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Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase (DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this double-blind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, SmaI restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2 (-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models (GG and CG), while 89.13% of healthy control subjects had dominant genetic models (CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls (P = 0.0002). The frequency of G alleles in the leukoaraiosis patients (71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower (χ2 = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes (Kruskal–Wallis H = 24.5955, P < 0.0001). In addition, the GG genotype of DDAH2 (-449 G/C) was more common in patients with leukoaraiosis. These findings suggest that the G allele of DDAH2 (-449 G/C) is a risk factor for leukoaraiosis morbidity and is correlated with high levels of asymmetric dimethylarginine. This study was approved by the Institutional Ethics Committee of the 2nd Affiliated Hospital of Harbin Medical University of China (approval No. KY2016-177) on July 28, 2016.

Genome-wide association studies with an Illumina Bovine50K chip have detected 105 SNPs associated with one or multiple milk production traits in the Chinese Holstein population. Of these, 38 significant SNPs detected with high confidence by both L1-TDT and MMRA methods were selected to further mine potential key genes affecting milk yield and milk composition. By blasting the flanking sequences of these 38 SNPs with the bovine genome sequence combined with comparative genomics analysis, 26 genes were found to contain or be near to such SNPs. Among them, the C14H8orf33 gene is merely 87 bp away from the significant SNP, Hapmap30383-BTC-005848. Hence, we report herein genotype-phenotype associations to further validate the genetic effects of the C14H8orf33 gene. By pooled DNA sequencing of 14 unrelated Holstein sires, a total of 18 with seven novel SNPs were identified. Among them, nine SNPs were in the 5′ regulatory region, one in exon 6 and the other in the 3′ UTR and 3′ regulatory region. A total of nine of these identified SNPs were successfully genotyped and analyzed by mass spectrometry for association with five milk production traits in an independent resource population. The results showed that these SNPs were statistically significant for more than two traits [P

To investigate the risk factors for leukoaraiosis (LA) and the correlation between risk factors and LA. The study comprised 92 patients with diagnoses of LA (LA group) and 56 non-LA individuals (control group). Data were collected for the following: age, gender, fasting blood glucose, total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, uric acid, creatinine, and histories of smoking, hypertension, and diabetes. Levels of serum asymmetric dimethylarginine (ADMA) were detected by enzyme-linked immunosorbent assay. Univariate analysis showed statistical significance between the 2 groups in age, histories of hypertension and smoking, uric acid, creatinine, and levels of serum ADMA (P

The incidence of Parkinson's disease (PD) is increasing as the global population ages. 6-hydroxydopamine (6-OHDA) can induce PD-like neuropathology and biochemical changes in both in vitro and in vivo models. Therefore, clarification of the molecular mechanism of 6-OHDA-induced cell death might contribute to the understanding of the pathogenesis of PD.With this goal in mind, we investigated the role of protein kinase C delta (PKC delta) in 6-OHDA-dependent death using the pheochromocytoma cell line, PC12. Cells were treated with 6-OHDA to induce toxicity with or without pretreatment using rottlerin (a PKC delta inhibitor), bisindolylmaleimide I (a general PKC inhibitor), Gö6976 (a PKC inhibitor selective for calcium-dependent PKC isoforms), or phorbol-12-myristate-13-acetate (PMA, a PKC activator).Phorbol-12-myristate-13-acetate decreased cell survival and increased the rate of apoptosis while rottlerin increased cell survival and decreased the rate of apoptosis. In contrast, neither bisindolylmaleimide I nor Gö6976 affected 6-OHDA-induced cell death. Western analysis demonstrated that phosphorylation of PKC delta on Thr 505 as well as extracellular signal-regulated kinase (ERK) phosphorylation increased after exposure to 6-OHDA. This increase in PKC delta phosphorylation was potentiated by PMA. However, rottlerin attenuated the 6-OHDA-stimulated increase in PKC delta and ERK phosphorylation.These data suggest that PKC delta, rather than classic-type PKC (alpha, beta1, beta2, gamma), participates in 6-OHDA-induced neurotoxicity in PC12 cells, and PKC delta activity is required for subsequent ERK activation during cell death.

This study was aimed to investigate the effect of AG490, a JAK2 inhibitor, on expression of PHLPP and p-Akt in K562. K562 cells were treated with different concentrations of AG490. The proliferation of K562 cells was examined by WST-1 assay and apoptosis of K562 cells was detected by flow cytometry with Annexin V-FITC/PI double staining. The expressions of PHLPP, phosphorate-Akt (p-Akt) and total Akt protein were detected by Western blot. The results indicated that AG490 inhibited the proliferation of K562 cells in concentration-and time-dependent manners, with the IC(50) 338.0 µmol/L in 48 h. AG490 100 µmol/L also induced apoptosis of K562 cells in a time-dependent manner. AG490 100 µmol/L time-dependently down-regulated the protein expression of p-Akt and PHLPP, but without significant effect on expression of total Akt. It is concluded that AG490 can inhibit proliferation and induce apoptosis of K562 cells through down-regulation of p-Akt expression, but inhibiting efficacy of AG490 on K562 proliferation also may be limited due to the down-regulation of p-Akt regulatory protein PHLPP expression.

To summarize the experience in the diagnosis and surgical treatment of carcinoid tumors of the appendix.From 1972 to 2006, 64 patients with carcinoid tumors of the appendix received surgical treatment in our hospitals. The clinical data of those patients were retrospectively analyzed.Of the 64 cases, only 6 cases (9.4%) were correctly diagnosed preoperatively, while 58 (90.6%) not confirmed, with a misdiagnosis rate of 90.6%. All patients underwent surgical treatment, including appendectomy in 54, ileocecectomy in 4, right hemicolectomy in 2 and right hemicolectomy with regional lymph node dissection in 4 cases. The operation modes were determined according to the doctor's judgments based on the age of the patients, the nature, size, location, infiltration depth and lymph node metastasis of the tumors. Of the 64 patients, 58 were followed up with a longest follow-up period of 13 years, while 6 lost follow-up. Fifty-seven of those were still surviving, only one died of liver metastasis at 13 years after operation.Carcinoid tumor of the appendix is rare with a high rate of misdiagnosis before operation. Surgical resection is the only effective treatment for this disease and proper operation mode is the key to achieve good survival.

To investigate the effect of trichostatin A(TSA) on SGC- 7901 cells.Cytotoxicity and cell viability of gastric cancer cell line SGC- 7901 were assayed by MTT method. Morphologic assessment of apoptosis was performed with fluorescence microscope. Cell cycle and apoptosis rate were analyzed by flow cytometry. Histone H3 acetylation was detected by Western blot.TSA showed apparently cytotoxicity in SGC- 7901 cells. The growth curve showed the growth ratio decreased with the increase of TSA concentration. Apoptosis rate were significantly different between TSA treated group(75 ng/ml for 72 h)and control group (P0.05). Morphologic changes of apoptosis including nuclear chromatin condensation and fluorescence strength were observed with fluorescence microscope.TSA treatment (75 ng/ml for 72 h) sensitively induced apoptosis in the cell,which was demonstrated by the migration of many cells to the sub- G1 phase,the reduction of G1- phase cells and the increment of apoptosis rate (29.54%) in flow cytometric analysis. The expression of acetylated histone H3 was increased in TSA group(75 ng/ml) for 48 h compared with control group by Western blot.TSA can induce SGC- 7901 cell apoptosis. The expression of acetylated histone H3 may contribute to the apoptosis.

To study the anatomy of the small intestine,and investigate the optimal selection of donors,recipients,and their small intestine vessels in piglet small intestine transplantation.The weight and length of 30 piglets were measured. Angiography and pigments perfusion were used to observe the main vessels of the small intestine,and the length of the small intestine,and the external diameter of the main vessels of the small intestine were measured in vivo and ex vivo.The length of the small intestine was 11.5 times as long as the body length, and its weight accounted for 2.3% of the body weight. The outer diameters of abdominal aorta (AT), mesenteric anterior artery (MAA) and its 5(th)-6(th) branches in vivo and ex vitro were 4.3/4.6mm, 2.5/2.7mm and 1.9/2.2mm respectively. The total number of MAA's branches was 6-8 in general and its 5(th)-6(th) branches were the longest [(20.0 +/- 7.0) mm, (22.0 +/- 8.2) mm]. The outer diameter of mesenterial anterior vein (MAV) was 1-2 mm wider than that of MAA.AT, MAA and its 5(th)-6(th) branches are the preferable vessels for small intestine transplantation. In segmental small intestine transplantation, the length of the small intestine and body weight can be used to primarily select the suitable animals.