A critical review on antiviral peptides derived from viral glycoproteins and host receptors to decoy herpes simplex virus

The health of the human population has been continuously challenged by viral infections. Herpes simplex virus (HSV) is one of the common causes of illness and can lead to death in immunocompromised patients. Existing anti-HSV therapies are not completely successful in eliminating the infection due to anti-viral drug resistance, ineffectiveness against the latent virus and high toxicity over prolonged use. There is a need to update our knowledge of the current challenges faced in anti-HSV therapeutics and realize the necessity of developing alternative treatment approaches. Protein therapeutics are now being explored as a novel approach due to their high specificity and low toxicity. This review highlights the significance of HSV viral glycoproteins and host receptors in the pathogenesis of HSV infection. Proteins or peptides derived from HSV glycoproteins gC, gB, gD, gH and host cell receptors (HSPG, nectin and HVEM) that act as decoys to inhibit HSV attachment, entry, or fusion have been discussed. Few researchers have tried to improve the efficacy and stability of the identified peptides by modifying them using a peptidomimetic approach. With these efforts, we think developing an alternative treatment option for immunocompromised patients and drug-resistant organisms is not far off.     

Inappropriate defibrillator shock due to oversensing. What is the mechanism?

Implantable cardioverter defibrillator (ICD) is often advised for secondary prevention of sudden cardiac death. Inappropriate shocks from ICD is uncommon but can seriously affect the quality of life. One of the reasons for inappropriate ICD shock is loose set screw, which may remain undetected by device interrogation and/or fluoroscopy. A 55-year lady presented with multiple inappropriate shocks few hours after an ICD implantation. The discrepancy between near field (NF, tip to ring) and far field (FF, Can to RV coil) signals helped us to suspect noise related to loose set screw, as the underlying problem. Re-exploration of the pocket had to be performed as the last resort to confirm the diagnosis and rectify the problem.     

Elevating PI3P drives select downstream membrane trafficking pathways

Phosphoinositide signaling lipids are essential for several cellular processes. The requirement for a phosphoinositide is conventionally studied by depleting the corresponding lipid kinase. However, there are very few reports on the impact of elevating phosphoinositides. That phosphoinositides are dynamically elevated in response to stimuli suggests that, in addition to being required, phosphoinositides drive downstream pathways. To test this hypothesis, we elevated the levels of phosphatidylinositol-3-phosphate (PI3P) by generating hyperactive alleles of the yeast phosphatidylinositol 3-kinase, Vps34. We find that hyperactive Vps34 drives certain pathways, including phosphatidylinositol-3,5-bisphosphate synthesis and retrograde transport from the vacuole. This demonstrates that PI3P is rate limiting in some pathways. Interestingly, hyperactive Vps34 does not affect endosomal sorting complexes required for transport (ESCRT) function. Thus, elevating PI3P does not always increase the rate of PI3P-dependent pathways. Elevating PI3P can also delay a pathway. Elevating PI3P slowed late steps in autophagy, in part by delaying the disassembly of autophagy proteins from mature autophagosomes as well as delaying fusion of autophagosomes with the vacuole. This latter defect is likely due to a more general defect in vacuole fusion, as assessed by changes in vacuole morphology. These studies suggest that stimulus-induced elevation of phosphoinositides provides a way for these stimuli to selectively regulate downstream processes.     

Synthesis of Some New N-Substituted Imidazole Derivatives and Their In Vitro Antibacterial Investigation

Russian Journal of Bioorganic Chemistry - Here we reported the synthesis of N-substituted imidazole derivatives (VIa–o) that involves Suzuki coupling reaction between...     

Liquid chromatography–electrospray ionization mass spectrometric analysis of corticosterone in rat plasma using selected ion monitoring

A simple and fast yet highly sensitive and specific method based on HPLC coupled to electrospray ionization mass spectrometry has been developed for the quantitation of corticosterone in rat plasma. After extraction of rat plasma (100 μl) with diethyl ether using 5-pregnen-3β-ol-20-one-16α-carbonitrile (Sigma) as internal standard, HPLC was performed on a short C₈ column (Zorbax-Eclipse, 50×4.6 mm I.D.) using a steep methanol–water gradient (methanol 54% to 90% in 6 min). Detection was performed on a single quadruple mass spectrometer in selected ion monitoring mode (m/z 369 for corticosterone and 364 for the internal standard). The detection limit of the assay was 9 fmol (3 pg) of corticosterone on column. In vitro data were subjected to curve fitting (cubic, r²=0.9999). Recovery of corticosterone after extraction ranged from 81 to 93%. The relative standard deviations for intra- and inter-assay precision ranged from 0.8 to 3.6% and 5.2 to 12.9%, respectively. Corticosterone did not undergo any appreciable degradation when stored in plasma at −20°C for 2 months. The assay is routinely used in our laboratory to examine corticosterone levels as a marker of stress in rats and may also be used for the determination of 18-hydroxy-11-deoxycorticosterone.     

Cadherin-Mediated Adhesion Is Required for Normal Growth Regulation of Human Gingival Epithelial Cells

The cadherins are a family of cell membrane proteins that mediate calcium-dependent cell-cell adhesion. E-cadherin is required for the formation, differentiation, polarization and stratification of epithelia; P-cadherin is also expressed on many epithelia. We report here the first study of cadherin expression in immortalized human gingival epithelial cells (IHGK) and examine the role of cadherins in growth regulation of these cells. We found that the IHGK cells are similar to normal gingival epithelial cells in their cadherin expression and density-dependent inhibition of growth.

The IHGK cells proliferate more rapidly at low calcium concentration (0.15 mM) than at physiological concentrations of calcium (1.8 mM) and magnesium (0.65 mM; Ca/Mg medium) suggesting that calcium is required for density-dependent regulation of proliferation. To evaluate the possibility that cadherin function is required for contact inhibition in these cells, we grew them in Ca/Mg medium in the presence of adhesion-blocking anti-cadherin monoclonal antibodies. At anti-E-cadherin concentrations sufficient to disrupt cell-cell adhesion, the proliferation of the IHGK cells was similar to that observed in medium containing 0.2 mM EDTA. Anti-P-cadherin had a much weaker effect on cell proliferation than anti-E-cadherin, and cells grown in medium containing both antibodies grew at intermediate rates. The increased proliferation of the IHGK cells in either low calcium medium or Ca/Mg medium containing adhesion-blocking anti-cadherin antibodies suggests that cadherin-medi-ated adhesion is required for density-dependent regulation of growth of these cells.