Formation of hydroxyl radicals by irradiated 1-nitronaphthalene (1NN): oxidation of hydroxyl ions and water by the 1NN triplet state

The excited triplet state of 1-nitronaphthalene ((3)1NN*) reacts with OH(-) with a second-order reaction rate constant of (1.66 ± 0.08)×10(7) M(-1) s(-1) (μ±σ). The reaction yields the ˙OH radical and the radical anion 1NN(-)˙. In aerated solution, the radical 1NN(-)˙ would react with O(2) to finally produce H(2)O(2) upon hydroperoxide/superoxide disproportionation. The photolysis of H(2)O(2) is another potential source of ˙OH, but such a pathway would be a minor one in circumneutral (pH 6.5) or in basic solution ([OH(-)] = 0.3-0.5 M). The oxidation of H(2)O by (3)1NN*, with rate constant 3.8 ± 0.3 M(-1) s(-1), could be the main ˙OH source at pH 6.5.     

1,4-dihydroxyxanthone modulates the adhesive property of endothelial cells by inhibiting intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin

Cell adhesion molecules, particularly intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1) and E-selectin, play important roles in the recruitment of leukocytes to the site of inflammation. Blocking the expression of these molecules or preventing their interaction with the receptors has been shown to be important in controlling various inflammatory diseases. These cell adhesion molecules are induced on endothelial cells by various proinflammatory cytokines like IL-1beta and TNF-alpha and also by bacterial LPS. We demonstrate here that 1,4-Dihydroxyxanthone (1,4 DHX) inhibits the expression of cell adhesion molecules, such as ICAM-1, VCAM-1 and E-selectin, on endothelial cells in a concentration and time dependent manner. The inhibition by 1,4 DHX is reversible. On further analysis, our results also show that 1,4 DHX inhibits the adhesion of peripheral neutrophils to the endothelial cell monolayers. 1,4 DHX, therefore, could be used as a novel target for controlling various pathological conditions associated with upregulation of endothelial leukocyte adhesion molecules.     

Synthesis of 4-(1-oxo-isoindoline) and 4-(5,6-dimethoxy-1-oxo-isoindoline)-substituted phenoxypropanolamines and their beta1-, beta2-adrenergic receptor binding studies

Phenoxypropanolamines with 1-oxo-isoindoline and 5,6-dimethoxy-1-oxo-isoindoline groups at the para position were synthesized. beta1, beta2-Adrenergic receptor binding affinities for the synthesized compounds were tested and compared with propranolol and atenolol. It was found that the incorporation of para-amidic functionality within the 1-oxo-isoindoline ring and 5,6-dimethoxy-1-oxo-isoindoline ring system led to a high degree of cardioselectivity in the phenoxypropanolamines. Two of the compounds and possessed beta1-adrenergic receptor affinity comparable with that of atenolol and both showed a better cardioselectivity than atenolol. Both and are undergoing further pharmacological evaluation.     

Xanthones as inhibitors of microsomal lipid peroxidation and TNF-alpha induced ICAM-1 expression on human umbilical vein endothelial cells (HUVECs)

Xanthones bearing different functionalities, namely 1-hydroxyxanthone (1), 3-hydroxyxanthone (2), 1,4-dihydroxyxanthone (3), 2,6-dihydroxyxanthone (4), 1,2-diacetoxyxanthone (5), 2,6-diacetoxyxanthone (6), 3-methoxyxanthone (7), 1,3,7-trimethoxyxanthone (8) and 1,5-dihydroxy-6-methoxyxanthone (9) were synthesised and examined for their effect on nicotinamide adenine dinucleotide phosphate (NADPH)-catalysed liver microsomal lipid peroxidation and on tumour necrosis factor-alpha (TNF-alpha) induced expression of intercellular adhesion moledule-1 (ICAM-1) on endothelial cells, with a view to establish structure-activity relationship. Hydroxy- and acetoxyxanthones showed potent inhibitory effects on NADPH-catalysed lipid peroxidation and TNF-alpha induced expression of ICAM-1 on endothelial cells.     

Role of GhHDA5 in H3K9 deacetylation and fiber initiation in Gossypium hirsutum

Cotton fibers are single‐celled trichomes that initiate from the epidermal cells of the ovules at or before anthesis. Here, we identified that the histone deacetylase (HDAC ) activity is essential for proper cotton fiber initiation. We further identified 15 HDAC s homoeologs in each of the A‐ and D‐subgenomes of Gossypium hirsutum . Few of these HDAC homoeologs expressed preferentially during the early stages of fiber development [?1, 0 and 6 days post‐anthesis (DPA )]. Among them, GhHDA 5 expressed significantly at the time of fiber initiation (?1 and 0 DPA). The in vitro assay for HDAC activity indicated that GhHDA 5 primarily deacetylates H3K9 acetylation marks. Moreover, the reduced expression of GhHDA 5 also suppresses fiber initiation and lint yield in the RNA interference (RNA i) lines. The 0 DPA ovules of GhHDA 5 RNA i lines also showed alterations in reactive oxygen species homeostasis and elevated autophagic cell death in the developing fibers. The differentially expressed genes (DEG s) identified through RNA ‐seq of RNA i line (DEP 12) and their pathway analysis showed that GhHDA 5 modulates expression of many stress and development‐related genes involved in fiber development. The reduced expression of GhHDA 5 in the RNA i lines also resulted in H3K9 hyper‐acetylation on the promoter region of few DEG s assessed by chromatin immunoprecipitation assay. The positively co‐expressed genes with GhHDA 5 showed cumulative higher expression during fiber initiation, and gene ontology annotation suggests their involvement in fiber development. Furthermore, the predicted protein interaction network in the positively co‐expressed genes indicates HDA 5 modulates fiber initiation‐specific gene expression through a complex involving reported repressors.     

Design and synthesis of a luminescent iridium complex-peptide hybrid (IPH) that detects cancer cells and induces their apoptosis

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) triggers the cell-extrinsic apoptosis pathway by complexation with its signaling receptors such as death receptors (DR4 and DR5). TRAIL is a C₃-symmetric type II transmembrane protein, consists of three monomeric units. Cyclometalated iridium(III) complexes such as fac-Ir(tpy)₃ (tpy?=?2-(4-tolyl)pyridine) also possess a C₃-symmetric structure and are known to have excellent luminescence properties. In this study, we report on the design and synthesis of a C₃-symmetric and luminescent Ir complex-peptide hybrid (IPH), which contains a cyclic peptide that had been reported to bind to death receptor (DR5). The results of MTT assay of Jurkat, K562 and Molt-4 cells with IPH and co-staining experiments with IPH and an anti-DR5 antibody indicate that IPH binds to DR5 and induces apoptosis in a manner parallel to the DR5 expression level. Mechanistic studies of cell death suggest that apoptosis and necrosis-like cell death are differentiated by the position of the hydrophilic part that connects Ir complex and the peptide units. These findings suggest that IPHs could be a promising tool for controlling apoptosis and necrosis by activation of the extra-and intracellular cell death pathway and to develop new anticancer drugs that detect cancer cells and induce their cell death.     

Combinatorial Interactions of Biotic and Abiotic Stresses in Plants and Their Molecular Mechanisms: Systems Biology Approach

Plants are continually facing biotic and abiotic stresses, and hence, they need to respond and adapt to survive. Plant response during multiple and combined biotic and abiotic stresses is highly complex and varied than the individual stress. These stresses resulted alteration of plant behavior through regulating the levels of microRNA, heat shock proteins, epigenetic variations. These variations can cause many adverse effects on the growth and development of the plant. Further, in natural conditions, several abiotic stresses causing factors make the plant more susceptible to pathogens infections and vice-versa. A very intricate and multifaceted interactions of various biomolecules are involved in metabolic pathways that can direct towards a cross-tolerance and improvement of plant’s defence system. Systems biology approach plays a significant role in the investigation of these molecular interactions. The valuable information obtained by systems biology will help to develop stress-resistant plant varieties against multiple stresses. Thus, this review aims to decipher various multilevel interactions at the molecular level under combinatorial biotic and abiotic stresses and the role of systems biology to understand these molecular interactions.