Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights.

In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.

Designing and Synthesis of Novel Fexofenadine-Derived Hydrazone-Schiff Bases as Potential Urease Inhibitors: In-Vitro, Molecular Docking and DFT Investigations.

Thirteen novel hydrazone-Schiff bases (3-15) of fexofenadine were succesfully synthesized, structurally deduced and finally assessed their capability to inhibit urease enzyme (in vitro). In the series, six compounds 12 (IC50=10.19±0.16 µM), 11 (IC50=15.05±1.11 µM), 10 (IC50=17.01±1.23 µM), 9 (IC50=17.22±0.81 µM), 13 (IC50=19.31±0.18 µM), and 14 (IC50=19.62±0.21 µM) displayed strong inhibitory action better than the standard thiourea (IC50=21.14±0.24 µM), while the remaining compounds displayed significant to less inhibition. LUMO and HOMO showed the transferring of charges from molecules to biological transfer and MEP map showed the chemically reactive zone appropriate for drug action are calculated using DFT. AIM charges, non-bonding orbitals, and ELF are also computed. The urease protein binding analysis benefited from the docking studies.

Discovery of (S)-flurbiprofen-based novel azine derivatives as prostaglandin endoperoxide synthase-II inhibitors: Synthesis, in-vivo analgesic, anti-inflammatory activities, and their molecular docking.

The anti-inflammatory and analgesic drugs currently used are associated with several adverse effects and found to be highly unsafe for long-term use. Currently, nineteen novel bis-Schiff base derivatives (1-19) of flurbiprofen have been designed, prepared and assessed for in-vivo analgesic, anti-inflammatory and in vivo acute toxicity evaluation. The structures of the acquired compounds were deduced through modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR. Amongst the series, compounds 7, 9, and 10 attributed potent activities with 93.89, 92.50, and 90.47% decreased edema, respectively compared to flurbiprofen (90.01%), however, compounds 11 and 15 exhibited significant activity of 90.00% decrease. Out of them, fourteen compounds (1-6, 8, 12-14, and 16-19) displayed good activity in the range of 68.96-86.95%. In case of an analgesic study, all the derivatives significantly (p 0.001) increased the pain threshold time particularly compound 7 had the best analgesic effect (24 ± 2.08 s) in comparison with flurbiprofen (21.66 ± 2.02 s) using hot plate test. Similarly, in the acetic acid-induced writhing test, compound 7 determined a potent inhibitory effect (60.47 %) close to flurbiprofen (59.28%). All the synthesized derivatives were found safe up to the dose of 30 mg/kg, in acute toxicity study. On a molecular scale, the synthesized compounds were modeled through a ligand-based pharmacophore study and molecular docking to have insight into the different possible interactions leading to high inhibition levels against the COX-2 enzyme.

Genomic background of a colistin-resistant and highly virulent MCR-1-positive Escherichia coli ST6395 from a broiler chicken in Pakistan.

The convergence of high virulence and multidrug resistance (MDR) in Gram-negative pathogens circulating at the human-animal interface is a critical public health issue. We hereby report the genomic characteristics and virulent behavior of a colistin-resistant Escherichia coli, serotype ONT:H26, belonging to ST6395, isolated from a healthy broiler in Pakistan. This strain harbored multiple antimicrobial resistance genes, including mcr-1.1 and blaCARB-2, besides cma (colicin M) and astA [heat-stable enterotoxin 1 (EAST1) toxin] virulence genes. In vivo experiments carried out with the Galleria mellonella infection model revealed that MCR-1-positive E. coli ST6395 killed 96.4% of the larvae at 18 hour post-infection. Interplay between resistance and virulence in clinically important pathogens could be a potential threat, representing a serious challenge to global public health.

Removal of copper from an electroplating industrial effluent using the native and modified spirogyra.

In the present study, biosorption behavior of a green filamentous alga, spirogyra in its native and modified states was investigated for copper removal from an electroplating industrial effluent. For this, the effluent containing 194 mg·L-1 Cu2+ in sulfate medium was contacted with both forms of spirogyra, under the parametric variations of effluent pH, adsorbent dosage, contact time, and sorption temperature. The study revealed spirogyra as a prominent candidate for removing contaminant metal cation; however, at the same condition, biosorption capacity of modified biomass in gel form was higher than the native spirogyra. At the optimized condition with 6 g sorbent dosage treated to 100 mL effluent for 30 min at pH 6.0 and temperature 20 °C, the maximum 82.8% and 96.4% copper could be adsorbed by the native and modified spirogyra, respectively. The batch sorption data using native biomass followed pseudo-first-order kinetic; exhibiting the multilayer sorption mechanism via surface diffusion could be defined by the Freundlich model. In contrast, the sulfuric acid treated modified spirogyra followed pseudo-second-order kinetics and intra particle diffusion as the rate-limiting step.

A Concise Review of MicroRNA Exploring the Insights of MicroRNA Regulations in Bacterial, Viral and Metabolic Diseases.

MicroRNA (miRNA) is a small section of ribonucleic acid (RNA) that reduces the protein formation by making the pair of the complementary piece of mRNA. The genes of miRNA are present as transcriptional or polycistronic units in the chromosomes. The cellular multiplication, separation and existence like the multitude of genetic functions are affected by miRNA. Nearly 50% of identified miRNA are located in the residence in the intronic part of the genes. The mature miRNA is yielded in two steps. Drosha and RNA-induced silencing complex are the catalysts that play an important role in miRNA synthesis. The miRNA may function by just hindering the translation or complete vitiation of miRNA that occurs to control the genes. The microRNA antagonists and miRNA mimics are therapeutics approaches for the treatment of abnormalities. The upregulation and downregulation of miRNAs are linked to a number of diseases as miR-122 is associated with viral hepatitis, and some members of let-7 and other miRNAs are concerned with various diseases. Overexpressed miRNAs may function as both oncogenes and regulator of cellular processes. The miRNA functions can be altered by single-point mutations in miRNA target and epigenetic silencing of transcription units. There are numerous molecular targets for miRNA as degradation by nuclease and phosphodiesterase. Thus, miRNA has potential applications in disease diagnosis along with therapy, but the mechanisms involved in miRNA systems and its targeted delivery of miRNA are much more important to achieve its therapeutic applications.

Scimitar syndrome with absent right pulmonary artery and severe pulmonary hypertension treated with coil occlusion of aortopulmonary collaterals in a term neonate.

Scimitar syndrome (SS) is a rare congenital malformation with an estimated incidence of approximately 2 in 100 000 births. A wide clinical spectrum is observed in children with this syndrome. The common clinical presentation in infancy is respiratory distress and tachypnoea due to associated pulmonary hypoplasia, pulmonary overcirculation and/or pulmonary hypertension. Babies with SS presenting with cardiac failure are prone to develop exaggerated pulmonary vascular disease. Hence early intervention, using either coil embolisation or surgical intervention, is indicated. We are reporting a case of a term baby boy who presented with respiratory failure during the first 24 h of life. Echocardiogram and CT angiogram revealed SS. The baby needed intubation due to respiratory failure. Aortopulmonary collaterals, identified on aortic angiogram, were successfully occluded with detachable coils.

Level of maternal education is a significant determinant of neonatal survival: a PEARL study analysis.

The study analyzed the demographic and socio-economic determinants of neonatal mortality. The variables included one fetal variable (gender), three maternal variables (level of education, occupation, age), three paternal variables (level of education, occupation, age), and seven household (family) variables (nationality, consanguinity, family income, house ownership, type of housing, family type, domestic help). One calendar year data (January to December 2011) was extracted from Qatar's National Perinatal Registry and analyzed using a univariate regression model. Qatar had a total of 20,583 live births and 102 neonatal deaths during 2011 (NMR 4.95/1000). Less than secondary school maternal education level, as compared to secondary school or above maternal education level, was the only variable significantly associated with neonatal mortality (OR 2.08, 95% CI 1.23 - 3.53, p=0.009). The association between the remaining thirteen variables and neonatal mortality was non-significant. Priority investment to raise female literacy above secondary school level may significantly improve neonatal survival.

Genotoxicity assessment of amaranth and allura red using Saccharomyces cerevisiae.

Amaranth (E123) and Allura red (E129), very important food azo dyes used in food, drug, paper, cosmetic and textile industries, were assessed for their genotoxic potential through comet assay in yeast cells. Comet assay was standardized by with different concentration of H(2)O(2). Concentrations of Amaranth and Allura red were maintained in sorbitol buffer starting from 9.76 to 5,000 µg/mL and 1 × 10(4) cells were incubated at two different incubation temperatures 28 and 37°C. Amaranth (E123) and Allura red (E129) were found to exhibit their genotoxic effect directly in Saccharomyces cerevisiae. No significant genotoxic activity was observed for Amaranth and Allura red at 28°C but at 37°C direct relation of Amaranth concentration with comet tail was significant and no positive relation was seen with time exposure factor. At 37°C the minimum concentration of Amaranth and Allura red at which significant DNA damage observed through comet assay was 1,250 µg/mL in 2nd h post exposure time. The results indicated that food colors should be carefully used in baking products as heavy concentration of food colors could affect the fermentation process of baking.

Improvements in Birth Weight-specific Neonatal Mortality Rates in the State of Qatar between 2003 & 2010 and a Comparative Analysis with the Vermont Oxford Network Database Report of 2007: A PEARL Study Review.

OBJECTIVE: The study aimed to develop a national reference on birth weight-specific neonatal survival in the State of Qatar to facilitate parental counseling. STUDY DESIGN: This was a retrospective, analytic, and comparative study. MATERIALS AND METHODS: The birth weight-specific neonatal mortality data for the years 2003 and 2010, collected from the admission and discharge registers of the neonatal intensive care unit, were stratified using the stratifications given in Vermont Oxford Network (VON) 2007 annual report. Category-wise birth weight-specific mortality and relative risk (RR) of death were compared between Qatar data (2003 and 2010) and VON 2007 report. RESULTS: Qatar's neonatal mortality rate (NMR) dropped from 5 of 1000 in 2003 to 4.4 of 1000 in 2010 (P=0.443) which was significant for birth weight categories 501-750 g and 751-1000 g (P=0.026 and P=0.05, respectively). Qatar's NMR in 2010 was significantly lower than VON's NMR during 2007 (P<0.001) though VON's NMR was significantly lower among birth weight categories 751-1000 g and 1001-1500 g (P=0.001 and P=0.003, respectively). The RR of mortality decreased with increasing birth weight. The decline was very sharp for birth weight categories between 500 and 1500g. The RR was 25 times higher in babies with birth weight less than 750 g as compared to babies with birth weight ≥ 2550 g, both in Qatar and VON data. For birth weight categories 751-1000 g and 1001-1500 g, the RR was twice in Qatar as compared to the VON report (16.8 versus 7.8, and 5.5 versus 2.7, respectively). CONCLUSIONS: Qatar's current overall and birth weight-specific NMRs are comparable with the VON report except in birth weight categories 751-1000 g and 1001-1500 g which were higher in Qatar. This needs further in-depth qualitative analysis.

The incidence of low birth weight and intrauterine growth restriction in relationship to maternal ethnicity and gestational age at birth - A PEARL study analysis from the State of Qatar.

OBJECTIVE: To analyze the association between maternal ethnicity and gestational age with the incidence of low birth weight and intrauterine growth restriction. STUDY DESIGN: Prospective, analytic study Methods: The study was conducted between March 14th and April 4th 2011 in Women's Hospital HMC. The data was ascertained from the delivery register of labor ward on daily basis using predesigned, structured questionnaire. Data was stratified according to the maternal ethnicity groups and gestational age at birth (term and preterm). RESULTS: The total deliveries during the study period were 890; 35.5% Qatari (n 316) and 64.5% non-Qatari (n 574). The incidence of LBW was 12.36% (n 110). The difference of LBW incidence between Qatari (13.6% n 43) and non-Qatari (11.67% n 67) groups was non significant (RR 1.17, 95% CI 0.82-1.67, p = 0.401). The same was between non-Qatari sub groups (p < 0.05). The incidence of IUGR was 6% (n 54; 49.09% of LBW). The incidence of IUGR between Qatari (5.7% n 18) and non-Qatari (6.27% n 36) groups was significant (RR 0.45, 95% CI 0.3-0.6 p>0.05). The incidence of LBW was 7.85% (n 60) in term babies and 39.68% (n 50) in preterm babies. The incidence if IUGR was 3.79% (n 29) in term babies and 19.84% (n 25) in preterm babies. Preterm babies had a five times higher risk of both being LBW (RR 5.05; 95%CI 3.65-6.99; p < 0.001) and IUGR (RR 5.23; 95% CI 3.17-8.62; p < 0.001). CONCLUSION: The incidence of low birth weight is independent of maternal ethnicity in Qatar. However, the incidence of IUGR is significantly higher among the non-Qatari population. The relative risk of being LBW or IUGR is five times higher in preterm babies. Further in depth studies are indicated.

Respiratory distress syndrome due to a novel homozygous ABCA3 mutation in a term neonate.

The authors report, for the first time in the literature, a case of respiratory distress syndrome in a term baby due to homozygosity for a p.Trp308Arg/W308R substitution in the ATP-binding cassette transporter 3. The sequence was confirmed by genetic analysis of the baby and both parents. Management and long-term outcome of a patient carrying this novel genetic defect have not been reported in the literature before. Currently, lung transplant appears to be the only long-term survival option available, for which, our patient is being evaluated.