International journal of molecular medicine
-
This study deals with the effects of daily intermittent fasting for 15 h upon the development of diabetes in sand rats exposed to a hypercaloric diet. The same pattern of daily intermittent fasting was imposed on sand rats maintained on a purely vegetal diet (control animals). Over the last 30 days of the present experiments, non-fasting animals gained weight, whilst intermittently fasting sand rats lost weight. ⋯ Before the switch in food intake, the peak glycemia at the 30th min of an intraperitoneal glucose tolerance test was already higher in the diabetic than non-diabetic rats. In both the non-diabetic and diabetic sand rats, intermittent fasting prevented the progressive deterioration of glucose tolerance otherwise observed in non-fasting animals. These findings reveal that, at least in sand rats, intermittent daily fasting prevents the progressive deterioration of glucose tolerance otherwise taking place when these animals are exposed to a hypercaloric diet.
-
Civilian and military trauma patients consist of a disproportional number of young people, causing a considerable burden to society in terms of disability and premature death. Hemorrhage is a leading cause of mortality in this group of patients and the novel methods to reduce bleeding would be welcomed. Management of bleeding following major trauma includes hemostatic agents that offer effective clotting. ⋯ A recombinant PAI-1 with very long half-life developed in our laboratory (a two-point mutant, VLHL PAI-1, half-life over 700 h) has clinical potential as an agent to promote hemostasis in several scenarios including surgical injury, trauma, and PAI-1 deficiency. Here we report testing of VLHL PAI-1 as a potent inactivator of fibrinolysis reducing total blood loss while applied systemically or topically in experimental animals. The very long half-life of VLHL PAI-1 may provide an advantage in the important physiological mechanism to protect clots from premature dissolution, when applied topically or systemically to prevent excessive bleeding in the surgical and trauma setting and possibly in PAI-1 deficient patients.
-
Gene therapy and virotherapy are among the approaches currently used to treat malignant tumors. Gene therapy and virotherapy use a specific therapeutic gene that causes death in cancer cells. In early attempts at gene therapy, therapeutic genes were driven by ubiquitous promoters such as the CMV promoter, which induce non-specific toxicity to normal cells and tissues in addition to the cancer cells. ⋯ In this review, we describe cancer and/or tissue-specific gene therapy systems for the treatment of cancer. In particular, we will discuss three systems for gene therapy and virotherapy: i) tissue-specific promoter systems, ii) cancer-specific promoter systems, and iii) oncolytic virotherapy. We will also discuss the major challenges of cancer-targeting vector systems and future directions in this area.
-
Hepatocellular dysfunction occurs early in sepsis and this appears to be caused by Kupffer cell-derived TNF-alpha production from the liver as a result of the increased release of the sympathetic neurotransmitter, norepinephrine, from the gut. Ghrelin, a novel stomach-derived peptide, is down-regulated in sepsis and administration of ghrelin into rodents decrease pro-inflammatory cytokines, attenuates hepatic and other organ injuries and improves survival. Ghrelin's beneficial effect in sepsis is mediated by the inhibition of the sympathetic nervous system (SNS), as evidenced by the reduced gut-derived norepineprine (NE) release in sepsis after ghrelin treatment. ⋯ To further confirm the effect of NE on MKP-1, normal rats were infused with NE for 2 h through the portal vein and MKP-1 mRNA from the liver was examined. Infusion with NE produced a significant 73.7% decrease in MKP-1 mRNA. Therefore, ghrelin's inhibitory effect on gut-derived NE release in sepsis leading to the downregulation of pro-inflammatory cytokines is mediated by MKP-1.
-
Neuropeptides B (NPB) and W (NPW) have been identified as endogenous ligands of two G-protein-coupled receptors, neuropeptides B/W receptor 1 (NPBWR1, formerly known as GPR7) and neuropeptides B/W receptor 2 (NPBWR2, formerly known as GPR8). In rodents where NPBWR2 is absent, its counterpart is named the similar to neuropeptides B/W receptor 2 (similar to NPBWR2, formerly GPR8-like). Both NPB and NPW play a role in the control of feeding, neuroendocrine axis functions, memory and learning processes as well as in pain regulation. ⋯ Neither NPB nor NPW changed osteocalcin secretion by cultured osteoblast-like cells while both neuropeptides inhibited their proliferative activity. Results of the present study suggest that the systems of NPW, NPB and NPBWR1 directly regulate proliferative activity of cultured rat calvaria osteoblast-like cells. The physiological significance of this osteoblastic system remains unclear, and requires further investigation.