Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis

Apoptosis is essential for clearance of potentially injurious inflammatory cells and subsequent efficient resolution of inflammation. Here we report that human neutrophils contain functionally active cyclin-dependent kinases (CDKs), and that structurally diverse CDK inhibitors induce caspase-dependent apoptosis and override powerful anti-apoptosis signals from survival factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF). We show that the CDK inhibitor R-roscovitine (Seliciclib or CYC202) markedly enhances resolution of established neutrophil-dependent inflammation in carrageenan-elicited acute pleurisy, bleomycin-induced lung injury, and passively induced arthritis in mice. In the pleurisy model, the caspase inhibitor zVAD-fmk prevents R-roscovitine-enhanced resolution of inflammation, indicating that this CDK inhibitor augments inflammatory cell apoptosis. We also provide evidence that R-roscovitine promotes apoptosis by reducing concentrations of the anti-apoptotic protein Mcl-1. Thus, CDK inhibitors enhance the resolution of established inflammation by promoting apoptosis of inflammatory cells, thereby demonstrating a hitherto unrecognized potential for the treatment of inflammatory disorders.     

Effect of long and short photoperiod on vasotocin neurons of paraventricular nuclei and adrenal function of water deprived Japanese quail

The responses of magnocellular neurons of paraventricular nuclei (PVN) and changes to adrenal activity to water deprivation in Japanese quail maintained under gonado-inhibitory and stimulatory photoperiods were examined. Water deprivation of 4 days resulted in a 12% decrease in body weight of sexually regressed short day (SD, 6L:18D) quail, while the decrease was more (18%) in sexually stimulated long day (LD, 16L:8D) quail. The increase in plasma osmolality following water deprivation was also more (47%) in LD than to SD quail (36%). Under the LD condition, quail had increased numbers, sizes and immunostaining of ir-AVT neurons of PVN compared to SD condition. A significant increase in the number of ir-AVT neurons was observed following 4 days of water deprivation in both SD and LD quail compared to their respective fully hydrated controls. However, the degree of response was more under the LD compared to the SD condition suggesting that gonado-stimulatory long days increase the activity/response of the AVT system. Increased adrenal ascorbic acid content (i.e., activity) was also observed to quail of LD when compared to SD treatment. However, osmotic stress led to adrenal hypertrophy and hyperactivity of quail of both of the photoperiodic regimes. Our findings indicate that not only osmotic stress but also photo-gonadal stimulation upregulates the expression of hypothalamic AVT genes and increases the localization of ir-AVT in many neurons of PVN. The above results support the existence of a parallel adrenal-gonad relationship and increase in adrenal function during osmotic stress, which also leads to simultaneous increase in AVT system. We conclude that photo-sexual conditions alter hypothalamic vasotocinergic and adrenal activity in Japanese quail and the degree of stimulation of the two systems following osmotic stress is higher under gonado-stimulatory LD conditions.     

Lauric acid dependent enhancement in hepatic SCPx protein requires an insulin deficient environment

Sterol carrier protein X (SCPx) is a peroxisomal protein with both lipid transfer and thiolase activity. Treating with the fatty acid, lauric acid, induced SCPx mRNA levels in rat liver and in rat hepatoma H4IIE cells but enhanced protein levels of SCPx and the thiolase produced as a post-translational modification of SCPx were only seen in H4IIE cells. Further investigation revealed that the presence of insulin can mask lauric acid effects on the SCPx gene especially at the protein level. These data are in agreement with the findings that diabetes, a medical condition characterized by high levels of fatty acids in an insulin deficient environment, enhances the hepatic expression of SCPx.     

Zwitterions for Organic/Perovskite Solar Cells,Light‐Emitting Devices,and Lithium Ion Batteries: Recent Progress and Perspectives

Zwitterions, a class of materials that contain covalently bonded cations and anions, have been extensively studied in the past decades owing to their special features, such as excellent solubility in polar solvents, for solution processing and dipole formation for the transfer of carriers and ions. Recently, zwitterions have been developed as electrode modifiers for organic solar cells (OSCs), perovskite solar cells (PVSCs), and organic light‐emitting devices (OLEDs), as well as electrolyte additives for lithium ion batteries (LIBs). With the rapid advances of zwitterionic materials, high‐performance devices have been constructed with enhanced efficiencies by introducing them as interface layers and electrolyte additives. In this review, recent progress in OSCs, PVSCs, OLEDs, and LIBs by using zwitterions is highlighted. The authors also elaborate the role of various zwitterionic materials as interfacial layers and additives for highly efficient OSCs, PVSCs, OLEDs, and LIBs. This article presents an overview of device performance of zwitterionic materials. The structure–property relationship is also discussed. Finally, the prospects of zwitterion materials are also addressed.     

Overexpression and purification of folded domain of prostate cancer related proteins MSMB and PSA

Overexpression of domains of a human protein using recombinant DNA technology has been challenging because individual domains intend to accumulate as non-soluble aggregate when expressed separately. Studies on identifying right sequences for a domain to be able to fold independently may help understand the folding pattern and underlying protein-engineering events to isolate the functional domains of a protein. In this report, individual domains of prostate cancer related biomarkers; MSMB and PSA were overexpressed in bacterial system and purified in their folded forms using affinity chromatography. The western blotting experiment using domain specific antibodies further confirmed these proteins. The designed nucleotide sequences domains were truncated using fold index software and folding were predicted by phyre2 and I-TASSER software. Other parameters were optimized for their overexpression and purification using Co-NTA affinity chromatography. Purified domains of each protein showed secondary structures such as α + β type for PSA, α/β and β type for the each domains of PSA and MSMB respectively. This is the first report on producing PSA and MSMB individual domains in functional folded forms. This study may help produce the folded domain of many such proteins to be used for better diagnostic purpose.     

Effects of thyroid status on arginine vasotocin receptor VT2R expression and adrenal function in osmotically stimulated domestic fowl

The role of thyroid hormones in the regulation of adrenal function during stress has been documented in mammals, but only limited reports are available in avian species. The present study was undertaken to analyze the effect of hyper- or hypothyroidism on the adrenal activity under control (hydrated) and osmotically stressed (water deprived, WD) conditions, with special emphasis on the expression of arginine vasotocin receptor VT2 (VT2R) in pituitary corticotrophs. Chickens were made hyper- or hypothyroidic by injecting thyroxine (T4) and 2-thiouracil (TU), respectively for 14 days. After 10 days of injections, one sub-group of both, T4- or TU-treated chickens were subjected to osmotic stress by water deprivation. Hyperthyroidism stimulated adrenal steroidogenic activity compared to euthyroid control birds, but no change was observed in the expression of VT2R. On the other hand, TU-induced hypothyroidism however showed no effect on adrenal gland, but a significant increase in the expression of VT2R was observed. Neither hyper- nor hypothyroidism altered pro-opiomelanocortin (POMC) mRNA levels. Following osmotic stress, no effect was observed either on the adrenal gland or on the VT2R expression in hyperthyroidic birds, but in hypothyroidic birds, osmotic stress stimulated adrenal steroidogenic activity and decreased VT2R expression in comparison to its respective controls (T4 or TU). Expression of POMC mRNA was again unaltered following osmotic stress. Although exact mechanism is not clear, the data indicate that high plasma T4 level stimulates adrenal activity and may also modulate function of the pituitary–adrenal axis during dehydration.     

Momordica charantia trypsin inhibitor II inhibits growth and development of Helicoverpa armigera

Abstract  Bitter gourd ( Momordica charantia L.) seeds contain several squash-type serine proteinase inhibitors (PIs), which inhibit the digestive proteinases of the polyphagous insect pest Helicoverpa armigera . In the present work isolation of a DNA sequence encoding the mature peptide of a trypsin inhibitor McTI-II, its cloning and expression as a recombinant protein using Pichia pastoris have been reported. Recombinant McTI-II inhibited bovine trypsin at 1: 1 molar ratio, as expected, but did not inhibit chymotrypsin or elastase. McTI-II also strongly inhibited trypsin-like proteinases (81% inhibition) as well as the total proteolytic activity of digestive proteinases (70% inhibition) from the midgut of H. armigera larvae. The insect larvae fed with McTI-II-incorporated artificial diet suffered over 70% reduction in the average larval weight after 12 days of feeding. Moreover, ingestion of McTI-II resulted in 23% mortality in the larval population. The strong antimetabolic activity of McTI-II toward H. armigera indicates its probable use in developing insect tolerance in susceptible plants.