Facile synthesis and characterization of novel pyrazole-sulfonamides and their inhibition effects on human carbonic anhydrase isoenzymes

In the current study, a series of pyrazole-sulfonamide derivatives (2–14) were synthesized, characterized, and the inhibition effects of the derivatives on human carbonic anhydrases (hCA I and hCA II) were investigated as in vitro. Structures of these sulfonamides were confirmed by FT-IR, ¹H NMR, ¹³C NMR and LC–MS analysis. ¹H NMR and ¹³C NMR revealed the tautomeric structures. hCA I and hCA II isozymes were purified from human erythrocytes and inhibitory effects of newly synthesized sulfonamides on esterase activities of these isoenzymes have been studied. The K_i values of compounds were 0.062–1.278 μM for hCA I and 0.012–0.379 μM for hCA II. The inhibition effects of 7 for hCA I and 4 for hCA II isozymes were almost in nanomolar concentration range.     

Tumor Selective Hyperthermia Induced by Short-Wave Capacitively-Coupled RF Electric-Fields

There is a renewed interest in developing high-intensity short wave capacitively-coupled radiofrequency (RF) electric-fields for nanoparticle-mediated tumor-targeted hyperthermia. However, the direct thermal effects of such high-intensity electric-fields (13.56 MHZ, 600 W) on normal and tumor tissues are not completely understood. In this study, we investigate the heating behavior and dielectric properties of normal mouse tissues and orthotopically-implanted human hepatocellular and pancreatic carcinoma xenografts. We note tumor-selective hyperthermia (relative to normal mouse tissues) in implanted xenografts that can be explained on the basis of differential dielectric properties. Furthermore, we demonstrate that repeated RF exposure of tumor-bearing mice can result in significant anti-tumor effects compared to control groups without detectable harm to normal mouse tissues.     

Common Oncogenic Mutations Are Infrequent in Oral Squamous Cell Carcinoma of Asian Origin

Objectives

The frequency of common oncogenic mutations and TP53 was determined in Asian oral squamous cell carcinoma (OSCC).

Materials and Methods

The OncoCarta^™ panel v1.0 assay was used to characterize oncogenic mutations. In addition, exons 4-11 of the TP53 gene were sequenced. Statistical analyses were conducted to identify associations between mutations and selected clinico-pathological characteristics and risk habits.

Results

Oncogenic mutations were detected in PIK3CA (5.7%) and HRAS (2.4%). Mutations in TP53 were observed in 27.7% (31/112) of the OSCC specimens. Oncogenic mutations were found more frequently in non-smokers (p = 0.049) and TP53 truncating mutations were more common in patients with no risk habits (p = 0.019). Patients with mutations had worse overall survival compared to those with absence of mutations; and patients who harbored DNA binding domain (DBD) and L2/L3/LSH mutations showed a worse survival probability compared to those patients with wild type TP53. The majority of the oncogenic and TP53 mutations were G:C > A:T and A:T > G:C base transitions, regardless of the different risk habits.

Conclusion

Hotspot oncogenic mutations which are frequently present in common solid tumors are exceedingly rare in OSCC. Despite differences in risk habit exposure, the mutation frequency of PIK3CA and HRAS in Asian OSCC were similar to that reported in OSCC among Caucasians, whereas TP53 mutations rates were significantly lower. The lack of actionable hotspot mutations argue strongly for the need to comprehensively characterize gene mutations associated with OSCC for the development of new diagnostic and therapeutic tools.     

Ethanol production from rice hull using Pichia stipitis and optimization of acid pretreatment and detoxification processes

The goal of this study was to produce ethanol from rice hull hydrolysates (RHHs) using Pichia stipitis strains and to optimize dilute acid hydrolysis and detoxification processes by response surface methodology (RSM). The optimized conditions were found as 127.14°C, solid:liquid ratio of 1:10.44 (w/v), acid ratio of 2.52% (w/v), and hydrolysis time of 22.01 min. At these conditions, the fermentable sugar concentration was 21.87 g/L. Additionally, the nondetoxified RHH at optimized conditions contained 865.2 mg/L phenolics, 24.06 g/L fermentable sugar, no hydroxymethylfurfural (HMF), 1.62 g/L acetate, 0.36 g/L lactate, 1.89 g/L glucose, and 13.49 g/L fructose + xylose. Furthermore, RHH was detoxified with various methods and the best procedures were found to be neutralization with CaO or charcoal treatment in terms of the reduction of inhibitory compounds as compared to nondetoxified RHH. After detoxification procedures, the content of hydrolysates consisted of 557.2 and 203.1 mg/L phenolics, 19.7 and 21.60 g/L fermentable sugar, no HMF, 0.98 and 1.39 g/L acetate, 0 and 0.04 g/L lactate, 1.13 and 1.03 g/L glucose, and 8.46 and 12.09 g/L fructose + xylose, respectively. Moreover, the base‐line mediums (control), and nondetoxified and detoxified hydrolysates were used to produce ethanol by using P. stipitis strains. The highest yields except that of base‐line mediums were achieved using neutralization (35.69 and 38.33% by P. stipitis ATCC 58784 and ATCC 58785, respectively) and charcoal (37.55% by P. stipitis ATCC 58785) detoxification methods. Results showed that the rice hull can be utilized as a good feedstock for ethanol production using P. stipitis. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:872–882, 2016     

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II

Sulfonamide-bearing thiazole compounds were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase I and II were evaluated. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of the 12 synthesized sulfonamide (5a–l) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (Ki) were determined. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. Among them 5b was found to be the most active (IC_50?=_?0.35?μM; Ki: 0.33?μM) for hCA I and hCA II.     

Evaluation of carbon sources for the production of inulinase by Aspergillus niger A42 and its characterization

Bioprocess and Biosystems Engineering - Inulinases are used for the production of high-fructose syrup and fructooligosaccharides, and are widely utilized in food and pharmaceutical industries. In...     

Microbiological and chemical quality of a traditional salted-fermented fish (Hout-Kasef) product of Jazan Region,Saudi Arabia

The Hout-Kasef is traditional salted fermented fish product of natural fermentation of salted mullet fish of coastal area of Jazan region of Saudi Arabia. The present study was carried out to investigate the microbiological and chemical characteristic of Hout-Kasef. A total of twenty-four salted fish samples were purchased from fish market in Jazan and Abu-Arish at different times of the year. The microbial studies of salted-fermented fish revealed a total bacterial count ranging from 2.81 to 4.72 Log₁₀ CFU/g, yeast and mold counts ranging from 0.48 to 3.14 Log₁₀ CFU/g, total staphylococci count 2.71–3.85 Log₁₀ CFU/g, halophile bacteria count 3.26–5.14 Log₁₀ CFU/g, and coliforms count <1 Log₁₀ CFU/g. However, pathogenic bacteria such as Listeria monocytogenes, Vibrio spp., Campylobacter spp. and Yersinia species were not detected. The major bacteria species isolated and identified from the salted fermented fish were Bacillus Subtilus, Bacillus mycoides, Bacillus licheniformis, Bacillus pumilus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus xylosus, Staphylococcus saprophticus and Staphylococcus cahnii subsp cahnii. The chemical analysis of salted fermented fish showed high content of moisture (47.96%), protein (25.71%), ash (19.6%) and salt (15.19%) but low contents of lipid (7.25%). The salted-fermented fish also showed high level of total volatile basic nitrogen (78.86 mg/100 gm sample) and thiobarbutric acid number (32.32 mg malonaldehyde/kg) with a pH value of pH 6.3. Finally, this study showed the presence of gram positive and gram negative bacteria in the fish product. The predominant microorganisms found were Bacillus and Staphylococcus spp. The fish product had high content of salt and TVB-N levels.     

Soil microbes alter plant fitness under competition and drought

Plants exist across varying biotic and abiotic environments, including variation in the composition of soil microbial communities. The ecological effects of soil microbes on plant communities are well known, whereas less is known about their importance for plant evolutionary processes. In particular, the net effects of soil microbes on plant fitness may vary across environmental contexts and among plant genotypes, setting the stage for microbially mediated plant evolution. Here, we assess the effects of soil microbes on plant fitness and natural selection on flowering time in different environments. We performed two experiments in which we grew Arabidopsis thaliana genotypes replicated in either live or sterilized soil microbial treatments, and across varying levels of either competition (isolation, intraspecific competition or interspecific competition) or watering (well‐watered or drought). We found large effects of competition and watering on plant fitness as well as the expression and natural selection of flowering time. Soil microbes increased average plant fitness under interspecific competition and drought and shaped the response of individual plant genotypes to drought. Finally, plant tolerance to either competition or drought was uncorrelated between soil microbial treatments suggesting that the plant traits favoured under environmental stress may depend on the presence of soil microbes. In summary, our experiments demonstrate that soil microbes can have large effects on plant fitness, which depend on both the environment and individual plant genotype. Future work in natural systems is needed for a complete understanding of the evolutionary importance of interactions between plants and soil microorganisms.