Short-Chained Linear Scorpion Peptides: A Pool for Novel Antimicrobials.

Scorpion venom peptides are generally classified into two main groups: the disulfide bridged peptides (DBPs), which usually target membrane-associated ion channels, and the non-disulfide bridged peptides (NDBPs), a smaller group with multifunctional properties. In the past decade, these peptides have gained interest because most of them display functions that include antimicrobial, anticancer, haemolytic, and anti-inflammatory activities. Our current study focuses on the short (9-19 amino acids) antimicrobial linear scorpion peptides. Most of these peptides display a net positive charge of 1 or 2, an isoelectric point at pH 9-10, a broad range of hydrophobicity, and a Grand Average of Hydropathy (GRAVY) Value ranging between -0.05 and 1.7. These features allow these peptides to be attracted toward the negatively charged phospholipid head groups of the lipid membranes of target cells, a force driven by electrostatic interactions. This review outlines the antimicrobial potential of short-chained linear scorpion venom peptides. Additionally, short linear scorpion peptides are in general more attractive for large-scale synthesis from a manufacturing point of view. The structural and functional diversity of these peptides represents a good starting point for the development of new peptide-based therapeutics.

Effect of Tribulus terrestris L. supplementation on Exercise-Induced Oxidative Stress and Delayed Onset Muscle Soreness Markers: A Pilot Study.

Tribulus terrestris L. contains compounds with antioxidant and anti-inflammatory properties, but its effects on exercise-induced oxidative stress and inflammatory responses are unclear. The aim of this study was to examine whether Tribulus terrestris L. supplementation can attenuate oxidative stress and inflammatory responses to acute aerobic exercise and improve DOMS. In a randomized, double-blind, crossover design study, thirteen healthy men received either a daily supplement of Tribulus terrestris L. or a placebo for 4 weeks (2-week wash-out period between trials). Before and after the supplementation periods, participants performed an exercise test to exhaustion (75% VO2max). DOMS, thigh girth, and knee joint range of motion (KJRM) were assessed before and after the exercise (2, 24, and 48 h). Blood samples were analyzed for reduced (GSH) and oxidized (GSSG) glutathione, GSH/GSSG ratio, protein carbonyls, total antioxidant capacity, creatine kinase activity, white blood cell count, and TBARS. Acute exercise to exhaustion induced inflammatory responses and changed the blood redox status in both Tribulus and Placebo groups (p < 0.050). Tribulus terrestris L. improved GSH fall (p = 0.005), GSSG rise (p = 0.001) and maintained a higher level of GSH/GSSG ratio at the 2 h point (p = 0.034). TBARS were lowered, protein carbonyls, creatine kinase activity, and white blood cell count elevation diminished significantly (p < 0.050). Tribulus terrestris L. administration did not affect DOMS, thigh girth, or KJRM (p > 0.050). 4-weeks of Tribulus terrestris L. supplementation effectively attenuates oxidative stress responses but cannot improve DOMS.

Ligand and Structure-Based Virtual Screening in Combination, to Evaluate Small Organic Molecules as Inhibitors for the XIAP Anti-Apoptotic Protein: The Xanthohumol Hypothesis.

Herein, we propose two chalcone molecules, (E)-1-(4-methoxyphenyl)-3-(p-tolyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl) prop-2-en-1-one, based on the anticancer bioactive molecule Xanthohumol, which are suitable for further in vitro and in vivo studies. Their ability to create stable complexes with the antiapoptotic X-linked IAP (XIAP) protein makes them promising anticancer agents. The calculations were based on ligand-based and structure-based virtual screening combined with the pharmacophore build. Additionally, the structures passed Lipinski's rule for drug use, and their reactivity was confirmed using density functional theory studies. ADMET studies were also performed to reveal the pharmacokinetic potential of the compounds. The candidates were chosen from 10,639,400 compounds, and the docking protocols were evaluated using molecular dynamics simulations.

Seroprevalence of immunoglobulin G antibodies against SARS-CoV-2 in Cyprus.

Monitoring the levels of IgG antibodies against the SARS-CoV-2 is important during the coronavirus disease 2019 (COVID-19) pandemic, to plan an adequate and evidence-based public health response. After this study we report that the plasma levels of IgG antibodies against SARS-CoV-2 spike protein were higher in individuals with evidence of prior infection who received at least one dose of either an mRNA-based vaccine (Comirnaty BNT162b2/Pfizer-BioNTech or Spikevax mRNA-1273/Moderna) or an adenoviral-based vaccine (Vaxzervia ChAdOx1 nCoV-19 /Oxford-Astra Zeneca) (n = 39) compared to i) unvaccinated individuals with evidence of prior infection with SARS-CoV-2 (n = 109) and ii) individuals without evidence of prior infection with SARS-CoV-2 who received one or two doses of one of the aforementioned vaccines (n = 342). Our analysis also revealed that regardless of the vaccine technology (mRNA-based and adenoviral vector-based) two doses achieved high anti- SARS-CoV-2 IgG responses. Our results indicate that vaccine-induced responses lead to higher levels of IgG antibodies compared to those produced following infection with the virus. Additionally, in agreement with previous studies, our results suggest that among individuals previously infected with SARS-CoV-2, even a single dose of a vaccine is adequate to elicit high levels of antibody response.

Cyprus health system review.

The health system in Cyprus comprises separate public and private systems of similar size. The public system, which is financed by the state budget, is highly centralized and tightly controlled by the Ministry of Health. Entitlement to receive free health services is based on residency and income level. The private system is almost completely separate from the public system and for the most part is unregulated and largely financed out of pocket. In many ways there is an imbalance between the public and private sectors. The public system suffers from long waiting lists for many services, a situation that has been worsened by the recent economic crisis, while the private sector has an overcapacity of expensive medical technology that is underutilized. To try to address these and other inefficiencies, a new national health insurance scheme funded by taxes and social insurance contributions has been designed to offer universal coverage and introduce competition between the public and private sectors through changes in provider payment methods. However, the scheme has not been implemented due to cost concerns. Despite the low share of economic resources dedicated to health care and access issues for some vulnerable population groups, overall Cypriots enjoy good health comparable to other high-income countries.

Pleiotrophin expression and role in physiological angiogenesis in vivo: potential involvement of nucleolin.

BACKGROUND: Pleiotrophin (PTN) is a heparin-binding growth factor with significant role(s) in tumour growth and angiogenesis. Although implication of endogenous PTN has been studied in several in vivo models of tumour angiogenesis, its role in physiological angiogenesis has not been addressed. In the present work, we studied expression and functional significance of endogenous PTN during angiogenesis in the chicken embryo chorioallantoic membrane (CAM). METHODS: Using molecular, cellular and biochemical assays, we studied the expression pattern of PTN in CAM and human endothelial cells and its possible interaction with nucleolin (NCL). CAM cells were transfected with a pCDNA3.1 vector, empty (PC) or containing full length cDNA for PTN in antisense orientation (AS-PTN). Angiogenesis was estimated by measuring total vessel length. In vitro, human endothelial cells migration was studied by using a transwell assay, and down-regulation of NCL was performed by using a proper siRNA. RESULTS: Endogenous PTN mRNA and protein levels, as well as protein levels of its receptor protein tyrosine phosphatase beta/zeta (RPTPß/ζ) were maximal at early stages, when CAM angiogenesis is active. Application of AS-PTN onto CAM at days of active angiogenesis was not toxic to the tissue and led to dose-dependent decreased expression of endogenous PTN, ERK1/2 activity and angiogenesis. Interestingly, endogenous PTN was also immunolocalized at the endothelial cell nucleus, possibly through interaction with NCL, a protein that has a significant role in the nuclear translocation of many proteins. Down-regulation of NCL by siRNA in human endothelial cells significantly decreased nuclear PTN, verifying this hypothesis. Moreover, it led to abolishment of PTN-induced endothelial cell migration, suggesting, for the first time, that PTN-NCL interaction has a functional significance. CONCLUSIONS: Expression of endogenous PTN correlates with and seems to be involved in angiogenesis of the chicken embryo CAM. Our data suggest that NCL may have a role, increasing the number of growth factors whose angiogenic/tumorigenic activities are mediated by NCL.

Insights into ectopic estrogen receptor expression, nucleocytoplasmic distribution and interaction with chromatin obtained with new antibodies to estrogen receptors α and ß.

Recent reports have indicated that in cells ectopically expressing only ERα or the full-length hormone-binding isoform of ERß (ERß1), the receptors interact with chromatin with different efficacies and that antibodies capable of probing such interactions by chromatin immunoprecipitation (ChIP) are scarce. We therefore produced nine subtype and isoform-specific antibodies to ERα or ERß and validated their performance in receptor probing in cell lines and tissue biopsies by various immunochemical methods, including ChIP. We also produced clones of HEK-293 cells stably transfected with an estrogen response element (ERE)-dependent luciferase reporter and ERα or ERß1, in order to comparatively study their interaction with reporter ERE. We show that ERα was located in the nucleus and ERß1 in the cytoplasm as well as the nucleus of the stably transfected cells, while both receptors were found predominantly in the nucleus in transiently transfected cells and in all estrogen target tissues examined using the same antibodies. The cells displayed wild-type transcriptional activity and canonical regulation of ERE-dependent luciferase expression by estrogen agonists and antagonists. However, unlike ERα, ERß1 recruitment to the reporter ERE could be probed only by sequential ChIP with antibodies to receptor N- and C-terminus. These data suggest that in HEK-293 cells stably expressing ERα or ERß1, ER subtype-specific constraints apply to ERß1 nuclear entry; and that in cells displaying cytoplasmic as well as nuclear localization of ERß1, sequential ChIP with different antibodies to the receptor is the method of choice for probing its interaction with chromatin.

Synthesis and sst(2) binding profiles of new [Tyr(3)]octreotate analogs.

One of the main objectives of our current work is the development of new somatostatin analogs that would retain the general characteristics of [Tyr(3)]octreotate (Tate) while showing potential for clinical application. In this respect, study of their interaction with the sst(2) is crucial in providing preliminary structure-activity relationships data. In the present work we report on the synthesis and the preliminary biological evaluation of a total of 15 new structurally modified [Tyr(3)]octreotate analogs. The binding affinities were determined during competition binding assays in sst(2)-positive rat acinar pancreatic AR4-2J cell membranes using [(125)I-Tyr(3)]octreotide as the radioligand.