Molecular Dynamics Simulations in Protein-Protein Docking.

Concerted interactions between all the cell components form the basis of biological processes. Protein-protein interactions (PPIs) constitute a tremendous part of this interaction network. Deeper insight into PPIs can help us better understand numerous diseases and lead to the development of new diagnostic and therapeutic strategies.

Role of -terminus in function and dynamics of sirtuin 7: an study.

The sirtuin family comprises seven NAD-dependent histone deacetylases named SIRT1 to SIRT7. The least investigated SIRT7 is currently considered as a promising therapeutic target for cardiovascular diseases, diabetes and different types of cancer. So far, its structure was not experimentally resolved, except of a fragment of its -terminus.

Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.

Background: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs).

Methods: In this 12-month, double-blind, active-controlled and placebo-controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5-mg dose taken orally twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months (53).

Vaccination among Polish university students. Knowledge, beliefs and anti-vaccination attitudes.

Anti-vaccination movement has existed as long as the vaccines themselves, but its mode of action and social influences evolved over time. Such attitude with no doubt has negative impact on vaccination rates and eradication of infectious diseases. In this study, we used an online survey to examine vaccination attitudes of Polish university students of various degree and specialties.

Apremilast in Patients With Active Rheumatoid Arthritis: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

Objective: To study the efficacy/safety of apremilast, an oral phosphodiesterase 4 inhibitor, compared with placebo in patients with active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX).

Methods: Patients were randomized 1:1:1 to receive placebo, apremilast 20 mg twice a day, or apremilast 30 mg twice a day. Patients whose swollen and tender joint counts had not improved by ≥20% were considered nonresponders at week 16 and were required to enter the protocol-defined early escape.

Quantitative analysis of elastase and cathepsin G mRNA levels in peripheral blood CD14(+) cells from patients with rheumatoid arthritis.

In rheumatoid arthritis (RA) activity of serine proteases is an important factor contributing to destructive changes in the joints. The aim of this study was to compare elastase (ELANE) and cathepsin G (CTSG) mRNA levels in peripheral blood CD14(+) cells obtained from RA patients, healthy subjects (HS) and patients with osteoarthritis (OA). CD14(+) cells were isolated from peripheral blood by positive magnetic selection.

Asp327Asn polymorphism of sex hormone-binding globulin gene is associated with systemic lupus erythematosus incidence.

Endogenous sex hormones have been observed to have a role in systemic lupus erythematosus (SLE) predisposition. Sex hormone-binding globulin (SHBG) regulates the bioavailability of sex hormones to target tissues. Therefore, we examined the distribution of the SHBG functional polymorphism Asp327Asn (rs6259) in SLE patients (n = 150) and controls (n = 150) in a Polish population.

The CD3Z 844 T>A polymorphism within the 3'-UTR of CD3Z confers increased risk of incidence of systemic lupus erythematosus.

Recently, a family-based association analysis showed that the haplotype carrying a low expression of the variant CD3Z 844 T>A (rs1052231) polymorphism located in the 3'-untranslated region of CD3Z predisposes to systemic lupus erythematosus (SLE) incidence. We analyzed the prevalence of the CD3Z 844 T>A polymorphism in SLE patients (n = 152) and controls (n = 304) in Poland. We observed that women with the CD3Z AA and CD3Z AT genotypes exhibited a 1.

Differential roles of MAPKs and MSK1 signalling pathways in the regulation of c-Jun during phenylephrine-induced cardiac myocyte hypertrophy.

Gq-protein-coupled receptor (GqPCR) signalling is associated with the induction of cardiac myocyte hypertrophy, which is characterized by an increase in expression of immediate early genes via activation of pre-existing transcription factors. Here, we explore the role of MSK1 and MAPK signalling pathways in the regulation of the immediate early gene c-jun. The results provide further support for the role of MSK1 in cardiac myocyte hypertrophy and indicate that PE activates distinct signalling mechanisms which culminate with a complex activation of c-jun.

Regulation of BAD protein by PKA, PKCdelta and phosphatases in adult rat cardiac myocytes subjected to oxidative stress.

H2O2, as an example of oxidative stress, induces cardiac myocyte apoptosis. Bcl-2 family proteins are key regulators of the apoptotic response while their functions can be regulated by post-translational modifications including phosphorylation, dimerization or proteolytic cleavage. In this study, we examined the role of various protein kinases in regulating total BAD protein levels in adult rat cardiac myocytes undergoing apoptosis.

[Effect of fluvastatin extended release on the protein-lipid structure of erythrocyte membrane and C-reactive protein in patients with hyperlipidemia].

Unlabelled: The aim of the study was to estimate the effects of 4-weeks therapy of fluvastatin extended release (XL) on lipids serum, C-reactive protein (CRP), erythrocyte structure membrane (thiobarbituric acid reactive substances--TBARS concentrations, membrane cholesterol and the activity of Na+K(+)-ATPase in erythrocytes) in patients with hyperlipidemia without any clinical signs of atherosclerosis.

Material And Methods: The study comprised 37 persons, including 15 healthy volunteers and 22 patients with hyperlipidemia (TC > 200 mg/dl, LDL-C > 130 mg/dl, TG < 400 mg/dl) treated with fluvastatin XL 80 mg/d. Before and after 4 weeks of active treatment the following parameters were determined: lipids (by enzymatic method using BioMerieux tests), CRP (by immunoturbidimetric method), TBARS concentrations (by method of Stock and Dormandy), membrane cholesterol (method of Ilcy), Na+K(+)-ATPase activity (method of Bartosz et al.

Ischemic but not mechanical preconditioning attenuates ischemia/reperfusion induced myocardial apoptosis in anaesthetized rabbits: the role of Bcl-2 family proteins and ERK1/2.

Objective: Recent studies suggest that ischemic preconditioning (IPC) inhibits myocardial apoptosis after ischemia and reperfusion. This study aimed first, to examine whether short mechanical stretch with acute pressure overload (MPC), which has been shown to reduce infarct size after ischemia/reperfusion, mimics IPC in attenuating myocardial apoptosis and second, to evaluate whether induced cardioprotection involves modulation of the expression of the Bcl-2 family proteins and phosphorylation of prosurvival kinases.

Methods And Results: A model of anaesthetized rabbit was used and the preconditioning protocol included one cycle of short ischemia/reperfusion, or short mechanical stretch with acute pressure overload.

[The anti-inflammatory and antioxidants effects of micronized fenofibrate in patients with visceral obesity and dyslipidemia].

Unlabelled: In recent studies it was observed the pleiotropic properties beyond hypolipemic effects of fenofibrate: anti-inflammatory, antioxidants effects, positive impact on glucose metabolism, thrombosis, fibrinolytic system endothelial dysfunction.

The Aim Of The Study: To estimate the effects of 4-weeks therapy of micronized fenofibrate in dose 267 mg/d on C-reactive protein (CRP), fibrinogen, thiobarbituric acid reaction substances (TBARS) concentrations in isolated erythrocyte membranes and the activities of antioxidants enzymes such: catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) in erythrocytes in patients with visceral obesity and atherogenic dyslipidemia.

Material And Methods: The study comprised 55 patients (pts), including 20 healthy volunteers and 35 pts with visceral obesity and dyslipidemia (TG>180 mg/dl, HDL-C < 40 mg/dl for men, <50 mg/dl for women) treated with micronized fenofibrate (267 mg/d).

Myogenin-dependent nAChR clustering in aneural myotubes.

During development of the neuromuscular junction, nerve-derived agrin and the cell substrate laminin stimulate postsynaptic nAChR clustering. This clustering is dependent on activation of the tyrosine kinase, MuSK, which signals receptor clustering via a rapsyn-dependent mechanism. Myogenin is a muscle-specific transcription factor that controls myoblast differentiation and nAChR gene expression.

CaM kinase II-dependent phosphorylation of myogenin contributes to activity-dependent suppression of nAChR gene expression in developing rat myotubes.

During development of the neuromuscular junction (NMJ), extrajunctional expression of genes, whose products are destined for the synapse, is suppressed by muscle activity. One of the best-studied examples of activity-dependent gene regulation in muscle are those encoding nicotinic acetylcholine receptor (nAChR) subunits. We recently showed that nAChR gene expression is inhibited by calcium/calmodulin-dependent protein kinase II (CaMKII) and CaMKII inhibitors block activity-dependent suppression of these genes.

Synthesis and cytotoxicity of 4-amino-5-oxopyrido[2,3-d]pyrimidine nucleosides.

A number of nucleoside analogues have been either used clinically as anticancer drugs or evaluated in clinical studies, while new nucleoside analogues continue to show promise. In this article, we report synthesis and cytotoxicity of a series of new pyrido[2, 3-d]pyrimidine nucleosides. 2-Amino-3-cyano-4-methoxypyridine was converted, in two steps, to 4-amino-5-oxopyrido[2,3-d]pyrimidine.

Cytogenetic analysis of bovine parthenotes after spontaneous activation in vitro.

We conducted a cytogenetic study of bovine parthenotes derived from oocytes matured and cultured in vitro. In vitro maturation was carried out by culturing follicular oocytes for 24 h in TCM199 supplemented with estrous cow serum (ECS) and hormones at 39 degrees C in 5% CO2. Matured oocytes were incubated for 20 h in sperm TALP without the addition of spermatozoa, after which they were cultured in maturation droplets for 48 to 72 h.

Reversible inhibition of IL-8 receptor B mRNA expression and proliferation in non-small cell lung cancer by antisense oligonucleotides.

We examined the importance of IL-8 receptor B mRNA expression in the growth of non-small cell lung cancer (NSCLC). Using antisense oligonucleotide ICN 197, we were able to inhibit IL-8 R B mRNA expression in vitro. The sequence specific effect of antisense oligonucleotide and down-regulation of IL-8 R B mRNA was shown by Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Southern blot analysis.

Circadian variations in plasma melatonin, FSH, LH, and prolactin and testosterone levels in infertile men.

Circadian patterns of plasma melatonin, FSH, LH, prolactin, and testosterone were studied in 10 healthy men, 20 men with oligozoospermia, and 8 men with azoospermia. Circadian rhythms were found in concentrations of melatonin and prolactin, with higher values at night in comparison with daytime levels. In patients with oligozoospermia and azoospermia an elevation in melatonin levels was observed, and an increase in melatonin concentrations occurred before onset of darkness (i.

Gastrin and somatostatin levels in patients with gastric cancer.

Gastrin and somatostatin-like immunoreactivity (SLI) levels were studied by means of radioimmunoassay in peripheral venous blood of healthy volunteers and patients suffering from gastric adenocarcinoma or duodenal and gastric ulcers. Gastrin and SLI levels were also evaluated in patients in blood drawn from gastric veins during surgery. The elevations of gastrin and SLI levels were found in patients with gastric cancer as compared with healthy people and patients suffering from ulcers.

Effect of bromocriptine and metoclopramide on serum prolactin levels in patients with amyotrophic lateral sclerosis.

Secretion of prolactin in nine patients with amyotrophic lateral sclerosis and in seven healthy men was investigated with the use of metoclopramide stimulation and bromocriptine inhibition tests. Blood serum prolactin concentration was determined in the basal state and 30, 60 and 120 minutes after oral administration of 10 mg metoclopramide or 2.5 mg bromocriptine.