Probing the interaction of anticancer drug temsirolimus with human serum albumin: molecular docking and spectroscopic insight

The binding interaction between temsirolimus, an important antirenal cancer drug, and HSA, an important carrier protein was scrutinized making use of UV and fluorescence spectroscopy. Hyper chromaticity observed in UV spectroscopy in the presence of temsirolimus as compared to free HSA suggests the formation of complex between HSA and temsirolimus. Fluorescence quenching experiments clearly showed quenching in the fluorescence of HSA in the presence of temsirolimus confirming the complex formation and also confirmed that static mode of interaction is operative for this binding process. Binding constant values obtained through UV and fluorescence spectroscopy reveal strong interaction; temsirolimus binds to HSA at 298 K with a binding constant of 2.9 × 10⁴ M^?1implying the strength of interaction. The negative Gibbs free energy obtained through Isothermal titration calorimetry as well as quenching experiments suggests that binding process is spontaneous. Molecular docking further provides an insight of various residues that are involved in this binding process; showing the binding energy to be -12.9 kcal/mol. CD spectroscopy was retorted to analyze changes in secondary structure of HSA; increased intensity in presence of temsirolimus showing changes in secondary structure of HSA induced by temsirolimus. This study is of importance as it provides an insight into the binding mechanism of an important antirenal cancer drug with an important carrier protein. Once temsirolimus binds to HSA, it changes conformation of HSA which in turn can alter the functionality of this important carrier protein and this altered functionality of HSA can be highlighted in variety of diseases.     

Gypsochroa renitidata (Lepidoptera: Geometridae: Desmobathrinae), a genus and species new for the fauna of Iran

Both the genus and the species Gypsochroa renitidata (Hübner, 1817) are reported for the first time from Iran. Diagnostic characters of the species including figures of the wing and genitalia are presented. The record is confirmed by means of DNA barcoding.     

Intra-erythrocyte Magnesium Is Associated with Gamma-Glutamyl Transferase in Obese Children and Adolescents

This study aims at determining the association between markers of hepatic injury and serum, urinary, and intra-erythrocyte magnesium concentrations and dietary magnesium intake in obese children and adolescents. In a case–control study, 42 obese children and adolescents (8–18 years) and 42 sex- and puberty-matched controls were studied. Serum, urinary, and intra-erythrocyte magnesium levels, indices of insulin sensitivity, and liver enzymes were measured. Dietary magnesium intake was assessed using a food frequency questionnaire. Obese children and adolescents exhibited insulin resistance as determined by a higher fasting insulin and the HOMA-IR (p < 0.001) and lower QUICKI indices (p = 0.001); in addition these subjects had significantly higher intra-erythrocyte magnesium (IEM) concentrations, than non-obese ones (3.99 ± 1.05 vs. 3.35 ± 1.26 mg/dL of packed cell; p = 0.015). Among liver enzymes, only gamma-glutamyl transferase (GGT) was significantly higher in obese than in non-obese subjects (22.7 ± 9.4 vs. 17.1 ± 7.9 U/l; p = 0.002). A positive association was found between GGT and IEM in both groups; however in multivariate analysis, in obese subjects, only GGT (p = 0.026) and, in non-obese subjects, only age (p = 0.006) remained as significant predictors of IEM. In conclusion, increased IEM concentration was seen in insulin-resistant obese children and adolescents; furthermore, serum GGT was associated with IEM, independently of body mass index and HOMA-IR.     

The influence of salinity on cell ultrastructures and photosynthetic apparatus of barley genotypes differing in salt stress tolerance

A hydroponic experiment was conducted to elucidate the difference in growth and cell ultrastructure between Tibetan wild and cultivated barley genotypes under moderate (150 mM NaCl) and high (300 mM NaCl) salt stress. The growth of three barley genotypes was reduced significantly under salt stress, but the wild barley XZ16 (tolerant) was less affected relative to cultivated barley Yerong (moderate tolerant) and Gairdner (sensitive). Meanwhile, XZ16 had lower Na⁺ and higher K⁺ concentrations in leaves than other two genotypes. In terms of photosynthetic and chlorophyll fluorescence parameters, salt stress reduced maximal photochemical efficiency (F _v/F _m), net photosynthetic rate (Pn), stomatal conductance (Gs), and intracellular CO₂ concentration (Ci). XZ16 showed relatively smaller reduction in comparison with the two cultivated barley genotypes. The observation of transmission electron microscopy found that fundamental cell ultrastructure changes happened in both leaves and roots of all barley genotypes under salt NaCl stress, with chloroplasts being most changed. Moreover, obvious difference could be detected among the three genotypes in the damage of cell ultrastructure under salt stress, with XZ16 and Gairdner being least and most affected, respectively. It may be concluded that high salt tolerance in XZ16 is attributed to less Na⁺ accumulation and K⁺ reduction in leaves, more slight damage in cell ultrastructure, which in turn caused less influence on chloroplast function and photosynthesis.     

Adipose-Derived Stromal Cell Therapy Affects Lung Inflammation and Tracheal Responsiveness in Guinea Pig Model of COPD

The effects of adipose derived stromal cells (ASCs) were evaluated on tracheal responsiveness and biochemical parameters in guinea pigs model of chronic obstructive pulmonary disease (COPD). Thirty six guinea pigs were divided into 6 groups including: Control, COPD, COPD+intratracheal delivery of PBS (COPD+ITPBS), COPD+intravenous delivery of PBS (COPD+IVPBS), COPD+intratracheal delivery of ASCs (COPD+ITASC) and COPD+intravenous injection of ASCs (COPD+IVASC). COPD was induced by exposing animals to cigarette smoke for 3 months. Cell therapy was then performed and after 14 days, tracheal responsiveness, concentration of interleukin-8 (IL-8) in serum and broncho-alveolar lavage fluid (BALF), as well as total and differential white blood cells (WBC) counts were evaluated. Tracheal responsiveness, total WBC counts, neutrophil and eosinophil percentage in BALF as well as concentration of IL-8 in serum and BALF significantly increased but lymphocyte percentage decreased in COPD compared to the control group (P<0.05 to p<0.001). Cell therapy was able to restore the tracheal hyper-responsiveness and the increased IL-8 concentration in serum and BALF of COPD-ITASC but not COPD-IVASC animals (P<0.05 for all cases). Total WBC in BALF also showed a significant decrease in both treated groups and the percentages of eosinophils, neutrophils and lymphocytes in BALF were reversed in COPD-ITASC compared to COPD-ITPBS animals (P<0.05 to P<0.001). Therefore, intratracheal cell therapy with ASC can decrease tracheal hyperresponsiveness and lung inflammation in cigarette smoke induced-COPD which may be helpful in attenuation of the severity of disease in patients suffering from COPD.     

Global transition of human serum albumin to prefibrillar aggregates induced by temsirolimus: Insight into implications of anti‐renal cancer drug

In our study, we have characterized the prefibrillar aggregates of human serum albumin (HSA) induced by temsirolimus, anti‐renal cancer drug. Molecular docking was retorted to confirm binding of HSA and temsirolimus. Temsirolimus caused the structural transition of native HSA to non‐native species after prolonged incubation of 20 days. These non‐native species were characterized as prefibrillar aggregates as evident by decreased intrinsic fluorescence and enhanced 8‐anilino‐1‐naphthalene‐sulphonic acid (ANS) fluorescence. Further, enhanced thioflavin T fluorescence and shift in congo red (CR) spectra of temsirolimus‐incubated HSA as compared to native HSA are suggestive of global transition of HSA in presence of temsirolimus towards prefibrillar aggregates. Circular dichroism spectroscopy revealed α to β transition upon prolonged incubation with temsirolimus suggesting the formation of prefibrillar aggregates as aggregates are known to possess high β content. Scanning electron microscopy confirmed these non‐native species to be prefibrillar aggregates evident by observed sheath‐like structures. Comet assay was retorted to confirm genotoxic nature of these prefibrillar aggregates; DNA damage was observed for temsirolimus‐incubated HSA confirming the genotoxic nature of prefibrillar aggregates. These prefibrillar aggregates are observed at heart of many pathological conditions, thus making our study clinically significant.     

Distribution of chigger mites (Acari: Trombiculidae) over hosts,parasitopes, collection localities,and seasons in northern Iran

We studied the distribution of chigger mite species over mammal hosts, attachment sites on the host body, habitats, and seasons in Iran. The study was based on 2155 specimens of 36 chigger species collected from 10 species of Muridae, Cricetidae, and Soricidae across six provinces of northern Iran. A high level of mixed infestation by chiggers was recorded—76% of hosts parasitized by chiggers were infested by more than one (2–8) species. Statistically significant differences in the preference for anterior and posterior parts of the host body were found. Three species—Neotrombicula lubrica, N. delijani, and Cheladonta firdousii—preferred the posterior part of the host body; 12 species were characterized by the occurrence in the anterior part and differed from one another by the frequency of presence in the posterior part. One species, Hirsutiella alpina, was found only in the anterior part of the host body (inside the ears of rodents). The most diverse chigger fauna was on the fringe of Golestan National Park (species richness?=?21, Shannon–Wiener index?=?2.823). The chigger fauna of the high-mountain localities on the Alborz Range was the least diverse (species richness?=?16, Shannon–Wiener index?=?2.439). The seasonal aspect of activity was evident for Neotrombicula elegans, which exposed the autumn–winter period of the occurrence on hosts, and N. vernalis, with the winter-spring peak of abundance.

     

Effect of concentration and shell thickness on the optical behavior of aqueous CdTe/ZnSe core/shell quantum dots (QDs) exposed to ionizing radiation

In this work CdTe/ZnSe core/shell quantum dots (QDs) were synthesized via a simple, rapid and room temperature photochemical approach. Optical properties of aqueous prepared CdTe/ZnSe QDs were studied systematically under gamma irradiation with dose range of 0 Gy to 20 kGy. The obtained results showed a regular red shift behavior versus gamma irradiation dose, in photoluminescence peak and absorption edge of the CdTe/ZnSe QDs. Structural properties of CdTe/ZnSe QDs before and after gamma irradiation were characterized by means of X-ray diffraction (XRD), Raman and Fourier-transform infrared (FT-IR) analyses. The obtained results showed that the crystalline structure of CdTe/ZnSe core/shell QDs did not change after gamma irradiation. Concentration and shell thickness as two important factors on the sensitivity of CdTe/ZnSe QDs in front of gamma irradiation have been investigated. Based on this study, CdTe/ZnSe QDs are suggested as good candidates for gamma dosimeter.