or inability to support or defend the cells that are under attack, cause these cells to revert to an ancient, unicellular mode of survival, therefore cutting links with the overarching organism and defend themselves from the threat as if they were individual entities. We hypothesize that strengthening the organism, specifically the immune system, is a more promising approach toward a cure for cancer than attempting to exterminate cancer cells. The hypothesis can be tested by experiments that are designed to strengthen the immune system by both traditional means (e.g., ingestion of natural substances known to increase the activity of the immune system, such as fruits, vegetables, and nuts), diminish immune system inhibitors released by cancer cells (e.g., TGF-β), and by the injection of heat-killed or genetically altered pathogenic bacteria to trigger a massive response (fever response) of the immune system into the affected area and compare those results to traditionally used methods.

Calcification of the pulmonary artery has been found in a large number of racing horses. The majority of calcified lesions are found immediately distal to the primary arterial bifurcation. Increased arterial wall stress levels have been previously demonstrated at these locations, with the wall stress levels increasing under intra-luminal pressures associated with exercise. We hypothesize therefore that the formation of calcified lesions is mediated by transient and repeated increases in pulmonary artery intra-luminal pressure. The presence of calcified lesions would likely further exacerbate the levels of wall stress, leading to growth of the lesions. A level of wall stress may exist above which calcified lesions form, and a second level may exist above which the calcified lesions grow at an increased rate. A computer model of pulmonary artery wall stress with calcified lesions was created, and wall stress levels were found to be greatest at the periphery of the calcified lesions. Osteo/chondrocyte-like cells have also been found at the periphery of the calcified lesions and could be responsible for collagen deposition and lesion growth, mediated by local wall stress levels. These increased levels of wall stress could place racehorses at a greater risk of acute pulmonary arterial rupture at the site of the calcified lesions, due to the high levels of intra-luminal pressure within the pulmonary artery during exercise. The hypothesis may also have implications in the etiology of human vascular diseases.

To investigate the reactive oxygen species (ROS) distribution in living animal tissues, two ROS indicators, dichlorofluorescin diacetate (DCFH-DA) and MitoSOX™ Red were applied to visualize ROS on the frontal interior abdominal wall of living SD-rats by tail vein injection and local smearing respectively. Revealed was an unexpected ROS distribution pattern. ROS were demonstrated in a few vertical fluorescent lines, which related to neither veins nor nerves but could be almost perfectly superimposable on a standard human acupuncture meridian network. The phenomenon that cells with high ROS content should be aligned in a regular manner is interesting as well as its resemblance to meridian system.

Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory manifestation that occurs subsequent to initiation of highly active antiretroviral therapy in terminal (HAART) HIV infection, mainly due to the restoration of robust immune responses directed against latent microbial antigens. IRIS is believed to be multifactorial and less studied. Herein, we postulate that hypothalamo–pituitary–adrenal (HPA) dysregulation, a well-documented manifestation in HIV/AIDS, could possibly disturb the balance between pro-inflammatory and anti-inflammatory cytokines leading to clinical IRIS. Drugs, opportunistic infections, stress and numerous intrinsic and extrinsic factors have been described to be the possible causes of IRIS in HIV illness.

We examine the properties of intracellular transport of particles (vesicles, organelles, virus, etc.) in the realm of models that describe the dynamics of interacting molecular motors moving along microtubules. We use a continuum description of motor distribution and argue that certain features of cargo movement have their origins on its ability to perturb the existing motor profile and to surf at the resulting shock wave fronts that separate regions of different motor concentrations. In this case, the observed bidirectionality of cargo movement is naturally associated with reversals of shock direction. Comparison of the quantitative results predicted by this model with available data suggests that the geometrical characteristics of cargo may be related to the extension and intensity of the perturbation they produce and thus, to their kinetics. Possible implications of these ideas to understand features of the movement of virus particles within the cell body are discussed in connection with their distinguished morphological characteristics.

Colon cancer is one of the leading causes of cancer-related death worldwide. Genetic changes leading to aberrant activation of APC/β-catenin/TCF (canonical Wnt) pathway are considered as the initiating step in colon cancer. Abundant studies revealed that colon cancer is “Wnt addiction” and reduced the Wnt signal is of therapeutic value. Deregulation of the Rb/E2F1 pathway, as a result of alterations in members of the pathway, is a hallmark of many human cancers, but mutations in this pathway are rare in colon cancers. In contrast, suppression of E2F1 activity through mutation of the CDK8 pathway is common in colon cancer. Active E2F1 is found to repress the activity of β-catenin transcription and promote cell apoptosis. The mutually exclusive expression pattern and function between E2F1 and Wnt pathway suggest an antagonistic relationship between these two pathways in colon cancer evolution. We hypothesize that E2F1 functions as a barrier of aberrant Wnt signal, and that E2F1 repression is necessary for colon cancer development. This hypothesis suggests that reactivation of E2F1 might have therapeutic potential for most of the colon cancers, as most of the colon cancers have aberrantly activated Wnt signal.

Smoking is one of the main risk factors for cardiovascular disease. The smokers exhibit different degrees of insulin resistance. The pathway of acylation-stimulating protein (ASP) and its specific receptor, C5a-like receptor 2 (C5L2), involves in the effective clearance of plasma glucose and triglyceride. ASP and insulin play similar but distinct roles in adipose metabolism. High level of ASP is indicative of ASP resistance and insulin resistance. Low level of ASP indicates increased insulin sensitivity. We proposed that the abnormality of ASP–C5L2 pathway contributes to insulin resistance in smokers.