Single‐nucleotide polymorphism c.474G>A in the SEPT12 gene is a predisposing factor in male infertility

SEPT12 is a testis‐specific gene involved in the terminal differentiation of male germ cells. SEPT12 protein is required for sperm head‐tail formation and acts as a fundamental constituent of sperm tail annulus. In this study, we screened genetic variations in exons 5, 6, 7 of the SEPT12 and assessed the annulus status in teratozoospermic, globozoospermic, and patients with immotile short tail sperm. DNA sequencing was performed for 90 teratozoospermic and 30 normozoospermic individuals. Immunocytochemistry, transmission electron microscopy and western blotting were conducted to evaluate annulus status and the expression level of SEPT12 in patients with a distinct exonic variation (c.474G>A), respectively. Five polymorphisms identified within the desired regions of the SEPT12, among them c.474G>A had the potential to induce aberrant splicing results in the expression of a truncated protein. The annulus was detected in most of the spermatozoa from teratozoospermic and normozoospermic men with c.474G>A. In contrast, in the patient with short tail sperm defect carrying c.474G>A, 99% of spermatozoa were devoid of the annulus. Based on our findings there would be no association between exons 5, 6, 7 polymorphisms of the SEPT12 gene and the occurrence of mentioned disease but c.474G>A would be a predisposing factor in male infertility.     

Association of polymorphisms in glutamate-cysteine ligase catalytic subunit and microsomal triglyceride transfer protein genes with nonalcoholic fatty liver disease

Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to examine the single nucleotide polymorphism (SNP) -129C/T (rs17883901) in glutamate-cysteine ligase catalytic subunit (GCLC) and SNPs I128T (rs3816873) and Q95H (rs61733139) in microsomal triglyceride transfer protein (MTTP) in NAFLD. Eighty-three patients with a diagnosis of NAFLD and 93 healthy subjects were included in the study. Tetra amplification refractory mutation system-polymerase chain reaction was designed to detect the SNPs. There were no significant differences in the polymorphism of -129C/T (rs17883901) of the GCLC gene among NAFLD and control groups (p?>?0.05). A significant difference was observed between NAFLD and control group regarding the SNP I128T (rs3816873) in the coding region of the MTTP gene (p?相似文献   

Antimicrobial susceptibility profiles associated with bacterial meningitis among children: a referral hospital-based study in Iran

Bacterial meningitis continues to be associated with high morbidity and mortality rate worldwide, especially in the pediatric age group. This study was performed to identify the microbial etiologies of meningitis among 31 children, who were admitted in the Emergency Ward of a referral pediatric hospital in Iran. Culture identification showed that Streptococcus pneumoniae (12 subjects), Haemophilus influenzae (11 subjects) were the most common bacteria, followed by Escherichia coli (7 cases) and Neisseria meningitidis (only one case). Antibiotic susceptibility tests revealed that vancomycin had the best effect on S. pneumoniae in comparison with other antibiotics, whereas H. influenzae and E. coli were more susceptible to ceftriaxone, ceftazidime, and ceftizoxime than other antibiotics. In conclusion, despite the advances in antibiotic therapy and vaccine development, bacterial meningitis still is a health problem. S. pneumoniae, H. influenzae, and N. meningitidis are the main sources of bacterial meningitis, but other organisms such as E. coli should also be suspected, when a case is admitted to a referral pediatric hospital.     

Core structure of flavonoids precursor as an antihyperglycemic and antihyperlipidemic agent: an in vivo study in rats

trans-Chalcone is the core structure of naringenin chalcone, located halfway in the biosynthesis pathway of flavonoids. Flavonoids have been reported as mammalian alpha-amylase inhibitors, a property which could be useful in the management of postprandial hyperglycemia in diabetes and related disorders. As a mammalian alpha-amylase inhibitor in vitro, the putative beneficial effect of trans-chalcone on diabetes was tested in a streptozotocin-induced rat model of diabetes type 1, and the results analyzed with commonly used statistical methods. Significant reduction of blood glucose levels and beneficial effect on dyslipidemia were observed in diabetic rats, as well as reduction of disturbing consequences of diabetes such as high urine volume and water intake. trans-chalcone was observed to have a weight loss-inductive effect, alongside with a reduction in food intake, which is suggestive of a therapeutic potential of this compound in overweight and obese patients.     

Role of the 5-HT1A Serotonergic System in Anxiolytic-Like Effects of Silymarin

We investigated the effects of silymarin, a component of the extract from milk thistle (Silybum marianum) on the level of anxiety in rats and also the potential role of the serotonergic system in the modulatory influences of silymarin on anxiety-related behavior. The elevated plus-maze test was used for testing the above level. Oral administrations of silymarin (35, 70, 140, and 280 mg per rat) for 2 weeks induced an anxiolytic-like effect shown by specific increases in normalized values of the open arm time (OAT) and open arm entries (OAE) in the elevated plus-maze. Intraventricular infusion of a 5-HT_1A receptor agonist, 8-OH-DPAT (5, 10, and 25 ng per rat), increased the OAT and OAE, indicating that this agent also possesses an anxiolytic effect. Similar injections of a 5-HT_1A receptor antagonist, NAN190 (0.25, 0.5, and 1.0 μg per rat), intensified anxiety-related behavior. The least effective dose of intraventricularly injected 8-OH-DPAT (5 ng per rat), when co-administered with silymarin (35, 70, and 140 mg per rat, pretreatment for 2 weeks), decreased the anxiety-related behavior significantly. An effective dose of NAN190 (0.5 μg per rat) combined with silymarin in the above-mentioned dosage provided significant decreases in the OAT and OAE. These results demonstrate that the effects of silymarin on anxiety are mediated, at least partly, by 5-HT_1A receptors of serotonin.     

Optimization of low-cost biosurfactant production from agricultural residues through response surface methodology

Biosurfactants are surface-active compounds capable of reducing surface tension and interfacial tension. Biosurfactants are produced by various microorganisms. They are promising replacements for chemical surfactants because of biodegradability, nontoxicity, and their ability to be produced from renewable sources. However, a major obstacle in producing biosurfactants at the industrial level is the lack of cost-effectiveness. In the present study, by using corn steep liquor (CSL) as a low-cost agricultural waste, not only is the production cost reduced but a higher production yield is also achieved. Moreover, a response surface methodology (RSM) approach through the Box–Behnken method was applied to optimize the biosurfactant production level. The results found that biosurfactant production was improved around 2.3 times at optimum condition when the CSL was at a concentration of 1.88 mL/L and yeast extract was reduced to 25 times less than what was used in a basic soybean oil medium (SOM). The predicted and experimental values of responses were in reasonable agreement with each other (Pred-R² = 0.86 and adj-R² = 0.94). Optimization led to a drop in raw material price per unit of biosurfactant from $47 to $12/kg. Moreover, the biosurfactant product at a concentration of 84 mg/L could lower the surface tension of twice-distilled water from 72 mN/m to less than 28 mN/m and emulsify an equal volume of kerosene by an emulsification index of (E24) 68% in a two-phase mixture. These capabilities made these biosurfactants applicable in microbial enhanced oil recovery (MEOR), hydrocarbon remediation, and all other petroleum industry surfactant applications.     

The effects of Fe(II) and Fe(III) concentration and initial pH on microbial leaching of low-grade sphalerite ore in a column reactor

In this study the effects of initial concentration of Fe(II) and Fe(III) ions as well as initial pH on the bioleaching of a low-grade sphalerite ore in a leaching column over a period of 120 days with and without bacteria were investigated. Four different modifications of medium were used as column feed solutions to investigate the effects of initial concentration of Fe(II) and Fe(III) ions on zinc extraction. The experiments were carried out using a bench-scale, column leaching reactor, which was inoculated with mesophilic iron oxidizing bacteria, Acidithiobacillus ferrooxidans, initially isolated from the Sarcheshmeh chalcopyrite concentrate (Kerman, Iran). The effluent solutions were periodically analyzed for Zn, total Fe, Fe(II) and Fe(III) concentrations as well as pH values. Bacterial population was measured in the solution (free cells). Maximum zinc recovery in the column was achieved about 76% using medium free of initial ferrous ion and 11.4 g/L of ferric ion (medium 2) at pH 1.5. The extent of leaching of sphalerite ore with bacteria was significantly higher than that without bacteria (control) in the presence of ferrous ions. Fe(III) had a strong influence in zinc extraction, and did not adversely affect the growth of the bacteria population.     

Adjuvant therapy with γ‐tocopherol‐induce apoptosis in HT‐29 colon cancer via cyclin‐dependent cell cycle arrest mechanism

Resistance to chemotherapy with 5‐fluorouracil (5‐FU) in patients with colorectal cancer (CRC) is the major obstacle to reach the maximum efficiency of CRC treatment. Combination therapy has emerged as a novel anticancer strategy. The present study evaluates the cotreatment of γ‐tocopherol and 5‐FU in enhancing the efficacy of chemotherapy against HT‐29 colon cancer cells. Cytotoxic effect of this combination was examined using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and a synergistic effect was evaluated by a combination index technique. Nuclear morphology was studied via 4′,6‐diamidino‐2‐phenylindole staining and flow cytometric assays were conducted to identify molecular mechanisms of apoptosis and cell cycle progression. We investigated the expression of Cyclin D1, Cyclin E, Bax, and Bcl‐2 by a quantitative real‐time polymerase chain reaction. The IC₅₀ values for 5‐FU and γ‐tocopherol were 21.8 ± 2.5 and 14.4 ± 2.6 μM, respectively, and also this combination therapeutic increased the percentage of apoptotic cells from 35% ± 2% to 40% ± 4% (P < .05). Furthermore, incubation HT‐29 colon cells with combined concentrations of two drugs caused significant accumulation of cells in the subGsubG1 phase. Our results presented the combination therapy with 5‐FU and γ‐tocopherol as a novel therapeutic approach, which can enhance the efficacy of chemotherapy.     

<Emphasis Type="Italic">Trans</Emphasis>-chalcone: a novel small molecule inhibitor of mammalian alpha-amylase

Trans-chalcone (1,3-diphenyl-2-propen-1-one), a biphenolic core structure of flavonoids precursor was tested for inhibitory activity toward alpha-amylase. Porcine pancreatic alpha-amylase was observed to be effectively inhibited by this compound, which showed competitive behavior with a K _i of 48 μM. Soluble starch (the natural substrate of the enzyme) was used in this study in order to obtain more realistic results. The possible binding mode of the compound was assessed in silico, and the two residues Trp59, and Tyr62 were proposed as main interacting residues with trans-chalcone. In conclusion, this compound could be used to design effective inhibitors of alpha-amylase.