Electroacupuncture alleviates cerebral ischemia and reperfusion injury via modulation of the ERK1/2 signaling pathway.

Electroacupuncture (EA) has anti-oxidative and anti-inflammatory actions, but whether the neuroprotective effect of EA against cerebral ischemia-reperfusion (I/R) injury involves modulation of the extracellular regulated kinase 1/2 (ERK1/2) signaling pathway is unclear. Middle cerebral artery occlusion (MCAO) was performed in Sprague-Dawley rats for 2 hours followed by reperfusion for 24 hours. A 30-minute period of EA stimulation was applied to both Baihui (DU20) and Dazhui (DU14) acupoints in each rat (10 mm EA penetration depth, continuous wave with a frequency of 3 Hz, and a current intensity of 1-3 mA) when reperfusion was initiated. EA significantly reduced infarct volume, alleviated neuronal injury, and improved neurological function in rats with MCAO. Furthermore, high mRNA expression of Bax and low mRNA expression of Bcl-2 induced by MCAO was prevented by EA. EA substantially restored total glutathione reductase (GR), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels. Additionally, Nrf2 and glutamylcysteine synthetase (GCS) expression levels were markedly increased by EA. Interestingly, the neuroprotective effects of EA were attenuated when ERK1/2 activity was blocked by PD98059 (a specific MEK inhibitor). Collectively, our findings indicate that activation of the ERK1/2 signaling pathway contributes to the neuroprotective effects of EA. Our study provides a better understanding of the regulatory mechanisms underlying the therapeutic effectiveness of EA.

Hsp90ß is involved in the development of high salt-diet-induced nephropathy via interaction with various signalling proteins.

A high-salt diet often leads to a local intrarenal increase in renal hypoxia and oxidative stress, which are responsible for an excess production of pathogenic substances. Here, Wistar Kyoto/spontaneous hypertensive (WKY/SHR) rats fed a high-salt diet developed severe proteinuria, resulting from pronounced renal inflammation, fibrosis and tubular epithelial cell apoptosis. All these were mainly non-pressure-related effects. Hsp90ß, TGF-ß, HIF-1α, TNF-α, IL-6 and MCP-1 were shown to be highly expressed in response to salt loading. Next, we found that Hsp90ß might play the key role in non-pressure-related effects of salt loading through a series of cellular signalling events, including the NF-κB, p38 activation and Bcl-2 inactivation. Hsp90ß was previously proven to regulate the upstream mediators in multiple cellular signalling cascades through stabilizing and maintaining their activities. In our study, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) or Hsp90ß knockdown dramatically alleviated the high-salt-diet-induced proteinuria and renal damage without altering blood pressure significantly, when it reversed activations of NF-κB, mTOR and p38 signalling cascades. Meanwhile, Co-IP results demonstrated that Hsp90ß could interact with and stabilize TAK1, AMPKα, IKKα/ß, HIF-1α and Raptor, whereas Hsp90ß inhibition disrupted this process. In addition, Hsp90ß inhibition-mediated renal improvements also accompanied the reduction of renal oxidative stress. In conclusion, salt loading indeed exhibited non-pressure-related impacts on proteinuria and renal dysfunction in WKY/SHR rats. Hsp90ß inhibition caused the destabilization of upstream mediators in various pathogenic signalling events, thereby effectively ameliorating this nephropathy owing to renal hypoxia and oxidative stress.

Electroacupuncture Attenuates Cerebral Ischemia and Reperfusion Injury in Middle Cerebral Artery Occlusion of Rat via Modulation of Apoptosis, Inflammation, Oxidative Stress, and Excitotoxicity.

Electroacupuncture (EA) has several properties such as antioxidant, antiapoptosis, and anti-inflammatory properties. The current study was to investigate the effects of EA on the prevention and treatment of cerebral ischemia-reperfusion (I/R) injury and to elucidate possible molecular mechanisms. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. EA stimulation was applied to both Baihui and Dazhui acupoints for 30 min in each rat per day for 5 successive days before MCAO (pretreatment) or when the reperfusion was initiated (treatment). Neurologic deficit scores, infarction volumes, brain water content, and neuronal apoptosis were evaluated. The expressions of related inflammatory cytokines, apoptotic molecules, antioxidant systems, and excitotoxic receptors in the brain were also investigated. Results showed that both EA pretreatment and treatment significantly reduced infarct volumes, decreased brain water content, and alleviated neuronal injury in MCAO rats. Notably, EA exerts neuroprotection against I/R injury through improving neurological function, attenuating the inflammation cytokines, upregulating antioxidant systems, and reducing the excitotoxicity. This study provides a better understanding of the molecular mechanism underlying the traditional use of EA.

Use of improved tracheal catheters in patient of tracheostomy tube-induced tracheoesophageal fistula: a case report.

Tracheostomy tube might cause tracheoesophageal fistula (TEF) due to high cuff pressure or direct mechanical trauma. Surgical repair provides the ideal way to deal with TEF but it necessitates the weaning the patient from mechanical ventilation. Here we report a spontaneous closure of TEF by managing it with improved tracheal catheters in a patient who is dependent on mechanical ventilation.

Enhancement effect of ultrasound-induced microbubble cavitation on branched polyethylenimine-mediated VEGF(165) transfection with varied N/P ratio.

One isoform of the vascular endothelial growth factor, VEGF(165), has been reported to be a dominant mediator and regulator of angiogenic process, which plays an important role in treating cardiovascular diseases and chronically ischemic wounds. Branched polyethylenimine (bPEI) has been widely used as a non-viral delivery vector for gene therapy. Although bPEI-mediated DNA transfection efficiency can be raised by increasing the PEI nitrogen:DNA phosphate (N/P) ratio, cytotoxicity increases as well. In this study, the enhancement effect of microbubble inertial cavitation (IC) on bPEI-mediated VEGF(165) transfection was investigated, in an effort to optimize transfection efficiency using low N/P ratios. HEK 293T cells, mixed with bPEI:VEGF(165) complexes, were exposed to 1-MHz ultrasound pulses. The results show that: (1) IC activity induced by microbubble destruction can be quantified as an IC "dose" (ICD) and will increase with increasing acoustic driving pressure; (2) larger sonoporation pores can be generated by increasing ICD; (3) the transfection efficiency can be enhanced by increasing ICD until reaching a saturation level; and (4) microbubble IC activity has less cytotoxicity than bPEI, although a combinatorial effect of microbubble IC activity and bPEI could be observed on cell viability. The results suggest that, with appropriate ultrasound parameters, it is possible to optimize bPEI-mediated VEGF transfection efficiency using relatively low N/P ratios by employing ultrasound-induced microbubble inertial cavitation.

CDH1 gene polymorphisms, plasma CDH1 levels and risk of gastric cancer in a Chinese population.

The genetic polymorphisms in E-cadherin gene (CDH1) may affect invasive/metastatic development of gastric cancer by altering gene transcriptional activity of epithelial cell. Our study aims to explore the associations among CDH1 gene polymorphisms, and predisposition of gastric cancer. We genotyped four potentially functional polymorphisms (rs13689, rs1801552, rs16260 and rs17690554) of the CDH1 gene in a case-control study of 387 incident gastric cancer cases and 392 healthy controls by polymerase chain reaction-ligation detection reaction methods (PCR-LDR) and measured the plasma CDH1 levels using enzyme immunoassay among the subjects. The median and inter-quartile range were adopted for representing the mean level of non-normally distributed data, and we found the level of plasma CDH1 in gastric cancer patients (median: 171.00 pg/ml; inter-quartile range: 257.10 pg/ml) were significantly higher than that of controls (median: 137.40 pg/ml; inter-quartile range: 83.90 pg/ml, P = 0.003). However, none of the four polymorphisms or their haplotypes achieved significant differences in their distributions between gastric cancer cases and controls, and interestingly, in the subgroup analysis of gastric cancer, we found that CA genotype of rs26160 and CG genotype of rs17690554 were associated with the risk of diffuse gastric cancer, compared with their wild genotypes (OR = 2.98, 95 % CI: 1.60-5.53; OR = 2.10, 95 % CI: 1.14-3.85, respectively, P < 0.05). In conclusion, our results indicated that plasma CDH1 levels may serve as a risk marker against gastric cancer and variant genotypes of rs26160 and rs17690554 may contribute to the etiology of diffuse gastric cancer in this study. Further studies are warranted to verify these findings.

[Expression of monocyte chemoattractant protein-1 in sudden death due to viral myocarditis and its medicolegal significance].

OBJECTIVE: To explore the expression and significance of monocyte chemoattractant protein-1 (MCP-1) in myocardium in sudden death caused by viral myocarditis (VMC). METHODS: To investigate the expression of MCP-1 in VMC sudden death group and control group using improved immunohistochemical technique and to compare the difference of the expression of MCP-1 between two groups with statistical method. RESULTS: In VMC sudden death group, MCP-1 was positively expressed in 17 of 20 cases. While only 4 of the 20 cases in the control group showed a mildly positive expression sparsely in myocardium, and the rest cases were completely negative. The rate of positive expression of MCP-1 in VMC group was obviously higher than that of the control group (P<0.01). CONCLUSION: The expression of MCP-1 detected by immunohistochemistry provides an objective morphologic evidence for the diagnosis of VMC sudden death in forensic pathology.

[Expression of Bcl-2 and Bax proteins in myocardial cells after Macleaya cordata alkaloids poisoning in rats].

OBJECTIVE: To observe the expression of Bcl-2 and Bax proteins in rat's myocardial cells after Macleaya cordata alkaloids poisoning, and to provide certain molecular biology references for the detection of Macleaya cordata alkaloids poisoning. METHODS: Experimental model of Macleaya cordata alkaloids poisoning was established, the expression levels of Bcl-2 and Bax proteins in these cells were detected by immunohistochemistry, and the results were analyzed by computer image system. RESULTS: The expression levels of Bcl-2 and Bax proteins in myocardial cells in poisoning groups were much greater than those in the control groups (P<0.05). CONCLUSION: If the clinical symptoms may not be obvious, the detection of Bcl-2 and Bax proteins level by immunohistochemistry still could be ancillary method.

[A preliminary study of serum free testosterone and testosterone secreting index in men with erectile dysfunction].

OBJECTIVE: To observe the changes of serum free testosterone (FT) and testosterone secreting index (TSI) in ED patients, and to assess the contribution of these two indexes to the diagnosis of ED caused by endocrine factors. METHODS: We studied 120 ED patients and 30 healthy men undergoing pre-marital medical check-up in Jiangsu Province Hospital of TCM by analyzing the scores on erectile function and desire domain in IIEF, testing the serum total testosterone, luteinizing hormone by chemiluminescent enzyme immunoassay (CLIA), measuring free testosterone by radioimmunoassay( RIA), and calculating TSI. RESULTS: Of the 120 ED patients, 5% and 1538% were below the reference norm of TT and FT values respectively. TT, FT and TSI decreased with age, with statistical with FT and TSI, but not with TT. FT and TSI statistically declined with lower IIEF score on ED domain, but this was not the case with TT. There were no significant differences in TI, FT and TSI among different sexual desire groups the ED patients. CONCLUSION: FT is much more valuable than TF in the diagnosis of ED with hypogonadism. Both FT and TSI are important parameters in assessing the severity of ED.

[The expression of GFAP after brain concussion in rats].

OBJECTIVE: To study the expression of GFAP and pathologic changes after rats brain concussion, so that to provide evidence on brain concussion for forensic identification. METHODS: Forty-five SD rats were divided into 3, 6, 12, 24 h and 2, 4, 7, 10 d and normal control groups in terms of different wounding time after brain concussion model established, and the expression of GFAP after rats brain concussion were then observed by using SP immunohistochemical method. RESULTS: In normal control brain, low-level GFAP expressions could be observed. After six hours' brain concussion, GFAP positive cells increased obviously. The trend reached to the peak at 7d, partly declined at 10d, then decreased gradually. CONCLUSION: Brain concussion induced the expression of GFAP. The detection of GFAP could be useful for diagnosis of brain concussion on forensic pathology, and could be a reference index for timing of injury after brain concussion.