Genistein effect in cultured ovine ovarian granulosa cells.

Genistein, an isoflavone has the potential to mimic, augment, or dysregulate the steroid hormone production pathways. We hypothesized that genistein affects the granulosa cell (GCs) functions through a series of biochemical, molecular, and genomic cascades. The present study was conducted to evaluate the impact of genistein exposure on GCs viability, apoptosis, and steroidogenesis. The present study involved 3/5 days of exposure to genistein on GCs collected from abattoir-derived ovine ovaries at doses of 0, 1, 10, 25, 50, and 100 µM. The harvested GCs were used for growth, cytotoxicity, and gene expression studies related to apoptosis, growth, and steroidogenesis. We observed that genistein had both stimulatory at 10 and 25 µM levels as well as inhibitory effects at 50 and 100 µM levels on the growth and proliferation of GCs. Genistein significantly decreased the levels of 17ß-estradiol at higher exposure (50 and 100 µM), whereas the progesterone level increased significantly as the genistein exposure increased. Additionally, genistein could also alter the mRNA expression of the steroidogenic receptor, enzymes, proteins, and growth-related genes suggesting that genistein could potentially alter the steroidogenic pathways. We conclude that genistein can interfere with cell survival and steroidogenesis by exhibiting a dose-dependent biphasic response on the viability, growth-related parameters, and the synthesis of 17ß-estradiol in the cultured GCs.

ß-D-Glucopyranose-silver+ (1:1) complex as a small gas molecule scavenger.

In this article, density functional theory computations at the PBE0-D3/def2-TZVP level are reported to unveil the type of bonding between ß-D-glucopyranose-silver ion (1:1) complex ([Ag(C6 H12 O6 )]+ ) and seven gas molecules, namely, H2 , C2 H2 , C2 H4 , CO, N2 , NO and O2 . Moreover, the relative preference of trapping among these molecules within the sight of Ag metal ion in the complex is explored. The nature of interaction of these small molecules with the [Ag(C6 H12 O6 )]+ ion is studied. Exergonic nature of binding is noted with the metal center for all the chosen small molecules except O2 . Thermochemical data reveals the binding preference of C2 H4 > C2 H2 > CO > NO > N2 > H2 . Natural bond orbital analysis, contour plot of the Laplacian of electron density, electron density descriptors, and gradient isosurface help in understanding the nature of interactions. Maximum bond formation is noted between the Ag-complex and CO molecule. Assessed energy decomposition analysis discloses the nature of interaction as mainly orbital between the bound small gas molecules and the Ag-complex. Frontier molecular orbital pictures further help in understanding the type of interaction as orbital. To disclose the kinetic stability of the gas molecule bound Ag complexes an ab initio molecular dynamics study is done at different temperatures up to 2 ps. These studies help in understanding the type of adsorption. Calculated conceptual density functional theory (CDFT) based reactivity descriptors corroborate well with results. ß-D-glucopyranose-silver ion (1:1) complex may be used as small gas molecule scavenger.

Daboialipase, a phospholipase A2 from Vipera russelli russelli venom posesses anti-platelet, anti-thrombin and anti-cancer properties.

Snake venoms are known to contain toxins capable of interfering with normal physiological processes of victims. Specificity of toxins from snake venoms give scope to identify new molecules with therapeutic action and/or help to understand different cellular mechanisms. Russell's viper venom (RVV) is a mixture of many bioactive molecules with enzymatic and non-enzymatic proteins. The present article describes Daboialipase (DLP), an enzymatic phospholipase A2 with molecular mass of 14.3 kDa isolated from RVV. DLP was obtained after cation exchange chromatography followed by size-exclusion high performance liquid chromatography (SE-HPLC). The isolated DLP presented strong inhibition of adenosine di-phosphate (ADP) and collagen induced platelet aggregation. It also showed anti-thrombin properties by significantly extending thrombin time in human blood samples. Trypan blue and resazurin cell viability assays confirmed time-dependent cytotoxic and cytostatic activities of DLP on MCF7 breast cancer cells, in vitro. DLP caused morphological changes and nuclear damage in MCF7 cells. However, DLP did not cause cytotoxic effects on non-cancer HaCaT cells. Peptide sequences of DLP obtained by O-HRLCMS analysis showed similarity with a previously reported PLA2 (Uniprot ID: PA2B_DABRR/PDB ID: 1VIP_A). An active Asp at 49th position, calcium ion binding site and anticoagulant activity sites were identified in 1 VIP_A. These findings are expected to contribute to designing new anti-platelet, anticoagulant and anti-cancer molecules.

Cooperative and Bifunctional Adsorbent-Catalysts Materials for In-situ VOCs Capture-Conversion.

Volatile organic compounds (VOCs) are gases that are emitted into the air from products or processes and are major components of air pollution that significantly deteriorate air pollution and seriously affect human health. Different types of metals, metal oxides, mixed-metal oxides, polymers, activated carbons, zeolites, MOFs and mixed-matrixed materials have been developed and used as adsorbent or catalysts for diversified VOC capture, removal, and destruction. In this comprehensive review, we first discuss the general classification of VOC removal materials and processes and outline the historical development of bifunctional and cooperative adsorbent-catalysts for the removal of volatile organic compounds (VOCs) from air. Subsequently, particular attention is devoted to design strategies for cooperative adsorbent-catalysts, along with detailed discussions on the latest advances on these bifunctional materials, reaction mechanisms, long-term stability, and regeneration for VOCs removal processes. Finally, challenges and future opportunities for the environmental implementation of these bifunctional and cooperative adsorbent-catalysts are identified and outlined with the intent of providing insightful guidance on the design and fabrication of more efficient materials and systems for VOCs removal in the future.

Impact of Static-Oriented Electric Fields on the Kinetics of Some Representative Suzuki-Miyaura and Metal-Cluster Mediated Reactions.

In order to examine the effect of oriented (static) electric fields (OEF) on the kinetics of some representative Suzuki-Miyaura and metal-cluster mediated reactions at ambient temperatures, density functional theory-based calculations are reported herein. Results indicate that, in general, OEF can facilitate the kinetics of the concerned reactions when applied along the suitable direction (parallel or anti-parallel with respect to the reaction axis). The reverse effect happens if the direction of the OEF is flipped. OEF (when applied along the 'right' direction) helps to polarize the transition states in the desired direction, thereby facilitating favorable bonding interactions. Given the growing need for finding appropriate catalysts among the scientific community, OEF can prove to be a vital route for the same.

Biological activities of Vipegrin, an anti-adhesive Kunitz-type serine proteinase inhibitor purified from Russell's viper venom.

Vipegrin is a 6.8 kDa Kunitz-type serine proteinase inhibitor purified from Russell's viper (Vipera russelii russelii) venom. Kunitz-type serine proteinase inhibitors are non-enzymatic proteins and are ubiquitous constituents of viper venoms. Vipegrin could significantly inhibit the catalytic activity of trypsin. It also posseses disintegrin-like properties and could inhibit collagen and ADP-induced platelet aggregation in a dose-dependent manner. Vipegrin is cytotoxic to MCF7 human breast cancer cells and restricts its invasive property. Confocal microscopic analysis revealed that Vipegrin could induce apoptosis in MCF7 cells. Vipegrin disrupts cell to cell adhesion of MCF7 cells through its disintegrin-like activity. It also causes disruption of attachment of MCF7 cells to synthetic (poly L-lysine) and natural (fibronectin, laminin) matrices. Vipegrin did not cause cytotoxicity on non-cancerous HaCaT, human keratinocytes. The observed properties indicate that Vipegrin may help the development of a potent anti-cancer drug in future.

Structure and stability of the sH binary hydrate cavity and host-guest versus guest-guest interactions therein: A DFT approach.

The intrinsic ability of clathrate hydrates to encage gaseous molecules is explored. Encapsulation ability depends on the cavity size and the type of guest gaseous species in addition to the physical parameters, temperature and pressure. Here we have reported the structure, stability and nature of interaction in dissimilar guest occupied sH hydrate cavity. Diatomic gas molecules and small polyatomic hydrocarbons are considered as guests. The irregular icosahedron (512 68 ) cavity of sH hydrate is the host. Different thermodynamic parameters for the guest molecules encapsulation were calculated using three different hybrid DFT functionals, B3LYP, M05-2X, M06, and moreover using dispersion correction (PBE0-D3). With the consideration of large H-bonded systems the 6-31G* and cc-pVTZ basis sets were used for two set of computations. To disclose the nature of interaction between the host-guest systems as well as the interaction between the guest molecules inside the host the non-covalent interaction (NCI) indices and energy decomposition analysis (EDA) were done. Impact of host-guest and guest-guest interactions are discussed.

Global DNA methylation, DNA methyltransferase and stress-related gene expression in ovine oocytes and embryos after exposure to metabolic stressors.

DNA methylation, considered the most prominent epigenetic mark was important for the gene regulation in embryonic development. The present study aimed at evaluating the effects of metabolic stressors [Non-esterified fatty acid (NEFA), ß-hydroxy-butyric acid (BHB), ammonia and urea] exposure during the in vitro ovine oocyte maturation, global DNA methylation, DNA methyltransferase and stress-related gene expression. Colorimetric analysis of global DNA methylation and the expression of the DNA methyltransferase genes (DNMT1, DNMT3A, and DNMT3B) were assessed in the matured oocytes, 2-cell embryos and blastocysts produced in vitro from oocytes exposed with the metabolic stressors during 24 h of the in vitro maturation (IVM). Further, the mRNA expression of the stress-related genes (SOD1, SOD2) in the matured oocytes, 2-cell embryos and blastocysts produced was assessed. Significant difference in global DNA methylation levels between all the treatments tested was observed when compared with control in oocytes, two-cell embryos and blastocysts. Elevated concentration of metabolic stressors resulted in increased expressions of several stress-related genes, i.e., SOD1, SOD2 and in mRNA expression of DNA methyltransferase genes. The present study is the first to report that the DNA methylation was sensitive to the effects of the metabolic stressors in ovine oocytes/embryos. The aberrant expressions of genes during oocyte development targeted in the present study can provide evidence for the early embryo developmental arrest and blastocysts quality. These results highlighted the sensitivity of the early embryogenesis and more precisely of the reprogramming period to metabolites challenges, in a realistic situation of elevated concentration of metabolic stressors.

Antibacterial and Antibiofilm Activities of ß-Lapachone by Modulating the Catalase Enzyme.

BACKGROUND: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of ß-Lapachone (ß-Lap), a novel synthetic compound. METHODS: The antibacterial activity of the ß-Lap compound was examined against laboratory strains by agar well diffusion method and broth dilution assay. Growth kinetics in presence of ß-Lap on Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa (ATCC 27853) were assessed by microplate alamarBlue assay. Crystal violet blue assay was used for biofilm inhibition and biofilm eradication. P. aeruginosa catalase (KatA) complexed with ß-Lap was modeled using molecular docking approach. RESULTS: ß-Lap exhibited potent antimicrobial activity against laboratory strains of bacteria with MIC of 0.2 mM for S. saprophyticus and Staphylococcus aureus, and 0.04 mM for Staphylococcus epidermidis and Pseudomonas aeruginosa ATCC 27853. The inhibition of catalase enzyme was found to be the cause for its antibacterial activity. Bioinformatics analysis suggests that ß-Lap can inhibit KatA activity by interacting with catalase proximal active site and heme binding site. The activity of some commercial antibiotics was enhanced in association with ß-Lap. In addition, ß-Lap inhibited the biofilm formation and eradicated the already formed and ultra-mature biofilms of aforesaid bacterial strains. CONCLUSION: These observations indicated that ß-Lap could be a promising antibacterial agent for the treatment and prevention of infectious diseases.

Cell cycle protein BORA is associated with colorectal cancer progression by AURORA-PLK1 cascades: a bioinformatics analysis.

Colorectal cancer (CRC) is the third most diagnosed cancer in the world. A better understanding of the molecular mechanism of CRC is essential for making novel strategies for the CRC management and its prevention. The present study aims to explore the molecular mechanism through integrated bioinformatics analysis by analyzing genes and their co-expression pattern in normal and CRC states. GSE110223, GSE110224 and GSE113513 gene expression profiles were analyzed in this study. The co-expression networks for normal and tumor samples were constructed separately and analyzed to identify the modules, sub-networks and key genes. Gene regulatory network analysis was done to understand the regulatory mechanism of selected genes. Survival analysis was performed for the identified sub-networks and key genes to understand their role in CRC progression. A total of seven modules were detected and the KEGG pathway analysis revealed these modules were mainly enriched with cell cycle, metabolism and signaling-related pathways. E2F6 and ETV4 transcription factors regulating the activity of multiple genes of identified modules were found to be up-regulated in CRC. Six Sub-networks and seven key genes, BORA, CCT7, DTL, RUVBL1, RUVBL2, THEM6 and TMEM97 associated with the CRC progression were identified. Disease-gene association analysis identified a novel association of the BORA gene with CRC that activates and regulates the AURORA-PLK1 cascades in the cell cycle. Survival analysis indicates that the overexpressed BORA is associated with unfavourable overall survival in CRC. The mechanistic role of BORA in the regulation of cell cycle progression suggests that BORA might act as a potential therapeutic target for CRC.

SPAD-1, a serine proteinase associated disintegrin from Russell's viper venom disrupts adhesion of MCF7 human breast cancer cells.

Serine Proteinase Associated Disintegrin-1 (SPAD-1) is a low molecular mass (26 kDa) positively charged protein purified from Russell's viper venom (RVV) possessing cytotoxic activity on MCF7, human breast cancer cells. Primary sequence analysis of the protein confirms that it is a novel Snake Venom Serine Proteinase (SVSP) and a member of the trypsin family. SPAD-1 contains a conserved triad of Histidine (H), Aspartic acid(D) and Serine(S) residues at its active site for proteinase activity and also an adjacent histidine-glycine-aspartic acid (HGD) disintegrin-like motif. The serine proteinase and disintegrin parts are functionally active and independent. SPAD-1 showed proteolytic digestion of fibrinogen and fibronectin, but laminin digestion was below the detectable limit. Proteolytically inactivated SPAD-1 inhibited collagen and ADP-induced platelet aggregation. This study proposes considering Serine Proteinase Associated Disintegrin (SPAD) as a new group of snake venom proteins. Members of this group contain a serine proteinase catalytic triad and a disintegrin-like motif. SPAD-1 caused visible morphological changes in MCF7 cells, including a reduction of the cell-to-cell attachments, rounding of cell shape and death, in vitro. SPAD-1 also showed a dose-dependent significant decrease in the invasive potency of breast cancer cells. Confocal microscopic analysis revealed the breakage of nuclei of the SPAD-1-treated cells. SPAD-1 also increased cell detachment from the poly L-lysine-coated, laminin-coated and fibronectin-coated culture plate matrices, confirming the disintegrin activity. This study concludes that SPAD-1 may be a good candidate for anti-tumour drug design in the future.

Quantifying the Workability of Calcium Sulfoaluminate Cement Paste Using Time-Dependent Rheology.

Poor workability is a common feature of calcium sulfoaluminate (CSA) cement paste. Multiple chemical admixtures, such as set retarders and dispersants, are frequently employed to improve the workability and delay the setting of CSA cement paste. A quantitative assessment of the compatibility, efficiency, and the effects of the admixtures on cement paste workability is critical for the design of an appropriate paste formulation and admixture proportioning. Very limited studies are available on the quantitative rheology-based method for evaluating the workability of calcium sulfoaluminate cement pastes. This study presents a novel and robust time-dependent rheological method for quantifying the workability of CSA cement pastes modified with the incorporation of citric acid as a set retarder and a polycarboxylate ether (PCE)-based superplasticizer as a dispersant. The yield stress is measured as a function of time, and the resulting curve is applied to quantify three specific workability parameters: (i) the rate at which the paste loses flowability, (ii) the time limit for paste placement or pumping, marking the onset of acceleration to initial setting, and (iii) the rate at which the paste accelerates to final setting. The results of the tested CSA systems show that the rate of the loss of flowability and the rate of hardening decrease monotonously, while the time limit for casting decreases linearly with the increase in citric acid concentration. The dosage rate of PCE has a relatively small effect on the quantified workability parameters, partly due to the competitive adsorption of citrate ions. The method demonstrated here can characterize the interaction or co-influence of multiple admixtures on early-age properties of the cement paste, thus providing a quantitative rheological protocol for determining the workability and a novel approach to material selection and mixture design.

Examining the Effect of a Chitosan Biopolymer on Alkali-Activated Inorganic Material for Aqueous Pb(II) and Zn(II) Sorption.

Biopolymers and alkali-activated materials have attracted a great deal of attention as adsorbents for the removal of heavy metal contaminants from aqueous solutions. Both materials are sustainable and feature unique properties, but biopolymers are relatively more expensive or difficult to prepare and exhibit low mechanical and surface properties, a narrow pH range, and thermal stability. In this study, hybrid adsorbents were prepared from both types of material, by alkali activation of low-cost fly ash precursors accompanied by incorporation of 0-2%mass chitosan biopolymer. Two types of alkaline activating solutions, NaOH and Na2SiO3, were employed to generate two sets of hybrid adsorbents with varying chitosan contents. The effect of the chitosan dosage on the aqueous Pb(II) and Zn(II) sorption efficiency was also investigated. The adsorbents exhibited 98-100% removal efficiencies for both metals, but the sorption of Zn(II) was generally higher than that of Pb(II). The addition of 0.1-2.0%mass chitosan resulted in very little improvement in the overall efficiency of the adsorbents. In contrast, 0.05%mass chitosan led to a decrease in the sorption efficiency; this was linked to the decrease in the adsorbents' ζ potential. The Na2SiO3-activated materials featured larger BET surface areas and better overall sorption performance, while the NaOH-activated materials showed the worst Pb(II) sorption performance and hence more noticeable improvement upon addition of chitosan. Mechanistic investigation shows that the sorption process follows second-order kinetics and is a chemisorption-driven process.

A global analysis on the differential regulation of RNA binding proteins (RBPs) by TNF-α as potential modulators of metabolic syndromes.

Metabolic syndrome (MetS) is associated with a group of conditions, which enhances the risk of diabetes, heart diseases and stroke in the affected individuals. Earlier reports from our lab have shown that Tumor necrosis factor-α (TNF-α) significantly modulates the expression of 56 genes at the alternative splicing level which are involved in various signaling and metabolic pathways (MetS genes) connected to MetS. These MetS genes were predicted to interact with various RNA-binding proteins (RBPs) when exposed to TNF-α, resulting changes in their alternative splicing patterns. Here we are presenting data of an RNA-Seq analysis, which identified 1218 unique, and significantly regulated genes by TNF-α, 15% of which are RBPs . Among the 1218 genes, 204 genes have been identified as MetS genes by the ingenuity pathway analysis, and 10% of the MetS genes are found as RBPs. Our results also show that TNF-α changes the phosphorylation status of certain RBPs such as SR proteins, crucial players in alternative splicing, possibly via changing the activation status of certain upstream signaling molecules which also act as upstream kinases for these proteins. Taken together, these findings suggest that TNF-α influences the regulation of the RBPs at the various levels for their expression, which may lead to the alteration of the splicing pattern of the MetS genes. MetS genes acting as RBPs and are modulated by TNF-α, predict the existence of highly interconnected mechanisms which require further analysis to understand their dual roles on the onset of these diseases.

Nano zinc supplementation in goat (Capra hircus) ration improves immunity, serum zinc profile and IGF-1 hormones without affecting thyroid hormones.

The trial was aimed at evaluating probable superiority, if any of nano zinc (NZn) over inorganic zinc (Zn) on immunity, serum minerals and T3 , T4 , and IGF-1 hormone profiles in goats. NZn was synthesized by using 0.45 M aqueous solution of Zn nitrate and 0.9 M aqueous solution of sodium hydroxide (average particle size 74 nm). Twenty-four male goats were grouped into four groups as per their body weight and were supplemented with either a basal diet with concentrate and straw at 50:50 ratio (Negative control, NC) alone or supplemented with 50 mg/kg Zn (Control) from inorganic Zn source, that is ZnO (IZn-50), 50 mg/kg Zn from NZn (NZn-50) or 25 mg/kg Zn from NZn (NZn-25). No change was observed in thyroid hormone status on zero and 90th day of experimental feeding, but NZn supplementation improved (p < 0.05) IGF-1 level on 90th day serum samples. Zn supplementation improved the humoral immunity in all the groups irrespective of the source. Similarly, cell-mediated immunity (CMI) measured by skinfold thickness after injecting Con-A, was also improved in Zn supplemented groups than control at 6, 12 and 48 h of incubation. NZn-50 animals showed highest HI (haemagglutination inhibition) titre as well as skin thickness. The CD 4 + (cluster of differentiation in %) was more (p < 0.05) in Zn supplemented groups. NZn-50 showed higher (p < 0.05) CD 8 + count than NC and similar (p > 0.05) to IZn-50 and NZn-25 groups without affecting (p > 0.05) the ratio of CD 4 + , CD 8 + among the treatment groups. Thus, NZn supplementation at 25 mg/kg had similar immunity and serum T3 , T4 and IGF-1 profiles compared with IZn at 50 mg/kg dose.

Investigating the microstructure of high-calcium fly ash-based alkali-activated material for aqueous Zn sorption.

The performance of adsorbents prepared by alkali activation of high calcium fly ash was investigated for removing aqueous Zn. Two formulations involving the use of NaOH and Na2SiO3 activating solutions were used to prepare the adsorbents that feature different microstructural characteristics. The Zn sorption data indicates a sorption process that is controlled by both chemisorption and intra-particle diffusion. The Na2SiO3-activated material displayed higher sorption rates compared to the NaOH-activated material. The sorption kinetics show strong dependence on the microstructures of the adsorbents, wherein the Na2SiO3-activated material featuring higher contents of amorphous phases (96 %mass) in the hydrated phase assemblage, with attendant improved porosity and surface area, performed better than the NaOH-activated material (86 %mass amorphous phases) which showed higher degree of crystallinity and coarse morphology. The Na2SiO3-activated material exhibited 100% Zn removal efficiency within the first 5 min in all studied initial adsorbate concentrations(corresponding to sorption capacity of up to 200 mg/g), while the NaOH-activated analogue tends to lag, reaching 99.99% Zn removal efficiency after about 240 min in most cases. The two formulations were also examined with thermodynamic modeling and the results agree with experimental data in indicating that the use of alkali-silicate activating solution is most suitable for converting high calcium fly ash into efficient adsorbent for removing aqueous heavy metals.

Correction: Quinacrine inhibits GSTA1 activity and induces apoptosis through G1/S arrest and generation of ROS in human non-small cell lung cancer cell lines.

[This corrects the article DOI: 10.18632/oncotarget.27558.].

Structure-Property Relationship of Geopolymers for Aqueous Pb Removal.

The geopolymer-an inorganic polymeric material synthesized from the reaction of aluminosilicate precursors and alkaline activating solutions-has gained wide research attention in recent decades as a promising adsorbent for the removal of aqueous heavy metals. However, the high variability of the material and several unanswered questions have limited its development and general adoption in the industry. This study evaluates the impacts of composition and microstructure on the performance of geopolymers for aqueous lead (Pb) removal to elucidate the composition-structure-property relationship. The Pb sorption kinetics and efficiency of four geopolymers, prepared using different fly ash precursors and activating solutions, were investigated. Although all the four geopolymer compositions studied displayed a high Pb removal efficiency of over 99.5%, with a slight decrease in efficiency with increasing Ca/(Si + Al) and Al/Si contents, the results show that the sorption kinetics decreases exponentially with increasing Ca/(Si + Al) and Al/Si molar ratios. The performance of the geopolymers also shows strong correlation to the microstructure, wherein the sorption kinetics increases exponentially, while the efficiency increases slightly, with increasing mass fraction of the amorphous phase in the geopolymer's phase assemblage. The results of this research indicate that using appropriate precursor formulation and curing conditions to evoke the best microstructures, geopolymer materials can be optimized for high performance in removing heavy metals, thereby improving the chances of the material's general acceptability in the adsorbent industry.

Quinacrine inhibits GSTA1 activity and induces apoptosis through G1/S arrest and generation of ROS in human non-small cell lung cancer cell lines.

BACKGROUND: Quinacrine (QC) is popular for its anti-malarial activity. It has been reported exhibiting anti-cancerous properties by suppressing nuclear factor-κB and activating p53 signaling; however, its effect on cellular pathways in human non-small cell lung cancer (NSCLC) has not been studied. MATERIALS AND METHODS: Binding of QC with GSTA1 was studied computationally as well as through GST activity assay kit. Cell viability, cell cycle and mitochondrial membrane potential activity were studied using flow cytometry. RT-PCR and western blot were carried out to understand the involvement of various genes at their mRNA as well as protein level. RESULTS: QC inhibited the activity of GSTA1 approximately by 40-45% which inhibits cell survival and promotes apoptosis. QC reduced viability of NSCLC cells in a dose-dependent manner. It also causes nuclear fragmentation, G1/S arrest of cell cycle and ROS generation; which along with disruption of mitochondrial membrane potential activity leads to apoptotic fate. CONCLUSIONS: Results revealed, QC has promising anti-cancer potential against NSCLC cells via inhibition of GSTA1, induction of G1/S arrest and ROS mediated apoptotic signaling.

A Machine Learning Approach for Drug-target Interaction Prediction using Wrapper Feature Selection and Class Balancing.

Drug-Target interaction (DTI) plays a crucial role in drug discovery, drug repositioning and understanding the drug side effects which helps to identify new therapeutic profiles for various diseases. However, the exponential growth in the genomic and drugs data makes it difficult to identify the new associations between drugs and targets. Therefore, we use computational methods as it helps in accelerating the DTI identification process. Usually, available data driven sources consisting of known DTI is used to train the classifier to predict the new DTIs. Such datasets often face the problem of class imbalance. Therefore, in this study we address two challenges faced by such datasets, i. e., class imbalance and high dimensionality to develop a predictive model for DTI prediction. The study is carried out on four protein classes namely Enzyme, Ion Channel, G Protein-Coupled Receptor (GPCR) and Nuclear Receptor. We encoded the target protein sequence using the dipeptide composition and drug with a molecular descriptor. A machine learning approach is employed to predict the DTI using wrapper feature selection and synthetic minority oversampling technique (SMOTE). The ensemble approach achieved at the best an accuracy of 95.9 %, 93.4 %, 90.8 % and 90.6 % and 96.3 %, 92.8 %, 90.1 %, and 90.2 % of precision on Enzyme, Ion Channel, GPCR and Nuclear Receptor datasets, respectively, when evaluated excluding SMOTE samples with 10-fold cross validation. Furthermore, our method could predict new drug-target interactions not contained in training dataset. Selected features using wrapper feature selection may be important to understand the DTI for the protein categories under this study. Based on our evaluation, the proposed method can be used for understanding and identifying new drug-target interactions. We provide the readers with a standalone package available at https://github.com/shwetagithub1/predDTI which will be able to provide the DTI predictions to user for new query DTI pairs.