Predictive Role of Cluster Bean (Cyamopsis tetragonoloba) Derived miRNAs in Human and Cattle Health.

MicroRNAs (miRNAs) are small non-coding conserved molecules with lengths varying between 18-25nt. Plants miRNAs are very stable, and probably they might have been transferred across kingdoms via food intake. Such miRNAs are also called exogenous miRNAs, which regulate the gene expression in host organisms. The miRNAs present in the cluster bean, a drought tolerant legume crop having high commercial value, might have also played a regulatory role for the genes involved in nutrients synthesis or disease pathways in animals including humans due to dietary intake of plant parts of cluster beans. However, the predictive role of miRNAs of cluster beans for gene-disease association across kingdoms such as cattle and humans are not yet fully explored. Thus, the aim of the present study is to (i) find out the cluster bean miRNAs (cb-miRs) functionally similar to miRNAs of cattle and humans and predict their target genes' involvement in the occurrence of complex diseases, and (ii) identify the role of cb-miRs that are functionally non-similar to the miRNAs of cattle and humans and predict their targeted genes' association with complex diseases in host systems. Here, we predicted a total of 33 and 15 functionally similar cb-miRs (fs-cb-miRs) to human and cattle miRNAs, respectively. Further, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the participation of targeted genes of fs-cb-miRs in 24 and 12 different pathways in humans and cattle, respectively. Few targeted genes in humans like LCP2, GABRA6, and MYH14 were predicted to be associated with disease pathways of Yesinia infection (hsa05135), neuroactive ligand-receptor interaction (hsa04080), and pathogenic Escherichia coli infection (hsa05130), respectively. However, targeted genes of fs-cb-miRs in humans like KLHL20, TNS1, and PAPD4 are associated with Alzheimer's, malignant tumor of the breast, and hepatitis C virus infection disease, respectively. Similarly, in cattle, targeted genes like ATG2B and DHRS11 of fs-cb-miRs participate in the pathways of Huntington disease and steroid biosynthesis, respectively. Additionally, the targeted genes like SURF4 and EDME2 of fs-cb-miRs are associated with mastitis and bovine osteoporosis, respectively. We also found a few cb-miRs that do not have functional similarity with human and cattle miRNAs but are found to target the genes in the host organisms and as well being associated with human and cattle diseases. Interestingly, a few genes such as NRM, PTPRE and SUZ12 were observed to be associated with Rheumatoid Arthritis, Asthma and Endometrial Stromal Sarcoma diseases, respectively, in humans and genes like SCNN1B associated with renal disease in cattle.

Molecular Docking Study of Isoxazole Indole Derivatives (B2A2 Series) as Promising Selective Estrogen Receptor Modulators & Anticancer Drugs.

A series of 7 compounds with isoxazole - indole - γ-resorcylic acid scaffold, segregated into B2 & A2 series, wherein, B2 comprises Compounds: 13, 14, 15 & 16 and A2 comprises Compounds: 10, 11 & 12, on the basis of the variable substituents at the indole, resorcinol and isoxazole end of the scaffold as in Figure: 1, were designed and docked with human estrogen receptor: 1ERRα. The Binding affinity (BA) and the interacting amino acids compared with reference selective estrogen receptor modulators (SERM's) such as Raloxifene, Estradiol, Bazedoxifene, Bisphenol, Genistein, Daidzein, Ormiloxifene, Tamoxifen, 6-hydroxy-naphthalen-2yl-benzo(D)-isoxazol-6-ol(1) using PyRx software and their ADME properties predicted with SWISS ADME online tool. Significant similarities and minor differences in the binding pattern between the key interacting aminoacids such as Arg 394, Glu 353, Asp 351, Leu 346, Leu 525, Trp 383, Phe 404, Ala 350, Leu 387, Met 421 responsible for ER agonist/antagonist affinity found in the binding cavity of a 1 Errα -Bazedoxifene/1 Errα -raloxifene/1 Errα -estradiol docked complex AND 1 Errα -isoxazole-indole- resorcinol docked complex indicate their promising potential to serve as potent ER agonists in bone or ER antagonists against breast cancer and other cancer diseases. The Compounds with highest BA is of the order: BA (A1series)>B1series>//=BA (B2 series) exceptions: compounds: 4, 5 of B1 series & compound:13 of B2 series with identical and least BA values.BA(6)=BA(8)>BA(7)>BA(2)>BA(9)=BA(1)>BA(12)>BA(10)=BA(15)=BA(11)=BA(3)>BA(14)=BA(16)>BA(4)=BA(5)=BA(13).

Insilico Docking Study of Isoxazole Indole Linked Resorcinol Derivatives as Promising Selective Estrogen Receptor Modulators & Anticancer Drugs.

A series of 9 compounds with isoxazole-indole-γ-resorcylic acid scaffold, segregated into B1 & A1 series, wherein, B1 comprises compounds:1,3,4,5, & 9 and A1comprises compounds: 2,6,7, & 8 , on the basis of variable substituents at the indole , resorcinol and isoxazole end of the scaffold as in Fig. 1, were designed and docked with human estrogen receptor:1ERRα. The binding affinity (BA) and the interacting amino acids compared with reference selective estrogen receptor modulators (SERMs) such as Raloxifene, Estradiol, Bazedoxifene, Bisphenol, Genistein, Daidzein, Ormiloxifene,Tamoxifen,6-hydroxy-naphthalen-2yl-benzo(D)-isoxazol-6-ol(1)(WAY-397) using PyRx software and their ADME properties predicted with SWISS ADME online tool. Significant similarities and minor differences in the binding pattern between the key interacting aminoacids such as Arg 394,Glu 353, Asp 351, Leu 346, Leu 525, Trp 383,Phe 404 ,Ala 350, Leu 387, Met 421 responsible for ER agonist/antagonist activity found in the binding cavity of a 1 Errα -Bazedoxifene/1 Errα -raloxifene/1 Errα -estradiol docked complex AND 1 Errα -isoxazole-indole- resorcinol docked complex indicate their promising potential to serve as potent ER agonists in bone or ER antagonists against breast cancer and other cancer diseases. The Compounds with Highest BA is of the order: BA (A1series)>B1 series & BA(6)=BA(8)>BA(7)>BA(2)>BA(9)=BA(1)>BA(3)>BA(4)=BA(5).

Nanomedicines: A Focus on Nanomaterials as Drug Delivery System with Current Trends and Future Advancement.

The rapid advancement of nanomedicine presents novel alternatives that have the potential to transform health care. Targeted drug delivery as well as the synthesis of nanocarriers is a growing discipline that has been intensively researched to reduce the complexity of present medicines in a variety of diseases and to develop new treatment and diagnostic techniques. There are several designed nanomaterials used as a delivery system such as liposomes, micelles, dendrimers, polymers, carbon-based materials, and many other substances, which deliver the drug moiety directly into its targeted body area reducing toxic effect of conventional drug delivery, thus reducing the amount of drug required for therapeutic efficacy and offering many more advantages. Currently, these are used in many applications, including cancer treatment, imaging contrast agents, and biomarker detection and so on. This review provides a comprehensive update in the field of targeted nano-based drug delivery systems, by conducting a thorough examination of the drug synthesis, types, targets, and application of nanomedicines in improving the therapeutic efficiency.

Vibrational and conformational analysis of structural phase transition in Estradiol 17ß valerate with temperature.

Estradiol 17ß valerate (E2V) is a hormonal medicine widely used in hormone replacement therapy. E2V undergoes a reversible isosymmetric structural phase transition at low temperature (Ì´ 250 K) which results from the reorientation of the valerate chain. The reversible isosymmetric structural phase transition follows Ehrenfest's classification when described as first-order and Buerger's classification when classified as order-disorder. The conformational difference also induces changes in molecular torsional angles and on the hydrogen bond pattern. In combination with density functional theory (DFT) calculations, vibrational spectroscopy has been used to correlate the valerate chain modes with the modifications of the dihedral angles on phase transition. We are expecting improvement in our understanding of the phase transition mechanism driven by the temperature. The Conformational analysis reveals the feasible structures corresponding to changes in the dihedral angles associated with the valerate chain. The infrared spectra of calculated conformers are in good agreement with the experimental spectra of E2V structure recorded at room temperature revealing that the changes in valerate chain modes at 1115 cm-1, 1200 cm-1and 1415 cm-1 fingerprint the molecular conformation. An investigation made to determine the ligand-protein interaction of E2V through docking against estrogen receptor (ER) reveals the inhibitive and agonist nature of E2V.

Knock-on effect of anthrax lethal toxin on macrophages potentiates cytotoxicity to endothelial cells.

Herein we report the knock-on cytotoxic effect of lethal toxin (LeTx) on human umbilical vascular endothelial cells (HUVECs). HUVECs were treated either directly with LeTx or indirectly with LeTx conditioned medium (LeTxCM) prepared from RAW264.7 macrophage cells. Cytotoxicity assays were done on HUVECs and A549 cells using LeTx. HUVECs were more susceptible to LeTx (61-74% survivals) as compared to A549 cells (83-94% survivals, P < 0.005). However, LeTxCM from RAW264.7 further potentiated killing of HUVECs (37% survival) compared to the LeTxCM from A549 cells (up to 70-100% survivals). LeTxCM challenge induced an apoptotic cell death in HUVECs, and this was confirmed by reduction of BCL-2 levels to 54%. Protective antigen (PA) binding to macrophage cell line RAW264.7 > HUVECs >> A549 cells. Thus, we postulate that after the initial prodormal phase of pulmonary entry, LeTx causes not only significant direct damage to macrophages and endothelial cells, but also mediates additional indirect damage to endothelial cells mediated by a knock-on effect of LeTx on macrophages that causes apoptotic cell death in endothelial cells.

Synthesis and biological activities of some new dibenzopyranones and dibenzopyrans: search for potential oestrogen receptor agonists and antagonists.

Continuing our search for newer oestrogen agonists or antagonists and extending our work on the exploration of benzopyran related compounds, some new tricyclic molecules bridged between the active molecules of 3,4-diaryl chroman and 2,3-diaryl benzopyrans have been synthesised. Structural modifications at different positions with elements known to impart agonist or antagonist activities have been carried out to prepare the desired molecules. The target compounds were screened for their anti-osteoporotic (agonist) and anti-uterotrophic (antagonist) activities and were found to be moderately active.

Synthesis of some new diaryl and triaryl hydrazone derivatives as possible estrogen receptor modulators.

1,2-Bis(4-substituted phenyl)-2-methyl ethanone (2,4-dinitrophenyl)hydrazones and 1-naphthyl-1-(4-substituted phenyl)-methanone (2,4-dinitrophenyl)hydrazones have been synthesized and evaluated for their anti-implantation, uterotrophic, antiuterotrophic, anticancer and antimicrobial activities. Diphenolic hydrazone (compound 6) showed maximum uterotrophic inhibition of 70%, whereas compound 20 exhibited cytotoxicity in the range of 50-70% against MCF-7 and ZR-75-1 human malignant breast cell lines.