Spatial and temporal distribution of physicochemical parameters of water in Gorgan Bay (the southeast of the Caspian Sea - Iran): Fundamentals for the monitoring of the Caspian Sea coastal areas.

Gorgan Bay as a main part of the Miankaleh (a natural biosphere reserve registered by UNESCO) is one of the richest ecological area in the West Asia and very important internationally recognized refuge for the wildlife. To date, multi physicochemical parameters have not been examined on a large scale. To fill this knowledge gap, the present study aimed to explore the seasonal and spatial variability of water quality parameters of the bay. The results showed that except for depth and transparency, there are significant variations in most parameters across the four seasons. The patterns of these changes in the bay vary, as evidenced by a comparison of the distribution maps of the various factors throughout the year. Notably, alkalinity declined from east to west, reaching its highest levels at important entry points such as the Qarasu River, Bandar-Gaz, and the pier. TDS, on the other hand, increased westward, reaching its highest concentration in the shallow western regions. Maximum depth (310 cm) and transparency (250 cm) were observed in the central bay. While the pH was higher in deeper areas, the distribution of PO4 was more uniform. With lower levels in the east (salinity = 0.40 ‰) and higher levels in the west (salinity = 28.9 ‰), the salinity showed a coherent gradient. Agricultural land use in the basin of the bay and fluxes of nutrients and sediments of the rivers entering the bay has significant contribution to the bay pollution situation. These results will serve as a guide for improving our understanding of the Gorgan Bay ecosystem. They also have implications for informed conservation and management plans adapted to the specifics of this special region within the Caspian Sea.

Combinatorial targeting of telomerase and DNA-PK induces synergistic apoptotic effects against Pre-B acute lymphoblastic leukemia cells.

BACKGROUND: Due to the high demand for novel approaches for leukemia-targeted therapy, this study investigates the impact of DNA-PK inhibitor NU7441 on the sensitivity of pre-B ALL cells to the telomerase inhibitor MST-312. METHODS: The study involved NALM-6 cells treated with MST-312 and NU7441, assessing their viability and metabolic activity using trypan blue and MTT assays. The study also evaluated apoptosis, gene expression changes, and DNA damage using flow cytometry, qRT-PCR, and micronucleus assays. The binding energy of MST-312 in the active site of telomerase was calculated using molecular docking. RESULTS: The study's findings revealed a synergistic decline in both cell viability and metabolic activity in NALM-6 cells when exposed to the combined treatment of MST-312 and NU7441, and this decrease occurred without any adverse effects on healthy PBMC cells. Furthermore, the combination treatment exhibited a significantly higher induction of apoptosis than treatment with MST-312 alone, as observed through flow cytometry assay. qRT-PCR analysis revealed that this enhanced apoptosis was associated with a notable downregulation of Bcl-2 expression and an upregulation of Bax gene expression. Moreover, the combination therapy decreased expression levels of hTERT and c-Myc genes. The micronucleus assay indicated that the combination treatment increased DNA damage in NALM-6 cells. Also, a good conformation between MST-312 and the active site of telomerase was revealed by docking data. CONCLUSIONS: The study suggests that simultaneous inhibition of telomerase and DNA-PK in pre-B ALL presents a novel targeted therapy approach.

Concomitant Expression of IL-6 and TGF-ß Cytokines and their Receptors in Peripheral Blood of Patients with Multiple Sclerosis: The Effects of INFß Drugs.

BACKGROUND: Concomitant signals from IL-6 and TGF-ß have a central role in the Th17 cells development and differentiation, and these cells are the main promoters of demyelinating inflammation in the central nervous system (CNS) resulting in multiple sclerosis (MS). OBJECTIVES: To evaluate the simultaneous IL-6 and TGF-ß gene and their receptor protein expression in patients with Relapsing-Remitting (RR)-MS. MATERIALS AND METHODS: IL-6 and TGF-ß mRNA and their receptor expression on the surface of CD4+T cells were evaluated using real-time PCR (RT-PCR) and flow cytometry, respectively. RESULTS: The IL-6 mRNA expression in patients with RRMS was significantly higher than in the controls (p= 0.019). When patients who did not receive any other treatment were compared with the controls, the significant difference was substantial (p=0.006). The TGF-ß mRNA expression in patients was lower than in the controls (p = 0.03). However, in patients receiving IFNß, it increased compared with the other patients (p= 0.036). There was no difference in cytokine receptor expression between patients and the control group. CONCLUSION: Our data conclude an increase and decrease in mRNA expression levels of IL-6 and TGF-ß in patients with RRMS, respectively. Moreover, there were no significant differences in receptor expression of either cytokines. Based on our data the balance of TGF and IL-6 appears to have a positive impact on the disease control.

Association of Herpes simplex virus I&II infections with rs187084 SNP of TLR9 and male infertility.

Since TLR9 recognises unmethylated CpG motifs in viral DNA, its polymorphisms may contribute to the susceptibility to Herpes simplex virus I&II infection. In the present study, to evaluate the role of rs187084 SNP (single nucleotide polymorphism) of TLR9 in Herpes simplex virus I&II infection and male infertility, 103 infertile and 27 fertile blood and semen samples were analysed. We assessed the micro and macro properties of semen specimens and the presence of HSV immunoglobulins. Tetra-primer ARMS PCR was used to detect SNP and to investigate the genotype distribution of TLR9-rs187084 SNPs, and the correlation between polymorphisms of TLR9 gene and male infertility. Moreover, the odds ratio (OR) and 95% confidence intervals were used to estimate the strength of the association. Based on our finding, a significant correlation was observed between HSV infection, agglutination and polymorphism (TT) under dominant (OR = 1.28, 95% CI = 0.94-1.75) and recessive (OR = 0.44, 95% CI = 0.21-0.94) models for the data, which was complied with Hardy-Weinberg equilibrium (HWE) (OR = 2.91, 95% CI = 1.02-8.30). The result showed a significant association between HSV IgM and agglutination in HSV infection (p < .001), and in addition, there were associations between alleles so that rs187084 SNP might be considered as a risk factor for the incidence of HSV infection.