Inhibition of miR-17-5p promotes mesenchymal stem cells to repair spinal cord injury.

OBJECTIVE: The aim of this study was to explore the role of microRNA-17-5p (miR-17-5p) in the pathogenesis of spinal cord injury repair by mesenchymal stem cells (MSCs), and to investigate the possible underlying mechanism. MATERIALS AND METHODS: MiR-17-5p mimics and negative controls were transfected into MSCs. Dual-luciferase reporter gene assay was used to verify the functional binding between miR-17-5p and its target mRNA. After overexpression or knockdown of miR-17-5p, the expression level of target genes in MSC cells was analyzed by Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot. The proliferation ability of cells was detected by cell counting kit-8 (CCK-8) assay. The effect of miR-17-5p and VEGF-A on angiogenesis was assessed by HUVEC assay. T8 spinal cord injury model was constructed in nude mice. All mice were divided into the negative control group, the SCI group, the miR-17-5p-NC group, the miR-17-5p-inhibitor group, and the miR-17-5p-inhibitor + sh-VEGF-A group. After injection of different treated MSCs at the lesion site, the proportion of intact tissue as well as reduced lumen volume was measured at 28 d. Meanwhile, the motor function of hind limbs was scored based on the Basso Beattie Bresnahan (BBB) standard scale at 7 d, 14 d, 21 d, and 28 d after transplantation, respectively. RESULTS: A binding site of miR-17-5p was found on the mRNA of VEGF-A. The protein expression of VEGF-A was strikingly altered after overexpression or knockdown of miR-17-5p. Knocking down miR-17-5p expression significantly increased the protein level of VEGF-A and GDNF. Meanwhile, miR-17-5p down-regulation significantly enhanced the viability and the angiogenic ability of MSCs. However, simultaneous knockdown of miR-17-5p and VEGF-A showed the opposite results. After spinal cord injury, the proportion of intact spinal cord tissues in mice was significantly reduced, whereas reduced lumen volume was remarkably increased. After injection of MSCs alone, the proportion of intact tissues was significantly increased. After knocking down miR-17-5p, the proportion was further increased. However, no significant effect was found on the amount of intact tissues after knocking out VEGF-A. Moreover, the reduction in cavity volume appeared to present an opposite trend comparable to the proportion of intact tissues. The BBB scores were significantly decreased in the mice model, while remarkably increased after MSC transplantation. Furthermore, the BBB score was the highest in the miR-17-5p knockout group, while VEGF-A knockout had little effect on it. In addition, no significant difference was found in the mRNA expression GFP in the spinal cord of mice in different groups after MSCs treatment. CONCLUSIONS: Inhibition of miR-17-5p up-regulates the expression of VEGF-A and GDNF in MSCs, and promotes the repair of spinal cord injury by MSCs.

Lixisenatide rescues spatial memory and synaptic plasticity from amyloid ß protein-induced impairments in rats.

Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by cognitive impairment, but effective strategies against AD are currently not available. Interestingly, glucagon-like peptide-1 (GLP-1) used in type 2 diabetes mellitus (T2DM) has shown neuroprotective effects in preclinical studies of AD. Lixisenatide, an effective GLP-1 receptor (GLP-1R) agonist with much longer half life than GLP-1, has been licensed in the EU as a treatment for T2DM. However, the neuroprotective effects of lixisenatide in the brain remain to be clarified. In the present study, we report for the first time the effects of lixisenatide on the amyloid ß (Aß) protein-induced impairments in spatial learning and memory of rats, and investigated its electrophysiological and molecular mechanisms. We found that: (1) bilateral intrahippocampal injection of Aß25-35 resulted in a significant decline in spatial learning and memory of rats, as well as a suppression of in vivo hippocampal long-term potentiation (LTP); (2) lixisenatide treatment effectively prevented the Aß25-35-induced impairments; (3) lixisenatide inhibited the Aß25-35 injection-induced activation of glycogen synthase kinase 3ß (GSK3ß), with a significant increase in the phosphorylation of ser9 and a significant decrease in the phosphorylation of Y216. These results indicate that lixisenatide, by affecting the PI3K-Akt-GSK3ß pathway, can prevent Aß-related impairments in synaptic plasticity and spatial memory of rats, suggesting that lixisenatide may be a novel and effective treatment for AD.

Fine needle aspiration biopsy diagnosis of cysticercosis. A case report.

A case of cysticercosis was initially diagnosed by fine needle aspiration biopsy (FNAB). A tender, hard mass in a muscle was clinically suspected of being a benign tumor. An FNAB smear showed many eosinophils and a part of cestode. After 10 minutes the patient felt a short-lived local hot sensation and pain. The diagnosis was confirmed on a histologic section of an incisional biopsy specimen from another site.

Protective effect of puerarin against myocardial reperfusion injury. Myocardial metabolism and ultrastructure.

To ascertain the beneficial effect of puerarin on the myocardium against reperfusion injury, studies on myocardial metabolism and ultrastructure were made. Twelve dogs divided into two equal groups were placed on moderate hypothermic cardiopulmonary bypass, and their hearts were subjected to 140 minutes cold cardioplegic arrest and 60 minute reperfusion. In the control group, the hearts were perfused with crystalloid cardioplegic solution (CPS) every 20 minutes during arrest. In the treated group, the hearts received CPS containing puerarin (2 mg/kg). Myocardial oxygen consumption, lactate production, creatine phosphokinase (CPK) release, water content and ultrastructural alterations were determined before ischemia, during cardiac arrest and at reperfusion. The results showed that intermittent infusion of CPS containing puerarin significantly decreased myocardial lactate production during ischemia, as well as myocardial oxygen consumption, CPK release and water content during reperfusion. Under electronmicroscopy, the degree of ischemic damage judged by a scoring method was less pronounced in the puerarin group than in the control. The authors conclude that puerarin has protective effects on the function of hearts that have undergone long periods of arrest and reperfusion.

The protective effect of puerarin against myocardial reperfusion injury. Study on cardiac function.

In order to find out if puerarin could protect the hearts from myocardial reperfusion injury after cardiac arrest, twelve dogs divided into two equal groups were placed on moderately hypothermic cardiopulmonary bypass and their hearts were subjected to 140 min of cold cardioplegic arrest and 60 min of reperfusion. In the control group, the hearts were perfused with a crystalloid cardioplegic solution (CPS) through the aortic root every 20 min during arrest. In the treated group, the hearts received CPS containing puerarin (2 mg/kg). Cardiac hemodynamic variables were monitored throughout the experiments. Left ventricular function curves were formed before ischemia and after 60 min of reperfusion. The results showed that the recovery of left ventricular function in the treated group was significantly better than that in the controls (81 +/- 11% versus 39 +/- 7%, P less than 0.01). Compared with preischemic values, the increase of coronary blood flow (CBF) at cardiac arrest in the puerarin-treated group was higher than that in the control group (214 +/- 11 versus 177 +/- 4 ml/min, P less than 0.01). The data indicate that puerarin has protective effects on the cardiac function after prolonged arrest and reperfusion.

Epidemic non-A, non-B hepatitis in Xinjiang. Clinical and pathologic observations.

131 cases of epidemic hepatitis from two villages in Xinjiang, were admitted to the provisional infectious diseases hospital from February to April 1987. In 125 (95%) patients neither anti-HAV IgM nor anti-HBc IgM were positive. 118 (90%) were drinking water from a local stream of the Hotan River. The study was conducted on 125 patients aged from 5 to 90 years, with a mean of 26.4 years. There were slightly more males than females, a ratio of 1.5 to 1. The incubation period was roughly estimated to be 17 to 37 days (mean 24.8 days). All subjects were jaundiced. 12 patients (including 6 pregnant women) had cholestatic symptoms. Except one woman who died of postpartum bleeding, all patients ran a benign course without fulminant hepatic failure. Pathologic changes of liver biopsies from 35 cases included lobular damage and inflammation, ballooned hepatocytes with clear cytoplasm and delineated cell membrane which were named "clear cell". There were cholestasis of different degrees in the acute icteric stage and fatty changes in the convalescent stage. It was seen under the electron microscope that the livers of 8 cases had neither tubular structure nor sponge-like inclusions, but had nuclear changes including curled edge of nuclear membrane and nuclear heterochromatin condensed in masses. Liver biopsies were repeated in 7 cases followed up for 6-13 months, and hepatohistology was normal in 5. Of the other two cases there was one of each.

Cytologic diagnosis by transthoracic fine needle sampling without aspiration.

The cytologic findings of transthoracic fine needle sampling without aspiration (fine needle capillary [FNC] sampling) are reported. Eleven patients were examined by FNC sampling while four were examined by the classic fine needle aspiration (FNA) method. In contrast to FNA sampling, FNC sampling produced less patient trauma and admixture of the sample with blood, while giving a better perception of the tumor and its consistency. The quality of the samples obtained by the FNC technique was equal to that of the FNA samples. The results demonstrate that fine needle sampling without aspiration may be used in the study of deep-seated as well as of superficial organs.

Preoperative diagnosis and management of pheochromocytoma.

To improve the diagnosis and management of pheochromocytoma, the results from a comparative study of 34 patients with pheochromocytoma, 33 patients with essential hypertension and 36 normal volunteers are presented. Our data suggest that clinical characteristics indicate the possibility of pheochromocytoma only, while the definite diagnosis of pheochromocytoma must be based on comprehensive analysis of all data obtained from both clinical and laboratory studies. The plasma concentration of free norepinephrine in peripheral veins is helpful in establishing the presence or absence of pheochromocytoma. Both CT scan and meta-I-131-iodobenzylguanidine images are useful noninvasive techniques for localization of pheochromocytoma. Phenoxybenzamine is of benefit in both diagnosis and management of patients with pheochromocytoma.

Giant retroperitoneal pleomorphic lipoma.

A 65-year-old man developed a progressively enlarging abdominal mass that ultimately resulted in a weight gain of 25 kg., leg edema and an inability to walk. His condition was initially considered to be inoperable but exploration resulted in the removal of a 19.5 kg., 50 cm. intraabdominal pleomorphic lipoma. The patient remains well 4 years post-operatively.

[Verrucous carcinoma (carcinoma cuniculatum)--clinicopathologic study on 10 cases].

10 cases of verrucous carcinoma occurring in different sites were studied clinicopathologically. Clinically, the tumor grew slowly and presented as an ulcerous or cauliflower-like mass. The tumor, existing in the skin, had openings like the sinus tracts on the surface from which foul, grey and greasy material oozed out when pressured. There was no exudation if the lesion grew in the mucosa. Histologically, the tumor was composed of mature and well-differentiated squamous cells showing papilloma-like growth upwards, their epidermal rete showing spheroid expansions downwards. Prickle cell masses invaded into the soft tissue in the deeper layer. In view of the tumors having location either in the skin or mucosa with or without effusion, similar histologic features and biologic behavior, we suggest that the verrucous carcinoma and carcinoma cuniculatum be two different variants of the disease. Finally, its diagnosis, differential diagnosis and treatment are discussed with a review of the literature.