Naringin prevents ultraviolet‐B radiation‐induced oxidative damage and inflammation through activation of peroxisome proliferator‐activated receptor γ in mouse embryonic fibroblast (NIH‐3T3) cells

The present study, we investigate the preventive role of naringin, a dietary flavonoid, against ultraviolet‐B (UVB) radiation (280‐320 nm) induced oxidative damage and inflammatory responses in mouse embryonic fibroblast cell lines (NIH‐3T3). In this study, 20 mJ/cm ² of UVB radiation induces cell cytotoxicity, reactive oxygen species (ROS) generation, DNA damage, and antioxidants depletion in NIH‐3T3 cells. Treatment with naringin (60 µM) prior UVB exposure prevented the cell cytotoxicity, ROS generation, DNA damage, and antioxidants depletion in NIH‐3T3 cells. Furthermore, naringin prevents UVB‐induced mitogen‐activated protein kinase families and nuclear factor‐κB (NF‐κB)‐mediated activation of inflammatory factors, that is TNF‐α, IL‐6, IL‐10, and COX‐2 in NIH‐3T3 cells. Peroxisome proliferator‐activated receptor γ (PPARγ) is an anti‐inflammatory agent and it suppressed the UVB‐mediated oxidative and inflammatory responses. In this study, naringin activates PPARγ and prevents inflammatory biomarkers in NIH‐3T3 cells. Thus, naringin prevents UVB‐mediated inflammation and oxidative damage in NIH‐3T3 cells probably over controlling NF‐κB expression and activation of PPARγ.     

Identification of novel dysregulated circular RNAs in early-stage breast cancer

Breast cancer is a major cause of cancer-related death in women worldwide. Non-coding RNAs are a potential resource to be used as an early diagnostic biomarker for breast cancer. Circular RNAs are a recently identified group of non-coding RNA with a significant role in disease development with potential utility in diagnosis/prognosis in cancer. In this study, we identified 26 differentially expressed circular RNAs associated with early-stage breast cancer. RNA sequencing and two circRNA detection tools (find_circ and DCC) were used to understand the circRNA expression signature in breast cancer. We identified hsa_circ_0006743 (circJMJD1C) and hsa_circ_0002496 (circAPPBP1) to be significantly up-regulated in early-stage breast cancer tissues. Co-expression analysis identified four pairs of circRNA-miRNA (hsa_circ_0023990 : hsa-miR-548b-3p, hsa_circ_0016601 : hsa_miR-1246, hsa_circ_0001946 : hsa-miR-1299 and hsa_circ_0000117:hsa-miR-502-5p) having potential interaction. The miRNA target prediction and network analysis revealed mRNA possibly regulated by circRNAs. We have thus identified circRNAs of diagnostic implications in breast cancer and also observed circRNA-miRNA interaction which could be involved in breast cancer development.     

Ecdysteroid Stimulated Protein Synthesis in the Male Accessory Reproductive Glands of Spodoptera litura

Summary

20-hydroxyecdysone stimulates protein synthesis in the male accessory reproductive glands of pharate adults of Spodoptera litura both in vivo and in vitro. Juvenile hormone-I has no synergistic effect when given in conjunction with ecdysone in vivo but it inhibits ecdysone-stimulated protein synthesis in vitro.     

Translocation of human ribosomal protein S3 to sites of DNA damage is dependant on ERK-mediated phosphorylation following genotoxic stress

Besides its role in translation and ribosome maturation, human ribosomal protein S3 (hS3) is implicated in DNA damage recognition as reflected by its affinity for abasic sites and 7,8-dihydro-8-oxoguanine (8-oxoG) residues in DNA in vitro. Here, we demonstrate that hS3 is capable of carrying out both roles by its ex vivo translocation from the cytoplasm to the nucleus as a consequence of genotoxic stress. The translocation of hS3 is dependent on ERK1/2-mediated phosphorylation of a threonine residue (T42) of hS3. Two different ectopically expressed site-directed mutants of T42 failed to respond to conditions of genotoxic stress, thus providing a link between DNA damage and ERK1/2 dependent phosphorylation of hS3. Lastly, hS3 was traced in exposed cells to its co-localization with 8-oxoG foci, raising the possibility that hS3 is a member of a cellular DNA damage response pathway that results in its interaction with sites of DNA damage.     

Structure is lost incrementally during the unfolding of barstar

Coincidental equilibrium unfolding transitions observed by multiple structural probes are taken to justify the modeling of protein unfolding as a two-state, N <==> U, cooperative process. However, for many of the large number of proteins that undergo apparently two-state equilibrium unfolding reactions, folding intermediates are detected in kinetic experiments. The small protein barstar is one such protein. Here the two-state model for equilibrium unfolding has been critically evaluated in barstar by estimating the intramolecular distance distribution by time-resolved fluorescence resonance energy transfer (TR-FRET) methods, in which fluorescence decay kinetics are analyzed by the maximum entropy method (MEM). Using a mutant form of barstar containing only Trp 53 as the fluorescence donor and a thionitrobenzoic acid moiety attached to Cys 82 as the fluorescence acceptor, the distance between the donor and acceptor has been shown to increase incrementally with increasing denaturant concentration. Although other probes, such as circular dichroism and fluorescence intensity, suggest that the labeled protein undergoes two-state equilibrium unfolding, the TR-FRET probe clearly indicates multistate equilibrium unfolding. Native protein expands progressively through a continuum of native-like forms that achieve the dimensions of a molten globule, whose heterogeneity increases with increasing denaturant concentration and which appears to be separated from the unfolded ensemble by a free energy barrier.     

Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells

Truncated Notch receptors have transforming activity in vitro and in vivo. However, the role of wild-type Notch signaling in neoplastic transformation remains unclear. Ras signaling is deregulated in a large fraction of human malignancies and is a major target for the development of novel cancer treatments. We show that oncogenic Ras activates Notch signaling and that wild-type Notch-1 is necessary to maintain the neoplastic phenotype in Ras-transformed human cells in vitro and in vivo. Oncogenic Ras increases levels and activity of the intracellular form of wild-type Notch-1, and upregulates Notch ligand Delta-1 and also presenilin-1, a protein involved in Notch processing, through a p38-mediated pathway. These observations place Notch signaling among key downstream effectors of oncogenic Ras and suggest that it might be a novel therapeutic target.     

Acetylcholinesterase mediated susceptibility of soldiers and workers of formosan subterranean termite (Isoptera: Rhinotermitidae) to chlorpyrifos

Target site studies were undertaken to examine the difference in susceptibility of Formosan subterranean termite, Coptotermes formosanus Shiraki, workers and soldiers to chlorpyrifos. Workers exhibited significantly greater acetylcholinesterase activity per insect than soldiers (118.63 +/- 48.51 versus 47.98 +/- 22.59 mOD/min/insect equivalent). Likewise, enzyme activity (mean +/- SD) per milligram of protein was greater in workers than soldiers (440.30 +/- 267.43 versus 311.53 +/- 149.83 mOD/min/mg protein). The enzyme of soldiers was more sensitive to the acetylcholinesterase (AChE) inhibitors eserine and chlorpyrifos-oxon than that of workers. The I50s of chlorpyrifos-oxon were 2.66 and 4.59 nM for soldiers and workers, respectively, whereas the I50s of eserine were 16.56 and 25.41 nM for soldiers and workers, respectively. The amount of protein was significantly higher in workers than in soldiers with mean values of 0.270 +/- 0.102 and 0.154 +/- 0.054 mg/insect equivalent, respectively. We suggest that the differential response of workers and soldiers to chlorpyrifos may be due to the difference in AChE sensitivity to inhibition and the amount of protein between them.     

Synthesis,Characterization, and Biological Activities of Pendant Arm‐Pyridyltetrazole Copper(II) Complexes: DNA Binding/Cleavage Activity and Cytotoxic Studies

2‐(1H‐Tetrazol‐5‐yl)pyridine ( L ) has been reacted separately with Me₂NCH₂CH₂Cl?HCl and ClCH₂CH₂OH to yield two regioisomers in each case, N,N‐dimethyl‐2‐[5‐(pyridin‐2‐yl)‐1H‐tetrazol‐1‐yl]ethanamine ( L1 )/N,N‐dimethyl‐2‐[5‐(pyridin‐2‐yl)‐2H‐tetrazol‐2‐yl]ethanamine ( L2 ) and 2‐[5‐(pyridin‐2‐yl)‐1H‐tetrazol‐1‐yl]ethanol ( L3 )/2‐[5‐(pyridin‐2‐yl)‐2H‐tetrazol‐2‐yl]ethanol ( L4 ), respectively. These ligands, L1 – L4 , have been coordinated with CuCl₂?H₂O in 1 : 1 composition to furnish the corresponding complexes 1 – 4 . EPR Spectra of Cu complexes 1 and 3 were characteristic of square planar geometry, with nuclear hyperfine spin 3/2. Single X‐ray crystallographic studies of 3 revealed that the Cu center has a square planar structure. DNA binding studies were carried out by UV/VIS absorption; viscosity and thermal denaturation studies revealed that each of these complexes are avid binders of calf thymus DNA. Investigation of nucleolytic cleavage activities of the complexes was carried out on double‐stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment under various conditions, where cleavage of DNA takes place by oxidative free‐radical mechanism (OH ^? ). In vitro anticancer activities of the complexes against MCF‐7 (human breast adenocarcinoma) cells revealed that the complexes inhibit the growth of cancer cells. The IC₅₀ values of the complexes showed that Cu complexes exhibit comparable cytotoxic activities compared to the standard drug cisplatin.     

A Comprehensive in Silico Analysis for Identification of Immunotherapeutic Epitopes of HPV-18

International Journal of Peptide Research and Therapeutics - Human papillomavirus (HPV) remains the major cause of cervical cancer, globally. High risk HPV (Hr-HPV) 16 and 18 together account for...     

Inhibition of lipoxygenase by soy isoflavones: evidence of isoflavones as redox inhibitors

Hydroperoxides, the products of lipoxygenase mediated pathways, play a major role in the manifestation of chronic inflammatory diseases. Soy isoflavones act as antioxidants due to their ability to scavenge free radicals. Isoflavones inhibit the activity of soy lipoxygenase-1 and 5-lipoxygenase, from human polymorph nuclear lymphocyte in a concentration dependent manner. Spectroscopic and enzyme kinetic measurements have helped to understand the nature and mechanism of inhibition. Genistein is the most effective inhibitor of soy lipoxygenase 1 and 5-lipoxygenase with IC(50) values of 107 and 125 microM, respectively. Genistein and daidzein are noncompetitive inhibitors of soy lipoxygenase 1 with inhibition constants, K(i), of 60 and 80 microM, respectively. Electron paramagnetic resonance and spectroscopic studies confirm that isoflavones reduce active state iron to ferrous state and prevent the activation of the resting enzyme. A model for the inhibition of lipoxygenase by isoflavones is suggested.