Search

Background: Heatstroke (HS) is a serious disease caused by central nervous system (CNS) injuries, such as delirium, convulsion, and coma. Currently, mesenchymal stem cells (MSCs) have demonstrated novel neuroprotective effects; therefore, this research explores the neuroprotective effects and mechanisms of MSCs against HS injury., Methods: HS rat models were induced in a 40°C and 65% humidity environment until the rectal temperature reached 42°C. The verified HS injury model rats were divided into the HS and MSCs-treated groups. Each rat in the treated group was infused with 1x10 6 MSCs suspended in 0.3 ml physiological saline via the tail vein. The HS- or MSCs-treated rats were further divided into early-stage (3d) and late-stage (28d). HS rat models were induced by a high-temperature and high-humidity environment at a specific time, the mortality was analyzed, and an automatic biochemical analyzer measured levels of liver and kidney function indicators in the blood. The neurons' morphologic changes were observed through Nissl staining, and neurological deficit scores were performed. Moreover, the levels of inflammatory factors in brain tissue were measured using a multi-cytokine detection platform, and the expression of BDNF, phosphorylated TrkB and P38 were detected by the Western Bolt., Results: MSCs injection significantly reduced mortality and alleviated liver and kidney function. Moreover, the neurological deficit and neuronic edema of the hippocampus caused by HS at 3d and 28d were significantly ameliorated by MSCs administration. Specifically, the injection of MSCs inhibited high levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and IL-17A caused by HS but elevated the levels of IL-10 and IL-13 in the early period (3d); while in the later period (28d), MSCs significantly increased the levels of IL-10 and IL-13 continuously and inhibited the high level of IL-17A. Furthermore, MSCs injection increased the expressions of BDNF and phosphorylated TrkB (BDNF receptor), meanwhile inhibiting the expression of phosphorylated P38 (inflammatory factor) in the brains of HS rats in the early period (3d) but had no significant influence on the later period (28d)., Conclusion: These results suggested that MSCs injection may provide therapeutic effects for HS in rats by improving liver and kidney function and reducing CNS damage. Moreover, MSCs injection inhibited the brain inflammatory response of HS rats, and the BDNF-TrkB and P38/MAPK signal pathways may be involved, providing a potential mechanism for HS therapy by MSCs administration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To study the effect of leptin on neuron apoptosis in mice with cerebral ischemia injury., Methods: Seventy-five male Kuming mice were randomly divided into 3 groups:sham, model and leptin intervention group, respectively. Focal cerebral ischemia/reperfusion injury model in mice was established by middle cerebral artery occlusion. Leptin intervention group was injected with leptin (1 μ g/g weight, I. P.) at 0 min of ischemic injury. Neuron apoptosis was detected by TUNEL staining. The mRNA expression of apoptosis relative gene bcl-2 and caspase-3 were detected by RT-PCR. The protein expression of bcl-2 and caspase-3 were detected by immunohistochemistry., Results: In model group, most of the neurons in the central area of cerebral ischemia had necrosis obviously, and the amount of neuron apop-tosis was much higher than that in sham group ( P <0.01). Compared with sham group, both expression of pro-apoptosis gene caspase-3 and anti-apoptosis gene bcl-2 increased significantly in model group ( P <0.01). Compared with model group, the amount of neuron apoptosis and expression level of caspase-3 were decreased significantly ( P <0.01), whereas the mRNA and protein expression of bcl-2 were increased sig-nificantly in leptin intervention group ( P <0.01)., Conclusions: Leptin could reduce neuron apoptosis through down-regulation the expression of caspase-3 and up-regulation the expression of bcl-2. It suggests that leptin could play a neuroprotective role in cerebral ischemia injury.

Objective: To investigate the effect of rosuvastatin therapy on C-C chemokine receptor(CCR2)expression in mononuclear cells in patients with carotid atherosclerosis and explore the possible upstream mechanism., Methods: Twenty patients without previous statin treatment were enrolled. Rosuvastatin were given 5 to 20 mg/day for 3 months. At baseline and 12 weeks, lipid profile and plasma monocyte chemotactic protein-1 (MCP-1) levels were examined. The mRNA and protein expressions of CCR2 in the mononuclear cells were measured with RT-PCR and flow cytometry, respectively. The mRNA and protein expression of peroxidase proliferator-activated receptor(PPAR β) were detected with RT-PCR and Western blot, respectively., Results: After 3-months rosuvastatin treatment, the patients' low-density lipoprotein cholesterol (LDL-C) levels decreased significantly ( P <0.01). Compared with baseline, the mRNA and protein expressions of CCR2 in the mononuclear cells showed significantly decrease, as well as plasma MCP-1 levels ( P <0.05). Both mRNA and protein expressions of PPAR β in the mononuclear cells increased ( P <0.05)., Conclusions: Rosuvastatin may attenuate MCP-1/CCR2 through PPARβ upstream pathway.

Objective: To explore the effect of leptin on expression of Cx43 after rat cerebral ischemia/ reperfusion injury and its related mechanism., Methods: Forty-five male kunming mice were randomly divided into 3 groups: sham group, model group and leptin group. Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for 2 h followed by 24 h reperfusion in model and leptin group. Mice of leptin group were intraperitoneally injected with 1 mg/kg leptin at 0 minute after ischemia. The infarct volume and neurological deficit scores following leptin treatment were determined using TTC staining and the Longa's score, respectively, to evaluate the protective effect of leptin against ischemic cerebral injury. The histopathological changes in the brain were observed with HE staining. The astrocytes of SD rat cerebral cotex were cultured primaryly and purified, and then divided them into four groups: control, model, leptin 100 microg/L, and leptin 500 microg/L. The cerebral astrocytes with hypoxia/reoxygenation injury were induced. The cellular viability of injury was detected by MTT assay. The effect of leptin on Cx43 expression was detected by Western blot in brain tissues and astrocytes., Results: Compared with the model group, the neurological deficits and cerebral infarct volume of leptin group were reduced (P< 0.05), the histopathological injury in the brain tissues was alleviated and the expression of Cx43 was decreased markedly (P < 0.01). The survival rate of astrocytes was increased significantly in leptin 500 microg/L group (P < 0.01), whereas the Cx43 expression of astrocytes decreased (P < 0.01). But the difference of leptin 100 mcirog/L was not significant (P > 0.05)., Conclusion: Leptin can ameliorate cerebral pathological changes in the event of IR injury by suppressing the expression of Cx43 both in vivo and vitro experiments.

Objective: To study the effect of Leptin on neuron apoptosis in mice with cerebral ischemia injury and its mechanism., Methods: Seventy-five mice were randomly divided into three groups. Focal cerebral ischemia/reperfusion injury model in mice was reproduced by middle cerebral artery occlusion for 2 hours followed by reperfusion. In Leptin intervention group mice were given Leptin 1 μg/g during cerebral ischemia by intraperitoneal injection. Mice in the model group were given equal amount of phosphate buffer saline. After reperfusion for 24 hours, the neuron apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The mRNA and protein expression of apoptosis relative gene caspase-3 and bcl-2 were determined by reverse transcription-polymerase chain reaction (RT-PCR) and immuno histochemistry., Results: Most of neuron necrosis was observed in cerebral ischemia center in model group. Compared with sham-operation group, neuron apoptosis rate, mRNA and protein expression of caspase-3 and bcl-2 in model group increased significantly [apoptosis rate: (68.65 ± 0.79)% vs. (4.40 ± 0.00)%, caspase-3 mRNA: 2.563 ± 0.250 vs. 0.153 ± 0.020, bcl-2 mRNA: 0.337 ± 0.100 vs. 0.125 ± 0.030, caspase-3 protein (absorbance value, A value): 0.57 ± 0.05 vs. 0.37 ± 0.03, bcl-2 protein (A value): 0.51 ± 0.04 vs. 0.35 ± 0.01, all P<0.01]. The apoptosis rate of penumbra neurons was reduced in Leptin intervention group significantly compared with model group [(42.30 ± 8.45)% vs. (68.65 ± 0.79)%, P<0.01]. Compared with model group, the mRNA and protein expression of caspase-3 in Leptin intervention group were reduced significantly [caspase-3 mRNA: 2.267 ± 0.040 vs. 2.563 ± 0.250, caspase-3 protein (A value): 0.45 ± 0.04 vs. 0.57 ± 0.05, P>0.05 and P<0.01], and the mRNA and protein expression of bcl-2 in Leptin intervention group upregulated significantly [bcl-2 mRNA: 0.662 ± 0.040 vs. 0.337 ± 0.100, bcl-2 protein (A value): 0.76 ± 0.09 vs. 0.51 ± 0.04, both P<0.01]., Conclusion: Leptin could reduce apoptosis of neurons through down-regulation of the expression of caspase-3 and up-regulation of the expression of bcl-2. The results suggest that Leptin plays a neuroprotective role in cerebral ischemia injury.

The objective of this study was to elucidate the correlation of killer immunoglobulin-like receptor (KIR) gene diversity with nasopharyngeal carcinoma (NPC) in the Chinese southern Han population. KIR genotyping of peripheral blood samples from 67 patients with NPC and 77 randomly-selected healthy controls was performed by PCR-SSP, the relative risk (RR) value was calculated by means of Wolf method. The results showed that the KIR2DL3 gene frequency in NPC patient group was significantly lower than that in healthy controls (χ²>3.84, p < 0.05, RR = 0.08), whereas the KIR2DS5 and KIR2DL5B gene frequencies in patient group were significantly higher than those in healthy controls (χ²>3.84, p < 0.05, RR > 1), the other KIR gene frequencies were no statistically different between two groups. It is concluded that the KIR2DL3, KIR2DS5 and KIR2DL5B genes may be correlated with pathogenesis of NPC in the Chinese southern Han population.

Objective: To investigate the effect of leptin on apoptosis of rat cerebral astrocytes with ischemia/ hypoxia injury and its mechanism., Methods: The cerebral astrocytes with ischemic/hypoxia injury were induced in neonatal SD rats. The cellular viability of injury of astrocytes was detected by MTT assay. The apoptosis of astrocyte were detected with Annexin V-FITC kit. The effect of leptin on the expression of apoptosis factor bcl-2, bax, caspase-3 was detected by RT-PCR and Western blot., Results: Compared with the ischemia group, the cellular viability of leptin intervention group increased significantly (P < 0.01), while the astrocytes apoptosis of leptin intervention group decreased significantly (P < 0.01). The mRNA and protein expression level of antiapoptosis factor bcl-2 in leptin intervention group was much higher than that of ischemia group (P < 0.01), whereas the mRNA and protein expression of bax and caspase-3 was much lower than that of ischemia group (P < 0.01)., Conclusion: Leptin could significantly decrease the apoptosis of astrocytes with ischemia/hypoxia injury, and it i relevant to the increase of bcl-2 expression and the decrease of bax caspase-3 expression level.

Objective: To explore the effect of ethyl pyruvate (EP) and alkaline phosphatase (ALP) on injuries of sepsis and the mechanism involved., Methods: A murine sepsis model of cecal ligation and puncture was reproduced, and 90 male Kunming mice were divided randomly into sham-operation, model and EP-intervention groups. 75 mg/kg EP was intraperitoneally injected in EP groups 1 hour after establishment of model, and the mice in model group were given a same volume of Ringer's solution. The eyeballs were removed in the latter two groups, and mice were sacrificed at 15 minutes and 1, 3 and 6 hours in subgroups of 10 mice each. ALP, uric acid (UA) and ratio of lactic acid and pyruvic acid were determined in serum and homogenized lung tissue by autonomous biochemical analyzer, and pathological changes in intestine were observed by hematoxylin-eosin (HE) staining., Results: Compared with sham-operation group, serum ALP in model groups and EP groups decreased significantly (P<0.05 or P<0.01), and ALP level of EP group was significantly lower than model group at 6 hours after injury (P<0.05). Compared with sham-operation group, serum UA in model group increased significantly at 1 hour, and reached the highest level at 3 hours (both P<0.05) but decreased significantly later. UA in EP group was significantly lower than that in model group at 1 hour and 3 hours (both P<0.05). Lactic acid/pyruvic acid ratio in lung homogenate of EP group was significantly lower than that of the model group at all the time points (all P<0.05). Intestinal structural damages were distinctly improved in EP group compared with model group at 3 hours and 6 hours (both P<0.05 )., Conclusion: EP promotes the utilization of serum ALP, decreases serum UA, ameliorates acidosis and intestinal damages, thus exerting a protective effect on sepsis-induced organ injuries.