Exploiting electronic strategies to stabilize a planar tetracoordinate carbon in cyclic aromatic hydrocarbons.

A new approach to stabilize compounds containing a planar tetracoordinate carbon (ptC), embedded in aromatic hydrocarbons, is presented herein. This is achieved by using ligands that promote the formation of a 3c-2e σ-bond with the ptC under two conditions: without altering the sp2 hybridization of the aromatic carbons; and containing empty orbitals perpendicular to the aromatic ring to participate in the aromatic π-electronic delocalization.

Role of ADH2 and ALDH2 gene polymorphisms in the development of Parkinson's disease in a Chinese population.

In this study, we investigated the role of ADH2 Arg47His and ALDH2 Glu487Lys genetic polymorphisms in the development of Parkinson's disease in a Chinese population. Between January 2013 and May 2014, 115 patients with Parkinson's disease and 214 healthy controls were recruited in our study. Genotyping of ADH2 Arg47His and ALDH2 Glu487Lys polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism method. In the dominant model, the GA + AA genotype of ALDH2 Glu487Lys was found to be significantly associated with elevated risk of Parkinson's disease when compared with the GG genotype [odds ratio = 1.71, 95% confidence interval (CI) = 1.02-2.84]. In the recessive model, the AA genotype of ALDH2 Glu487Lys showed a 4.87-fold increase (95%CI = 1.54-18.03) in the risk of Parkinson's disease when compared to the GG and GA genotypes. However, no significant association was found between the ADH2 Arg47His polymorphism and risk of Parkinson's disease in the co-dominant, dominant, or recessive models. In conclusion, our study suggests that the ALDH2 polymorphism could influence the development of Parkinson's disease in the Chinese population studied here.

Roles of microRNA-221/222 in type 2 diabetic patients with post-menopausal breast cancer.

The aim of the research was to examine the expression level of microRNA221/222 (miR-221/222) in the serum of patients with type 2 diabetes mellitus (T2DM) who are also diagnosed with post-menopausal breast cancer. We aimed to evaluate the differences in microRNA expression in patients with T2DM alone, patients with post-menopausal breast cancer alone, and patients with both T2DM and post-menopausal breast cancer. We selected 20 cases from a healthy control group, 30 cases from the group of patients with T2DM and obesity, 30 cases from the group of the patients with post-menopausal breast cancer, and 30 cases from the group of patients with both T2DM and post-menopausal breast cancer. The expression of miR-221/222 in the serum of the patients with post-menopausal breast cancer was higher than that of T2DM patients (P < 0.05), but lower than that of the T2DM patients who were also positive for post-menopausal breast cancer (P < 0.05); the expression of miR-221/222 in the serum of the T2DM patients was higher than that of the healthy controls (P < 0.05). BMI, HOMA-IR, HbA1c, and TG were positively correlated with the relative expression of miR-221/222 in the serum (P < 0.01). In conclusion, miR-221/222 participates in insulin resistance; the combination of miR- 221/222 and estrogen contributes to incidence of T2DM with post-menopausal breast cancer complications. MiR-221/222 may participate in the occurrence and progression of T2DM with post-menopausal breast cancer via down-regulation of CAVl.

Correlation between polymorphisms in the visfatin gene and its expression in the serum and coronary artery calcification.

We investigated the association between serum visfatin levels and single nucleotide polymorphisms (SNPs; rs61330082, rs2058539) in the visfatin gene and coronary artery calcification (CAC) in patients from Wenzhou, China. CAC patients (N = 206) were divided into two groups: mild CAC (MCAC) and moderate and severe CAC (MSCAC). Volunteers without CAC (N = 70) were included in the control group. The serum visfatin level was analyzed by enzyme-linked immunosorbent assay. SNPs (rs61330082, rs2058539) in the visfatin gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Clinical data, serum visfatin levels, and genotype and allele frequencies of rs61330082 and rs2058539 were compared among the three groups. MSCAC patients expressed significantly higher serum visfatin levels (30.58 ± 6.12 ng/mL) than individuals in the MCAC (29.03 ± 1.87 ng/mL) and control (24.45 ± 5.44 ng/mL) groups (P < 0.05). The genotype distributions and frequencies of rs61330082 differed significantly among the groups (P < 0.05), while those of rs2058539 did not. The serum visfatin level was positively correlated with the body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), and insulin resistance index (IRI), and negatively correlated with the triglyceride (TG) levels (P < 0.05) of patients. Serum visfatin is associated with the development of CAC. The T allele of the rs61330082 SNP in the visfatin gene had a cardioprotective effect on patients with CAC; the SNP at rs2058539 was not significantly associated with CAC. The BMI, HDL-C, IRI, and TG levels influenced the development of CAC.

Protective effects and mechanisms of Ndfipl on SH-SY5Y cell apoptosis in an in vitro Parkinson's disease model.

The aim of the current study was to examine the protective effects and mechanisms of Ndfipl on neurocytes in an experimental in vitro Parkinson's disease model induced by MPP+. The cell model was developed with dominant negative expression and suppressed expression of Ndfipl by means of transient transfection of Ndfipl-dominant negative and -inhibitory vectors. In total, four different Ndfipl cell models were established. Different methods were used to analyze the cells. The MTT method was used to detect the effect of Ndfipl on the survival rate and apoptosis of the cells induced by MPP(+). We further studied the roles of Ndfipl in inhibiting MPP(+)-induced SH-SY5Y apoptosis, protection, and ubiquitination of SH-SY5Y cells. Our results showed that Ndfipl reduced apoptosis and improved cell survival rate, indicating that Ndfipl has a neuroprotective effect. Furthermore, we found that Ndfipl binds to Nedd4-1, and that increased expression of Ndfipl significantly reduced Itch expression. We also found that increased ubiquitination played a role in Ndfipl-mediated processes, and that Ndfipl and α-synuclein interact. Additionally, the expression of Ndfipl reduced expression of α-synuclein. In conclusion, Ndfipl plays a significant role in protecting SH-SY5Y cells in in vitro Parkinson's disease models.

Correlation between chromosome 1p/19q status and VEGF mRNA expression in gliomas.

The chromosome 1p/19q deletion has been reported as a good prognosis marker for gliomas. However, the detection of 1p/19q status alone in glioma patients is not sufficient. The identification of a combination of molecular factors could effectively enhance the prediction accuracy. Thus far, the potential correlation between the 1p/19q status and vascular endothelial growth factor (VEGF) expression has not been elucidated. The level of VEGF mRNA expression in the tumor and the adjacent normal tissues was determined by real-time polymerase chain reaction. The 1p/19q status of glioma patients was determined by fluorescence in situ hybridization. The association between the 1p/19q status and VEGF mRNA expression, as well as the glioma grade, was evaluated. A higher VEGF mRNA expression level was observed in gliomas, compared to matched normal tissues (P < 0.01). The 1p/19q status was significantly correlated with glioma grade (P = 0.018) and VEGF mRNA expression in the tissues (P = 0.005). A higher percentage of patients with high-grade gliomas displayed an intact 1p/19q and higher VEGF mRNA expression than those with low-grade gliomas. A survival analysis revealed that patients (with high- and low-grade gliomas) with intact 1p/19q and higher VEGF mRNA expression showed a shorter overall survival time. Moreover, tissue VEGF mRNA expression and WHO grade were found to be independent risk factors for gliomas. In conclusion, the 1p/19q status and VEGF mRNA expression in tissues could be used in combination to predict the prognosis of gliomas.

Effects of hyperbaric oxygen on the Nrf2 signaling pathway in secondary injury following traumatic brain injury.

We investigated the effects of hyperbaric oxygen treatment on the Nrf2 signaling pathway in secondary injury following traumatic brain injury, using a rat model. An improved Feeney freefall method was used to establish the rat traumatic brain injury model. Sixty rats were randomly divided into three groups: a sham surgery group, a traumatic brain injury group, and a group receiving hyperbaric oxygen treatment after traumatic brain injury. Neurological function scores were assessed at 12 and 24 h after injury. The expression levels of Nrf2, heme oxygenase 1 (HO-1), and quinine oxidoreductase 1 (NQO-1) in the cortex surrounding the brain lesion were detected by western blotting 24 h after the injury. Additionally, the TUNEL method was used to detect apoptosis of nerve cells 24 h after traumatic injury and Nissl staining was used to detect the number of whole neurons. Hyperbaric oxygen treatment significantly increased the expression of nuclear Nrf2 protein (P < 0.05), HO-1, and NQO-1 in the brain tissues surrounding the lesion after a traumatic brain injury (P < 0.05) and also significantly reduced the number of apoptotic and injured nerve cells. The neurological function scores also improved with hyperbaric oxygen treatment (P < 0.05). Therefore, hyperbaric oxygen has a neuroprotective role in traumatic brain injury, which is mediated by up-regulation of the Nrf2 signaling pathway.

Protein expression levels in the medullary visceral zone of rats with subarachnoid hemorrhage.

We investigated protein expression in the medullary visceral zone (MVZ) of rats with multiple-organ dysfunction syndrome (MODS) caused by subarachnoid hemorrhage (SAH) to discuss the possible regulatory mechanism of the MVZ in the course of SAH-induced MODS. A SAH-induced MODS model was established in rats by injecting arterial blood into the Willis' circle. Protein expression in the MVZ was analyzed by immunohistochemistry assay. Protein expression in the MVZ peaked 24-36 h after SAH, and was significantly higher than in the control and sham operation groups. Organs at each time point exhibited inflammatory injuries to varying degrees after SAH, which reached a maximum at 24-36 h. Incidences of systemic inflammatory response syndrome and MODS were 100 and 71.67%, respectively, after SAH. There is a consistency between MVZ protein expression and inflammatory changes in each organ after SAH. This prompts the suggestion that the MVZ may be one of the direct regulative centers in SAH-induced MODS, and may be involved in the functional regulation of the surrounding organs after SAH.

A new method to induce myasthenia gravis models and the protective effect of soluble decay accelerating factors.

It is expensive to induce experimental autoimmune myasthenia gravis (EAMG) by active immunity, and difficult to obtain natural acetylcholine receptor (AChR). We sought a new method of inducing EAMG by immunizing rats with artificially synthesized AChR. The AChR mRNA in TE671 cells was extracted and reverse transcribed. The inclusion body was purified and protein concentration was determined, and the EAMG animal model was used for induction. The serum was extracted from rat blood. The antibody titer was determined using enzyme-linked immunosorbant assay (ELISA). The concentration of decay accelerating factor (DAF) in the rat serum was determined by ELISA, and the metabolism of serum rDAF was determined by western blot. We evaluated the inhibition of rDAF by determining the 50% complement hemolysis unit in the rat serum. The extracellular domain (ECD) nucleotide sequence clone produced by polymerase chain reaction was completely consistent with that in the human gene bank; it was induced by isopropyl ß-D-1-thiogalactopyranoside to express the protein after insertion into vector pET16b. Sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that the inclusion body protein was the exact target. The ECD protein was able to bind with mAb35 after dialysis and renaturation, which demonstrated protein activity. The soluble ECD protein was used to immunize rats and obtain the EAMG models. The inhibitory effect of the complement was unsatisfactory owing to high decay rate after rDAF injection into the EAMG models. It is easy to induce the EAMG model by obtaining the AChRTEα1 subunit ECD protein using the substitution method.

Leishmania mexicana: comparative fine structure of amastigotes and promastigotes in vitro and in vivo.

Amastigotes of Leishmania mexicana pifanoi were cultivated by serial transfers in cell-free medium UM-54 at 33 and 35 C. Electron microscopy was used to analyze the structural relationships among promastigotes, axenically cultured amastigotes, and amastigotes in footpads of infected hamsters. These studies revealed very close structural similarities between culture and hamster derived amastigotes. However, both of these amastigotes differed from the promastigotes in the following aspects. The flagellum of promastigotes contained a paraxial rod originating at the axosome level within the flagellar pocket, whereas the flagellum of amastigotes lacks this structure. The flagellar pocket of promastigotes was usually small whereas amastigotes had a distended reservoir. Subpellicular microtubules of promastigotes terminated at the posterior end, whereas those of amastigotes ended subterminally. Membrane bounded vesicles were present only in amastigotes. These results along with the biologic and antigenic comparisons indicate that amastigotes obtained from axenic cultures are related very closely to amastigotes from infected hamster footpads and that their relationship to promastigotes is far more distant.