Tropisetron improved testicular inflammation in the streptozotocin-induced diabetic rats: The role of toll-like receptor 4 (TLR4) and mir146a

As a serotonin antagonist, tropisetron positively affects blood glucose lowering, insulin synthesis, pancreas inflammation, and apoptosis in diabetes. Reproductive disorders are one of the diabetes-induced chronic complications. The present study aimed to evaluate the effect of tropisetron on diabetes-induced testicular inflammation, its signaling pathway, and mir146a. To this end, animals were assigned to the control, tropisetron, diabetes (DM), DM-tropisetron, and DM-glibenclamide groups. Streptozotocin (50 mg/kg) was intraperitoneally injected to provide diabetes. Tropisetron and glibenclamide were then administrated intraperitoneally for 2 weeks after diabetes induction. Testes histology, real-time polymerase chain reaction, western blot analysis, ELISA, and immunohistochemistry assays were also performed. The finding revealed that tropisetron significantly improved diabetes-induced testis damages, lowered TLR4, TRAF6, IRAK1, NF-κB, and caspase3 protein expressions, and decreased TNF-α and IL-1 levels. Moreover, the mir146a expression declined following the tropisetron treatment. This study demonstrated that the significant role of tropisetron in lowering testicular inflammation and apoptosis might have been due to the inhibition of the TLR4/IRAK1/TRAF6 signaling pathway and thereby the attenuation of NF-κB and caspase3 expression and inflammatory cytokines. Furthermore, the downregulation of mir146a, as an inflammatory microRNA interacting with TLR4, showed another pathway, through which tropisetron improved diabetes-induced testicular injuries.     

Conjugation of tetanus toxoid with Salmonella typhimurium PTCC 1735 O-specific polysaccharide and its effects on production of opsonizing antibodies in a mouse model

Serious enteric and extra-intestinal infections with Salmonella typhimurium are very common in many human populations. Phagocytosis is the main defense mechanism against this bacterium; however, the unique structure of S. typhimurium lipopolysaccharide (LPS) makes it resistant to opsonization by complement components. In the present study, the S. typhimurium LPS O-chain was purified and conjugated with tetanus toxoid and the effects of the conjugated vaccine (O-specific polysaccharide tetanus toxoid (O-SP-TT)) on induction of specific antibodies were investigated in a mouse model. In vitro assays measuring phagocytosis in the presence of opsonizing antibodies were performed. Three subcutaneous injections of the O-SP-TT conjugate conferred protection against the intraperitoneal challenge with S. typhimurium and the LD50 was greater for immunized animals than for controls. The mean number of ingested S. typhimirium / mouse peritoneal cell in the presence of sera obtained from immunized mice with purified O-chain, O-SP-TT conjugate, heat-killed bacteria, and negative control were 6.96, 14.24, 15.96, and 6.67, respectively. In summary, we developed an O-SP-TT conjugate that induced opsonizing antibodies that increased phagocytosis, as determined by in vitro assays. In addition, chemiluminescence results, an indicator of oxidative burst, indicated that peritoneal cells respond better to live S. typhimurium cells in the presence of sera obtained from O-SP-TT conjugate immunized mice.     

Cloning, Expression, Purification and Toxicity Evaluation of Helicobacter pylori Outer Inflammatory Protein A

The Helicobacter pylori outer membrane proteins play an important role in pathogenesis; the outer inflammatory protein A (OipA) is one of these proteins which play the main role in the development of inflammation. In this study, purification of recombinant H. pylori OipA was performed by Ni–NTA affinity chromatography. Gastric carcinoma epithelial cells (AGS cell) were treated by different concentrations of recombinant OipA for various lengths of time and cell viability was evaluated by the viability assay. Statistical analysis showed that OipA had toxic effects on AGS cells in a concentration of 500 ng/ml after 24 and 48 h, and this toxic dose was 256 ng/ml after 72 h. OipA had direct toxic effects on gastric epithelial cells and the toxicity was observed to depend on time and dose of H. pylori exposure. Attachment of H. pylori to gastric epithelial cells is a key part in the pathogenesis and enables H. pylori to damage the epithelial cells with OipA.     

A firefly luciferase assay for subnanomolar concentrations of amphipathic substances

A sensitive assay is described for accurately quantitating subnanomolar aqueous concentrations of a wide variety of amphipathic and hydrophobic biological materials. This paper extends a luciferase-luciferin method previously used to measure aqueous concentrations of anesthetics to a variety of hormones, metabolites, and membrane active agents. The assay can cover analyte ranges from picomolar to micromolar. The sensitivity of the assay is shown to correlate with the hydrophobic nature of the analyte. The mechanism of the assay appears to result from competition of analyte with luciferin for a hydrophobic binding site on the luciferase molecule. This assay allows measurement of the partitioning of analytes into lipid bilayers from aqueous solution.     

Use FMEA method for environmental risk assessment in ore complex on wildlife habitats

Human activities are the most effective cause of wildlife habitat destruction and loss of quality. Some of these activities are the construction, operation, and utilization of mines. The present study investigates factory activity in the GolGoharSirjanOre Complex (Kerman province) and environmental risk assessment of the activities done by this complex on wildlife habitat. In order to identify the significant aspects of the complex, the Failure Mode and Effects Analysis (FMEA) method is used. To determine the risk priority number, the significant aspects resulted from the multiplication of the criteria including probability of occurrence, the probability of detection, and severity of the effect. Based on the results of the current study, most of the activities of GolGoharSirjan Complex can have a significant adverse impact on the habitat of birds such as bustard Chlamydotisundulata (Vulnerable [VU]) and Podocespleskei, and mammals such as Striped Hyaena (Hyaenahyaena) (Near Threatened [NT]) and Capra aegagrus (Wild Goat) (VU). Some of the most important activities related to the activity include: Crusher (Risk Priority Number [RPN] = 720), the concentration of iron ore (RPN = 640), mining (RPN = 486), Stalker and Reclaiming (RPN = 504), and the transport of heavy machinery (RPN = 432). Significant aspects such as the emission of dust into the air; Nitrogen Oxide (NOX), Sulphur Oxide (SOX), and Hydrogen Sulfide (H2S) gas emissions to air; vibration; noise; and industrial waste discharges significantly influence the environment. The results of measurements of environmental pollutants that are carried out by reliable environmental laboratories have shown that the amount of pollutants mentioned are above the standard limit determined by the Iranian Department of Environment.     

Heterogeneous Determinants of Quality of Life in Different Phenotypes of Parkinson’s Disease

Objectives

Health-related quality of life (HRQoL) is considered a very important outcome indicator in patients with Parkinson’s disease (PD). A broad list of motor and non-motor features have been shown to affect HRQoL in PD, however, there is a dearth of information about the complexity of interrelationships between determinants of HRQoL in different PD phenotypes. We aimed to find independent determinates and the best structural model for HRQoL, also to investigate the heterogeneity in HRQoL between PD patients with different phenotypes regarding onset-age, progression rate and dominant symptom.

Methods

A broad spectrum of demographic, motor and non-motor characteristics were collected in 157 idiopathic PD patients, namely comorbidity profile, nutritional status, UPDRS (total items), psychiatric symptoms (depression, anxiety), fatigue and psychosocial functioning through physical examination, validated questionnaires and scales. Structural equation model (SEM) and multivariate regressions were applied to find determinants of Parkinson’s disease summary index (PDSI) and different domains of HRQoL (PDQ-39).

Results

Female sex, anxiety, depression and UPDRS-part II scores were the significant independent determinants of PDSI. A structural model consisting of global motor, global non-motor and co-morbidity indicator as three main components was able to predict 89% of the variance in HRQoL. In older-onset and slow-progression phenotypes, the motor domain showed smaller contribution on HRQoL and the majority of its effects were mediated through non-motor features. Comorbidity component was a significant determinant of HRQoL only among older-onset and non-tremor-dominant PD patients. Fatigue was not a significant indicator of non-motor component to affect HRQoL in rapid-progression PD.

Conclusions

Our findings showed outstanding heterogeneities in the pattern and determinants of HRQoL among PD phenotypes. These factors should be considered during the assessments and developing personalized interventions to improve HRQOL in PD patients with different phenotypes or prominent feature.     

HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans

Hypoxia inducible factors, including HIF1A and HIF2A, play central roles in response to high-altitude hypoxia and genetic variants of HIF1A or HIF2A were associated with high-altitude sickness or adaptation. However, it remains to determine whether they are associated with tolerance to different levels of high-altitude selection pressure among native Tibetans. We recruited 189 Tibetan subjects living at 2,700 meters (Low level of high altitude, LHA), 197 at 3,200 meters (Middle level of high altitude of high altitude, MHA), 249 at 3,700 meters (High level of high altitude, HHA) and 269 at 4,700 meters (Very high level of high altitude, VHA) and performed association analysis of twelve tSNPs (tagging SNPs) in HIF1A and HIF2A with high-altitude. We found (1) a increasing trend of HIF2A rs5621780-C(18.4%, 15.9%, 32.8% and 31.1%, respectively, in LHA, MHA, HHA and VHA)(P = 3.56E-9); (2) increasing trends of HIF2A rs6756667-A(68.7%, 73.4%, 79.9% and 89.6%), rs7589621- G(74.6%, 77.9%, 83.7%, and 92.1%) and rs1868092-A(64.1%, 67.3%, 75.1% and 84.4%) (P = 3.56E-9, 4.68E-16, 1.17E-13 and 7.09E-14, respectively); (3) a increasing trend of haplotype AG (68.7%, 73.1%, 79.9% and 89.6%) (P = 2.22E-7) which was constructed by rs6756667 and rs7589621; (4) a strong linear correlation between major alleles of rs6756667-A (R ² = 0.997, P = 0.002), rs7589621-G (R ² = 0.994, P = 0.003), rs1868092-A (R ² = 0.985, P = 0.008) and altitude by linear correlation test. The associations between HIF2A variants and different level of high altitude support that extremely high-altitude hypoxia challenge imposes selective effects on HIF2A variants among native Tibetans.