Thymoquinone attenuates doxorubicin‐cardiotoxicity in rats

Contrary to the fact that doxorubicin is a powerful chemotherapeutic agent for the treatment of neoplastic diseases, cardiotoxicity is too important to be ignored. Thymoquinone serves as a powerful free radical scavenger. In the study, the effects of thymoquinone against doxorubicin‐cardiotoxicity will be evaluated. Forty rats were divided into five groups. Group I: control group (n = 8); group II: olive oil group (n = 8); group III: thymoquinone group (n = 8); given 10 mg/kg thymoquinone intraperitoneally per day throughout the experiment; group IV: doxorubicin group (n = 8); injected with a single dose of 15 mg/kg ip doxorubicin on the 7th day of the experiment; group V: doxorubicin + thymoquinone group (n = 8); administered with 10 mg/kg thymoquinone per day during the experiment and 15 mg/kg doxorubicin ip on the 7th day. The experiment was planned for 14 days. Immunohistochemically, heat shock protein (HSP) 70 and HSP90, glucose‐regulated protein 78 (GRP78), caspase‐3 were stained. We made terminal deoxynucleotidyl transferase dUTP nick end labeling for apoptotic evaluation. Total oxidant status (TOS) levels and total antioxidant status (TAS) were measured in the heart tissue. Atrial natriuretic peptide (ANP) and pro‐B type natriuretic peptide (proBNP) were evaluated. In the study, HSP70, HSP90, GRP78, and caspase‐3 levels increased in group IV. TOS and TAS levels were significant compared to group I. Doxorubicin significantly increased ANP and NT‐proBNP levels. Thymoquinone revealed significant differences in these values. Thymoquinone can be an important cardioprotective agent against doxorubicin‐cardiotoxicity.     

In vitro inhibition of cytosolic carbonic anhydrases I and II by some new dihydroxycoumarin compounds

A new series of 6, 7-dihydroxy-3-(methylphenyl) chromenones, including three new derivatives, i.e. 6,7-dihydroxy-3-(2-methylphenyl)-2H-chromen-2-one (OPC); 6,7-dihydroxy-3-(3-methylphenyl)-2H-chromen-2-one (MPC); 6,7-dihydroxy-3-(4-methylphenyl)-2H-chromen-2-one (PPC) and one previously described, namely 6,7-dihydroxy-3-phenyl-2H-chromen-2-one (DPC), were synthesized. These compounds were investigated as inhibitors of human carbonic anhydrase I (hCA-I) and human carbonic anhydrase II (hCA-II) which had been purified from human erythrocytes on an affinity gel comprised of L-tyrosine-sulfonamide-Sepharose 4B.     

Purification of carbonic anhydrase from dog erythrocytes and investigation of in vitro inhibition by various compounds

The enzyme carbonic anhydrase (E.C. 4.2.1.1) has a stimulatory effect on glaucoma, an eye disease that has a risk to dogs, which are models for the human eye disease, that is similar to that in humans.

In this study, some sulfonamide derivatives, 2-(3-cyclohexene-1-carbamido)-1,3,4-thiadiazole-5-sulfonamide (CCTS), 4-(3-cyclohexene-1-carbamido) methyl-benzenesulfonamide (CCBS), 2-(9-octadecenoylamido)-1,3,4-thiadiazole-5-sulfonamide (ODTS), 2-(4,7,10-trioxa-tetradecanoylamido)-1,3,4-thiadiazole-5-sulfonamide (TDTS), and 2-(8-methoxycoumarine-3-carbamido)-1,3,4-thiadiazole-5-sulfonamide (MCTS), as well as some anionic compounds (perchlorate and chloride) and existing medicines (dorzolamide-HCl, gentamicine sulphate, tropicamide, and procaine-HCl) were assayed for their inhibition of dog carbonic anhydrase (dCA), which was purified from erythrocytes on an affinity gel of L-tyrosine-sulfonamide-Sepharose 4B. ODTS showed the highest potency amongst the synthetic compounds with IC₅₀ value 1.18 × 10^{? 5} M. Amongst the medicines tested, only dorzolamide showed inhibition with IC₅₀ value 5.05 × 10^{? 4} M. Procaine and tropicamide actually showed an activatory effect, whereas gentamicine sulfate had no significant effect. The inhibitory effects of anionic compounds such as perchlorate and chloride were also investigated; whereas perchlorate showed inhibition, chloride did not.     

Quantification of cuttlefish (Sepia officinalis) camouflage: a study of color and luminance using in situ spectrometry

Cephalopods are renowned for their ability to adaptively camouflage on diverse backgrounds. Sepia officinalis camouflage body patterns have been characterized spectrally in the laboratory but not in the field due to the challenges of dynamic natural light fields and the difficulty of using spectrophotometric instruments underwater. To assess cuttlefish color match in their natural habitats, we studied the spectral properties of S. officinalis and their backgrounds on the Aegean coast of Turkey using point-by-point in situ spectrometry. Fifteen spectrometry datasets were collected from seven cuttlefish; radiance spectra from animal body components and surrounding substrates were measured at depths shallower than 5 m. We quantified luminance and color contrast of cuttlefish components and background substrates in the eyes of hypothetical di- and trichromatic fish predators. Additionally, we converted radiance spectra to sRGB color space to simulate their in situ appearance to a human observer. Within the range of natural colors at our study site, cuttlefish closely matched the substrate spectra in a variety of body patterns. Theoretical calculations showed that this effect might be more pronounced at greater depths. We also showed that a non-biological method (“Spectral Angle Mapper”), commonly used for spectral shape similarity assessment in the field of remote sensing, shows moderate correlation to biological measures of color contrast. This performance is comparable to that of a traditional measure of spectral shape similarity, hue and chroma. This study is among the first to quantify color matching of camouflaged cuttlefish in the wild.     

Adequate magnesium nutrition mitigates adverse effects of heat stress on maize and wheat

Aims

Heat stress is a growing concern in crop production because of global warming. In many cropping systems heat stress often occurs simultaneously with other environmental stress factors such as mineral nutrient deficiencies. This study aimed to investigate the role of adequate magnesium (Mg) nutrition in mitigating the detrimental effects of heat stress on wheat (Triticum aestivum) and maize (Zea mays).

Methods

Wheat and maize plants were grown in solution culture with low or adequate Mg supply at 25/22 °C (light/dark). Half of the plants were, then, exposed to heat stress at 35/28 °C (light/dark). Development of leaf chlorosis and changes in root and shoot growth, chlorophyll and Mg concentrations as well as the activities of major antioxidative enzymes were quantified in the experimental plants. Additionally, maize plants were analyzed for the specific weights (e.g., dry or fresh weight per a given leaf surface area) and soluble carbohydrate concentrations of sink and source leaves.

Results

Visual leaf symptoms of Mg deficiency were aggravated in wheat and maize when exposed to heat stress. In both species, root growth was more sensitive to Mg deficiency than shoot growth, and the shoot-to-root ratios peaked when heat stress was combined with Mg deficiency. Magnesium deficiency markedly reduced soluble carbohydrate concentrations in young leaf; but resulted in substantial increase in source leaves. Magnesium deficiency also increased activities of antioxidative enzymes, especially when combined with heat stress. The highest activities of superoxide dismutase (up to 80 % above the control), glutathione reductase (up to 250 % above the control) and ascorbate peroxidase (up to 300 % above the control) were measured when Mg-deficient plants were subjected to heat, indicating stimulated formation of reactive oxygen species (ROS) in Mg deficient leaves under heat stress.

Conclusions

Magnesium deficiency increases susceptibility of wheat and maize plants to heat stress, probably by increasing oxidative cellular damage caused by ROS. Ensuring a sufficiently high Mg supply for crop plants through Mg fertilization is a critical factor for minimizing heat-related losses in crop production.     

Helophorus erzurumicus sp. n., a new species from Turkey and some notes on H. ponticus Angus, 1988 (Coleoptera: Hydrophilidae)

A new species of Helophorus Fabricius, 1775 is described from Erzurum, northeastern Turkey: Helophorus erzurumicus. In addition, distributional and morphological notes on H. ponticus Angus, 1988 are presented.     

Discovery of novel indolinone-based,potent, selective and brain penetrant inhibitors of LRRK2

Mutations in leucine-rich repeat kinase-2 (LRRK2) are the most common genetic cause of Parkinson’s disease (PD). The most frequent kinase-enhancing mutation is the G2019S residing in the kinase activation domain. This opens up a promising therapeutic avenue for drug discovery targeting the kinase activity of LRRK2 in PD. Several LRRK2 inhibitors have been reported to date. Here, we report a selective, brain penetrant LRRK2 inhibitor and demonstrate by a competition pulldown assay in vivo target engagement in mice.     

The Tyrosine Kinase Btk Regulates the Macrophage Response to Listeria monocytogenes Infection

In this study we investigated the role of Bruton''s tyrosine kinase (Btk) in the immune response to the Gram-positive intracellular bacterium Listeria monocytogenes (Lm). In response to Lm infection, Btk was activated in bone marrow-derived macrophages (BMMs) and Btk ^−/− BMMs showed enhanced TNF-α, IL-6 and IL-12p40 secretion, while type I interferons were produced at levels similar to wild-type (wt) BMMs. Although Btk-deficient BMMs displayed reduced phagocytosis of E. coli fragments, there was no difference between wt and Btk ^−/− BMMs in the uptake of Lm upon infection. Moreover, there was no difference in the response to heat-killed Lm between wt and Btk ^−/− BMMs, suggesting a role for Btk in signaling pathways that are induced by intracellular Lm. Finally, Btk ^−/− mice displayed enhanced resistance and an increased mean survival time upon Lm infection in comparison to wt mice. This correlated with elevated IFN-γ and IL-12p70 serum levels in Btk ^−/− mice at day 1 after infection. Taken together, our data suggest an important regulatory role for Btk in macrophages during Lm infection.