Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis.

(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer's development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

Characterisation of crevicular fluid microbiota in primary Sjögren's syndrome.

OBJECTIVES: To describe the taxonomy of the microbiota in crevicular fluid of primary Sjögren's syndrome (pSS) patients, and evaluate its association with clinical/serological variables, and oral quality of life. METHODS: Observational study that included 48 pSS without diabetes mellitus, no active neoplasia, no antibiotic use in the previous two weeks, and no current active infection. We registered demographics, oral/ocular sicca symptoms, parotid enlargement and anti-Ro/La serology. We assessed the non-stimulated whole salivary flow (NSWSF), the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), and the Xerostomia-related Quality of Life Scale (XeQoLS). Two periodontists determined the presence of periodontal disease and collected crevicular fluid from 6 teeth using filter paper. Samples were frozen at -86°C until processing. We included 17 sex- and age-matched control subjects. Bacterial DNA was extracted from the crevicular fluid sample using a commercial kit. 16SrRNA V3-V4 region was sequenced using reversible adaptor technology. Sequences were pre-processed and analysed using QIIME2 and phyloseq software programs. Functionality profiles were predicted using the Tax4Fun2 package. RESULTS: PSS patients had more bacteria of the genera Prevotella, Streptococcus, Veillonella, Fusobacterium, and Leptotrichia and fewer bacteria of the genus Selenomonas than controls. The pSS microbiota contained more genes encoding accessory secretory proteins. Microbiota also differed between patients with anti-Ro/La status, parotid gland enlargement, and periodontal disease severity, but did not correlate with NSWSF and XeQoLS. CONCLUSIONS: The crevicular fluid microbiota of pSS patients and controls differed significantly, even in SSP patients depending on their serology, parotid gland enlargement, and periodontal disease status.

Effect of smoking on the redox status of knee osteoarthritis: A preliminary study.

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.

Revolutionizing orthopedics: a comprehensive review of robot-assisted surgery, clinical outcomes, and the future of patient care.

Robotic-assisted orthopedic surgery (RAOS) is revolutionizing the field, offering the potential for increased accuracy and precision and improved patient outcomes. This comprehensive review explores the historical perspective, current robotic systems, advantages and limitations, clinical outcomes, patient satisfaction, future developments, and innovation in RAOS. Based on systematic reviews, meta-analyses, and recent studies, this article highlights the most significant findings and compares RAOS to conventional techniques. As robotic-assisted surgery continues to evolve, clinicians and researchers must stay informed and adapt their practices to provide optimal patient care. Evidence from published studies corroborates these claims, highlighting superior component positioning, decreased incidence of complications, and heightened patient satisfaction. However, challenges such as costs, learning curves, and technical issues must be resolved to fully capitalize on these advantages.

Suitable characteristics in the selection of human allogeneic chondrocytes donors to increase the number of viable cells for cartilage repair.

Autologous chondrocyte implantation has shown optimal long-term outcomes in the treatment of cartilage lesions. The challenge for a single-stage approach lies in obtaining sufficient number of cells with high viability. The answer could lie in supplementing or replacing them with allogenic chondrocytes coming from cadaveric donors. In the present work, we aimed to compare the number of viable cells isolated from cartilage of live and cadaveric donors and to determine the suitable characteristics of the best donors. A total of 65 samples from donors aged from 17 to 55 years, either women or men, were enrolled in this study (33 living vs. 32 cadaveric). The mean time of hours from death to processing samples in cadaveric donors was higher compared to live donors (64.3 ± 17.7 vs. 4.6±6.4). The number of isolated chondrocytes per gram of cartilage was higher in cadaveric donors (5.389 × 106 compared to 3.067 × 106 in living donors), whereas the average of cell viability was comparable in both groups (84.16% cadaveric, 87.8% alive). It is possible to obtain viable chondrocytes from cartilage harvested from cadaveric donors, reaching a similar cell number and viability to that obtained from the cartilage of living donors.

Inflammasome Genes Polymorphisms and Susceptibility to Gout. Is There a Link?

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.

Inflammasome genes polymorphisms and susceptibility to gout. Is there a link?

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.

SERPINA9 and SERPINB2: Novel Cartilage Lineage Differentiation Markers of Human Mesenchymal Stem Cells with Kartogenin.

OBJECTIVE: Human mesenchymal stem cells (hMSCs) are a promising source for regenerative medicine, especially mesodermal lineages. Clinical applications require an understanding of the mechanisms for transcriptional control to maintain the desired cell type. The aim of this study was to identify novel markers for differentiation of hMSCs into bone or cartilage with the use of Kartogenin, by RNA analysis using microarray technology, and explore the role of RhoA-Rho associated protein kinase (ROCK) inhibition in these. METHODS: Commercial human bone marrow derived primary mesenchymal stem cells were purchased from ATCC. Cells were differentiated in vitro in 2-dimensional cultures using Kartogenin as the main cartilage inducer and bone morphogenetic protein 2 for bone differentiation; cells were cultured with and without ROCK inhibitor Y-27632. After 21 days of culture, whole RNA was extracted and analyzed via Affimetrix microarrays. The most significant hits were validated by quantitative polymerase chain reaction. RESULTS: We found a total of 1,757 genes that were either up- or downregulated on differentiation, when compared to P1 hMSC (control) at day 0 of differentiation. Two members of the Serpin superfamily, SERPINA9 and SERPINB2, were significantly upregulated in the cartilage groups, whereas they were unchanged in the bone groups with and without ROCK inhibition. CONCLUSIONS: SERPINA9 and SERPINB2 are novel differentiation markers, and molecular regulator candidates for hMSC lineage commitment toward bone and cartilage, providing a new tool for regenerative medicine. Our study highlights the roles of these 2 genes, with significant upregulation of both in cell cultures stimulated with Kartogenin.

Efficacy of imiquimod 5% cream as first-line management in cutaneous leishmaniasis caused by Leishmania mexicana

Abstract Cutaneous leishmaniasis (CL) involves several differential diagnoses as it lacks a gold standard diagnostic test. Its diagnosis is easier in endemic regions; however, many cases come from travelers to endemic areas. A 22-year-old patient, who had recently visited Oaxaca, Mexico, developed two asymptomatic ulcers weeks later on the left auricle and the nose. Leishmania mexicana was identified using polymerase chain reaction. The patient was treated with imiquimod 5% cream three times/week, providing favorable results after 12 weeks, without relapse 2 months after therapy. To our knowledge, this is the first case of CL due to L. mexicana effectively treated with imiquimod.

NLRP3 Inflammasome: The Stormy Link Between Obesity and COVID-19.

Several countries around the world have faced an important obesity challenge for the past four decades as the result of an obesogenic environment. This disease has a multifactorial origin and it is associated with multiple comorbidities including type 2 diabetes, hypertension, osteoarthritis, metabolic syndrome, cancer, and dyslipidemia. With regard to dyslipidemia, hypertriglyceridemia is a well-known activator of the NLRP3 inflammasome, triggering adipokines and cytokines secretion which in addition induce a systemic inflammatory state that provides an adequate scenario for infections, particularly those mediated by viruses such as HIV, H1N1 influenza, and SARS-CoV-2. The SARS-CoV-2 infection causes the coronavirus disease 2019 (COVID-19) and it is responsible for the pandemic that we are currently living. COVID-19 causes an aggressive immune response known as cytokine release syndrome or cytokine storm that causes multiorgan failure and in most cases leads to death. In the present work, we aimed to review the molecular mechanisms by which obesity-associated systemic inflammation could cause a more severe clinical presentation of COVID-19. The SARS-CoV-2 infection could potentiate or accelerate the pre-existing systemic inflammatory state of individuals with obesity, via the NLRP3 inflammasome activation and the release of pro-inflammatory cytokines from cells trough Gasdermin-pores commonly found in cell death by pyroptosis.

Correction to: Afatinib is active in osteosarcoma cell lines.

The title of the article is incorrectly published in the original article. The correct article title is "Afatinib is active in osteosarcoma cell lines".

Cherry extracts attenuate inflammation and oxidative stress triggered by monosodium urate crystals in THP-1 cells.

The microwaves-assisted extraction (MAE) for concentration of cherry phytochemicals has seen explored. Polyphenols from cherries, Prunus avium (L.) L., were extracted using a microwave oven at 2,450 MHz, 453 W for a period of 60 s (T60), and was compared versus an unprocessed MAE extract (T0). The extracts were analyzed for total polyphenols, total anthocyanins, and antioxidant capacity. THP-1 cells were stimulated with monosodium urate (MSU) crystals at 150 µg/ml for 24 hr. Cherry extracts were added to cultures concurrently with MSU or 3 hr before MSU addition as pretreatments. Reactive oxygen species (ROS), IL-1ß levels, and MSU crystal phagocytosis were evaluated. T60 extract showed a higher concentration of polyphenols, anthocyanins, and antioxidant activity than T0 extract. ROS were inhibited using the 1:800 and 1:1,600 (v:v) dilutions from both extracts, even used as pretreatments. IL-1ß levels and MSU crystal phagocytosis were reduced. Cherry is a source of polyphenolic compounds with antioxidant and anti-inflammatory activity. PRACTICAL APPLICATIONS: The cherries and a cherry extract obtained via MAE has benefits as a possible coadjuvant to conventional gout therapy due to attenuate the inflammation and the oxidative stress triggered by monosodium urate crystals in THP-1 cells, which mimic an acute episode of gout.

Afatinib is active in osteosarcoma in osteosarcoma cell lines.

PURPOSE: Osteosarcoma is the most common bone tumor, mainly affecting adolescents and young adults, and metastatic disease has poor outcomes with a dismal overall survival. Currently, chemotherapy is the standard of care with limited results, finding that new therapies could improve these outcomes. Preclinical and clinical studies have suggested a possible important role of ErbB pathway aberrations in osteosarcoma etiology. The present study shows the effect of afatinib, an irreversible ErbB family blocker in osteosarcoma cell lines. METHODS: Within a panel of human osteosarcoma cell lines, we addressed cell viability assay using afatinib at increasing concentrations. Motility was measured in wound-healing assays and invasion capacity was assessed in Transwell chamber assays. Finally, to monitor ErbB pathway modulation by afatinib and related compounds, we used Western blot analyses. RESULTS: Cell viability inhibition, as well as a reduction of motility and migration of osteosarcoma cell line were observed after treatment with afatinib. Likewise, in the HOS cell line, afatinib decreased phosphorylation of key components in the ErbB signaling pathway. CONCLUSIONS: Afatinib shows relevant antitumor effect in several osteosarcoma cell lines, as it causes a significant impact on cell viability, motility, and migration with a significant decrease in the activation of ErbB pathway activity.

BRCA1 and VDR gene polymorphisms are associated with prostate cancer risk in Mexican men.

Prostate cancer (PC) is a polygenic disease with broad differences across ethnicities. BRCA1/2 and VDR have exhibited a featured genetic contribution to PC development in European populations. Nonetheless, its contribution in Latino populations specifically among Mexican men, where 70% of PC cases are detected in advanced stages, is still unknown. The contribution of seven polymorphisms in BRCA1/2 and VDR genes to PC susceptibility was evaluated in 370 incident PC cases and 759 age-matched (±5 years) controls belonging to the Mexican population. Based on Gleason score at diagnosis, PC cases were classified as well-differentiated PC (Gleason <7) and moderate or poorly differentiated PC (Gleason ≥7). Age at diagnosis was used to divided PC cases in earlier (<60 years) and late-onset PC (≥60 years). Prostate and breast cancer family histories were obtained through interview. Our results provided evidences about the contribution of BRCA1-rs1799966 (ORCC genotype = 2.30; 95% confidence interval [CI] = 1.36-3.91) to the moderate or poorly differentiated PC risk, independently of the family history of prostate, breast or ovary cancer. Further, VDR-rs2238135-G allele was associated with early-onset PC (ORG allele = 2.05; 95% CI = 1.06-3.95), and marginally with moderate or poorly differentiated PC risk. The present study revealed the crucial role of BRCA1 in PC aggressiveness risk, outstanding the gender imbalance regarding the breast cancer risk in women.

Impact of cadmium toxicity on cartilage loss in a 3D in vitro model.

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.

Impact of the gene-gene interactions related to the HIF-1α signaling pathway with the knee osteoarthritis development.

INTRODUCTION/OBJECTIVES: Articular cartilage is the target tissue of osteoarthritis (OA), and because it lacks capillary networks, the microenvironment is hypoxic. Hypoxia inducible factor-1 alpha (HIF-1α) regulates the homeostasis of this tissue. The aim of this study was to investigate whether genetic polymorphisms of the HIF-1α signaling pathway are involved in the development of knee OA. METHOD: We performed a case-control association study and genotyped 134 knee OA patients and 267 healthy controls. All participants were genotyped in order to evaluate 42 SNPs from 22 genes involved in the HIF-1α signaling pathway using the OpenArray technology. Gene-gene interactions (epistasis) were analyzed using the multifactor dimensionality reduction (MDR) method. RESULTS: The MDR analysis showed epistasis between AKT2 (rs8100018) and IGF1 (rs2288377), AKT2 (rs8100018) and IGF1 (rs35767), IGF1 (rs35767) and COL2A1 (rs1793953), and between GSK3B (rs6438552) and IGF1 (rs35767) polymorphisms, with information gain values of 21.24%, 8.37%, 9.93%, and 5.73%, respectively. Additionally, our model allowed us to identify high- and low-risk genotypes among COL2A1 rs1793953, GSK3B rs6438552, AKT2 rs8100018, and IGF1 rs35767 polymorphisms. CONCLUSIONS: Knowing the interactions of these polymorphisms involved in HIF-1α signaling pathway could provide a new diagnostic support tool to identify individuals at high risk of developing knee OA.

Cloning, expression, purification, and kinetic characterization of mitochondrial thioredoxin (TsTrx2), cytosolic thioredoxin (TsTrx1), and glutaredoxin (TsGrx1) from Taenia solium.

We report the complete coding sequences of mitochondrial thioredoxin (TsTrx2) and glutaredoxin (TsGrx1) from the cysticerci of T. solium. The full-length DNA of the TsTrx2 gene shows two introns of 88 and 77 bp and three exons. The TsTrx2 gene contains a single ORF of 423 bp, encoding 140 amino acid residues with an estimated molecular weight of 15,560 Da. A conserved C64NPC67 active site and a 30-amino acid extension at its N-terminus were identified. An insulin reduction reaction was used to determine whether it was a functional recombinant protein. The full-length DNA of the TsGrx1 gene shows one intron of 39 bp and a single ORF of 315 bp, encoding 105 amino acid residues with an estimated molecular weight of 12,582 Da. Sequence analysis revealed a conserved dithiol C34PYC37 active site, GSH-binding motifs (CXXC, Lys and Gln/Arg, TVP, and CXD), and a conserved Gly-Gly motif. The r-TsGrx1 kinetic constants for glutathione (GSH) and 2-hydroxyethyl disulfide (HED) were determined. In addition, cytosolic thioredoxin (TsTrx1), as reported by (Jiménez et al., Biomed Res Int 2015:453469, 2015), was cloned and expressed, and its catalytic constants were obtained along with those of the other two reductases. Rabbit-specific antibodies showed immune cross-reactions between TsTrx1 and TsTrx2 but not with TsGrx1. Both TsTGRs as reported by (Plancarte and Nava, Exp Parasitol 149:65-73, 2015) were biochemically purified to obtain and compare the catalytic constants for their natural substrates, r-TsTrx1, and r-TsTrx2, compared to those for Trx-S2E. coli. In addition, we determined the catalytic differences between the glutaredoxin activity of the TsTGRs compared with r-TsGrx1. These data increase the knowledge of the thioredoxin and GSH systems in T. solium, which is relevant for detoxification and immune evasion.

Epistasis between ADIPOQ rs1501299 and PON1 rs662 polymorphisms is potentially associated with the development of knee osteoarthritis.

Overweight produces oxidative stress (OS) on the articular cartilage, with the subsequent risk of developing knee osteoarthritis (OA). Associations between genetic polymorphisms related to OS and OA have been reported, but it is currently unknown whether there exist interactions among them that affect OA development. To identify and evaluate interactions between multiple SNPs related to OS in Mexican knee OA patients. Ninety-two knee OA patients were included in the study, which were compared to 147 healthy controls. Nine variants of six genes (PEPD, AGER, IL6, ADIPOQ, PON1, and CA6) related to OS were genotyped in both study groups through the OpenArray system. Epistasis was analyzed with the multifactor dimensionality reduction (MDR) method. The MDR analysis revealed a significant interaction (p = 0.0107) between polymorphisms rs1501299 (ADIPOQ) and rs662 (PON1), with an entropy value of 9.84%; in addition, high and low risk genotypes were identified between these two polymorphisms. The effect of the interaction between rs1501299 (ADIPOQ) and rs662 (PON1) polymorphisms seems to play an important role in OA pathogenesis; so the epistasis analysis may provide an excellent tool for identifying individuals at high risk for developing OA.

Role of HIF-1α signaling pathway in osteoarthritis: A systematic review / Papel da via de sinalização do HIF-1α; na osteoartrite: revisão sistemática

Abstract Osteoarthritis (OA) is the most common form of arthritis and is frequently diagnosed and managed in primary care; it is characterized by loss of articular hyaline cartilage, which is a unique connective tissue that physiologically lacks blood vessels. Articular cartilage survives in a microenvironment devoid of oxygen, which is regulated by hypoxia inducible factor (HIF-1α). HIF-1α is considered the main transcriptional regulator of cellular and developmental response to hypoxia. To date, the relevance of HIF-1α in the assessment of cartilage has increased since its participation is essential in the homeostasis of this tissue. Taking into account the new emerging insights of HIF-1α in the scientific literature in the last years, we focused the present review on the potential role of HIF-1α signaling pathway in OA development, especially in how some genetic factors may influence the maintenance or breakdown of articular cartilage.

Resumo A osteoartrite (OA) é a forma mais comum de artrite e frequentemente é diagnosticada e gerenciada na atenção primária; é caracterizada por perda da cartilagem articular hialina, um tecido conjuntivo único que fisiologicamente carece de vasos sanguíneos. A cartilagem articular sobrevive em um microambiente desprovido de oxigênio, que é regulado pelo fator induzível por hipóxia-1α (HIF-1α). O HIF-1α é considerado o principal regulador transcricional da resposta celular e de desenvolvimento à hipóxia. Na atualidade, a relevância do HIF-1α na avaliação da cartilagem tem aumentado, já que a sua participação é essencial na homeostase desse tecido. Considerando as novas perspectivas emergentes do HIF-1α na literatura científica nos últimos anos, foca-se a presente revisão no potencial papel da via de sinalização do HIF-1α no desenvolvimento da OA, especialmente no modo como alguns fatores genéticos podem influenciar na manutenção ou ruptura da cartilagem articular.

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.