Influence of genetic polymorphisms of glutathione S-transferase T1 (<Emphasis Type="Italic">GSTT1</Emphasis>) and M1 (<Emphasis Type="Italic">GSTM1</Emphasis>) on hematological parameters

To find the influence of genetic polymorphisms of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) on hematological parameters in smoker and non-smoker subjects, the present study was done. This cross-sectional study was conducted on 97 healthy males (24 smokers, 73 non-smokers). The genotypes were determined using a polymerase chain reaction based method. In non-smokers, there was no statistically association between number of active genes and the study parameters. However, in smokers, RBC count was significantly decreased in null genotypes of GSTT1 (t = 3.021, df = 22, P = 0.006) and GSTM1 (t = 2.141, df = 22, P = 0.044). Also, in smokers, RBC count significantly decreased in persons having GSTM1 and GSTT1 null genotypes in comparison with subjects having two active genes (F = 5.554; df = 2, 21; P = 0.012). Because elevated RBC count correlate well with risk of coronary heart disease, it might be concluded that GSTM1 and GSTT1 null genotypes have protective role(s) for developing coronary heart disease.     

Bioinformatics prediction and experimental validation of a novel microRNA: hsa-miR-B43 within human CDH4 gene with a potential metastasis-related function in breast cancer

As a class of short noncoding RNAs, microRNAs (miRNAs) play a key role in the modulation of gene expression. Although, the regulatory roles of currently identified miRNAs in various cancer types including breast cancer have been well documented, there are many as yet undiscovered miRNAs. The aim of the current study was to bioinformatically reanalyze a list of 189 potentially new miRNAs introduced in a previously published paper (PMID: 21346806) and experimentally explore the existence and function of a candidate one: hsa-miR-B43 in breast cancer cells. The sequences of 189 potential miRNAs were re-checked in the miRbase database. Genomic location and conservation of them were assessed with the University of California Santa Cruz (UCSC) genome browser. SSC profiler, RNAfold, miRNAFold, MiPred, and FOMmiR bioinformatics tools were furthermore utilized to explore potential hairpin structures and differentiate real miRNA precursors from pseudo ones. hsa-miR-B43 was finally selected as one of the best candidates for laboratory verification. The expression and function of hsa-miR-B43 were examined by real-time polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and wound-healing assays. DIANA-microT, RNAhybrid and Enrichr tools were used to predict the miRNA target genes and for further enrichment analysis. We could detect the exogenous and endogenous expression of hsa-miR-B43, as a real novel miRNA, in cancer cell lines. Gene Ontology enrichment, pathway analysis and wound-healing assay results furthermore confirmed that a metastasis-related function may be assigned to hsa-miR-B43. Our results introduced hsa-miR-B43, as a novel functional miRNA, which might play a role in the metastatic process. Further studies will be necessary to completely survey the existence and function of hsa-miR-B43 in other cancer types.     

Pericentric inversion of “fluorescent” segment in chromosome No. 3

During a short time span we identified 3 unrelated cases of pericentric inversion of the “fluorescent” segment in one chromosome No. 3. All 3 propositae were mentally defective female patients of a mental hospital; 1 case was familial with phenotypically normal father and grandfather.     

Mesenchymal stem cell mediated effects on microglial phenotype in cuprizone-induced demyelination model

Microglial cells have an essential role in neurodegenerative disorders, such as multiple sclerosis. They are divided into two subgroups: M1 and M2 phenotypes. Mesenchymal stem cells (MSC), with neuroprotective and immunomodulating properties, could improve these diseases. We evaluate the immunomodulating effects of MSC on microglial phenotypes and the improvement of demyelination in a cuprizone (CPZ) model of multiple sclerosis (MS). For inducing the chronic demyelination model, C57BL6 mice were given a diet with 0.2% CPZ (w/w) for 12 weeks. In the MSC group, cells were transplanted into the right lateral ventricle of mice. The expression of targeted genes was assessed by real-time polymerase chain reaction. M1 and M2 microglial phenotypes were assessed by immunohistochemistry of inducible nitric oxide synthase (iNOS) and Arg-1, respectively. Remyelination was studied by luxal fast blue (LFB) staining and electron microscopy (EM). We found that MSC transplantation reduced the expression level of M1-specific messenger RNA (mRNA; iNOS and CD86) but increased the expression level of M2 specific genes (CD206, Arg-1, and CX3CR1) in comparison to the CPZ group. Moreover, cell therapy significantly decreased the M1 marker (iNOS⁺ cells), but M2 marker (Arg-1⁺ cells) significantly increased in comparison with the CPZ group. In addition, MSC treatment significantly increased the CX3CL1 expression level in comparison with the CPZ group and led to improvement in remyelination, which was confirmed by LFB and EM images. The results showed that MSC transplantation increases the M2 and decreases the M1 phenotype in MS. This change was accompanied by decrease in demyelination and axonal injury and indicated that MSCs have a positive effect on MS by modification of microglia cells.     

Analytical Study of Carrier Generation Rate in Graphene Nanoscroll

Graphene nanoscroll introduced recently is another form of a graphene-based two-dimensional material, which is especially attractive in nanoelectronic applications. As carriers can travel ballistically or semi-ballistically, they can reach high-speed and energy if the channel length is enough. Therefore, they can collide and result in an excessive current called ionisation current. As a result, it is important to study this mechanism carefully. In this paper, we propose an analytical approach to calculate an ionisation coefficient.

     

Macrophage polarity in cancer: A review

Macrophages are the most abundant cells within the tumor stroma displaying noticeable plasticity, which allows them to perform several functions within the tumor microenvironment. Tumor-associated macrophages commonly refer to an alternative M2 phenotype, exhibiting anti-inflammatory and pro-tumoral effects. M2 cells are highly versatile and multi-tasking cells that directly influence multiple steps in tumor development, including cancer cell survival, proliferation, stemness, and invasiveness along with angiogenesis and immunosuppression. M2 cells perform these functions through critical interactions with cells related to tumor progression, including Th2 cells, cancer-associated fibroblasts, cancer cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells. M2 cells also have negative cross-talks with tumor suppressor cells, including cytotoxic T cells and natural killer cells. Programed death-1 (PD-1) is one of the key receptors expressed in M2 cells that, upon interaction with its ligand PD-L1, plays cardinal roles for induction of immune evasion in cancer cells. In addition, M2 cells can neutralize the effects of the pro-inflammatory and anti-tumor M1 phenotype. Classically activated M1 cells express high levels of major histocompatibility complex molecules, and the cells are strong killers of cancer cells. Therefore, orchestrating M2 reprogramming toward an M1 phenotype would offer a promising approach for reversing the fate of tumor and promoting cancer regression. Macrophage switching toward an anti-inflammatory M1 phenotype could be used as an adjuvant with other approaches, including radiotherapy and immune checkpoint blockades, such as anti-PD-L1/PD-1 strategies.     

Palmitate and inflammatory state additively induce the expression of PTP1B in muscle cells

The factors responsible for up-regulation of PTP1B, a negative regulator of insulin signaling, in insulin resistance state are not well understood. We performed a series of experiments in C2C12 muscle cells to determine the role of palmitate and an inflammatory state in regulation of PTP1B. Palmitate (0.75 mM) induced PTP1B mRNA and protein level only at 16 h. The combination of palmitate and macrophages, accompanied by a great increase of TNF-α and IL-6 in the culture media, additively caused a higher level of PTP1B protein levels in the muscle. Higher concentrations of palmitate reduced insulin stimulated glucose uptake in myotubes. A specific inhibitor of PTP1B partly increased insulin stimulated glucose uptake in palmitate treated cells. In conclusion, our results showing the additive influence of palmitate and the inflammatory state in the expression of PTP1B imply the involvement of these factors in the overexpression of PTP1B in insulin resistance state. We further provided the evidence suggesting the mediatory role for PTP1B in palmitate induced insulin resistance in myotubes.     

Moderate O3/O2 therapy enhances enzymatic and non-enzymatic antioxidant in brain and cochlear that protects noise-induced hearing loss

Mitochondrial damage and oxidative stress are known to contribute to the pathogenesis of noise-induced hearing loss (NIHL). In this study, we examined the protective effect of O₂/O₃ mixture (ozone/oxygen) therapy against mitochondrial induced damage and oxidative stress by noise exposure in rat brain and cochlear. For this purpose, rats were divided into four groups: 1 – control group; 2 – noise-exposed group (100?dB); 3 – noise?+?O₂/O₃, and 4 – O₂/O₃ (30 µg/ml). After 14 d, animals were anesthetised. Rat brain and cochlear tissue were removed for evaluation of the histopathological damages, oxidative stress, and mitochondrial dysfunction in both tissues. Our findings indicated that noise caused pathological damage, oxidative stress, and mitochondrial dysfunction in rat brain and cochlear. Also, daily administration of an O₂/O₃ therapy (30 µg/ml intravenous) efficiently increased enzymatic and non-enzymatic antioxidant in brain and cochlear that this action led to inhibition of pathological damages, oxidative stress, reactive oxygen species formation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and cytochrome c release resulting from noise. These findings suggest that the moderate O₂/O₃ therapy enhances the capacity of enzymatic and non-enzymatic antioxidant in brain and cochlear that protects against NIHL.