Unveiling New Druggable Pockets in Influenza Non-Structural Protein 1: NS1-Host Interactions as Antiviral Targets for Flu.

Influenza viruses are responsible for significant morbidity and mortality worldwide in winter seasonal outbreaks and in flu pandemics. Influenza viruses have a high rate of evolution, requiring annual vaccine updates and severely diminishing the effectiveness of the available antivirals. Identifying novel viral targets and developing new effective antivirals is an urgent need.

Trojan mosquitoes control dengue.

Dengue virus is transmitted by mosquitoes and causes the disease known as dengue. In a trial published in , Utarini and colleagues report that release of wolbachia-infected populations in a dengue endemic area reduces the number of symptomatic cases and of hospitalisations.

Likely a matter of time for Amyloid-β immunotherapy.

Amyloid-β peptide (Aβ) deposition in the brain is an early feature of Alzheimers' disease. In a phase II clinical trial recently published in , Mintun and colleagues report on the safety and efficacy of an antibody targeting Aβ peptide in amyloid plaques for the treatment of participants with early symptomatic Alzheimer's disease.

Recent major advances in cardiovascular pharmacotherapy.

The field of cardiovascular pharmacotherapy remains extremely active. The aim of this review is to summarize the recent major advances in cardiovascular pharmacotherapy, with a focus on (1) the new approved drug for treatment of heart failure with reduced ejection fraction-sacubitril/valsartan; (2) proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors; (3) the novel reversal agents for non-vitamin K oral anticoagulants (NOACs); and finally, (4) new evidence on pharmacological treatment of coronary artery disease.

Angiotensin II type 1/adenosine A receptor oligomers: a novel target for tardive dyskinesia.

Tardive dyskinesia (TD) is a serious motor side effect that may appear after long-term treatment with neuroleptics and mostly mediated by dopamine D receptors (DRs). Striatal DR functioning may be finely regulated by either adenosine A receptor (AR) or angiotensin receptor type 1 (ATR) through putative receptor heteromers. Here, we examined whether AR and ATR may oligomerize in the striatum to synergistically modulate dopaminergic transmission.

Agmatine attenuates reserpine-induced oral dyskinesia in mice: Role of oxidative stress, nitric oxide and glutamate NMDA receptors.

Dyskinesia consists in a series of trunk, limbs and orofacial involuntary movements that can be observed following long-term pharmacological treatment in some psychotic and neurological disorders such as schizophrenia and Parkinson's disease, respectively. Agmatine is an endogenous arginine metabolite that emerges as neuromodulator and a promising agent to manage diverse central nervous system disorders by modulating nitric oxide (NO) pathway, glutamate NMDA receptors and oxidative stress. Herein, we investigated the effects of a single intraperitoneal (i.

Immunoregulatory effects of HO-1: how does it work?

The heme-catabolizing enzyme heme oxygenase-1 (HO-1; encoded by the Hmox1 gene) inhibits the pathogenesis of several immune-mediated inflammatory diseases. This unusually broad salutary effect is thought to rely on the immunoregulatory actions of HO-1, exerted on innate and adaptive immune cells. According to this notion, HO-1 'dampens' innate and adaptive immune responses, limiting immune-mediated tissue injury and thus suppressing the pathogenesis of immune-mediated inflammatory diseases.

The influence of the loading mode on the stress distribution on the connector region of metal-ceramic and all-ceramic fixed partial denture.

Studies pertaining to the mechanical behavior of fixed partial dentures (FPDs) frequently found the highest tensile stress values at the connector region when load is applied at the pontic central region. The connector region is considered the weakest point of the prosthesis with the greatest potential of fractures, regardless of the material used. This 2D finite element study compared the stress distribution on three-element all-ceramic and metal-ceramic FPDs with different loading conditions.

All-ceramic and porcelain-fused-to-metal fixed partial dentures: a comparative study by 2D finite element analyses.

All-ceramic fixed partial dentures (FPDs) have an esthetic approach for oral rehabilitation. However, metal-ceramic FPDs are best indicated in the posterior area where the follow-up studies found a lower failure rate. This 2D finite element study compared the stress distribution on 3-unit all-ceramic and metal-ceramic FPDs and identified the areas of major risk of failure.

Heme oxygenase-1 and carbon monoxide suppress autoimmune neuroinflammation.

Heme oxygenase-1 (HO-1, encoded by HMOX1) dampens inflammatory reactions via the catabolism of heme into CO, Fe, and biliverdin. We report that expression of HO-1 dictates the pathologic outcome of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Induction of EAE in Hmox1(-/- )C57BL/6 mice led to enhanced CNS demyelination, paralysis, and mortality, as compared with Hmox1(+/+) mice.

The antiapoptotic effect of heme oxygenase-1 in endothelial cells involves the degradation of p38 alpha MAPK isoform.

Heme oxygenase-1 (HO-1) protects endothelial cells (EC) from undergoing apoptosis. This effect is mimicked by CO, generated via the catabolism of heme by HO-1. The antiapoptotic effect of CO in EC was abrogated when activation of the p38alpha and p38beta MAPKs was inhibited by the pyridinyl imidazole SB202190.