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BACKGROUND: Interstitial lung disease (ILD) is a complication in patients with systemic sclerosis (SSc). Accurate strategies to identify its presence in early phases are essential. We conducted the study aiming to determine the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to ascertain its potential in determining the disease progression. METHODS: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), auscultation, chest radiographs, and respiratory function tests (RFT) were performed. A rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. The patients were followed every 12 weeks for 48 weeks. RESULTS: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p = 0.0001). Anti-centromere antibodies (p = 0.005) and RSS (p = 0.004) showed an association with ILD. A positive correlation was demonstrated between the US and HRCT findings (p = 0.001). The sensitivity and specificity of US in detecting ILD were 91.2% and 88.6%, respectively. In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. CONCLUSIONS: US showed a high prevalence of subclinical ILD in SSc patients. It proved to be a valid, reliable, and feasible tool to detect ILD in SSc and to monitor disease progression.

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The ongoing pandemic of COVID-19 has caused more than 6.7 million tragic deaths, plus, a large percentage of people who survived it present a myriad of chronic symptoms that last for at least 6 months; this has been named as long COVID. Some of the most prevalent are painful symptoms like headache, joint pain, migraine, neuropathic-like pain, fatigue and myalgia. MicroRNAs are small non-coding RNAs that regulate genes, and their involvement in several pathologies has been extensively shown. A deregulation of miRNAs has been observed in patients with COVID-19. The objective of the present systematic review was to show the prevalence of chronic pain-like symptoms of patients with long COVID and based on the expression of miRNAs in patients with COVID-19, and to present a proposal on how they may be involved in the pathogenic mechanisms of chronic pain-like symptoms. A systematic review was carried out in online databases for original articles published between March 2020 to April 2022; the systematic review followed the PRISMA guidelines, and it was registered in PROSPERO with registration number CRD42022318992. A total of 22 articles were included for the evaluation of miRNAs and 20 regarding long COVID; the overall prevalence of pain-like symptoms was around 10 to 87%, plus, the miRNAs that were commonly up and downregulated were miR-21-5p, miR-29a,b,c-3p miR-92a,b-3p, miR-92b-5p, miR-126-3p, miR-150-5p, miR-155-5p, miR-200a, c-3p, miR-320a,b,c,d,e-3p, and miR-451a. The molecular pathways that we hypothesized to be modulated by these miRNAs are the IL-6/STAT3 proinflammatory axis and the compromise of the blood-nerve barrier; these two mechanisms could be associated with the prevalence of fatigue and chronic pain in the long COVID population, plus they could be novel pharmacological targets in order to reduce and prevent these symptoms.

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Rheumatoid arthritis (RA) is an autoimmune disease that affects approximately 1% of the worldwide population. In recent decades, oxidative stress (OS) has been shown to be involved in the progression of this disease through DNA, lipid and protein damage, resulting in synovial inflammation. There are many causes of OS; metabolism is involved in the production of reactive oxygen species (ROS) but pollution, diet and microbiota imbalances could lead to the overproduction of these ROS. A decade of research focused on understanding how OS is promoted by known RA risk factors is described herein. The use of antioxidants represents an integrative treatment for patients with rheumatoid arthritis, given the evidence of the damage caused by oxidative stress in this disease. Understanding the different factors that contribute to the development and progression of RA, such as OS, will pave the way not only for better pharmacological treatments but also for recommendations for dietary and health behaviours that will benefit patients with this disease.

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ABSTRACT Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1β release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1β rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.

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Background: The inflammatory response in gout disease is induced by the activation of NLR family pyrin domain-containing 3 (NLPR3) signaling pathway mediated by IL-1ß release. Objective: The objective of the study was to determine the association between single nucleotide polymorphisms (SNPs) within NLRP3 inflammasome genes and gout susceptibility. Methods: Mexican patients with gout from the National Rehabilitation Institute and General Hospital of Mexico were enrolled. A healthy control group was also included. We analyzed the frequency and allelic distribution of eight SNPs from seven different genes within the NLRP3 inflammasome signaling pathway: TLR4 rs2149356, CD14 rs2569190, NLRP3 rs3806268, NLRP3 rs10754558, CARD8 rs2043211, IL-1ß rs1143623, P2RX7 rs3751142, and PPARGC1B rs45520937 SNPs. Results: We found that the SNP rs45520937 of PPARGC1B was associated with the risk of developing gout when it was analyzed using the dominant model (Odds ratio [OR] = 2.30; 95% confidence interval [CI]: 1.09-4.86; p = 0.030), and it is proposed that the adaptor molecule CD14 rs2569190 polymorphism could be associated with a lower risk of gout under an additive model (OR= 0.41;95% CI: 0.16-1.05; p = 0.064). No significant associations were identified for the remaining SNPs. Conclusion: Our findings suggest that the PPARGC1B rs45520937 SNP is associated with gout susceptibility.

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Ultrasound (US) is a recognized imaging modality for the assessment of gout. Recently it is being explored for its potential role in the evaluation of subjects with asymptomatic hyperuricemia (AH). Preliminary reports demonstrated the presence of monosodium urate (MSU)-crystal deposits including aggregates, double contour sign and/or tophi in both intra-articular and periarticular tissues of AH individuals. Although these results are exciting, the value and potential application of US in AH remain to be clearly delineated. In this systematic literature review, we aim to summarise the recent publications regarding the role of US in the assessment of AH. We analyzed possible application of US in the daily clinical practice and its future clinical and research potential in the evaluation of AH individuals.

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INTRODUCTION: The NLR family pyrin domain containing 3 (NLRP3) signaling pathway has an important role in inflammation mediated by monosodium urate crystals in gout, and the characterization of single nucleotide polymorphisms (SNPs) have helped to recognize disease susceptibility. OBJECTIVE: The aim of this review is to provide an overview of the potential role of the inflammasome gene SNPs as a susceptibility factor for gout, discussing the current evidence available. METHODS: This review analyzes the relevant literature in the field of inflammasome SNPs and gout published in the last 10 years. The systematic research was performed in 16 articles, including both the SNPs associated and those not associated with gout, with the goal to have a complete overview. RESULTS: Sixty-nine SNPs from 10 different genes have been reported in the literature. Of these, 13 SNPs present association with gout susceptibility in different populations, while 56 have been established as not being associated with the disease. CONCLUSIONS: This review is a summary of the potential role of inflammasome gene SNPs and their association with gout risk, all of them related with NLRP3 inflammasome signaling, suggesting these polymorphisms are susceptibility candidates and genetic markers for gout. From the 69 SNPs analyzed in the literature, 13 of them have been associated with gout as follows: NLRP3 (rs3806268 and rs10754558), CARD8 (rs2043211), TLR4 (rs2149356), CD14 (rs2569190), IL-1ß (rs1143623), P2RX7 (rs2230911, rs1653624, rs7958316 and rs17525809) and PPARGC1B (rs45520937, rs10491360 and rs7712296) in different populations.

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INTRODUCTION AND OBJECTIVES: It is well-known that signaling mediated by the hepatocyte growth factor (HGF) and its receptor c-Met in the liver is involved in the control of cellular redox status and oxidative stress, particularly through its ability to induce hepatoprotective gene expression by activating survival pathways in hepatocytes. It has been reported that HGF can regulate the expression of some members of the NADPH oxidase family in liver cells, particularly the catalytic subunits and p22phox. In the present work we were focused to characterize the mechanism of regulation of p22phox by HGF and its receptor c-Met in primary mouse hepatocytes as a key determinant for cellular redox regulation. MATERIALS AND METHODS: Primary mouse hepatocytes were treated with HGF (50 ng/mL) at different times. cyba expression (gene encoding p22phox) or protein content were addressed by real time RT-PCR, Western blot or immunofluorescence. Protein interactions were explored by immunoprecipitation and FRET analysis. RESULTS: Our results provided mechanistic information supporting the transcriptional repression of cyba induced by HGF in a mechanism dependent of NF-κB activity. We identified a post-translational regulation mechanism directed by p22phox degradation by proteasome 26S, and a second mechanism mediated by p22phox sequestration by c-Met in plasma membrane. CONCLUSION: Our data clearly show that HGF/c-Met exerts regulation of the NADPH oxidase by a wide-range of molecular mechanisms. NADPH oxidase-derived reactive oxygen species regulated by HGF/c-Met represents one of the main mechanisms of signal transduction elicited by this growth factor.

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Osteoarthritis (OA) is the gradual loss of articular cartilage and decrease in subchondral space. One of the risk factors Exposure to cadmium (Cd) through tobacco smoke has been identified as a major OA risk factor. There are no reports addressing the role of Cd in OA progression at the molecular level. Our findings revealed that Cd can promote the activation of metalloproteinases (MMP1, MMP3, MMP9 y MMP13), affecting the expression of COL2A1 and ACAN, and decreasing the presence of glycosaminoglycans and proteoglycans through an inflammatory response related to IL-1ß y a IL-6, as well as oxidative by producing ROS like O2-• and H2O2. In conclusion, our findings suggest a cytotoxic role of Cd in the articular cartilage, which could affect OA development.

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Lung ultrasound (LUS) achieved an intriguing role in the management of pulmonary involvement in patients affected by connective tissues diseases (CTDs). Few studies have been performed to support its usefulness in the evaluation of the presence and the severity of interstitial lung disease (ILD), relating it to the information obtained with chest high-resolution computed tomography (HRCT). These results open up new fields of research in order to demonstrate the utility of LUS as screening tool to evaluate ILD in CTD. The aim of this review is to provide the "state of the art" of the role of LUS in the management of ILD associated with CTD.

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