Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta-analysis

Flap endonuclease 1 (FEN1) has emerged as an important enzyme in the maintenance of genomic instability and preventing carcinogenesis. The relationship between FEN1 −69G>A (rs174538)+4150G>T (rs4246215) polymorphisms and cancer susceptibility has been reported; however, results were inconclusive. In the present study, a meta-analysis of data from eligible reports was carried out to summarize the possible relationship between FEN1 polymorphisms and cancer risk. A total of 11 articles, including 20 studies with 7366 cases and 9028 controls and 18 studies with 6649 cases and 8325 controls for FEN1 rs174538 and FEN1 rs4246215 polymorphisms, respectively, were recruited for meta-analysis. Overall, meta-analyses showed that FEN1 rs174538 and rs4246215 polymorphisms are significantly associated with the decreased risk of cancer. The stratified analysis proposed that both variants were associated with protection against gastrointestinal cancer, breast cancer, hepatocellular cancer, esophageal cancer, gastric cancer, colorectal cancer, and lung cancer. In conclusion, this meta-analysis revealed an association between FEN1 polymorphisms and cancer risk. Additional studies in a larger study population that include subjects from a variety of ethnicities are warranted to further verify our findings.     

Major depressive disorder diagnosis based on effective connectivity in EEG signals: a convolutional neural network and long short-term memory approach

Deep learning techniques have recently made considerable advances in the field of artificial intelligence. These methodologies can assist psychologists in early diagnosis of mental disorders and preventing severe trauma. Major Depression Disorder (MDD) is a common and serious medical condition whose exact manifestations are not fully understood. So, early discovery of MDD patients helps to cure or limit the adverse effects. Electroencephalogram (EEG) is prominently used to study brain diseases such as MDD due to having high temporal resolution information, and being a noninvasive, inexpensive and portable method. This paper has proposed an EEG-based deep learning framework that automatically discriminates MDD patients from healthy controls. First, the relationships among EEG channels in the form of effective brain connectivity analysis are extracted by Generalized Partial Directed Coherence (GPDC) and Direct directed transfer function (dDTF) methods. A novel combination of sixteen connectivity methods (GPDC and dDTF in eight frequency bands) was used to construct an image for each individual. Finally, the constructed images of EEG signals are applied to the five different deep learning architectures. The first and second algorithms were based on one and two-dimensional convolutional neural network (1DCNN–2DCNN). The third method is based on long short-term memory (LSTM) model, while the fourth and fifth algorithms utilized a combination of CNN with LSTM model namely, 1DCNN-LSTM and 2DCNN-LSTM. The proposed deep learning architectures automatically learn patterns in the constructed image of the EEG signals. The efficiency of the proposed algorithms is evaluated on resting state EEG data obtained from 30 healthy subjects and 34 MDD patients. The experiments show that the 1DCNN-LSTM applied on constructed image of effective connectivity achieves best results with accuracy of 99.24% due to specific architecture which captures the presence of spatial and temporal relations in the brain connectivity. The proposed method as a diagnostic tool is able to help clinicians for diagnosing the MDD patients for early diagnosis and treatment.     

New Insight into the Interactions of Arbutin with Mushroom Tyrosinase

The Protein Journal - As a safe substitute for hydroquinone, β-arbutin, a natural plant substance, and its synthetic counterpart, α-arbutin, are used in depigmentation formulations....     

Genotyping of –374A/T, –429A/G,And 63 bp Ins/Del Polymorphisms of Rage By Rapid One-Step Hexaprimer Amplification Refractory Mutation System Polymerase Chain Reaction in Breast Cancer Patients

Several studies have focused on the RAGE genetic background and have demonstrated that its polymorphisms affect the receptor's activity, expression, and downstream signaling. However, there is only little information regarding RAGE polymorphism in breast cancer. In the present study, the authors studied RAGE polymorphisms in 71 patients with breast cancer and 93 healthy women. RAGE –374T/A, –429T/C, and 63 bp Ins/del polymorphisms were analyzed using a hexaprimer amplification refractory mutation system PCR (H-ARMS-PCR). The results showed that RAGE polymorphisms are not associated with breast cancer in the current study population. Larger studies are required to confirm these data in other populations.     

Covalent vs. Non‐Covalent Inhibition: Tackling Drug Resistance in EGFR – A Thorough Dynamic Perspective

A persistent challenge in the treatment of non‐small cell lung cancer (NSCLC) with EGFR is the emergence of drug‐resistant caused by somatic mutations. The EGFR L858R/T790 M double mutant (EGFR^DM) was found to be the most alarming variant. Despite the development of a wide range of inhibitors, none of them could inhibit EGFR^DM effectively. Recently, 11h and 45a , have been found to be potent inhibitors against EGFR^DM through two distinctive mechanisms, non‐covalent and covalent binding, respectively. However, the structural and dynamic implications of the two modes of inhibitions remain unexplored. Herein, two molecular dynamics simulation protocols, coupled with free‐energy calculations, were applied to gain insight into the atomistic nature of each binding mode. The comparative analysis confirmed that there is a significant difference in the binding free energy between 11h and 45a (ΔΔG_bind=?21.17 kcal/mol). The main binding force that governs the binding of both inhibitors is vdW, with a higher contribution for 45a . Two residues ARG841 and THR854 were found to have curtailed role in the binding of 45a to EGFR^DM by stabilizing its flexible alcohol chain. The 45a binding to EGFR^DM induces structural rearrangement in the active site to allow easier accessibility of 45a to target residue CYS797. The findings of this work can substantially shed light on new strategies for developing novel classes of covalent and non‐covalent inhibitors with increased specificity and potency.     

A cyclodextrin host-guest recognition approach to an electrochemical sensor for simultaneous quantification of serotonin and dopamine

An electrochemical sensor for simultaneous quantification of serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) using a β-cyclodextrin/poly(N-acetylaniline)/carbon nanotube composite modified carbon paste electrode has been developed. Synergistic effect of multi-walled carbon nanotube (MWCNT) in addition to the pre-concentrating effect of β-cyclodextrin (β-CD) as well as its different inclusion complex stability with 5-HT and DA was used to construct an electrochemical sensor for quantification of these important neurotransmitters. The overlapping anodic peaks of 5-HT and DA at 428 mV on bare electrode resolved in two well-defined voltammetric peaks at 202 and 363 mV vs. Ag/AgCl respectively. The oxidation mechanism of 5-HT and DA on the surface of the electrode was investigated by cyclic voltammetry and it was found that the electrode processes are pH dependent and electrochemical oxidation of 5-HT is totally irreversible while the electrode gave a more reversible process to DA. Under optimized conditions, linear calibration curves were obtained in the range of about 4-200 μM with a detection limits down to sub-μM levels (S/N=3) after 20-s accumulation, for both. The proposed sensor was shown to be remarkably selective for 5-HT and DA in matrices containing different species including ascorbic acid and uric acid. The suitability of the developed method was tested for the determination of 5-HT and DA in the Randox Synthetic Plasma samples and acceptable recoveries were obtained for a set of spiked samples.     

Association of polymorphisms in glutamate-cysteine ligase catalytic subunit and microsomal triglyceride transfer protein genes with nonalcoholic fatty liver disease

Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to examine the single nucleotide polymorphism (SNP) -129C/T (rs17883901) in glutamate-cysteine ligase catalytic subunit (GCLC) and SNPs I128T (rs3816873) and Q95H (rs61733139) in microsomal triglyceride transfer protein (MTTP) in NAFLD. Eighty-three patients with a diagnosis of NAFLD and 93 healthy subjects were included in the study. Tetra amplification refractory mutation system-polymerase chain reaction was designed to detect the SNPs. There were no significant differences in the polymorphism of -129C/T (rs17883901) of the GCLC gene among NAFLD and control groups (p?>?0.05). A significant difference was observed between NAFLD and control group regarding the SNP I128T (rs3816873) in the coding region of the MTTP gene (p?相似文献   

Sublethal effects of hexaflumuron on development and reproduction of the diamondback moth,Plutella xylostella (Lepidoptera: Yponomeutidae)

Abstract Effects of hexaflumuron at 10% lethal concentration (LC₁₀) and LC₂₅ on development and reproduction parameters of the diamondback moth, Plutella xylostella (Linnaeus, 1753) (Lep.: Yponomeutidae) were investigated. Estimated LC₅₀, LC₁₀ and LC₂₅ values of leaf dip bioassay of hexaflumuron on the third instar larvae of the P. xylostella were 1.48, 0.59 and 0.91 mg/L, respectively. Hexaflumuron decreased pupal weight in the parent generation at sublethal concentrations but in the offspring generation, this effect was not observed. Sublethal concentrations increased egg, first and second larval instar and pupa developmental time and shortened life span of adults, but did not change the third and fourth larval instars and pre‐pupa developmental period. Also fecundity of females reduced significantly but hatchability of treatments and control were similar. Survival rate of pre‐adult stages declined significantly at LC₂₅ concentration. Reproduction parameters such as reproductive rate (R₀) and intrinsic rate of increase in sublethal concentrations were significantly lower compared with control, but gross reproduction rate (GRR) at the LC₁₀ concentration was increased and it could be hormoligosis. Also hexaflumuron significantly increased doubling time (Dt). We conclude that the sublethal effects of hexaflumuron might exhibit significant effects on the population dynamics of P. xylostella.     

Inhibitory Effects of Akacid®plus on Growth and Aflatoxin Production by Aspergillus parasiticus

The effects of Akacid plus, a novel guanidine-based polymer first introduced as a biocidal and disinfectant agent were studied on Aspergillus parasiticus growth and its aflatoxin (AF) productivity. The fungus was cultured on yeast extract-sucrose (YES) broth in presence of various twofold serial dilutions of 25% Akacid plus (1.5-96 microL/50 mL medium) and then incubated in shaking condition with 150 rev./min at 28 degrees C for 96 h. Based on obtained results, Akacid plus was found to significantly inhibit both growth and aflatoxin B1 (AFB1) synthesis in very low concentrations in a dose-dependent manner. Fungal growth inhibition was determined in the range of 9.6-99.6% in mycelia exposed to the total concentration range of 1.5-48 microL. A final concentration of 96 microL was necessary to completely inhibit the growth of fungus. Under similar conditions, AFB1 synthesis was found to be strongly inhibited by 8.1-98.0% in presence of 1.5-24 microL Akacid plus with a maximum of 100% by 48 microL concentration. With respect to the unique physico-chemical properties of Akacid plus, its marked inhibitory effects on A. parasiticus growth and its AFB1 synthesis shown for the first time in this study make it a promising candidate for application in prevention programmes of AF contamination of susceptible crops.     

R-carrying genotypes of serum paraoxonase (PON1) 192 polymorphism and higher activity ratio are related to susceptibility against ischemic stroke

The polymorphic gene of serum paraoxonase (PON1) and its activity involved in atherosclerosis. The purpose of the study was to analyze PON1 192 Q/R polymorphism and the enzyme activities in ischemic stroke. The polymorphism as the most common polymorphism in PON1 gene coding sequence is associated with variation in the enzyme activity and vascular disease. The study included 85 stroke patients and 71 control subjects. PON1 192 polymorphism was genotyped using PCR protocol. Paraoxonase activity (Para) and arylesterase activity (Aryl) were determined spectrophotometrically using paraoxon and phenylacetate as the substrates. The QR and RR genotypes were more frequent in stroke population compared to controls, resulting in a higher frequency of the R allele in patients (0.24 vs 0.18, OR?=?1.41). Patients had significantly higher Para/Aryl ratio than that of controls (P?=?0.016). In stroke patients, Para/Aryl and Para/HDL ratios increased with this order: QQ?<?QR?<?RR. Hypertension significantly increased the risk of ischemic stroke by 15-fold among R-containing people, while this was significantly increased 4-fold for QQ homozygotes. Smoking increased the risk of having ischemic stroke in both QQ homozygote and QR?+?RR group (OR?=?2.84 and OR?=?2.33, respectively). In conclusion, these data highlight the importance of PON1 192 R allele and high Para/Aryl ratio in susceptibility to ischemic stroke in the population. The presence of the 192 R allele potentiates the risk of stroke especially in hypertensive people. Decreased Aryl and increased Para/Aryl, Para/HDL and Aryl/HDL ratios may be markers indicated the increased susceptibility to ischemic stroke in the population.