Alberto López-Reyes

Biphasic Regulation of the NADPH Oxidase by HGF/c-Met Signaling Pathway in Primary Mouse Hepatocytes

Redox signaling is emerging as an essential mechanism in the regulation of biological activities of the cell. The HGF/c-Met signaling pathway has been implicated as a key regulator of the cellular redox homeostasis and oxidative stress. We previously demonstrated that genetic deletion of c-Met in hepatocytes disrupts redox homeostasis by a mechanism involving NADPH oxidase. Here, we were focused to address the mechanism of NADPH oxidase regulation by HGF/c-Met signaling in primary mouse hepatocytes and its relevance. HGF induced a biphasic mechanism of NADPH oxidase regulation. The first phase employed the rapid increase in production of ROS as signaling effectors to activate the Nrf2-mediated protective response resulting in up-regulation of the antioxidant proteins, such as NAD(P)H quinone oxidoreductase and γ-glutamylcysteine synthetase. The second phase operated under a prolonged HGF exposure, caused a suppression of the NADPH oxidase components, including NOX2, NOX4, p22 and p67, and was able to abrogate the TGFβ-induced ROS production and improve cell viability. In conclusion, HGF/c-Met induces a Nrf2-mediated protective response by a double mechanism driven by NADPH oxidase.

Ultrasound in psoriatic arthritis. Can it facilitate a best routine practice in the diagnosis and management of psoriatic arthritis

Important advances from both therapeutic and clinical assessment have recently been reported in psoriatic arthritis (PsA). Moreover, the constant challenge to provide a more comprehensive assessment of this heterogeneous disease results in a variety of clinical instruments that help the clinician for a global evaluation of both disease activity and responsiveness. The current European League Against Rheumatism (EULAR) recommendations on the use of imaging suggest the use of ultrasound (US) in chronic arthritis to increase the diagnostic accuracy and improvement of its management as compared to clinical examination alone. Although US findings are not firmly established in daily clinical practice, it demonstrated several positive aspects such as good sensitivity and specificity, acceptable reliability, and adequate sensitivity to change, especially in the peripheral PsA. Additionally, recent works introduced the role of US in the assessment of skin and nails opening interesting area of research. The aim of this paper is to describe the potential role of US in the assessment of PsA and to discuss the current evidence supporting its application in daily clinical practice.

Molecular basis of oxidative stress in gouty arthropathy

Gout is a disorder of urate metabolism in which persistent high urate levels in the extracellular fluids result in the deposition of monosodium urate (MSU) crystal in joints and periarticular tissues. In recent years, this disease represents an increasingly common health problem, so the pace of investigation in the field has accelerated tremendously. New research advances in the pathogenesis of hyperuricemia and in the understanding of how MSU crystals induce an acute gouty attack have been focused in this review on the processes of inflammation and involvement of the innate immune response; in addition, we discuss new knowledge about the role of the reactive oxygen species in establishing oxidative stress in MSU crystal-induced arthritis.

The Overexpression of NALP3 Inflammasome in Knee Osteoarthritis Is Associated with Synovial Membrane Prolidase and NADPH Oxidase 2

Osteoarthritis is characterized by the presence of proinflammatory cytokines and reactive oxygen species. We aimed to clarify the role of prooxidant enzyme content at the synovial membrane level and how it correlates with the inflammatory process in patients with knee osteoarthritis (KOA). In synovial membranes from KOA patients and control group, we analyzed the protein content of prooxidant enzymes such as Nox2, xanthine oxidase (XO), and prolidase as well as the proinflammatory NALP3. Results show that protein content of prolidase and Nox2 increased 4.8- and 8.4-fold, respectively, and XO showed an increasing trend, while the NALP3 inflammasome increased 5.4-fold with respect to control group. Levels of prolidase and XO had a positive correlation between the levels of NALP3 and Nox2. By principal component analysis the protein expression pattern by study groups was evaluated. Three clusters were identified; protein expression patterns were higher for clusters two (prolidase) and three (XO and Nox2) between KOA patients and controls. Data suggest that prooxidant enzymes increase in synovial membrane of KOA patients and may contribute to the inflammatory state and degradation of the articular cartilage.

Emergent nanotherapies in microcrystal-induced arthritis

&NA; The anti‐inflammatory and immunomodulatory effects of nanoparticles in several chronic diseases have been extensively researched. The aim of this review is to examine how nanoparticles modulate the inflammatory pathways that characterize the most prevalent forms of microcrystal‐induced arthritis, including gout, pseudogout, and BCP‐induced arthritis. The nanoparticles of chitosan‐coated calcium phosphate, uricase, aceclofenac, and gold have been investigated in crystal‐inducedarthritis. The most important results of the studies outlined in this review show that nanoparticles can inhibit the expression and the release of some pro‐inflammatory mediators and proteolytic enzymes, and the activity of different transcriptional factors in vitro, as well as decrease the uric acid levels in several studies of in vitro and in vivo models of gout, which show interesting results in terms of decreasing the amount of crystals and tissue damage, respectively. In view of their multiple beneficial effects, nanoparticles can be considered a valuable therapy that contributes to the pharmacological treatment in crystalinduced arthritis. HighlightsNPs modulate the inflammatory pathways of crystal‐induced arthritis.NPs could inhibit the expression of several pro‐inflammatory mediators and proteolytic enzymes in crystal‐induced arthritis.NPs could induce activity of different transcriptional factors, as well as decrease uric acid levels.NPs alleviate inflammatory responses, decreasing the amount of crystals and tissue damage in gout and pseudogout.NPs can be considered a valuable therapy that contributes to the pharmacological treatment in crystal‐induced arthritis.

Common gene variants interactions related to uric acid transport are associated with knee osteoarthritis susceptibility

ABSTRACT Background: The presence of genetic variants in uric acid (UA) transporters can be associated with hyperuricemia, and therefore with an increased risk of monosodium urate (MSU) crystal precipitation. The inflammatory process triggered by these crystals leads to cartilage damage, which, in turn, could promote knee osteoarthritis (KOA). Objective: To determine whether genetic polymorphisms of the UA transporters and their interactions are associated with KOA. Materials and Methods: Two hundred forty-three unrelated Mexican-mestizo individuals were recruited for this case-control study. Ninety-three of them were KOA patients but without gout, and one hundred and fifty healthy individuals with no symptoms or signs of KOA were recruited as controls. Forty-one single-nucleotide polymorphisms (SNPs) involved in the UA transporters were genotyped with OpenArray technology in a QuantStudio 12K flex-System with both cases and controls. Results: After adjusting by age, gender, BMI, and ancestry, significant associations were found for eight SNPs: rs1260326 (GCKR), rs780093 (GCKR), rs17050272 (INHBB), rs1471633 (PDZK1), rs12129861 (PDZK1), rs7193778 (IGF1R), rs17786744 (STC1), and rs1106766 (R3HDM2). With respect to gene–gene interactions, the pairwise interactions of rs112129861 (PDZK1) and rs7193778 (IGF1R); rs17050272 (INHBB) and rs1106766 (R3HDM2); rs1106766 (R3HDM2) and rs780093 (GCKR); rs1260326 (GCKR) and rs17786744 (STC1); and rs17786744 (STC1) and rs1106766 (R3HDM2) make it possible to visualize the synergistic or antagonistic effect of their genotypes or alleles on KOA development. Conclusions: Our preliminary results show that the common gene variants related to UA transport are associated with KOA in the Mexican population. Further studies must be carried out to corroborate it.

Corrigendum to “The Overexpression of NALP3 Inflammasome in Knee Osteoarthritis Is Associated with Synovial Membrane Prolidase and NADPH Oxidase 2”

[This corrects the article DOI: 10.1155/2016/1472567.].

HIF1A (rs11549465) and AKNA (rs10817595) Gene Polymorphisms Are Associated with Primary Sjögren’s Syndrome

Objective. To evaluate the allele and genotype frequencies of polymorphic sites of HIF1A and ANKA genes in primary Sjögrens syndrome (pSS). Methods. We included 110 patients with pSS and 141 ethnically matched healthy controls. Three HIF1A gene polymorphisms (Pro582Ser, Ala588Thr, and C191T) and two AKNA gene polymorphisms (−1372C>A and Pro624Leu) were genotyped using TaqMan probes in a Real-Time PCR instrument. Associations between pSS and genotypes, alleles, and inheritance models of the SNPs of interest were evaluated by logistic regression adjusted by age and gender. Results. The C/T genotype and the T allele of the HIF1A Pro582Ser polymorphism protected against pSS (OR = 0.22; 95% CI = 0.09–0.52; P < 0.01; OR = 0.26; 95% CI = 0.12–0.58; P < 0.01, resp.), whereas under a recessive model adjusted by age and gender, the AKNA −1372C>A polymorphism A/A genotype was associated with an increased risk of pSS (OR = 2.60; 95% CI = 1.11–6.12; P = 0.03). Conclusions. We identified HIF1A Pro582Ser T allele and C/T genotype as well as AKNA −1372C>A polymorphism A/A genotype as genetic factors associated with pSS. Further studies in other populations are needed to validate our findings and research is warranted in order to shed some light on their functional implications across biological pathways in this disease.