Enhanced anticancer potency of doxorubicin in combination with curcumin in gastric adenocarcinoma

Gastric cancer (GC) is one of the prevalent human malignancies and the third most common cause of cancer‐related death worldwide. The doxorubicin hydrochloride is one of the important chemotherapeutic anticancer agents, with a limited therapeutic efficacy for treatment of GC. Therefore, taking advantage of synergistic effects by strategies like combination therapy seems appropriate and promising in treatment of GC. The aim of this study was to investigate a novel method to enhance the therapeutic efficacy of doxorubicin (as a chemotherapeutic agent) by co‐administration of curcumin (as a bioactive herbal compound) in GC treatment. In the present study, the effects of curcumin, doxorubicin, and their combinations (Dox‐Cur) were evaluated on the viability, morphological features, tumor spheroid formation, migration, invasion, and apoptosis of gastric adenocarcinoma cell line (AGS). Moreover, expression levels of BAX, BCL‐2, and CASP9 genes were assessed among AGS cells treated with curcumin, doxorubicin, and Dox‐Cur. The obtained results showed that all of curcumin, doxorubicin, and Dox‐Cur treatments significantly decreased the viability, tumor spheroid formation, migration, and invasion in the GC model cells. Furthermore, apoptosis rates in AGS cells were increased in a concentration‐ and time‐dependent manner in all of the treatment groups. Moreover, the anticancer activity of the Dox‐Cur combination was significantly more than curcumin and doxorubicin treatments alone. According to the results, Dox‐Cur combination therapy exerts more profound apoptotic and anticancer effects on the AGS cell line than curcumin or doxorubicin monotherapy.     

Toward community predictions: Multi‐scale modelling of mountain breeding birds' habitat suitability,landscape preferences,and environmental drivers

Across a large mountain area of the western Swiss Alps, we used occurrence data (presence‐only points) of bird species to find suitable modelling solutions and build reliable distribution maps to deal with biodiversity and conservation necessities of bird species at finer scales. We have performed a multi‐scale method of modelling, which uses distance, climatic, and focal variables at different scales (neighboring window sizes), to estimate the efficient scale of each environmental predictor and enhance our knowledge on how birds interact with their complex environment. To identify the best radius for each focal variable and the most efficient impact scale of each predictor, we have fitted univariate models per species. In the last step, the final set of variables were subsequently employed to build ensemble of small models (ESMs) at a fine spatial resolution of 100 m and generate species distribution maps as tools of conservation. We could build useful habitat suitability models for the three groups of species in the national red list. Our results indicate that, in general, the most important variables were in the group of bioclimatic variables including “Bio11” (Mean Temperature of Coldest Quarter), and “Bio 4” (Temperature Seasonality), then in the focal variables including “Forest”, “Orchard”, and “Agriculture area” as potential foraging, feeding and nesting sites. Our distribution maps are useful for identifying the most threatened species and their habitat and also for improving conservation effort to locate bird hotspots. It is a powerful strategy to improve the ecological understanding of the distribution of bird species in a dynamic heterogeneous environment.     

Discovery of potent, soluble and orally active TRPV1 antagonists. Structure-activity relationships of a series of isoxazoles

Systematic optimisation of a poorly soluble lead series of isoxazole-3-carboxamides was conducted. Substitution of the 4-position with specific polar functionality afforded the requisite balance of potency, solubility and physicochemical properties. Compound 21a was found to be efficacious in the rat Capsaicin Hargreaves assay following oral administration.     

Assessment of the effect of biosurfactant produced by Pseudomonas aeruginosa in lethality of Bacillus thuringiensis Berl. against 3rd instars larvae of white cabbage butterfly (Pieris brassicae L.)

Surfactant that is produced from cheap sources like oil sludge by biological agents such as bacteria can be used in various industrial processes. For example, it can be used in environmental processes such as bioremediation and elimination of environmental pollutants, and acts as synergistic agents and distributor pesticides on waxy leaves in agriculture. In this study, biosurfactant which is produced by Pseudomonas aeruginosa (isolated from petroleum sludge) at the intervals of 24, 48, 72 and 96?h, along with chemical surfactant Tween 80 and the biological control agent, Bacillus thuringiensis, in a pilot project for controlling one important cabbage pest (Pieris brassicae), their synergistic properties were evaluated. Statistical analysis of the results showed that B. thuringiensis in combination with biosurfactant produced at different times and B. thuringiensis in combination with chemical surfactant Tween 80 when compared with control treatments like B. thuringiensis alone and B. thuringiensis plus tween 80 as positive controls and distilled water as negative control have significant differences (p?<?0.05). This research showed that surfactant treatment produced at the intervals of 24 and 48?h in combination with B. thuringiensis has the greatest synergistic effect when compared to chemical surfactant treatment. This study concluded that biosurfactant can be used as a distributor and synergistic agent against plant pests and in addition to this, their biological roles in bioremediation can be used as a viable alternative to non-economical chemical surfactants that annually enter millions of tonnes of harmful chemical substances into the fields and underground water.     

Overexpression of <Emphasis Type="Italic">spoT</Emphasis> gene in coccoid forms of clinical <Emphasis Type="Italic">Helicobacter pylori</Emphasis> isolates

Helicobacter pylori (H. pylori) can convert to coccoid form in unfavorable conditions or as a result of antibiotic treatment. In order to adapt to harsh environments, H. pylori requires a stringent response which, encoded by the spoT gene, has a bifunctional enzyme possessing both (p)ppGpp synthetic and degrading activity. Our goal in this study was to compare spoT gene expression in spiral and induced coccoid forms of H. pylori with use of amoxicillin. First, clinical isolate coccoid forms were induced with amoxicillin; then, the viability test was analyzed by flow cytometer. After RNA extraction, cDNA synthesis and designing a specific primer for spoT gene, evaluation of the desired gene expression in both forms were studied. Bacterial isolates exposed to amoxicillin at MIC and 1/2 MIC induced morphological conversion better and faster than other MIC concentration. The expression of spoT gene was significantly downregulated in spiral forms of H. pylori, while the gene expression was upregulated and + 30.3-fold changes was seen in coccoid forms of bacterium. To summarize, spoT gene is one of the key factors for antibiotic resistance and its enhanced expression in coccoid form can be a valuable diagnostic marker for recognition of H. pylori during morphological conversion.     

Length‐weight and length–length relationships of three algae‐scraping cyprinid species from Iran

The study presents length–weight relationships (LWRs) and length–length relationships (LLRs) for three algae‐scraper species; Capoeta coadi from the Kouhrang River (Iran; 32°23′N, 50°08′E) a part of the Tigris drainage basin, Capoeta pyragyi from Cheshmeh Langan River (32°55′N, 50°10′E) a part of Zayanderud River basin and Capoeta umbla from Chooman River (35°57′N, 45°47′E). Fish were sampled by electro fishing (Samus1000; Power Out: 200 watts) in August, September and October 2017. Sampling was carried out each months in sites covering an area of about 100 m² including runs, riffles and pools at a water depth of 10–60 cm. The obtained LWRs and LLRs showed a high level of correlation (r² > 0.99).     

Localized Surface Plasmon Resonance (LSPR)-Based Nanobiosensor for Methamphetamin Measurement

Aptamers are DNA or RNA single-stranded molecules that bind specifically to target molecules with high affinity. Function of nucleic acid aptamers is based on organized tertiary structure of them that is related to primary sequence, length of nucleic acid molecule, and environmental conditions. Herein, a localized surface plasmon resonance (LSPR) nanobioprobe has been developed based on specific aptamer-conjugated gold nanoparticles for rapid detection of methamphetamine. Detection of methamphetamine was studied via monitoring the gold nanoparticles (GNPs) LSPR band alterations in the presence of different concentrations. The covalent conjugation has been confirmed with FT-IR spectroscopy, and size alterations of gold nanoparticles before and after the conjugation state were monitored using dynamic light scattering (DLS) technique. The results show high affinity of aptamer to methamphetamine. Moreover, the results show conjugated aptamer with GNP in different concentrations of methamphetamine that contribute to color changes that is visible with unaided eye. Also, 14 nm LSPR shift was seen after conjugation of aptamer with GNP. Nanoparticle diameter after conjugation with aptamer was increased from 30 to 91 nm and decreased after incubation with methamphetamine (due to folding) from 91 to 84 nm. Detection limit of this designed nanoprobe is 500 nM. Plasmonic nanoparticle-based nanobioprobe is a new field for development of sensitive detection systems.

     

Study of antihypertensive mechanism of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE activity

Tribulus terrestris is a natural herb used for treating many diseases including hypertension. According to previous reports, aqueous extract of tribulus fruits may have some antihypertensive effect with an unknown mechanism. The present study investigated the antihypertensive mechanism of tribulus in 2K1C hypertensive rats by measurement of circulatory and local ACE activity in aorta, heart, kidney and lung. Four groups of rats were selected; control, sham, operated or hypertensive and tribulus treated hypertensive group. Hypertension was induced using silver clip on renal artery by surgery. Four weeks after surgery, a single daily dose of 10 mg/kg of lyophilized aqueous extract of tribulus fruit were given orally to 2K1C rats for four weeks. ACE activity was determined by high performance liquid chromatography (HPLC). Blood pressure was measured by the tail-cuff method. The systolic blood pressure (SBP) was significantly increased in 2K1C rats compared to control rats. The SBP of tribulus fed hypertensive rats was significantly decreased compared to hypertensive rats. The ACE activity in all tissues of 2K1C rats including: aorta, heart, kidney, lung as well as serum were significantly increased compared to normal rats. The ACE activity in all tissues of tribulus fed hypertensive rats was significantly lower than that of hypertensive rats, which was more pronounced in kidney. These results indicated that there is a negative correlation between consumption of tribulus and ACE activity in serum and different tissues in 2K1C rats.     

Accuracy of Inferior Vena Cava Ultrasound for Predicting Dehydration in Children with Acute Diarrhea in Resource-Limited Settings

Introduction

Although dehydration from diarrhea is a leading cause of morbidity and mortality in children under five, existing methods of assessing dehydration status in children have limited accuracy.

Objective

To assess the accuracy of point-of-care ultrasound measurement of the aorta-to-IVC ratio as a predictor of dehydration in children.

Methods

A prospective cohort study of children under five years with acute diarrhea was conducted in the rehydration unit of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Ultrasound measurements of aorta-to-IVC ratio and dehydrated weight were obtained on patient arrival. Percent weight change was monitored during rehydration to classify children as having “some dehydration” with weight change 3–9% or “severe dehydration” with weight change > 9%. Logistic regression analysis and Receiver-Operator Characteristic (ROC) curves were used to evaluate the accuracy of aorta-to-IVC ratio as a predictor of dehydration severity.

Results

850 children were enrolled, of which 771 were included in the final analysis. Aorta to IVC ratio was a significant predictor of the percent dehydration in children with acute diarrhea, with each 1-point increase in the aorta to IVC ratio predicting a 1.1% increase in the percent dehydration of the child. However, the area under the ROC curve (0.60), sensitivity (67%), and specificity (49%), for predicting severe dehydration were all poor.

Conclusions

Point-of-care ultrasound of the aorta-to-IVC ratio was statistically associated with volume status, but was not accurate enough to be used as an independent screening tool for dehydration in children under five years presenting with acute diarrhea in a resource-limited setting.