High Concentration of Fluoride Can Be Increased Risk of Abortion

The presence of fluoride in drinking water can be either beneficial or harmful for human health, depending on its concentration. Most adverse effects of fluoride are observed at high concentrations (above 1.5 mg/L). This study was aimed to evaluate the effect of fluoride concentrations in drinking water on spontaneous abortion in two regions: one with low fluoride concentration and another with high fluoride concentration. The results showed that there is a relationship between the concentration of fluoride in drinking water and abortion, so that the risk of abortion increased at high concentrations of fluoride. However, further studies are needed to clarify this relationship due to the small area and population in this study.     

Length–weight relationships of two endemic species of Alburnoides nicolausi (Bogutskaya & Coad, 2009) and Alburnus zagrosensis (Coad, 2009) in Houzian River,Lorestan Province,Iran

This investigation prepares the length–weight relationships (LWRs) of two fish species, including Alburnoides nicolausi (Bogutskaya & Coad, 2009) and Alburnus zagrosensis (Coad, 2009) from Houzian River (latitude 33°22′15.20″ to 33°21′31.57″N; longitude 49°44′39.66″ to 49°44′17.67″E), Lorestan province, Iran. Fish specimens were collected monthly using seine net with 5 mm (Stretched) mesh size between April to September 2017. The LWRs for fish species were W = 0.0059L^3.405 (male) and W = 0.0053L^3.494 (female) for A. nicolausi, W = 0.0035L^3.341 (male) and W = 0.003L^3.387 (female) for A. zagrosensis, respectively. The highest value of r² was .931 for male of A. zagrosensis and lowest value was .964 for male of A. nicolausi.     

Prognostic Significance of Substance P and Neurokinin-1 Receptor in Bladder Cancer

Background:Bladder cancer is one of the most common genitourinary cancers with significant mortality. Finding reliable tumor markers and potential drug targets can improve early diagnosis, prognosis, and more effective therapeutic protocols. Previous studies have reported the involvement of the substance P (SP)/neurokinin-1 receptor (NK-1R) system in cancers. The potential prognostic role and the interaction of SP and NK-1R in bladder tumor are yet to be elucidated.Methods:Serum samples from 22 primarily diagnosed patients with bladder cancer as well as 22 healthy controls were examined for SP level using ELISA method. Tissue distribution of NK-1R in tumor samples and their adjacent normal tissues was evaluated through immunohistochemistry.Results:Serum SP levels in patients with bladder cancer were higher than the healthy group (p< 0.001) and had a significant correlation with NK-1R staining intensity (p< 0.001), percentage of stained cells (p< 0.001), and NK-1R tissue distribution. Also, the immunoreactivity of NK-1R in cancer samples increased significantly without correlation with tumor characteristics. However, no significant association was found between SP and NK-1R levels with clinical characteristics including tumor size (p= 0.33), tumor stage (p= 0.29), grade (p= 0.93), NK-1R staining intensity (p= 0.53), and percentage of stained cells (p= 0.32).DiscussionAccording to our findings, despite the lack of association between SP and NK-1R with clinical characteristics of bladder cancer, their serum levels were higher in patients with bladder cancer. Further studies are needed to confirm the potential prognostic role of SP and NK-1R in bladder cancer.Key Words: Biomarker, Bladder cancer, Neurokinin-1 receptor, Substance P, Prognosis     

Evaluation of Oxidative Stress,Apoptosis, and Expression of MicroRNA-208a and MicroRNA-1 in Cardiovascular Patients

Background:MicroRNA expression signature and reactive oxygen species (ROS) production have been associated with the development of cardiovascular diseases (CVDs). This study aimed to evaluate oxidative stress, inflammation, apoptosis, and the expression of miRNA-208a and miRNA-1 in cardiovascular patients.Methods:The study population included four types of patients (acute coronary syndromes (ACS), myocardial infarction (MI), arrhythmia, and heart failure (HF)), with 10 people in each group, as well as a control group. Quantitative real-time PCR was performed to measure mir-208 and miR-1 expression, the mRNAs of inflammatory mediators (TNFα, iNOS/eNOS), and apoptotic factors (Bax and Bcl2). XOX, MDA, and antioxidant enzymes (CAT, SOD, and GPx) were measured by ZellBio GmbH kits by an ELISA Reader.Results:The results showed significant decreases in the activity of antioxidant enzymes (CAT, SOD, and Gpx) and a significant increase in the activity of the MDA and XOX in cardiovascular patients. Significant increases in IL-10, iNos, iNOS / eNOS, and TNF-α in cardiovascular patients were also observed. Also, a significant increase in the expression of miR-208 (HF> arrhythmia> ACS> MI) and a significant decrease in the expression of miR-1 (ACS> arrhythmia> HF> MI) were found in all four groups in cardiovascular patients.Conclusion:The results showed increases in oxidative stress, inflammation, apoptotic factors, and in the expression of miR-208a in a variety of cardiovascular patients (ACS, MI, arrhythmia, and HF). It is suggested that future studies determine the relationships that miR-1, miR-208, and oxidative stress indices have with inflammation and apoptosis.Key Words: Apoptosis, Cardiovascular diseases, Inflammation, microRNA-208a, microRNA-1, Oxidative stress     

A proteomics view on the role of drought-induced senescence and oxidative stress defense in enhanced stem reserves remobilization in wheat

Drought is one of the major factors limiting the yield of wheat (Triticum aestivum L.) particularly during grain filling. Under terminal drought condition, remobilization of pre-stored carbohydrates in wheat stem to grain has a major contribution in yield. To determine the molecular mechanism of stem reserve utilization under drought condition, we compared stem proteome patterns of two contrasting wheat landraces (N49 and N14) under a progressive post-anthesis drought stress, during which period N49 peduncle showed remarkably higher stem reserves remobilization efficiency compared to N14. Out of 830 protein spots reproducibly detected and analyzed on two-dimensional electrophoresis gels, 135 spots showed significant changes in at least one landrace. The highest number of differentially expressed proteins was observed in landrace N49 at 20days after anthesis when active remobilization of dry matter was observed, suggesting a possible involvement of these proteins in effective stem reserve remobilization of N49. The identification of 82 of differentially expressed proteins using mass spectrometry revealed a coordinated expression of proteins involved in leaf senescence, oxidative stress defense, signal transduction, metabolisms and photosynthesis which might enable N49 to efficiently remobilized its stem reserves compared to N14. The up-regulation of several senescence-associated proteins and breakdown of photosynthetic proteins in N49 might reflect the fact that N49 increased carbon remobilization from the stem to the grains by enhancing senescence. Furthermore, the up-regulation of several oxidative stress defense proteins in N49 might suggest a more effective protection against oxidative stress during senescence in order to protect stem cells from premature cell death. Our results suggest that wheat plant might response to soil drying by efficiently remobilize assimilates from stem to grain through coordinated gene expression.     

Homodimerization Controls the Fibroblast Growth Factor 9 Subfamily's Receptor Binding and Heparan Sulfate-Dependent Diffusion in the Extracellular Matrix

Uncontrolled fibroblast growth factor (FGF) signaling can lead to human diseases, necessitating multiple layers of self-regulatory control mechanisms to keep its activity in check. Herein, we demonstrate that FGF9 and FGF20 ligands undergo a reversible homodimerization, occluding their key receptor binding sites. To test the role of dimerization in ligand autoinhibition, we introduced structure-based mutations into the dimer interfaces of FGF9 and FGF20. The mutations weakened the ability of the ligands to dimerize, effectively increasing the concentrations of monomeric ligands capable of binding and activating their cognate FGF receptor in vitro and in living cells. Interestingly, the monomeric ligands exhibit reduced heparin binding, resulting in their increased radii of heparan sulfate-dependent diffusion and biologic action, as evidenced by the wider dilation area of ex vivo lung cultures in response to implanted mutant FGF9-loaded beads. Hence, our data demonstrate that homodimerization autoregulates FGF9 and FGF20''s receptor binding and concentration gradients in the extracellular matrix. Our study is the first to implicate ligand dimerization as an autoregulatory mechanism for growth factor bioactivity and sets the stage for engineering modified FGF9 subfamily ligands, with desired activity for use in both basic and translational research.Fibroblast growth factor (FGF) signaling plays pleiotropic roles throughout the life spans of mammalian organisms, ranging from germ cell maturation, mesoderm induction, body plan formation, and organogenesis during embryonic development to serum phosphate homeostasis and glucose, bile acid, lipid, and cholesterol metabolism in the adult (3, 23, 27, 28, 57, 60, 62). The diversity of FGF signaling is underscored by virtue of the fact that aberrant FGF signaling leads to a wide array of human diseases, including skeletal and olfactory/reproductive syndromes, phosphate wasting disorders, and cancer (16, 60, 67). Recent data also implicate dysregulated FGF signaling in the etiology of neurodegenerative disorders, such as major depressive disorder and Parkinson''s disease (10, 63, 64).Based on pairwise sequence homology and phylogeny, the 18 bona fide mammalian FGFs (FGF1 to FGF10 and FGF16 to FGF23) are divided into six subfamilies (45). Five FGF subfamilies have high-to-moderate affinity for pericellular heparan sulfate (HS) glycosaminoglycans and thus diffuse locally within tissues to act in a paracrine fashion, whereas the poor affinity of the FGF19 subfamily for HS enables this subfamily to act in an endocrine manner (28, 38). All FGFs share a core homology region of about 120 amino acids, which fold into 12 antiparallel β strands (β1 to β12) that are arranged into three sets of four-stranded β sheets (β-trefoil fold) (39). The globular FGF core domain is flanked by highly divergent N- and C-terminal extensions, which are the principal regions responsible for the different biology of FGFs.FGFs exert their diverse actions by binding and activating FGF receptors (FGFRs) in an HS-dependent fashion (51, 53, 69). There are four distinct mammalian FGFR genes (FGFR1 to FGFR4), each coding for a single-pass transmembrane tyrosine kinase receptor whose ectodomain consists of three immunoglobulin-like domains (D1 to D3) connected by flexible linkers and whose intracellular domain contains the conserved tyrosine kinase domain flanked by the juxtamembrane (JM) and C-terminal regions (38). The 210-amino-acid-long D2-D3 segment of the ectodomain is both necessary and sufficient for ligand binding (20, 51, 52, 58, 70).FGF signaling is tightly regulated by spatial and temporal expression of ligands, receptors, HS cofactors, and most critically by means of FGF-FGFR binding specificity. The tissue-specific alternative splicing in the D3 domain of FGFR1 to FGFR3 is the main mechanism by which FGF-FGFR binding specificity is regulated. This splicing event gives rise to epithelial “b” isoforms (FGFR1b to FGFR3b) and mesenchymal “c” isoforms (FGFR1c to FGFR3c) (24, 25, 47, 68), which differ from one another at the primary sequences of their key ligand binding regions and thus in their FGF binding specificity/promiscuity profiles. Most FGFs are also expressed in either epithelial or mesenchymal tissues and exhibit specificity for FGFR isoforms expressed in the opposite tissues. This results in the establishment of a bidirectional signaling loop between the epithelium and mesenchyme that is essential for organogenesis and tissue homeostasis. It is well established that FGF7 and FGF10, which are expressed exclusively in the mesenchyme, activate specifically FGFR2b to mediate mesenchymal-to-epithelial signaling in the lung, prostate, and lacrimal, mammary, and salivary glands (19, 29, 35, 36, 59). Several lines of genetic and biochemical evidence suggest that the members of the FGF9 subfamily, which includes FGF9, FGF16, and FGF20, convey the reciprocal signaling from the epithelium to the mesenchyme. In the prostate, the epithelial-specific FGF9 has been shown to activate mesenchymal FGFR3c isoforms (25). In the heart, FGF9, FGF16, and FGF20 in the epicardium and endocardium stimulate myocardial proliferation and differentiation in vivo, acting redundantly through FGFR1c and FGFR2c (32). Analysis of FGF9-deficient mice has identified FGF9 as a reciprocal epithelial-to-mesenchymal signal required for morphogenesis of the lung, cecum, small intestine, and inner ear (14, 49, 65, 71). In addition, studies in zebra fish show that FGF16 and FGF20 are apical ectodermal ridge factors that are required for pectoral fin bud outgrowth and, in general, for cell proliferation and differentiation of the mesenchyme (41, 66).In light of the key role of the FGF9 subfamily in tissue homeostasis, it is essential to investigate the molecular mechanisms by which the activity of this subfamily is regulated. Our previous structural and in vitro studies of FGF9 showed that homodimerization masks FGF9''s key receptor binding sites, suggesting that ligand dimerization may autoinhibit FGF9''s biologic activity (50). In this report, we show that, like FGF9, FGF20 also homodimerizes in the crystal and in solution. Characterization of the dimer interface mutations in vitro and in living cells demonstrates that ligand homodimerization autoinhibits FGF9 and FGF20 signaling by suppressing both receptor binding and HS-dependent diffusion in the extracellular matrix (ECM). Our study is the first to implicate ligand dimerization as an autoregulatory mechanism in growth factor bioactivity.     

Deoxyribonucleic acid repair gene X-ray repair cross-complementing group 1 polymorphisms and non-carcinogenic disease risk in different populations: A meta-analysis

PURPOSE:

This study aims to assess a meta-analysis of the association of X-ray repair cross-complementing group 1 (XRCC1) polymorphisms with the risk of various non-carcinogenic diseases in different population.

MATERIALS AND METHODS:

This meta-analysis was performed by critically reviewing reveals 38 studies involving 10043 cases and 11037 controls. Among all the eligible studies, 14 focused on Arg194Trp polymorphism, 33 described the Arg399Gln and three articles investigated on Arg280His. Populations were divided into three different ethnic subgroups include Caucasians, Asians and other (Turkish and Iranian).

RESULTS:

Pooled results showed no correlation between Arg194Trp and non-carcinogenic disease. There was only weak relation in the recessive (odds ratio [OR] =1.11, 95% confidence interval [CI]: 0.86-1.44) model in Asian population and dominant (OR = 1.04, 95% CI: 0.66-1.63) model of other populations. In Arg399Gln polymorphism, there was no relation with diseases of interest generally. In the pooled analysis, there were weak relation in the dominant (OR = 1.08, 95% CI: 0.86-1.35) model of Asian population and quite well-correlation with recessive (OR = 1.49, 95% CI: 1.19-1.88), dominant (OR = 1.23, 95% CI: 0.94-1.62), and additive (OR = 1.23, 95% CI: 0.94-1.62) models of other subgroup. For Arg280His, there was a weak relation only in the dominant model (OR = 1.06, 95% CI: 0.74-1.51).

CONCLUSION:

The present meta-analysis correspondingly shows that Arg399Gln variant to be associated with increased non-carcinogenic diseases risk through dominant and recessive modes among Iranian and Turkish population. It also suggests a trend of dominant and recessive effect of Arg280His variant in all population and its possible protective effect on non-carcinogenic diseases.     

In silico Analysis of Different Signal Peptides for the Excretory Production of Recombinant NS3-GP96 Fusion Protein in Escherichia coli

International Journal of Peptide Research and Therapeutics - Escherichia coli is one of the simplest hosts which is widely being used to express heterologous proteins. However, without appropriate...