Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6.

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. A critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies are in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high throughput structure-based computational screening using ensemble docking for small molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein.

Ultrathin-strut versus thin-strut stent healing and outcomes in preclinical and clinical subjects.

Background: Compared with thin-strut durable-polymer drug-eluting stents (DP-DES), ultrathin-strut biodegradable-polymer sirolimus-eluting stents (BP-SES) improve stent-related clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Reduced stent strut thickness is hypothesised to underlie these benefits, but this conjecture remains unproven.

Aims: We aimed to assess the impact of strut thickness on stent healing and clinical outcomes between ultrathin-strut and thin-strut BP-SES.

Examining the association between coping strategies and perceived social support among Vietnamese infertile women undergoing IVF treatment.

The purpose of the study was to examine the association between coping strategies and perceived social support among women diagnosed with infertility and undergoing IVF treatment. A total of 383 Vietnamese women were invited to participate in this study. Participants completed a questionnaire consisting of The Multidimensional Scale of Perceived Social Support, the Copenhagen Multi-centre Psychosocial Infertility coping scales and the Fertility Problem Inventory, and other relevant questions.

Biomimetic Nanomaterials for the Immunomodulation of the Cardiosplenic Axis Postmyocardial Infarction.

The spleen is an important mediator of both adaptive and innate immunity. As such, attempts to modulate the immune response provided by the spleen may be conducive to improved outcomes for numerous diseases throughout the body. Here, biomimicry is used to rationally design nanomaterials capable of splenic retention and immunomodulation for the treatment of disease in a distant organ, the postinfarct heart.

Nanoparticles and cytokine response.

Synthetic nanoparticles (NPs) are non-viral equivalents of viral gene delivery systems that are actively explored to deliver a spectrum of nucleic acids for diverse range of therapies. The success of the nanoparticulate delivery systems, in the form of efficacy and safety, depends on various factors related to the physicochemical features of the NPs, as well as their ability to remain "stealth" in the host environment. The initial cytokine response upon exposure to nucleic acid bearing NPs is a critical component of the host response and, unless desired, should be minimized to prevent the unintended consequences of NP administration.

Effect of Molecular Weight on the Dissolution Profiles of PEG Solid Dispersions Containing Ketoprofen.

Solid dispersions are typically binary systems with a hydrophilic matrix polymer and a lipophilic active substance. During formulation, the drug undergoes a crystalline to amorphous phase transition, which leads to a supersaturated solution providing enhanced bioavailability. The interaction of the active substance and the polymer is unique and influences the level of supersaturation.

Myofibroblast-specific inhibition of the Rho kinase-MRTF-SRF pathway using nanotechnology for the prevention of pulmonary fibrosis.

Pulmonary fibrosis is characterized by the accumulation of myofibroblasts in the lung and progressive tissue scarring. Fibroblasts exist across a spectrum of states, from quiescence in health to activated myofibroblasts in the setting of injury. Highly activated myofibroblasts have a critical role in the establishment of fibrosis as the predominant source of type 1 collagen and profibrotic mediators.

When are children satisfied with life? An initiative qualitative study from vietnamese children sample.

In the context of research on children's life satisfaction, considering children as active participants are very scarce, the main purpose of the present study was to examine children's perspectives on their life satisfaction. The study used a convenient sample of 228 students from primary and secondary schools, living in urban and suburban areas in Vietnam. The subjects' average age is 9.

Sex differences in human mate preferences vary across sex ratios.

A wide range of literature connects sex ratio and mating behaviours in non-human animals. However, research examining sex ratio and human mating is limited in scope. Prior work has examined the relationship between sex ratio and desire for short-term, uncommitted mating as well as outcomes such as marriage and divorce rates.

Platelet Detection Using a Glycoprotein IIb/IIIa-Targeted Near-Infrared Fluorescence Imaging Probe.

Platelets play a prominent role in multiple diseases, in particular arterial and venous thrombosis and also in atherosclerosis and cancer. To advance the study of the biological activity of this cell type from a basic experimental focus to a clinical focus, new translatable platelet-specific molecular imaging agents are required. Herein, we report the development of a near-infrared fluorescence probe based upon tirofiban, a clinically approved small-molecule glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa).

Molecular dynamics analysis of the binding of human interleukin-6 with interleukin-6 α-receptor.

Human interleukin-6 (hIL-6) is a multifunctional cytokine that regulates immune and inflammatory responses in addition to metabolic and regenerative processes and cancer. hIL-6 binding to the IL-6 receptor (IL-6Rα) induces homodimerization and recruitment of the glycoprotein (gp130) to form a hexameric signaling complex. Anti-IL-6 and IL-6R antibodies are clinically approved inhibitors of IL-6 signaling pathway for treating rheumatoid arthritis and Castleman's disease, respectively.

Sex Differences in Mate Preferences Across 45 Countries: A Large-Scale Replication.

Considerable research has examined human mate preferences across cultures, finding universal sex differences in preferences for attractiveness and resources as well as sources of systematic cultural variation. Two competing perspectives-an evolutionary psychological perspective and a biosocial role perspective-offer alternative explanations for these findings. However, the original data on which each perspective relies are decades old, and the literature is fraught with conflicting methods, analyses, results, and conclusions.

The mental health continuum-short form: The structure and application for cross-cultural studies-A 38 nation study.

Objective: The Mental Health Continuum-Short Form (MHC-SF) is a brief scale measuring positive human functioning. The study aimed to examine the factor structure and to explore the cross-cultural utility of the MHC-SF using bifactor models and exploratory structural equation modelling.

Method: Using multigroup confirmatory analysis (MGCFA) we examined the measurement invariance of the MHC-SF in 38 countries (university students, N = 8,066; 61.

A benzotriazole-mediated route to protected marine-derived hetero-2,5-diketopiperazines containing proline.

A procedure for the cyclization of dipeptidoyl benzotriazolides containing proline derivatives promoted by triethylamine under MW activation is introduced. The reaction is general for a variety of dipeptidoyl benzotriazolides and represents a very practical and convenient method for the preparation of Pro- or Hyp-derived 2,5-diketopiperazines (2,5-DKPs) and bis-DKPs with a disulfide linker. This method can be used for the construction of 2,5-DKP compound libraries and for the synthesis of natural products with diketopiperazine cores.

Tandem deprotection-dimerization-macrocyclization route to C(2) symmetric cyclo-tetrapeptides.

Dimerization-macrocyclization has been a long-standing problem in the cyclization of peptides since, together with the desired cyclic product, many cyclic oligomers and linear polymers may also be formed during the reaction. Therefore, the development of a process that affords the cyclic dimer predominantly is difficult. A novel and versatile strategy for the synthesis of symmetric cyclo-tetrapeptides by palladium-promoted tandem deprotection/cyclo-dimerization from readily available Cbz-dipeptidoyl benzotriazolides is reported (Cbz=carboxybenzyl).

Conformationally assisted lactamizations for the synthesis of symmetrical and unsymmetrical bis-2,5-diketopiperazines.

Open-chain N-Cbz-protected-peptidoyl benzotriazolides are converted by a novel lactamization strategy using proline as a turn introducer into both symmetrical (5a-c and 11a-c) and unsymmetrical (19a-e) bis-2,5-diketopiperazines (bis-2,5-DKPs), previously recognized as difficult targets.

Quality of life in borderline personality disorder.

Objective: To review the literature on quality of life (QoL) in borderline personality disorder (BPD) by examining the use of QoL instruments, the extent of QoL impairments in BPD, and the impact of treatment on QoL in BPD.

Methods: Studies were identified through PubMed and PsycINFO searches for articles from 1980 to 2011 using the following keywords: quality of life OR health-related quality of life OR QOL OR HRQOL AND borderline personality disorder. We focused our search on studies that actually measured QoL.

Sexual satisfaction and quality of life in major depressive disorder before and after treatment with citalopram in the STAR*D study.

Objective: Major depressive disorder (MDD) patients often experience impaired sexual satisfaction (ISS) and poor quality of life (QOL). Selective serotonin reuptake inhibitors (SSRIs), the first-line treatment for MDD, can cause sexual dysfunction, potentially worsening ISS and QOL. This study examined the impact of MDD and the SSRI citalopram on sexual satisfaction and QOL in level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial (July 2001-September 2006).

S- to N-Acyl transfer in S-acylcysteine isopeptides via 9-, 10-, 12-, and 13-membered cyclic transition states.

S-Acyl cysteine peptides containing α-, β- or γ-amino acid residues undergo long-range S- to N-acyl transfer to give analogs of native tripeptides and tetrapeptides containing additional carbon atoms in the chain. The ease of intramolecular S → N-acyl transfer relative to intermolecular transacylation is favored increasingly for 9 < 12 < 13 ~ 10-membered cyclic transition states; the observed order is explained on conformational and intermolecular interaction considerations.

A convenient synthesis of difficult medium-sized cyclic peptides by Staudinger mediated ring-closure.

Novel, efficient and mild preparation of 7- and 8-membered cyclic di- and 10-membered cyclic tripeptides containing α-, β- or γ-amino acid residues is effected by a Staudinger-mediated ring closure. Medium-sized cyclic di- and tripeptides--recognized as difficult targets--were obtained in moderate to good yields according to a straightforward sequence. Empirical force-field calculations were undertaken to determine their conformational behaviors and showed high levels of similarity with X-ray results.

Long-range intramolecular S → N acyl migration: a study of the formation of native peptide analogues via 13-, 15-, and 16-membered cyclic transition states.

The intramolecular long-range S → N acyl migration via 13-, 15-, and 16-membered cyclic transition states to form native tetra- and pentapeptide analogues was studied on S-acylcysteine peptides containing β- or γ-amino acids. The pH-dependency study of the acyl migration via a 15-membered cyclic transition state indicated that the reaction is favored at a pH range from 7.0 to 7.

The impact of psychotherapy, pharmacotherapy, and their combination on quality of life in depression.

Background: Quality of life (QOL) is known to be negatively affected during the course of major depressive disorder. Various studies have documented the benefits of pharmacotherapy or psychotherapy alone on QOL in depression, with few studies examining combined treatment. This review will examine the evidence for the impact of each modality, as well as their combination, on QOL in depression.

Attitude toward humor in patients experiencing depressive symptoms.

Objective: This study measures the correlation between disposition to humor and level of depression to investigate openness to humorous interventions for the treatment of depression.Design, Participants, and Measurement: Individuals (n=200) with depression received questionnaires to assess their sense of humor and attitude toward humor using the Svebak's Humor Questionnaire and a disposition toward humor questionnaire. The correlation between Svebak's Humor Questionnaire scores and Quick Inventory of Depressive Symptomatology-Self Report scores was then measured.

Microwave-assisted chemical ligation of S-acyl peptides containing non-terminal cysteine residues.

An efficient approach for the synthesis of a series of S-acyl peptides containing internal cysteine residues has been developed and the chemical long-range ligation of these S-acyl peptides via 5-, 8-, 11- and 14-membered cyclic transition states has been investigated. Our results include the first examples of successful isopeptide ligations starting from S-acyl peptides containing non-terminal cysteine residues and indicate that the cyclic transition states studied in this present paper are decreasingly favored in the order of their sizes 5≫14>11≫8.