RESUMEN

Pulmonary arterial hypertension (PAH) is a decimating ailment described by chronic precapillary pulmonary hypertension, an elevated mean pulmonary arterial pressure with a normal pulmonary capillary wedge pressure, and a raised pulmonary vascular resistance resulting in increased right ventricular afterload culminating in heart failure and death. Current PAH treatments regulate the vasodilatory/vasoconstrictory balance of pulmonary vessels. However, these treatment options are unable to stop the progression of, or reverse, an already established disease. Recent studies have advanced a metabolic dysregulation, featuring increased glutamine metabolism, as a mechanism driving PAH progression. Metabolic dysregulation in PAH leads to increased glutaminolysis to produce substrate to meet the high-energy requirement by hyperproliferative and apoptosis-resistant pulmonary vascular cells. This article explores the role of glutamate metabolism in PAH and how it could be targeted as an anti-remodeling therapeutic strategy.

RESUMEN

Micelle is a stable, passively targetable and solubilizing minute particle, and plays a key role to anticancer drug delivery for chemotherapy. With an increasing number of novel polymeric micelles synthesized, many anticancer drugs have been core-encapsulated in the micelles. However, only single drug was studied as the model drug at present researches. It is well known that combined medication is a very important and common method for chemotherapy in the clinic. Therefore, we hypotheses that multi-anticancer drugs encapsulated in the micelle may be proposed based on the cancer cell cycle. Briefly, cell cycle specific agents are chemically conjuncted into the micelles firstly, and then cell cycle non-specific agents are physically loaded in the compound of drugs and micelles. Thus combined administration using micelles as drug carriers is achieved. This hypothesis integrates advantages of the nano-micelles at present researches and drug combination in the clinic. So, it presents many merits for drug delivery, such as high efficiency, convenience and anti-resistance.

Asunto(s)

RESUMEN

Objective To observe the effects of electrical stimulation of paraventricular nucleus(PVN) on gastric mucosal cellular apoptosis,proliferation,and expression of BCL-2,BAX induced by gastric ischemia-reperfusion(GI-R) and the potential mechanisms of protection of PVN on GI-R injury.Methods After electrical stimulation of PVN,the experimental model of GI-R were established by clamping the celiac artery for 30 min and then reperfusing the artery for 30 min,1 h,3 h,or 6 h respectively.We used immunohistochemistry to detect the gastric mucosal cells apoptosis,proliferation and the expression of BCL-2,BAX.Results Compared with GI-R group,the electrical stimulation of PVN markedly decreased gastric mucosal cellular apoptosis,increased the proliferation,and promoted the protein expression of BCL-2,but markedly inhibited the protein expression of BAX at 30 min,1 h,3 h after reperfusion respectively.Conclusion The protective effect of PVN on GI-R injury is associated with up-regulation of expression of BCL-2 and down-regulation expression of BAX,and so inhibited gastric mucosal cellular apoptosis and promoted proliferation.