MicroRNA-127 targeting of mitoNEET inhibits neurite outgrowth, induces cell apoptosis and contributes to physiological dysfunction after spinal cord transection.

Neuroregeneration and apoptosis are two important pathophysiologic changes after spinal cord injury (SCI), but their underlying mechanisms remain unclear. MicroRNAs (miRNAs) play a crucial role in the regulation of neuroregeneration and neuronal apoptosis, research areas that have been greatly expanded in recent years. Here, using miRNA arrays to profile miRNA transcriptomes, we demonstrated that miR-127-3p was significantly down-regulated after spinal cord transection (SCT). Then, bioinformatics analyses and experimental detection showed that miR-127-3p exhibited specific effects on the regulation of neurite outgrowth and the induction of neuronal apoptosis by regulating the expression of the mitochondrial membrane protein mitoNEET. Moreover, knockdown of MitoNEET leaded to neuronal loss and apoptosis in primary cultured spinal neurons. This study therefore revealed that miR-127-3p, which targets mitoNEET, plays a vital role in regulating neurite outgrowth and neuronal apoptosis after SCT. Thus, modificatioin of the mitoNEET expression, such as mitoNEET activition may provide a new strategy for the treatment of SCI in preclinical trials.

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.

Propofol attenuates hepatic ischemia/reperfusion injury in an in vivo rabbit model.

BACKGROUND: Propofol has been demonstrated to improve hepatic perfusion in a rabbit model; however, the effects of propofol on hepatic ischemia/reperfusion injury are unknown. The aim of the present study was to determine whether propofol has a hepatoprotective effect using an in vivo ischemia/reperfusion model in rabbits. METHODS: A total of 48 rabbits were randomly assigned to two groups: a propofol group (0.6 mg · kg(-1) · min(-1)) or a control group (10% intralipid, 0.6 mg · kg(-1) · min(-1)). Each group was then further divided into three subgroups of 8 rabbits according to the duration (10, 30, and 60 min) of propofol infusion before an ischemic episode was induced by cross-clamping the left hepatic artery and hepatic portal vein. Hepatic ischemia was maintained for 30 min, and the rabbits were monitored for 60 min after reperfusion. Liver enzyme leakage and histopathologic examination were used to evaluate the extent of hepatic ischemia/reperfusion injury. RESULTS: The serum enzyme levels were the same in all groups before the ischemic episode. After the induction of ischemia/reperfusion, the liver enzymes were significantly increased in all rabbits compared with baseline values (P < 0.05). Propofol significantly decreased the leakage of liver enzymes and markedly reduced lesions in histologic examination of the liver compared with the control group (P < 0.05). However, no significant difference was found in serum enzyme levels among the three subgroups in the propofol group. CONCLUSIONS: Propofol reduced hepatic ischemia/reperfusion injury in an in vivo rabbit model; however, the duration of propofol infusion before the ischemic insult did not influence its hepatoprotective effects or the extent of hepatic injury.

[Protective effect of fospropofol disodium on in vivo liver ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the protective effect and mechanisms of Fospropofol disodium on in vivo liver ischemia-reperfusion injury in rats. METHODS: Forty SD rats were randomly divided into 5 groups: sham operation group, NS pretreated group (NS), Fospropofol disodium pretreated group (SP), Propofol pretreated group (P) and 10% fat milk pretreated group (Z). After the hepatic inflow was occluded for 30 min and reperfused for 90 min, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were determined, and the liver specimen were obtained for the determination of superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents and for microscopic examinations. RESULTS: The serum levels of ALT, AST and LDH in the rats in group NS, SP, P, and Z after liver ischemia-reperfusion were significantly higher than those with sham operations (P < 0.01). The serum levels of ALT, AST and LDH in the rats in group SP, P, Z were significantly lower than those in group NS (P < 0.01). The MDA contents and SOD activities in the livers of rats in group NS, SP, P and Z were significantly higher than in those with sham operations (P < 0.01). The MDA contents and SOD activities in the livers of rats in group SP, P and Z were significantly lower than those in group NS (P < 0.01). CONCLUSION: Fospropofol Disodium has a protective effect on rat livers against ischemia-reperfusion injury, which is related with antioxidation.

[Effect of etomidate on mitochondrial energy metabolism of rat livers in vitro].

OBJECTIVE: To investigate the change of energy metabolism in isolated rat liver mitochondria by the general anesthetic etomidate. METHODS: Nine healthy male SD rats weighted 230-280 g were used to isolate liver mitochondria. According to randomized block design, the isolated liver mitochondria wered divided into three groups: control group, 0.4 microg/mL etomidate group, and 4 microg/mL etomidate group. Then the samples were incubated at 37 degrees C for 7 min. The fluorescence intensities of lipophilic cation Rhodamine-123 and forward light scatter (FSC) were analyzed by flow cytometry. The size of the adenine nucleotides (AMP, ADP, ATP) in mitochondria was measured by high performance liquid chromatography (HPLC). The energy charge (EC) = (ATP + 0.5ADP)/(ATP + ADP + AMP). The inorganic phosphorus method was used to measure the H(+)-ATPase hydrolytic activity and the oligomycin-sensitive H(+)-ATPase activity. The enzyme activity was express as nmol Pi/(mg pro x min). RESULTS: The fluorescence intensities level of Rhodamine-123 in the 0.4 microg/mL etomidate group was higher than in the control group, but still lower than in the 4 microg/mL etomidate group (P<0.05). The size of FSC had no significant change in the 0.4 microg/mL etomidate group, whereas the 4 microg/mL etomidate group had increased size of FSC (P<0.05). Compared to the control group, no significant changes of content of adenine nucleotides, energy charge and hydrolytic activity of H(+)-ATPase were found in the 0.4 microg/mL etomidate group. However, the intra-mitochondrial ADP, ATP and energy charge levels decreased and the AMP increased in the 0.4 microg/mL etomidate group (P<0.05). The hydrolytic activity of H(+)-ATPase increased in the 4 microg/mL etomidate group (P<0.01), but it was not influenced by oligomycin (P>0.05). CONCLUSIONS: Etomidate at 0.4 microg/mL has no significant effect on isolated rat liver mitochonddia, but at 4 microg/mL it can lead to distruption of mitochondrial energy metabolism.

[Simultaneous pancreas-kidney transplantation (SPK) for an old age male with type 2 diabetes complicated with end-stage renal disease (ESRD): a case report].

We reported the first case of simultaneous pancreas-kidney transplantation (SPK) in our hospital. The recipient is a 65 year old male, who suffered type 2 diabetes for 15 years and renal dysfunction for 5 years and other diabetic complications such as retinopathy, peripheral neuropathy. SPK was performed successfully for him in March, 2007, in which the donor kidney was put in left iliac fossa, while the donor pancreas grafted to set in right iliac fossa of recipient, with pancreas exocrine drainage controlled by anastomosis to the small bowel and endocrine release done to the circulatory system. Serum C-peptide, Creatinine and Blood urea nitrogen became normal levels at day 1, 4 and 11 of post-operation respectively. The concentration of blood glucose was stabilized gradually to normal level and therefore the injected insulin was stopped using to the patient at day 16 of post-operative days. OGTT test showed the function of grafted pancreas was normal 3 weeks after transplant, and no transplantation-related complications occurred. With the recipient followed up for 6 months, both his blood glucose level and renal function maintained normal without using injected insulin, and he was getting to recover from other diabetic complications also.

[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.