Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord.

Patients with tumors that metastasize to bone frequently suffer from debilitating pain, and effective therapies for treating bone cancer are lacking. This study employed a novel strategy in which herpes simplex virus (HSV) carrying a small interfering RNA (siRNA) targeting platelet-derived growth factor (PDGF) was used to alleviate bone cancer pain. HSV carrying PDGF siRNA was established and intrathecally injected into the cavum subarachnoidale of animals suffering from bone cancer pain and animals in the negative group. Sensory function was assessed by measuring thermal and mechanical hyperalgesia. The mechanism by which PDGF regulates pain was also investigated by comparing the differential expression of pPDGFRα/ß and phosphorylated ERK and AKT. Thermal and mechanical hyperalgesia developed in the rats with bone cancer pain, and these effects were accompanied by bone destruction in the tibia. Intrathecal injection of PDGF siRNA and morphine reversed thermal and mechanical hyperalgesia in rats with bone cancer pain. In addition, we observed attenuated astrocyte hypertrophy, down-regulated pPDGFRα/ß levels, reduced levels of the neurochemical SP, a reduction in CGRP fibers and changes in pERK/ERK and pAKT/AKT ratios. These results demonstrate that PDGF siRNA can effectively treat pain induced by bone cancer by blocking the AKT-ERK signaling pathway.

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) improves brain ischemia-induced pulmonary injury in rats associated to TNF-α expression.

BACKGROUND: Bone marrow mesenchymal stem cell (BMSCs)-based therapy seems to be a promising treatment for acute lung injury, but the therapeutic effects of BMSCs transplantation on acute lung injury induced by brain ischemia and the mechanisms have not been totally elucidated. This study explores the effects of transplantation of BMSCs on acute lung injury induced by focal cerebral ischemia and investigates the underlying mechanism. METHODS: Acute lung injury model was induced by middle cerebral artery occlusion (MCAO). BMSCs (with concentration of 1 × 10(6)/ml) were transplanted into host through tail vein 1 day after MCAO. Then, the survival, proliferation and migration of BMSCs in lung were observed at 4 days after transplantation, and histology observation and lung function were assessed for 7 days. Meanwhile, in situ hybridization (ISH), qRT-PCR and western blotting were employed to detect the expression of TNF-α in lung. RESULTS: Neurobehavioral deficits and acute lung injury could be seen in brain ischemia rats. Implanted BMSCs could survive in the lung, and relieve pulmonary edema, improve lung function, as well as down regulate TNF-α expression. CONCLUSIONS: The grafted BMSCs can survive and migrate widespread in lung and ameliorate lung injury induced by focal cerebral ischemia in the MCAO rat models. The underlying molecular mechanism, at least partially, is related to the suppression of TNF-α.

[Fluid management in orthotopic liver transplantation].

OBJECTIVE: To investigate the influential factors of fluid management during orthotopic liver transplantation surgery. METHODS: Ninety-six patients scheduled for orthotopic liver transplantation were divided into two groups according to the liver function: the decompensatory group (Child-Pugh score C, n=50) and the compensatory group (Child-Pugh score A or B, n=46). According to the intraoperative bleeding amount, the compensatory group was further divided into subgroup A (< 2,000 ml) and subgroup B (> or = 2,000 ml). Plasma albumin concentration and the parameters of blood coagulation were measured before and after the surgery. The intraoperative bleeding amount and the amount of the blood products infused were recorded. RESULTS: Before the surgery, prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly longer in decompensatory group than in compensatory group (both P<0.05); blood platelets (PLT) and fibrinogen were significantly lower in decompensatory group than in compensatory group (both P<0.05). After the surgery, there were no significant differences in PT, APTT, PLT, and fibrinogen between the two groups (all P>0.05). The amounts of the blood products infused intraoperatively in subgroup A were significantly lower than those in the decompensatory group (all P<0.05). There was no significant difference in the amount of the infused blood products between the subgroup B and decompensatory group (all P>0.05). CONCLUSION: During orthotopic liver transplantation surgery, patients with decompensatory liver function, or those who suffered large amounts of intraoperative bleeding, need infusion of larger amount of blood products.