Phytochemical analysis, antimicrobial, antioxidant and enzyme inhibitory activities of ethanolic extract of Centaurea solstitialis L. and its different fractions

396-403Resistance to conventional antimicrobial regimes is one of the issues of concern in healthcare and it drives the need for development of new antimicrobial agents. Medicinal plants, as rich source of biochemical and bioactive compounds, serve as potential source for new drugs. Here, we evaluated the ethanolic extract of Centaurea solstitialis L. and its different fractions (n-hexane, choloroform and n-butanol soluble fraction) for antimicrobial, antioxidant and enzymes inhibitory activities. Antibacterial activity against two Gram-positive and three Gram-negative bacteria species were determined by using agar well diffusion and 96-wells microplate methods. Similarly, antifungal activity against two fungal strains was also evaluated by agar well diffusion method. Antioxidant activity analyzed by measuring the scavenging activity of DPPH radicals and acetylcholinesterase, butrylcholinesterase and chymotrypsin inhibitory activity was determined at 10 µg/mL and 1.0 mg/mL concentrations. Results revealed that the ethanolic extract of C. solstitialis and its different fractions possesses significant (P<0.05) antibacterial activity and effective against fungi Aspergillus niger and Macrophomina phaseolina. Significant (P<0.05) DPPH scavenging activity (88.52±0.23%) among all fractions was noted. n-Butanol fraction showed significant acetyl-cholinesterase (78.55±0.76%) and butrylcholinesterase inhibitory activity (78.1±0.41%) with IC50 values of 54.6±0.39 µg/mL and 211.9±0.15 µg/mL, respectively. Maximum chymotrypsin inhibition activity was shown by crude ethanolic extract (87.76±1.17) with IC50 value of 38.23±0.75 µg/mL. It is concluded that C. solstitialis extract and its fractions possess significant antimicrobial, antioxidant and enzyme inhibitory activity

A Framework for Assessing Impact of Brand Personality on Customer Satisfaction: The Moderating Role of Gender and Age

This study develops an empirical examination of brand personalities in cellular phone sector of Pakistan as a predictor of customer satisfaction. The purpose of this research is to develop a framework that how brand personality of cell phone can increase the level of customer satisfaction. This study also aims to test the moderating role of demographic characteristics (Gender and Age) in the relationship between brand personalities and customer satisfaction.&nbsp;A sample of 300 cell phone users from 5 cities of Pakistan is selected .Based on the survey of consumers of cell phones; the authors checked the effect of brand personality on customer satisfaction. Moderation Analysis was used to check the moderation effect of demographic characteristics (Gender and Age) on the relationship between brand personality and customer satisfaction. Results indicated that due to different dimensions of brand personality of cell phones, customer observed massive satisfaction level. So, since customer faced more satisfaction, they signified more intention towards brand. Further, our research also confirmed the moderating role of Customer Age.&nbsp; This study reveals that when cell phone manufacturing companies invest the human characteristics into their brand so that personality of their brand can develop, their customers can be more loyal towards organization and their level of satisfaction increased. Marketers and Brand Managers must develop marketing and advertisement activities in line with the personality of their cell phone brands.&nbsp;&nbsp

Association between gastric cancer and the intake of different types of iron and meats

Background: Heme and non-heme irons are two forms of iron in the diet. Few studies have evaluated the association between heme iron intake and the risk of gastric cancer (GC). We aimed to investigate the association between heme, non-heme and total iron intake and risk of GC in Iran. Methods: In a hospital-based case–control study, nutritionists interviewed 178 pathologically confirmed GC patients and 276 controls using a valid Diet History Questionnaire. Multiple logistic regression model was used to estimate Odds Ratios (OR) and 95% Confidence Intervals (CIs) for iron intake and risk of GC. Results: Subjects in the highest tertile of total iron intake were 46% less likely to get GC than those in the lowest (OR = 0.54, 95% CI: 0.32–0.92), however, the associations were not significant for intake of heme and non-heme iron. The risk of GC in the highest tertile of total meat intake was 2.51 times higher than the lowest. We found significant associations between GC and chicken (OR = 2.95; 95% CI: 1.66–5.22) and fish intake (OR = 1.89; 95% CI: 1.09–3.27), However, we found no associations between the risk of GC and intake of red meat, salted fish, and liver. Conclusion: Total iron intake was associated with a lower risk of GC which could be partly due to the high prevalence of anemia in Iran. Although, we could not find any significant association between the risk of GC and the intake of heme and non-hem iron among the Iranian population.publishedVersionPeer reviewe

Anti-Cancer Effects of Probiotic Lactobacillus acidophilus for Colorectal Cancer Cell Line Caco-2 through Apoptosis Induction

Background: Colorectal cancer is one of the most common cancers worldwide. Probiotics are useful and non-pathogenic microorganisms in the gastrointestinal tract, which can show anticancer activity through the induction of apoptosis. This study aimed to evaluate the antiproliferative effects of Lactobacillus acidophilus probiotic on the Caco-2 colorectal cancer cell line. Methods: The supernatant (secreted metabolites) and bacterial extract of L. acidophilus probiotics were prepared and used as an anti-proliferative agent on the colorectal cancer cell line, Caco-2 in vitro. The effects of supernatant and extract of L. acidophilus were evaluated on the viability and proliferation of cancer cells using MTT assay. Moreover, morphological alterations of cancer cells treated with supernatant and extract of L. acidophilus were evaluated by an inverted phase contrast microscope. The mRNA expression levels of apoptosis-related genes (SURVIVIN and SMAC) in treated cancer cells and untreated controls were evaluated using the Real-Time PCR method. Results: The results showed that the supernatant and extract of L. acidophilus inhibited the viability and proliferation of cancer cells in a dose and time-dependent manner. Moreover, various morphological alterations were observed in the treated cancer cells, which are indicators of apoptosis induction. The mRNA expression of SURVIVIN and SMAC genes were significantly up-regulated and downregulated in the treated cancer cells, respectively. Conclusion: The results of the present study suggested that the supernatant and extract of L.acidophilus could inhibit the viability and proliferation of colorectal cancer cell line, Caco-2through induction of apoptosis, increase the survival rate of colon cancer patients

Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

Witteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12

High-Throughput Chemical Screen Identifies a Novel Potent Modulator of Cellular Circadian Rhythms and Reveals CKIα as a Clock Regulatory Kinase

A novel compound “longdaysin” was found to dramatically slow down the speed of the circadian clock through simultaneous inhibition of protein kinases CKIδ, CKIα, and ERK2

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin