The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.

Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

A comprehensive review of hip arthroscopy techniques and outcomes.

Transforming the orthopedic landscape, hip arthroscopy pioneers a minimally invasive surgical approach for diagnosing and addressing hip pathologies. With its origins dating back to Burman's 1931 cadaveric study, this groundbreaking technique gained clinical relevance in 1939 through Takagi's report. However, the 1980s marked the actual emergence of hip arthroscopy for treating a wide range of hip disorders. Now, a staple in modern orthopedics, hip arthroscopy empowers patients with previously undiagnosed and untreated hip conditions, enabling them to obtain relief and reclaim their lives. By employing a compact camera and specialized tools, surgeons expertly navigate the hip joint, performing procedures from excising loose bodies and mending labral tears to addressing femoroacetabular impingement and tackling other intricate issues. This innovative approach has dramatically elevated patients' quality of life, allowing them to embrace targeted treatments and resume daily activities without resorting to lifestyle alterations.

Two-trace two-dimensional correlation spectra (2T2D-COS) analysis using FTIR spectra to monitor the immune response by COVID-19.

There is a growing trend in using saliva for SARS-CoV-2 detection with reasonable accuracy. We have studied the responses of IgA, IgG, and IgM in human saliva by directly comparing disease with control analyzing two-trace two-dimensional correlation spectra (2T2D-COS) employing Fourier transform infrared (FTIR) spectra. It explores the molecular-level variation between control and COVID-19 saliva samples. The advantage of 2T2D spectra is that it helps in discriminating remarkably subtle features between two simple pairs of spectra. It gives spectral information from highly overlapped bands associated with different systems. The clinical findings from 2T2D show the decrease of IgG and IgM salivary antibodies in the 50, 60, 65, and 75-years COVID-19 samples. Among the various COVID-19 populations studied the female 30-years group reveals defense mechanisms exhibited by IgM and IgA. Lipids and fatty acids decrease, resulting in lipid oxidation due to the SARS-CoV-2 in the samples studied. Study shows salivary thiocyanate plays defense against SARS-CoV-2 in the male population in 25 and 35 age groups. The receiver operation characteristics statistical method shows a sensitivity of 98% and a specificity of 94% for the samples studied. The measure of accuracy computed as F score and G score has a high value, supporting our study's validation. Thus, 2T2D-COS analysis can potentially monitor the progression of immunoglobulin's response function to COVID-19 with reasonable accuracy, which could help diagnose clinical trials. KEY MESSAGES: The molecular profile of salivary antibodies is well resolved and identified from 2T2D-COS FTIR spectra. The IgG antibody plays a significant role in the defense mechanism against SARS-CoV-2 in 25-40 years. 2T2D-COS reveals the absence of salivary thiocyanate in the 40-75 years COVID-19 population. The receiver operation characteristic (ROC) analysis validates our study with high sensitivity and specificity.

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.

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.

Dynamic response antibodies SARS-CoV-2 human saliva studied using two-dimensional correlation (2DCOS) infrared spectral analysis coupled with receiver operation characteristics analysis.

COVID-19 has affected the entire world due to the rapid spread of SARS-CoV-2, mainly through airborne particles from saliva, which, being easily obtained, help monitor the progression of the disease. Fourier transform infrared (FTIR) spectra combined with chemometric analysis could increase the diagnostic efficiency of the disease. However, two-dimensional correlation spectroscopy (2DCOS) is superior to conventional spectra as it helps to resolve the minute overlapped peaks. In this work, we aimed to use 2DCOS and receiver operating characteristic (ROC) analyses to compare the immune response in saliva associated with COVID-19, which could be important in biomedical diagnosis. FTIR spectra of human saliva samples from male (575) and female (366) patients ranging from 20 to 85 ± 2 years of age were used for the study. Age groups were segregated as G1 (20-40 ± 2 years), G2 (45-60 ± 2 years), and G3 (65-85 ± 2 years). The results of the 2DCOS analysis showed biomolecular changes in response to SARS-CoV-2. 2DCOS analyses of the male G1 + (1579,1644) and -(1531,1598) cross peaks evidenced changes such as amide I > IgG. Female G1 cross peaks -(1504,1645), (1504,1545) and -(1391,1645) resulted in amide I > IgG > IgM. The asynchronous spectra in 1300-900 cm-1 of the G2 male group showed that IgM is more important in diagnosing infections than IgA. Female G2 asynchronous spectra -(1027,1242) and + (1068,1176) showed that IgA > IgM is produced against SARS-CoV-2. The G3 male group evidenced antibody changes in IgG > IgM. The absence of IgM in the female G3 population diagnoses a specifically targeted immunoglobulin associated with sex. Moreover, ROC analysis showed sensitivity (85-89 % men; 81-88 % women) and specificity (90-93 % men; 78-92 % women) for the samples studied. The general classification performance (F1 score) of the studied samples is high for the male (88-91 %) and female (80-90 %) populations. This high PPV (positive predictive value) and NPV (negative predictive value) verify our segregation of COVID-19 positive and negative sample groups. Therefore, 2DCOS with ROC analysis using FTIR spectra have the potential for a non-invasive approach to monitoring COVID-19.

Implication of myddosome complex genetic variants in outcome severity of COVID-19 patients.

BACKGROUND/PURPOSE(S): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. METHODS: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. RESULTS: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21-4.9) with deceased outcomes. CONCLUSION: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

The impact of short-chain fatty acid-producing bacteria of the gut microbiota in hyperuricemia and gout diagnosis.

INTRODUCTION/OBJECTIVES: Persistent hyperuricemia is a key factor in gout; however, only 13.5% of hyperuricemic individuals manifest the disease. The gut microbiota could be one of the many factors underlying this phenomenon. We aimed to assess the difference in taxonomic and predicted functional profiles of the gut microbiota between asymptomatic hyperuricemia (AH) individuals and gout patients. METHODS: The V3-V4 region of the 16S rRNA gene of the gut microbiota of AH individuals, gout patients, and controls was sequenced. Bioinformatic analyses were carried out with QIIME2 and phyloseq to determine the difference in the relative abundance of bacterial genera among the study groups. Tax4fun2 was used to predict the functional profile of the gut microbiota. RESULTS: AH individuals presented a higher abundance of butyrate- and propionate-producing bacteria than gout patients; however, the latter had more bacteria capable of producing acetate. The abundance of Prevotella genus bacteria was not significantly different between the patients but was higher than that in controls. This result was corroborated by the functional profile, in which AH individuals had less pyruvate oxidase abundance than gout patients and less abundance of an enzyme that regulates glutamate synthetase activation than controls. CONCLUSION: We observed a distinctive taxonomic profile in AH individuals characterized by a higher abundance of short-chain fatty acid-producing bacteria in comparison to those observed in gout patients. Furthermore, we provide scientific evidence that indicates that the gut microbiota of AH individuals could provide anti-inflammatory mediators, which prevent the appearance of gout flares. Key Points • AH and gout patients both have a higher abundance of Prevotella genus bacteria than controls. • AH individuals' gut microbiota had more butyrate- and propionate-producing bacteria than gout patients. • The gut microbiome of AH individuals provides anti-inflammatory mediators that could prevent gout flares.

Comparison of the Immune Response in Vaccinated People Positive and Negative to SARS-CoV-2 Employing FTIR Spectroscopy.

Various immunopathological events characterize the systemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Moreover, it has been reported that coronavirus disease 2019 (COVID-19) vaccination and infection by SARS-CoV-2 induce humoral immunity mediated by B-cell-derived antibodies and cellular immunity mediated by T cells and memory B cells. Immunoglobulins, cytokines, and chemokines play an important role in shaping immunity in response to infection and vaccination. Furthermore, different vaccines have been developed to prevent COVID-19. Therefore, this research aimed to analyze and compare Fourier-transform infrared (FTIR) spectra of vaccinated people with a positive (V-COVID-19 group) or negative (V-Healthy group) real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) test, evaluating the immunoglobulin and cytokine content as an immunological response through FTIR spectroscopy. Most individuals that integrated the V-Healthy group (88.1%) were asymptomatic; on the contrary, only 28% of the V-COVID-19 group was asymptomatic. Likewise, 68% of the V-COVID-19 group had at least one coexisting illness. Regarding the immunological response analyzed through FTIR spectroscopy, the V-COVID-19 group showed a greater immunoglobulins G, A, and M (IgG, IgA, and IgM) content, as well as the analyzed cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-ɑ), and interleukins 1ß, 6, and 10 (IL-1ß, IL-6, and IL-10). Therefore, we can state that it was possible to detect biochemical changes through FTIR spectroscopy associated with COVID-19 immune response in vaccinated people.

Metabolic Reprogramming in SARS-CoV-2 Infection Impacts the Outcome of COVID-19 Patients.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

Association of the Transmembrane Serine Protease-2 (TMPRSS2) Polymorphisms with COVID-19.

SARS-CoV-2 uses the ACE2 receptor and the cellular protease TMPRSS2 for entry into target cells. The present study aimed to establish if the TMPRSS2 polymorphisms are associated with COVID-19 disease. The study included 609 patients with COVID-19 confirmed by RT-PCR test and 291 individuals negative for the SARS-CoV-2 infection confirmed by RT-PCR test and without antibodies anti-SARS-CoV-2. Four TMPRSS2 polymorphisms (rs12329760, rs2298659, rs456298, and rs462574) were determined using the 5'exonuclease TaqMan assays. Under different inheritance models, the rs2298659 (pcodominant2 = 0.018, precessive = 0.006, padditive = 0.019), rs456298 (pcodominant1 = 0.014, pcodominant2 = 0.004; pdominant = 0.009, precessive = 0.004, padditive = 0.0009), and rs462574 (pcodominant1 = 0.017, pcodominant2 = 0.004, pdominant = 0.041, precessive = 0.002, padditive = 0.003) polymorphisms were associated with high risk of developing COVID-19. Two risks (ATGC and GAAC) and two protectives (GAGC and GAGT) haplotypes were detected. High levels of lactic acid dehydrogenase (LDH) were observed in patients with the rs462574AA and rs456298TT genotypes (p = 0.005 and p = 0.020, respectively), whereas, high heart rate was present in patients with the rs462574AA genotype (p = 0.028). Our data suggest that the rs2298659, rs456298, and rs462574 polymorphisms independently and as haplotypes are associated with the risk of COVID-19. The rs456298 and rs462574 genotypes are related to high levels of LDH and heart rate.

The Critical Role of Hypoxia in the Re-Differentiation of Human Articular Chondrocytes.

The preservation of the chondrogenic phenotype and hypoxia-related physiological microenvironment are major challenges in the 2D culture of primary human chondrocytes. To address this problem, we develop a 3D culture system generating scaffold-free spheroids from human chondrocytes. Our results highlight the chondrogenic potential of cultured human articular chondrocytes in a 3D system combined with hypoxia independently of the cartilage source. After 14 days of culture, we developed spheroids with homogenous diameter and shape from hyaline cartilage donors. Spheroids generated in hypoxia showed a significantly increased glycosaminoglycans synthesis and up-regulated the expression of SOX9, ACAN, COL2A1, COMP, and SNAI1 compared to those obtained under normoxic conditions. Therefore, we conclude that spheroids developed under hypoxic conditions modulate the expression of chondrogenesis-related genes and native tissue features better than 2D cultures. Thus, this scaffold-free 3D culture system represents a novel in vitro model that can be used for cartilage biology research.

Molecular Mechanisms of Inflammation in Sarcopenia: Diagnosis and Therapeutic Update.

Sarcopenia is generally an age-related condition that directly impacts the quality of life. It is also related to chronic diseases such as metabolic dysfunction associated with diabetes and obesity. This means that everyone will be vulnerable to sarcopenia at some point in their life. Research to find the precise molecular mechanisms implicated in this condition can increase knowledge for the better prevention, diagnosis, and treatment of sarcopenia. Our work gathered the most recent research regarding inflammation in sarcopenia and new therapeutic agents proposed to target its consequences in pyroptosis and cellular senescence. Finally, we compared dual X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and ultrasound (US) as imaging techniques to diagnose and follow up on sarcopenia, indicating their respective advantages and disadvantages. Our goal is for the scientific evidence presented here to help guide future research to understand the molecular mechanisms involved in sarcopenia, new treatment strategies, and their translation into clinical practice.

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.

The rs8176740 T/A and rs512770 T/C Genetic Variants of the ABO Gene Increased the Risk of COVID-19, as well as the Plasma Concentration Platelets.

We conducted a case-control study in order to evaluate whether ABO gene polymorphisms were associated with a high risk of developing COVID-19 in a cohort of patients. Six ABO gene polymorphisms (rs651007 T/C, rs579459 T/C, rs495828 T/G, rs8176746 A/C, rs8176740 T/A, and rs512770 T/C) were determined using TaqMan genotyping assays in a group of 415 COVID-19 patients and 288 healthy controls. The distribution of rs651007 T/C, rs579459 T/C, rs495828 T/G, and rs8176746 A/C polymorphisms was similar in patients and healthy controls. Nonetheless, under co-dominant (OR = 1.89, pCCo-dominant = 6 × 10-6), recessive (OR = 1.98, pCRecessive = 1 × 10-4), and additive (OR = 1.36, pCAdditive = 3 × 10-3) models, the TT genotype of the rs8176740 T/A polymorphism increased the risk of developing COVID-19. In the same way, under co-dominant, recessive, and additive models, the TT genotype of the rs512770 T/C polymorphism was associated with a high risk of developing COVID-19 (OR = 1.87, pCCo-dominant = 2 × 10-3; OR = 1.87, pCRecessive = 5 × 10-4; and OR = 1.35, pCAdditive = 4 × 10-3, respectively). On the other hand, the GTC and GAT haplotypes were associated with a high risk of COVID-19 (OR = 5.45, pC = 1 × 10-6 and OR = 6.33, pC = 1 × 10-6, respectively). In addition, the rs8176740 TT genotype was associated with high-platelet plasma concentrations in patients with COVID-19. Our data suggested that the ABO rs512770 T/C and rs8176740 T/A polymorphisms increased the risk of developing COVID-19 and the plasma concentration of platelets.

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01-3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01-3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10-2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

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.

Therapeutic Potential of Bioactive Compounds in Honey for Treating Osteoarthritis.

Dysregulation of joint tissue homeostasis induces articular degenerative changes and musculoskeletal diseases such as osteoarthritis. This pathology represents the first cause of motor disability in individuals over 60 years of age, impacting their quality of life and the costs of health systems. Nowadays, pharmacological treatments for cartilage disease have failed to achieve full tissue regeneration, resulting in a functional loss of the joint; therefore, joint arthroplasty is the gold standard procedure to cure this pathology in severe cases of Osteoarthritis. A different treatment is the use of anti-inflammatory drugs which mitigate pain and inflammation in some degree, but without significant inhibition of disease progression. In this sense, new therapeutic alternatives based on natural compounds have been proposed to delay osteoarthritis progression, particularly those agents that regulate articular homeostasis. Preclinical studies have shown a therapeutic application of honey and its bioactive compounds, ranging from treating wounds, coughs, skin infections, and are also used as a biological stimulant by exerting antioxidant and anti-inflammatory properties. In this article, we reviewed the current medicinal applications of honey with particular emphasis on its use regulating articular homeostasis by inhibiting inflammation and oxidative stress.

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

OBJECTIVE: To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. METHODS: Hypervariable V3-V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profiles using bioinformatics in order to identify differences in taxonomy and metabolic pathways. RESULTS: We identified a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifidobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabolism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed differences in key bacterial enzymes involved in urate synthesis, degradation, and elimination. CONCLUSION: Our findings revealed that taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.

Soluble inflammatory mediators of synoviocytes stimulated by monosodium urate crystals induce the production of oxidative stress, pain, and inflammation mediators in chondrocytes : Secretome of synoviocytes induces chondrocyte damage.

We hypothesized that the secretion of inflammatory mediators from synoviocytes affects the chondrocyte homeostasis of articular cartilage. This study was a preliminary attempt to elucidate the molecular mechanisms by which soluble mediators obtained from activated synoviocytes induce oxidative stress and inflammation in chondrocytes. We measured the concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), nerve growth factor (NGF), superoxide anion (O2•-), hydrogen peroxide (H2O2), and nitric oxide (NO•) from articular human cells. First, we created a conditional basal medium by exposing synoviocytes (HS) to monosodium urate crystals (CBM). The chondrocytes were exposed to either CBM (CCM), urate crystals directly (CMSU), or remained untreated (CC) as a negative control. Data were analyzed by ANOVA tests; Bonferroni test was performed for multiple comparisons between groups. Interestingly, we observed that mediators of inflammation and oxidative stress were significantly higher in CCM than CMSU and CC groups (P<0.01). The specific concentrations were as follows: 19.85 ng/mL of IL-6, 9.79 ng/mL of IL-8, 5.17 ng/mL of NGF, and 11.91 ng/mL of MCP-1. Of note, we observed the same trend for reactive oxygen and nitrogen species (P<0.001). Soluble mediators secreted by synoviocytes after being activated with MSU crystals (as observed in individuals who present gout attacks) trigger chondrocyte activation intensifying the articular inflammatory, oxidative, and pain states that damage cartilage in OA; this damage is more severe even when compared to HC directly exposed to monosodium urate crystals. Key Points • The molecular relation between MSU depositions and cartilage damage could be mediated by pro-inflammatory soluble mediators and oxidative molecules. • The secretion of pro-inflammatory mediators by activated synoviocytes is more harmful to chondrocytes than a direct activation in the chondrocyte culture. • Under this model, there is an important imbalance in the matrix homeostasis due to changes in several chemokines, cytokines, and other factors such as NGF, as well as oxidative mediators.