Hydrogen sulfide dysfunction in metabolic syndrome-associated vascular complications involves cGMP regulation through soluble guanylyl cyclase persulfidation.

Here, by using in vitro and ex vivo approaches, we elucidate the impairment of the hydrogen sulfide (HS) pathway in vascular complications associated with metabolic syndrome (MetS). In the in vitro model simulating hyperlipidemic/hyperglycemic conditions, we observe significant hallmarks of endothelial dysfunction, including eNOS/NO signaling impairment, ROS overproduction, and a reduction in CSE-derived HS. Transitioning to an ex vivo model using db/db mice, a genetic MetS model, we identify a downregulation of CBS and CSE expression in aorta, coupled with a diminished L-cysteine-induced vasorelaxation.

New biologic (Ab-IPL-IL-17) for IL-17-mediated diseases: identification of the bioactive sequence (nIL-17) for IL-17A/F function.

Objectives: Interleukin (IL) 17s cytokines are key drivers of inflammation that are functionally dysregulated in several human immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD). Targeting these cytokines has some therapeutic benefits, but issues associated with low therapeutic efficacy and immunogenicity for subgroups of patients or IMIDs reduce their clinical use. Therefore, there is an urgent need to improve the coverage and efficacy of antibodies targeting IL-17A and/or IL-17F and IL-17A/F heterodimer.

Hydrogen sulfide donor AP123 restores endothelial nitric oxide-dependent vascular function in hyperglycemia via a CREB-dependent pathway.

Diabetes is associated with severe vascular complications involving the impairment of endothelial nitric oxide synthase (eNOS) as well as cystathionine γ-lyase (CSE) activity. eNOS function is suppressed in hyperglycaemic conditions, resulting in reduced NO bioavailability, which is paralleled by reduced levels of hydrogen sulfide (HS). Here we have addressed the molecular basis of the interplay between the eNOS and CSE pathways.

Interleukin-17 (IL-17) triggers systemic inflammation, peripheral vascular dysfunction, and related prothrombotic state in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is one of the most prevalent forms of neurodegenerative disorders. Previously, we have shown that in vivo administration of an IL-17 neutralizing antibody (IL-17Ab) rescues amyloid-β-induced neuro-inflammation and memory impairment, demonstrating the pivotal role of IL-17 in AD-derived cognitive deficit. Recently, AD has been recognized as a more intriguing pathology affecting vascular networks and platelet function.

Anti-inflammatory and immunomodulatory activity of Mangifera indica L. reveals the modulation of COX-2/mPGES-1 axis and Th17/Treg ratio.

In the context of inflammation and immunity, there are fragmented and observational studies relating to the pharmacological activity of Mangifera indica L. and its main active component, mangiferin. Therefore, we aimed to analyze the potential beneficial effects of this plant extract (MIE, 90 % in mangiferin) in a mouse model of gouty arthritis, to allow the evaluation of cellular immune phenotypes and the biochemical mechanism/s beyond MIE activity.

Phosphodiesterases S-sulfhydration contributes to human skeletal muscle function.

The increase in intracellular calcium is influenced by cyclic nucleotides (cAMP and cGMP) content, which rating is governed by phosphodiesterases (PDEs) activity.Despite it has been demonstrated a beneficial effect of PDEs inhibitors in different pathological conditions involving SKM, not much is known on the role exerted by cAMP-cGMP/PDEs axis in human SKM contractility. Here, we show that Ssulfhydration of PDEs modulates human SKM contractility in physiological and pathological conditions.

In Silico, In Vitro, and In Vivo Analysis of Tanshinone IIA and Cryptotanshinone from as Modulators of Cyclooxygenase-2/mPGES-1/Endothelial Prostaglandin EP3 Pathway.

Tanshinone IIA (TIIA) and cryptotanshinone (CRY) from Bunge were investigated for their inhibitory activity against the cyclooxygenase-2 (COX-2)/microsomal prostaglandin E synthase-1 (mPGES-1)/endothelial prostaglandin 3 (EP3) pathway using in silico, in vitro, in vivo, and ex vivo assays. From the analysis of the docking poses, both diterpenoids were able to interact significantly with COX-2, 5-lipoxygenase (5-LO), platelet-activating factor receptor (PAFR), and mPGES-1. This evidence was further corroborated by data obtained from a cell-free assay, where CRY displayed a significant inhibitory potency against mPGES-1 (IC = 1.

Interleukin-17A (IL-17A): A silent amplifier of COVID-19.

One of the hallmarks of COVID-19 is the cytokine storm that provokes primarily pneumonia followed by systemic inflammation. Emerging evidence has identified a potential link between elevated interleukin-17A (IL-17A) levels and disease severity and progression. Considering that per se, IL-17A can activate several inflammatory pathways, it is plausible to hypothesize an involvement of this cytokine in COVID-19 clinical outcomes.

Supplementation with ribonucleotide-based ingredient (Ribodiet®) lessens oxidative stress, brain inflammation, and amyloid pathology in a murine model of Alzheimer.

Alzheimer's disease (AD) is the most common type of dementia worldwide, characterized by the deposition of neurofibrillary tangles and amyloid-β (Aβ) peptides in the brain. Additionally, increasing evidence demonstrates that a neuroinflammatory state and oxidative stress, iron-dependent, play a crucial role in the onset and disease progression. Besides conventional therapies, the use of natural-based products represents a future medical option for AD treatment and/or prevention.

IL-17-induced inflammation modulates the mPGES-1/PPAR-γ pathway in monocytes/macrophages.

Background And Purpose: Recent biochemical and pharmacological studies have reported that in several tissues and cell types, microsomal PGE synthase (mPGES) and PPAR-γ expression are modulated by a variety of inflammatory factors and stimuli. Considering that very little is known about the biological effects promoted by IL-17 in the context of mPGES-1/PPAR-γ modulation, we sought to investigate the contribution of this unique cytokine on this integrated pathway during the onset of inflammation.

Experimental Approach: We evaluated effects of PF 9184 (mPGES-1 inhibitor) and troglitazone (PPAR-γ agonist) in vitro, using the mouse macrophage cell line J774A.

Present Status and Future Trends of Natural-Derived Compounds Targeting T Helper (Th) 17 and Microsomal Prostaglandin E Synthase-1 (mPGES-1) as Alternative Therapies for Autoimmune and Inflammatory-Based Diseases.

Several natural-based compounds and products are reported to possess anti-inflammatory and immunomodulatory activity both in vitro and in vivo. The primary target for these activities is the inhibition of eicosanoid-generating enzymes, including phospholipase A2, cyclooxygenases (COXs), and lipoxygenases, leading to reduced prostanoids and leukotrienes. Other mechanisms include modulation of protein kinases and activation of transcriptases.

The functional link between microsomal prostaglandin E synthase-1 (mPGES-1) and peroxisome proliferator-activated receptor γ (PPARγ) in the onset of inflammation.

Many years have elapsed since the discovery of anti-inflammatories as effective therapeutics for the treatment of inflammatory-related diseases, but we are still uncovering their various mechanisms of action. Recent biochemical and pharmacological studies have shown that in different tissues and cell types lipid mediators from thearachidonic acid cascade, play a crucial role in the initiation and resolution of inflammation by shifting from pro-inflammatory prostaglandin (PG)E to anti-inflammatory PGD and PGJ. Considering that until now very little is known about the biological effects evoked by microsomal prostaglandin E synthase-1 (mPGES-1) and contextually by peroxisome proliferator-activated receptor γ (PPARγ) modulation (key enzymes involved in PGE and PGD/PGJmetabolism), in this opinion paper we sought to define the coordinate functional regulation between these two enzymes at the "crossroads of phlogistic pathway" involved in the induction and resolution of inflammation.

Pharmacological and molecular docking assessment of cryptotanshinone as natural-derived analgesic compound.

Medicinal plants from traditional chinese medicine are used increasingly worldwide for their benefits to health and quality of life for the relevant clinical symptoms related to pain. Among them, Salvia miltiorrhiza Bunge is traditionally used in asian countries as antioxidant, anticancer, anti-inflammatory and analgesic agent. In this context, several evidences support the hypothesis that some tanshinones, in particular cryptotanshinone (CRY), extracted from the roots (Danshen) of this plant exhibit analgesic actions.

In-depth immunophenotyping data relating to IL-17Ab modulation of circulating Treg/Th17 cells and of infiltrated inflammatory monocytes in the onset of gouty inflammation.

The data supplied in this work are related to the research article entitled "IL-17A neutralizing antibody regulates monosodium urate crystal-induced gouty inflammation" [1]. This data article presents the results of the gating strategy applied to identify Treg population in peripheral blood of mice injected with MSU crystals and MSU crystals + interleukin-17 antibody (IL-17Ab). Lastly, this article provides in-depth immunophenotyping data relating to all specific and isotype control antibodies used in the phenotypical characterization of circulating Treg (defined as CD4CD25Foxp3), Th17 (defined as CD4IL-17) cells and joint-infiltrated () inflammatory monocytes (defined as B220GR1F480CD115).

Molecular reorientation by photoinduced modulation of rotational mobility.

To explain the large photoinduced molecular reorientation phenomena observed in dye-doped liquids and liquid crystals, the hypothesis was formed that the rotational mobility of dye molecules is strongly altered during their electronic excitation. Here, we report the direct measurement of a 30%-50% mobility decrease of photoexcited anthraquinone dye molecules dissolved in a cyanophenyl liquid host. This mobility reduction is ascribed to an excited-state reinforcement of intermolecular hydrogen bonding.