MicroRNA-4731-5p delivered by AD-mesenchymal stem cells induces cell cycle arrest and apoptosis in glioblastoma

Glioblastoma multiforme (GBM) exhibits the most malignant brain tumor with very poor prognosis. MicroRNAs (miRNAs) are regulatory factors that can downregulate the expression of multiple genes. Several miRNAs acting as tumor-suppressor genes have been identified so far. The delivery of miRNA by mesenchymal stem cell (MSC) due to their ability to specifically target tumors is a new, hopeful therapeutic approach for glioblastoma. The objective of our study is the investigation of the effect of lentivirus-mediated microRNA-4731 (miR-4731) genetic manipulated adipose-derived (AD)-MSC on GBM. The downregulation of miR-4731 in human GBM tumor was detected using the GEO dataset. To evaluate the function of miR-4731, we overexpressed miR-4731 using lentiviral vectors in U-87 and U-251 GBM cell lines. The effects of miR-4731 on cell proliferation and cell cycle of glioma cells were analyzed by wound test and flow-cytometry assay. miR-4731 inhibited the proliferation of GBM cancer cells. Coculturing was used to study the antiproliferative effect of miR-4731-AD-MSCs on GBM cell lines. Direct and indirect coculture of GBM cell lines with miR-4731-AD-MSCs induced cell cycle arrest and apoptosis. Our findings suggest that AD-MSCs expressing miR-4731 have favorable antitumor characteristics and should be further explored in future glioma therapy.     

MicroRNAs in breast cancer: Roles,functions, and mechanism of actions

Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer.     

Cytoplasmic Ig alpha serine/threonines fine-tune Ig alpha tyrosine phosphorylation and limit bone marrow plasma cell formation

Igα serine 191 and 197 and threonine 203, which are located in proximity of the Igα ITAM, dampen Igα ITAM tyrosine phosphorylation. In this study, we show that mice with targeted mutations of Igα S191, 197, and T203 displayed elevated serum IgG2c and IgG2b concentrations and had elevated numbers of IgG2c- and IgG2b-secreting cells in the bone marrow. BCR-induced Igα tyrosine phosphorylation was slightly increased in splenic B cells. Our results suggest that Igα serine/threonines limit formation of IgG2c- and IgG2b-secreting bone marrow plasma cells, possibly by fine-tuning Igα tyrosine-mediated BCR signaling.     

Association of genetic polymorphisms of glutathione-S-transferase genes (GSTT1, GSTM1, and GSTP1) and susceptibility to nonalcoholic fatty liver disease in Zahedan, Southeast Iran

Oxidative damage is thought to play a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Glutathione-S-transferases (GSTs) are involved in cell protection against oxidative stress. We examined whether GSTM1, GSTT1, and GSTP1 polymorphisms are associated with NAFLD in a sample of the Iranian population. The current case-control study included 83 patients with NAFLD and 93 healthy subjects. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). The GSTP1 polymorphism was detected by tetra amplification refractory mutation system-PCR assay. The GSTM1-null genotype was significantly associated with the development of NAFLD (odds ratios [OR]=2.171, 95% confidence intervals [CI]=1.188-3.970, p=0.015). The GSTP1 Val allele was shown to be a risk factor for NAFLD (OR=1.739, 95% CI=1.089-2.777, p=0.024). The GSTT1 polymorphism was not significantly different between control and patient groups (p=0.221). This study showed that GSTM1 and GSTP1, but not GSTT1, genetic polymorphisms are associated with NAFLD in a sample of the Iranian population, and may be used to determine the risk of development of NAFLD.     

Optimization of biological sulfide removal in a CSTR bioreactor

In this study, biological sulfide removal from natural gas in a continuous bioreactor is investigated for estimation of the optimal operational parameters. According to the carried out reactions, sulfide can be converted to elemental sulfur, sulfate, thiosulfate, and polysulfide, of which elemental sulfur is the desired product. A mathematical model is developed and was used for investigation of the effect of various parameters on elemental sulfur selectivity. The results of the simulation show that elemental sulfur selectivity is a function of dissolved oxygen, sulfide load, pH, and concentration of bacteria. Optimal parameter values are calculated for maximum elemental sulfur selectivity by using genetic algorithm as an adaptive heuristic search. In the optimal conditions, 87.76% of sulfide loaded to the bioreactor is converted to elemental sulfur.     

Association of IL-15 and IP-10 Serum Levels with Cytomegalovirus Infection,CMV Viral Load and Cyclosporine Level after Kidney Transplantation

Background:Cytomegalovirus (CMV) infection is the most common complications following kidney transplantation. Natural killer (NK) cells demonstrated critical anti-viral role in controlling and elimination of CMV after transplantation. Interleukin-15 (IL-15) is a pleiotropic cytokine that promotes the activity of NK cells and strengthens the acquired immune system. Also, IP10 (CXCL10) is a chemotactic factor which regulates NK cell recruitment and antiviral immune response. We aimed to determine the correlation between the serum levels of IL-15 and IP-10 cytokines with CMV infection, CMV viral load, and cyclosporine as a major immunosuppressive treatment after transplantation.Methods:Fifty-eight kidney transplant recipient patients without evidence of CMV virus disease before transplantation surgery were included in the study. From the day of transplant surgery, the patients were evaluated based on the presence of CMV Ag pp65, CMV viral load, serum levels of IL-15 & IP-10, Cyclosporine levels (C0 & C2), Glomerular Filtration Rate (GFR), and hematological & biochemical Index, up to 75 days.Results:Comparison analysis of serum levels of IL-15 and IP-10 showed no significant association with CMV infection in kidney transplant recipients. In addition, CMV viral load and cyclosporine levels at C0 and C2 did not affect patients'' IL-15 and IP-10 levels.Conclusion:The levels of IP-10 and IL-15 cytokines are not affected with CMV infection, even if a viral infection occurs in the early days after transplantation or long afterwards. In addition, taking the different levels of cyclosporine did not affect the cytokines levels. Other mechanisms may play a role in maintaining the levels of these cytokines.Key Words: Cytokine, Cytomegalovirus, IP-10, Interleukin-15, Transplantation     

Ontogeny of the eotaxins in human lung

The ontogeny of the C-C chemokines eotaxin-1, eotaxin-2, and eotaxin-3 has not been fully elucidated in human lung. We explored a possible role for eotaxin in developing lung by determining the ontogeny of eotaxin-1 (CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), and the eotaxin receptor, CCR3. We tested discarded surgical samples of developing human lung tissue using quantitative RT-PCR (QRT-PCR) and immunostaining for expression of CCL11, CCL24, CCL26, and CCR3. We assessed possible functionality of the eotaxin-CCR3 system by treating lung explant cultures with exogenous CCL11 and analyzing the cultures for evidence of changes in proliferation and activation of ERK1/2, a signaling pathway associated with CCR3. QRT-PCR analyses of 22 developing lung tissue samples with gestational ages 10-23 wk demonstrated that eotaxin-1 mRNA is most abundant in developing lung, whereas mRNAs for eotaxin-2 and eotaxin-3 are minimally detectable. CCL11 mRNA levels correlated with gestational age (P < 0.05), and immunoreactivity was localized predominantly to airway epithelial cells. QRT-PCR analysis detected CCR3 expression in 16 of 19 developing lung samples. Supporting functional capacity in the immature lung, CCL11 treatment of lung explant cultures resulted in significantly increased (P < 0.05) cell proliferation and activation of the ERK signaling pathway, which is downstream from CCR3, suggesting that proliferation was due to activation of CCR3 receptors by CCL11. We conclude that developing lung expresses the eotaxins and functional CCR3 receptor. CCL11 may promote airway epithelial proliferation in the developing lung.     

Functional diversity of notch family genes in fetal lung development

In Drosophila, developmental signaling via the transmembrane Notch receptor modulates branching morphogenesis and neuronal differentiation. To determine whether the notch gene family can regulate mammalian organogenesis, including neuroendocrine cell differentiation, we evaluated developing murine lung. After demonstrating gene expression for notch-1, notch-2, notch-3, and the Notch ligands jagged-1 and jagged-2 in embryonic mouse lung, we tested whether altering expression of these genes can modulate branching morphogenesis. Branching of embryonic day (E) 11.5 lung buds increased when they were treated with notch-1 antisense oligodeoxynucleotides in culture compared with the corresponding sense controls, whereas notch-2, notch-3, jagged-1, or jagged-2 antisense oligos had no significant effect. To assess cell differentiation, we immunostained lung bud cultures for the neural/neuroendocrine marker PGP9.5. Antisense to notch-1 or jagged-1 markedly increased numbers of PGP9.5-positive neuroendocrine cells alone without affecting neural tissue, whereas only neural tissue was promoted by notch-3 antisense in culture. There was no significant effect on cell proliferation or apoptosis in these antisense experiments. Cumulatively, these observations suggest that interactions between distinct Notch family members can have diverse tissue-specific regulatory functions during development, arguing against simple functional redundancy.     

Partial distal 10q trisomy due to de novo amplification: A new case without furrows or ridges in fingers and palms

Background:

Here we describe a new case of partial distal 10q trisomy in a 6-year-old Iranian girl from healthy parents with mental, growth, and psychomotor retardations.

Methods:

Additional clinical features include dysmorphic craniofacial features, microcephaly, bilateral hydronephrosis without heart problems, small and rotated low-set ears, bow-shaped mouth, abnormal teeth, short neck, and as a first case reported, fingers with camptodactly (i.e., without any furrows or ridges in the palms and fingers).

Results:

Cytogenetic analysis (GTG-banding) revealed an unbalanced female karyotype with additional bands at the end of the long arm of chromosome 10, karyotype: 46,XX,dup(10)(q25q26).

Conclusion:

According to the banding pattern it is most likely that a duplication of the distal part of the long arm of chromosome 10 occurred.Key Words: Trisomy, 10q, Distal, de novo