HIV-1 Tat and methamphetamine co-induced oxidative cellular injury is mitigated by N-acetylcysteine amide (NACA) through rectifying mTOR signaling.

Methamphetamine (Meth) is an addictive psychostimulant whose abuse is intimately linked to increased risks for HIV-1 infection. Converging lines of evidence indicate that Meth also aggravates the symptoms of HIV-associated neurocognitive disorders (HAND), though the underlying mechanisms remain poorly understood. By using the lipophilic antioxidant N-acetylcysteine amide (NACA) as an interventional agent, we examined the roles of oxidative stress in autophagy and apoptosis induced by HIV-Tat (the transactivator of transcription), Meth or their combined treatment in human SH-SY5Y neuroblastoma cells and in the rat striatum. Oxidative stress was monitored in terms of the production of intracellular reactive oxygen species (ROS) and antioxidant reserves including glutathione peroxidase (GPx) and Cu,Zn-superoxide dismutase (SOD). NACA significantly reduced the level of ROS and restored GPx and SOD to levels comparable to that of normal control, implying a cytoprotective effect of NACA against oxidative stress elicited by Tat- and/or Meth. Protein expression of mammalian target of rapamycin (mTOR) was measured in SH-SY5Y cells and in the rat striatum to further explore the underlying mechanism of NACA protect against oxidative stress. The results support a beneficial effect of NACA in vivo and in vitro through rectification of the mTOR signaling pathway. Collectively, our study shows that NACA protects against Meth and/or Tat-induced cellular injury in vitro and in the rat striatum in vivo by attenuating oxidative stress, apoptosis and autophagy, at least in part, via modulation of mTOR signaling.

A functional polymorphism in IL-1A gene is associated with a reduced risk of gastric cancer.

Accumulating evidence has identified that polymorphism residing in the microRNA (miRNA) binding site of target genes can affect the strength of miRNA binding and influence individual susceptibility to cancer. Recently, an insertion/deletion polymorphism (rs3783553 ttca/-) at miRNA-122 binding site in the interleukin-1A 3' untranslated region has been demonstrated to be functional. We aimed to investigate the association between the rs3783553 polymorphism and the risk of gastric cancer (GC). We genotyped the rs3783553 polymorphism in 207 GC patients and 381 healthy controls by using a polymerase chain reaction method. We found that the ins/ins (ttca/ttca) genotype of the rs3783553 polymorphism was associated with a significantly decreased risk of GC (P = 0.02, odds ratio = 0.48, 95% confidence interval 0.26-0.90). This finding suggests that the rs3783553 polymorphism may be a protective factor for the development of GC.

[Establishment of cell lines derived from skin biopsies of crested ibis (Nipponia nippon) and their biological characteristics].

The crested ibis is among the rarest and most endangered species worldwide. To preserve its genetic resources and conveniently provide materials for biological research, we successfully established two cell lines from biopsies of a male and female adult crested ibis. The cultured cells from both specimens had typical fibroblast morphology. Immunofluorescence staining revealed that the cultured cells strongly expressed the marker of smooth muscle specific α-actin, clearly indicating the cells were from the smooth muscle tissue. Growth property analysis showed that the cells grew well past the first 10 passages and continued growing with reduced proliferation after 15 passages, but ceased by passage 25 as the cells could not grow to form a confluent monolayer. From these two cell lines, we harvested mitotic metaphase chromosomes and conducted different staining, banding, and fluorescent in situ hybridization. Throughout the process, cells maintained normal diploidy, with the karyotypes of these two cell lines being 2n=68, ZZ in the male and 2n=68, ZW in the female. Patterns of Ag staining, C- and G-bands of the crested ibis chromosomes were also studied. Banding analyses and fluorescent in situ hybridization also allowed identification of the sex chromosomes. We suggest that the external implants method for establishing primary cell lines used in this study may also be applicable to other birds, especially similarly endangered avian species.

Potential association of DRD2 and DAT1 genetic variation with heroin dependence.

The aim of our study was to investigate the potential association of dopamine receptor D2 gene (DRD2) TaqI RFLP A (rs1800497) and dopamine transporter gene (DAT) 3'untranslated region VNTR genetic variations with heroin addiction. Genotyping was performed using PCR-based techniques in 530 heroin abusers and 500 controls. Our results showed that DRD2 TaqI A1 allele carriers (genotypes A1A1 and A1A2) were prone to heroin abuse in models of dominance or co-dominance. We detected a 12 repeat allele and 6/6, 7/9, 9/11, 10/12 genotype in a Chinese/eastern Asian population for the first time. However, no significant differences in the DAT1 VNTR were found between the two groups in either genotypic or allelic distributions and there was no gene interaction between the two genetic loci.

[Genetic polymorphisms of 9 X-chromosome short tandem repeat loci in a Inner Mongolia Ewenki population and their forensic evaluation].

OBJECTIVE: To investigate the alleles and genotypes frequency of 9 short tandem repeat (STR) loci on the X chromosome (DXS6789, DXS101, DXS8378, DXS7132, DXS7133, DXS7423, DXS6804, DXS6799, HPRTB) of Ewenki individuals living in Inner Mongolia Autonomous Region of China. METHODS: The 9 X-chromosomal STR loci were analyzed with polymerase chain reation (PCR), followed by polyacylamide gel electrophoresis and silver staining. Software SPSS13.0, Genepop, Fstat and Powerstats were used to evaluate their polymorphism diversity and potential forensic application. RESULTS: Allele frequencies and genotype frequencies of 99 unrelated Ewenki individuals were obtained. Among the 9 loci, DXS6789, HPRTB showed less polymorphism and diversity in the population. The diversity of DXS7132 has no statistical difference between Ewenki population and other 4 Asian populations. CONCLUSION: Except DXS6789, HPRTB, the other 7 X-chromosomal STR loci are appropriate for individual identification, paternity test involving a female child, and studies on related disease. DXS7132 should be excluded when being used to distinguish diversity difference among populations.

Novel mutations in ubiquitin-specific protease 26 gene might cause spermatogenesis impairment and male infertility.

AIM: To study the incidence of single nucleotide polymorphisms in ubiquitin-specific protease 26 (USP26) gene and its involvement in idiopathic male infertility in China. METHODS: Routine semen analysis was performed. Infertility factors such as immunological, infectious and biochemical disorders were examined to select patients with idiopathic infertility. DNA was isolated from peripheral blood of the selected patients and control population, which were examined for mutations using polymerase chain reaction-single strand conformation polymorphism analysis. Furthermore, nucleotide sequences were sequenced in some patients and controls. RESULTS: Of 41 infertile men, 9 (22.0%, P = 0.01) had changes in USP26 gene on the X chromosome. A compound mutation (364insACA; 460G right triple arrow A) was detected in 8 patients (19.5%, P = 0.01) and a 1044T right triple arrow A substitution was found in 1 patient (2.4%, P > 0.05). All three variations led to changes in the coding amino acids. Two substitutions predict some changes: 460G right triple arrow A changes a valine into an isoleucine, and 1044T right triple arrow A substitutes a leucine for a phenylalanine. Another insertion of three nucleotides ACA causes an insertion of threonine. No other changes were found in the remaining patients and fertile controls. CONCLUSION: The USP26 gene might be of importance in male reproduction. Mutations in this gene might be associated with male infertility, and might negatively affect testicular function. Further research on this issue is in progress.

Alterations of serum cholinesterase in patients with gastric cancer.

AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance. METHODS: The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls. RESULTS: The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P = 0.0003). Age was significantly associated with the incidence of gastric cancer. CONCLUSION: Serum CHE activity has a close relation with the incidence of gastric cancer.