Vitamin A Positively Correlates with Secretory Immunoglobulin A: A Cross-Sectional Study in Omicron COVID-19 Outpatients.

Background: Respiratory tract infections remain among the leading causes of mortality worldwide. The COVID-19 pandemic has highlighted the importance of mucosal immunity in defending against infectious agents. Vitamin A is known to influence the production of secretory immunoglobulin A (SIgA) predominantly in the gut, where it is a critical component of the first line of defense on mucosal surfaces. Methods: This cross-sectional study, conducted 14 days post-positive COVID-19 diagnosis, aimed to determine the relationship between the nutritional status of vitamin A and SIgA levels in COVID-19 outpatients. Serum and saliva samples were collected. Vitamin A nutritional status was determined based on the assessment of dietary intake and the analysis of retinol-binding protein 4 (RBP4). SIgA levels were analyzed from salivary samples. In addition, serum antibodies were analyzed. Results: Dietary vitamin A intake and RBP4 levels positively correlated with SIgA. Patients with higher vitamin A intake showed higher SIgA/IgG1 and SIgA/IgG3 ratios, while those with higher RBP4 levels showed higher SIgA/IgM, SIgA/IgG1, and SIgA/IgG2 ratios. Conclusions: These findings underscore a significant correlation between vitamin A nutritional status and SIgA levels in COVID-19 outpatients, which may suggest the potential importance of maintaining optimal vitamin A levels for the prevention of viral infections.

STAT4 Gene Variant rs7574865 Is Associated with Rheumatoid Arthritis Activity and Anti-CCP Levels in the Western but Not in the Southern Population of Mexico.

Rheumatoid Arthritis (RA) is a multifactorial autoimmune disease. Currently, several genes play an important role in the development of the disease. The objective was to evaluate the association of the STAT4 rs7574865 and rs897200 gene variants with RA susceptibility, DAS28, RF, and anti-CCP in Western and Southern Mexico populations. Genotyping was performed on 476 samples (cases = 240; controls = 236) using the Taqman® system and qPCR probes. Disease activity was assessed using DAS28 and HAQ DI. CRP, ESR, RF, and anti-CCP were determined for clinical assessment. Our study showed there is a statistically significant association with susceptibility to RA for the rs7574865 variant in the Western population for the GT and TT genotypes. The same genotypes also showed a moderate-to-high activity according to DAS28 and positive anti-CCP compared to the control group. This association was not found in the Southern population. This work confirms the association of the rs7574865 variant with RA, as well as a moderate-to-high activity and positive anti-CCP in the Western population but not in the Southern population. No association of the rs897200 variant was found in any of the studied populations.

Seroprevalence of IgM/IgG and Neutralizing Antibodies against SARS-CoV-2 in Unvaccinated Young Adults from Mexico Who Reported Not Having Had a Previous COVID-19 Infection.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). It is estimated that more than half of new infections are transmitted by asymptomatic people; therefore, the isolation of symptomatic people is not enough to control the spread of the disease. Methods: A total of 171 unvaccinated young adults (18-35 years) from Sonora, Mexico, who underwent a structured survey to identify prior COVID-19 infections, were included in this study. A qualitative determination of anti-SARS-CoV-2 antibodies in serum was performed by lateral flow immunoassay (Certum IgG/IgM Rapid Test™ cassette kit) and neutralizing antibodies were also determined (GenScript cPass assay). Results: A total of 36 people reported a history of COVID-19 infection, and 135 reported no history of COVID-19. In contrast, 49.6% (67/135) of individuals who had not reported a previous SARS-CoV-2 infection were seropositive to the rapid anti-SARS-CoV-2 antibody test, and 48.1% (65/135) of them had neutralizing antibodies. Conclusions: These results suggest that in young adults, SARS-CoV-2 infections could be asymptomatic in a high percentage of individuals, which could contribute in part to the slow control of the current pandemic due to the large number of asymptomatic cases that are contagious and that could be a silent spread of the virus.

Relationship between lipid profile, anthropometric indicators, and appetite-regulating hormones in infants according to type of feeding / Relación entre perfil lipídico, indicadores antropométricos y hormonas reguladoras del apetito en lactantes según tipo de alimentación

Background: infants receiving full breastfeeding (FBF) regulate their appetites differently from those receiving human milk substitutes (HMS). In addition, early exposure to the dietary cholesterol in human milk could lead to better cholesterol regulation in later stages of life. Therefore, the purpose was to compare lipid profiles in 4-month-old infants and to correlate lipid profile with anthropometric indicators and appetite-regulating hormones according to the type of feeding. Methods: this was a cross-sectional and correlational study, which included 145 mother-infant dyads according to the type of feeding; 64 received FBF, 47 partial breastfeeding (PBF), and 34 HMS. The complete lipid profile, total ghrelin, leptin, peptide YY, and glucagon-like peptide type 1 were measured. Z-scores for weight/age, length/age, weight/length, triceps (TSF) and subscapular folds (SSF) and body mass index for age were also obtained. Results: there were significant differences in triglycerides and LDL cholesterol according to the type of feeding. In the HMS group, an inverse relationship was observed between ghrelin and triglycerides (p = 0.038), ghrelin and total cholesterol (TC) (p = 0.026), and peptide YY and HDL cholesterol (p = 0.017). In the PBF group, a direct relationship was observed between length/age (z) and triglycerides (p = 0.001) and between subscapular folds and TC (p = 0.049). In infants receiving HMS, a direct correlation was observed between weight/age (z) and TC (p = 0.045) and between length/age (z) and LDL cholesterol (p = 0.010). Conclusion: these findings show a relationship between growth, energy reserve, lipid profile, and modulation of appetite-regulating hormones according to the type of feeding they received. (AU)

Introducción: los lactantes que reciben lactancia materna completa (LMC) regulan su apetito de manera diferente a los que reciben sucedáneos de la leche humana (SLH). Además, la exposición temprana al colesterol en la leche humana conduciría a mejor regulación del colesterol en etapas posteriores de la vida. El propósito fue de comparar el perfil lípidos en lactantes de cuatro meses y correlacionarlo con indicadores antropométricos y hormonas reguladoras del apetito según el tipo de alimentación. Métodos: en un estudio transversal y correlacional se incluyeron 145 díadas madre-lactante según el tipo de alimentación; 64 recibieron LMC, 47 lactancia materna parcial (LMP) y 34 SLH. Se midió el perfil lipídico, grelina total, leptina, péptido YY y péptido tipo 1 similar al glucagón. Se obtuvieron puntajes Z para peso/edad, longitud/edad, peso/longitud, pliegue cutáneo tricipital y subescapular e índice de masa corporal para la edad. Resultados: hubo diferencias significativas en triglicéridos y colesterol LDL según el tipo de alimentación. En el grupo HMS se observó una relación inversa entre grelina y triglicéridos (p = 0,038), grelina y colesterol total (TC) (p = 0,026), y péptido YY y colesterol HDL (p = 0,017). En el grupo PBF hubo relación directa entre longitud/edad (z) y triglicéridos (p = 0,001) y entre pliegues subescapulares y CT (p = 0,049). En los lactantes que recibieron HMS, se observó una correlación directa entre peso/edad (z) y CT (p = 0,045) y entre longitud/edad (z) y colesterol LDL (p = 0,010). Conclusión: los hallazgos muestran una relación entre perfil lipídico, crecimiento, reserva energética y modulación de las hormonas reguladoras del apetito según el tipo de alimentación. (AU)

Evaluation of Serum Levels of Cytokines in Acute Apical Abscess: A Longitudinal Observational Study.

INTRODUCTION: Cytokine levels are related to the aethiopathogenia of acute apical abscesses (AAA); however, the specific cytokine profiles in these cases are unclear. This study aimed to investigate the changes in systemic cytokine levels in patients with AAA and trismus onset, postantibiotic treatment, and postroot canal disinfection. METHODS: In total, 46 AAA patients with trismus and 32 control subjects were included. After seven days of antibiotic therapy, root canal disinfection was performed in the AAA patients. The serum levels of cytokines were evaluated at basal, seven, and 14 days after endodontic treatment. Quantification of cytokines from T helper (Th) 1, Th2, Th17, and regulatory T cells profiles was determined using the BioPlex MagPix system, and the obtained data were analyzed using SPSS statistical software (P < .05). RESULTS: AAA patients showed higher tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6, and IL-10 levels than control subjects, at basal measurement (P < .05); there were similar levels of interferon gamma, IL-1ß, IL-4, and IL-17 between groups (P > .05). IL-6 and IL-10 levels decreased after antibiotic treatment (P < .05), which was also associated with clinical improvement in patients with AAA and trismus. Patients with AAA had a positive correlation with higher serum levels of IL-6 and IL-10. In addition, TNF-α levels decreased only after antibiotic and endodontic treatment. CONCLUSIONS: In conclusion, patients with AAA had increased systemic serum levels of TNF-α, IL-6, and IL-10. Moreover, increased levels of IL-6 and IL-10 are associated with acute inflammatory symptoms. However, IL-6 and IL-10 levels decreased after antibiotic treatment, while TNF-α levels decreased after antibiotic and endodontic treatment.

Relationship between lipid profile, anthropometric indicators, and appetite-regulating hormones in infants according to type of feeding.

Introduction: Background: infants receiving full breastfeeding (FBF) regulate their appetites differently from those receiving human milk substitutes (HMS). In addition, early exposure to the dietary cholesterol in human milk could lead to better cholesterol regulation in later stages of life. Therefore, the purpose was to compare lipid profiles in 4-month-old infants and to correlate lipid profile with anthropometric indicators and appetite-regulating hormones according to the type of feeding. Methods: this was a cross-sectional and correlational study, which included 145 mother-infant dyads according to the type of feeding; 64 received FBF, 47 partial breastfeeding (PBF), and 34 HMS. The complete lipid profile, total ghrelin, leptin, peptide YY, and glucagon-like peptide type 1 were measured. Z-scores for weight/age, length/age, weight/length, triceps (TSF) and subscapular folds (SSF) and body mass index for age were also obtained. Results: there were significant differences in triglycerides and LDL cholesterol according to the type of feeding. In the HMS group, an inverse relationship was observed between ghrelin and triglycerides (p = 0.038), ghrelin and total cholesterol (TC) (p = 0.026), and peptide YY and HDL cholesterol (p = 0.017). In the PBF group, a direct relationship was observed between length/age (z) and triglycerides (p = 0.001) and between subscapular folds and TC (p = 0.049). In infants receiving HMS, a direct correlation was observed between weight/age (z) and TC (p = 0.045) and between length/age (z) and LDL cholesterol (p = 0.010). Conclusion: these findings show a relationship between growth, energy reserve, lipid profile, and modulation of appetite-regulating hormones according to the type of feeding they received.

Introducción: Introducción: los lactantes que reciben lactancia materna completa (LMC) regulan su apetito de manera diferente a los que reciben sucedáneos de la leche humana (SLH). Además, la exposición temprana al colesterol en la leche humana conduciría a mejor regulación del colesterol en etapas posteriores de la vida. El propósito fue de comparar el perfil lípidos en lactantes de cuatro meses y correlacionarlo con indicadores antropométricos y hormonas reguladoras del apetito según el tipo de alimentación. Métodos: en un estudio transversal y correlacional se incluyeron 145 díadas madre-lactante según el tipo de alimentación; 64 recibieron LMC, 47 lactancia materna parcial (LMP) y 34 SLH. Se midió el perfil lipídico, grelina total , leptina , péptido YY y péptido tipo 1 similar al glucagón. Se obtuvieron puntajes Z para peso/edad, longitud/edad, peso/longitud, pliegue cutáneo tricipital y subescapular e índice de masa corporal para la edad. Resultados: hubo diferencias significativas en triglicéridos y colesterol LDL según el tipo de alimentación. En el grupo HMS se observó una relación inversa entre grelina y triglicéridos (p = 0,038), grelina y colesterol total (TC) (p = 0,026), y péptido YY y colesterol HDL (p = 0,017). En el grupo PBF hubo relación directa entre longitud/edad (z) y triglicéridos (p = 0,001) y entre pliegues subescapulares y CT (p = 0,049). En los lactantes que recibieron HMS, se observó una correlación directa entre peso/edad (z) y CT (p = 0,045) y entre longitud/edad (z) y colesterol LDL (p = 0,010). Conclusión: los hallazgos muestran una relación entre perfil lipídico, crecimiento, reserva energética y modulación de las hormonas reguladoras del apetito según el tipo de alimentación.

Transforming growth factor beta isoforms and TGF-ßR1 and TGF-ßR2 expression in systemic sclerosis patients.

Systemic sclerosis (SSc) is characterized by chronic inflammation and fibrosis, two processes associated with transforming growth factor ß (TGF-ß) functions. In the present study, we investigated the expression of TGF-ß isoforms in serum and the skin distribution of TGF-ß and two receptors (TGF-ßR1 and TGF-ßR2) and their relationship with some clinical, inflammatory, autoimmune (autoantibodies), and vascular (platelets) biomarkers in SSc patients. A total of 56 SSc patients and 120 control subjects (CS) were included. The serum levels of TGF-ß isoforms were quantified by immunoassay with magnetic microspheres, and the skin biopsies were processed by immunohistochemistry. The soluble levels of the three active TGF-ß isoforms were lower in SSc patients than in CS (p < 0.0001). However, sTGF-ß1 and sTGF-ß3 levels were positively correlated with C-reactive protein levels in SSc patients. Additionally, sTGF-ß2 and sTGF-ß3 levels were positively correlated with the number of platelets in SSc patients. In skin biopsies, TGF-ß1, TGF-ßR1, and TGF-ßR2 expression levels were higher in SSc patients than CS. In conclusion, this is the first study showing a joint decrease of the 3 active TGF-ß isoforms in SSc patients. However, TGF-ß1, TGF-ßR1, and TGF-ßR2 are possibly increased in clinically involved skin. Therefore, it is likely that a distinct role is played by TGF-ß at the local (skin lesions) and systemic levels in SSc patients.

TGFB1 mRNA expression and frequency of the + 869T>C and + 915G>C genetic variants: impact on risk for systemic sclerosis.

Systemic Sclerosis (SSc) is a chronic autoimmune disease characterized by immune disorder, microvascular damage, and fibrosis. TGFB1 gene encodes for the transforming growth factor isoform 1 (TGF-ß1), one of the most important pro-fibrotic cytokines. Therefore, variants in TGFB1 and changes in its expression could be associated with the pathogenesis of SSc. We aimed to evaluate the association of TGFB1 variants (+ 869T>C [rs1982073] and + 915G > C [rs1800471]) with the TGFB1 mRNA expression and SSc risk in the Southern Mexican population. We included 56 SSc patients and 112 control subjects (CS). The genetic variants were determined by the PCR-RFLP method. The TGFB1 mRNA expression was determined by qPCR. For the + 869T>C variant, the C allele was associated with SSc risk (OR = 1.733; CI = 1.087-2.762; p = 0.020). The C allele for the + 915G>C variant was also associated with SSc risk (OR = 11.168; CI = 1.289-96.754; p = 0.023). The relative expression of TGFB1 mRNA was 1.77-fold lower in SSc patients than in CS. Carriers of polymorphic alleles (TC or CC genotypes) for the + 869T>C variant showed 3.7-fold lower mRNA expression than the TT genotype in patients and 4.81-fold lower in CS. For the + 915G>C variant, patients with GA genotype had 1.78-fold lower mRNA expression than GG genotype carriers. In conclusion, the present study showed that + 869T>C and + 915G>C variants could be SSc risk factors for patients from Southern Mexico, and these genetic variants could induce lower mRNA expression of TGFB1.

In Peripheral Blood Mononuclear Cells Helicobacter pylori Induces the Secretion of Soluble and Exosomal Cytokines Related to Carcinogenesis.

Helicobacter pylori promotes the secretion of cytokines that regulate inflammation and carcinogenesis. Immune cells secrete cytokines into the extracellular medium or packaged in exosomes. The objective of this study was to analyze the profile of soluble and exosomal cytokines that were secreted by human peripheral blood mononuclear cells (PBMCs) that were infected with H. pylori and to build a network of interaction between cytokines and cellular proteins. PBMCs were obtained by density gradient centrifugation and infected with H. pylori for 24 h. The infection was verified by immunofluorescence and Western blot for CagA. The exosomes were obtained from culture supernatant by ultracentrifugation and characterized by transmission electron microscopy, particle size analysis, and Western blot for CD9 and CD81. Cytokines were quantified using a multiplex immunoassay in the culture supernatant, intact exosomes, and lysed exosomes. H. pylori adheres to lymphocytes and translocates CagA. In PBMCs, H. pylori induces an increase in the soluble and exosomal IL-1ß, IL-6, TNF-α, IL-10, IL-17A, IL-21, and IL-22. The protein-protein interaction (PPI) network shows that soluble and exosomal cytokines interact with proteins that participate in signaling pathways such as NF-κB, MAPK, PI3K-Akt, Jak-STAT, FoxO, and mTOR, that are related to carcinogenesis; moreover, TNF-α had the highest number of interactions. Cytokine-loaded exosomes represent another means of intercellular communication that is activated by H. pylori to stimulate inflammation, carcinogenesis, or cancer progression. Cytokine-loaded exosomes are likely to be associated with extragastrointestinal diseases of inflammatory origin.

Effect of flaxseed (Linum usitatissimum) supplementation on glycemic control and insulin resistance in prediabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Prediabetes and type 2 Diabetes Mellitus (T2DM) are characterized by increased blood sugar concentration and insulin resistance. Although there are only a few reports of potential benefits of flaxseed's consumption on different metabolic parameters, there is no evidence of its effect among people with these conditions. OBJECTIVES: The present systematic review and meta-analysis aimed to assess the effect of flaxseed supplementation on glycemic control variables and insulin resistance in prediabetes and T2DM. METHODS: A literature search was conducted through PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, to identify Randomized Control Trials (RCTs) that evaluated the effect of milled or ground flaxseed supplementation on fasting blood glucose, HbA1c, insulin concentrations, or HOMA-IR. The data were analyzed using Comprehensive Meta-Analysis (CMA) software version 3.3 in a fixed-effect model. RESULTS: Seven studies were included in the systematic review and the meta-analysis, the results showed a significant reduction on fasting blood sugar (SMD: -0.392, 95% CI: -0.596, -0.187, p = <0.001, I2 = 64.81%) insulin concentrations, (SMD: -0.287, 95% CI: -0.534, -0.041, p = 0.022, I2 = 32.53%), HbA1c (SMD: -0.442, 95% CI: -0.770, -0.114, p = 0.008, I2 = 11.058%), and HOMA-IR (SMD: -0.284, 95% CI: -0.530, -0.038, p = 0.024, I2 = 0.00%) after flaxseed supplementation. CONCLUSIONS: Flaxseed supplementation seems to improve glycemic control variables and insulin resistance in prediabetes and T2DM; however, more RCTs are needed to have more decisive evidence about doses, method of supplementation, and the possible effect of synergy with the dietetic treatment.

Th1/Th2 Balance in Young Subjects: Relationship with Cytokine Levels and Metabolic Profile.

PURPOSE: We aim to identify Th1 and Th2 cell clusters in young subjects, including their clinical and metabolic characteristics and the Th1/Th2 balance. PATIENTS AND METHODS: A total of 100 participants were included. The frequencies of Th1 and Th2 cells in peripheral blood were determined by flow cytometry. Serum C-reactive protein was measured using a turbidimetric assay, and insulin levels were quantified with an enzyme-linked immunosorbent assay. Circulating cytokine levels were analyzed using a multiplex system. RESULTS: A cluster analysis was performed to determine the Th1/Th2 balance in a group of young people, and 3 clusters were formed with the following characteristics: 1) subjects with a higher prevalence of hyperglycemia (38%), dyslipidemia (38-75%), and insulin resistance (50%), as well as a higher percentage of Th1 cells and Th1/Th2 ratio, including elevated IFN-É£ levels; 2) subjects with a lower prevalence of hyperglycemia (23%) and insulin resistance (15.4%), but a higher prevalence of dyslipidemia (8-85%) with a predominance of Th2 cells, and lower Th1/Th2 ratio; 3) subjects with a lower prevalence of hyperglycemia (6%), insulin resistance (41%), and dyslipidemia (10-63%), as well as a balance of Th1 and Th2 cells and lower Th1/Th2 ratio, including low IFN-É£ levels. Positive correlations between Th1 cells with IFN-γ, IL-12, and IL-1ß and between Th2 cells with IFN-γ, IL-2, and IL-4 were found (p < 0.05). A significant increase in Th1 cells was observed in the presence of hyperglycemia and high LDL-C levels, as well as increased Th2 cells in the absence of abdominal obesity and high blood pressure, including low HDL-C levels. The Th1/Th2 ratio was higher in the group with high cardiometabolic risk (p = 0.03). CONCLUSION: Th1/Th2 balance is related to metabolic abnormalities that may occur in young population, and thus the timely identification of different phenotypes may help predict an increased cardiometabolic risk.

A Comprehensive Descriptive Epidemiological and Clinical Analysis of SARS-CoV-2 in West-Mexico during COVID-19 Pandemic 2020.

This study aimed to summarize the epidemiological and clinical characteristics of COVID-19 from Western Mexico people during 2020. A retrospective analysis from an electronic database of people visiting a sentinel center for molecular SARS-CoV-2 confirmatory diagnosis by RT-PCR from April to December 2020 was carried out for epidemiological and clinical description of COVID-19. Out of 23,211 patients evaluated, 6918 (29.8%) were confirmed for SARS-CoV-2 infection (mean age 38.5 ± 13.99), mostly females (53.8%). Comorbidities, such as diabetes (34.7%), obesity (31.15%), and hypertension (31.8%), presented an increased odds OR = 1.27, CI = 1.14-1.41; OR = 1.08, CI = 1.01-1.16; and OR = 1.09, CI = 0.99-1.19, respectively, for viral-infection. Moreover, fever, headache, and dry cough were the most frequent symptoms. No infection difference among sex was found. Those patients >60 years old were prone to COVID-19 severity (OR = 3.59, CI = 2.10-6.14), evaluated by the number of manifested symptoms, increasing with age. In conclusion, a high SARS-CoV-2 prevalence was found in Western Mexico. Comorbidities were frequent in infected people; nevertheless, no association with disease outcomes was observed, in contrast with the highest disease severity risk found in older patients; however, continuous monitoring should be carried since comorbidities have been reported as aggravating factors. This study can help the health officials for the elaboration of planning efforts of the disease management and others in the future.

Macrophage migration inhibitory factor gene polymorphisms (SNP -173 G>C and STR-794 CATT5-8) confer risk of plaque psoriasis: A case-control study.

BACKGROUND: Macrophage inhibitory factor (MIF) is a pro-inflammatory cytokine secreted by several cells, including those in the immune system and the skin. The MIF gene contains the SNP -173 G> C and STR -794 CATT5-8 polymorphisms in the promoter region capable of affecting its activity. Our objective was to investigate the MIF polymorphisms as a risk factor for plaque psoriasis (PP) in the Mexican population. METHODS: We genotyped both MIF polymorphism (rs5844572 and rs755622) in 224 PP patients with a clinical and histopathological diagnosis and 232 control subjects (CS) by the PCR-RFLP method. MIF serum levels were determined by an ELISA kit. RESULTS: We found significant differences in the genotypic and allelic frequencies for the MIF -173 G>C polymorphism; carriers of the GC genotype (OR 1.51, 95% CI 1.026-2.228, p = 0.03) and the C allele (OR 1.34, 95% CI 1.005-1.807, p = 0.04) had higher odds to present with PP. Moreover, the 6C haplotype was associated with PP risk (OR 2.10, 95% CI 1.22-3.69, p < 0.01). Also, the -173 CC genotype was associated with high MIF serum levels (p < 0.05). CONCLUSIONS: The -173 GC genotype and the 6C haplotype of the MIF polymorphisms are associated with susceptibility to PP in the Mexican population.

The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.

Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid Arthritis Patients Evaluated by DAS28-ESR.

Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR. METHODOLOGY: 101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0. RESULTS: According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p <0.05). CONCLUSIONS: The results support the need for further study of the role of sCD74 as a soluble MIF decoy receptor, sequestering it to negatively regulate MIF signaling though its membrane receptors. The expression patterns of CXCR4 and CXCR7 show that the latter is a scavenger-type receptor that prevents endocytosis and even degradation of CXCR4 under inflammatory conditions.

Cytokine profiles and clinical characteristics in primary Sjögren´s syndrome patient groups.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease characterized by a lymphocytic infiltrate in salivary glands driving to epithelial damage. The pSS patients present heterogenic clinical and serological characteristics. This heterogenicity could be due to the cytokine microenvironment. Cytokine levels have been analyzed and reported individually, showing controversial results; for that reason, we considered essential to evaluate a cluster of cytokines and relate them with antibody levels and clinical characteristics to find pSS subgroups. METHODS: Ninety-nine pSS patients, diagnosed by the 2016 ACR/EULAR classification criteria, and 76 control subjects (CS) were included. Cytokine quantification was performed by Multiplex assay. Principal component analysis (PCA) was realized, and the K-mean test was used to identify clusters/groups. Groups were analyzed by the Kruskal-Wallis test and the Bonferroni test. RESULTS: Higher IFN-γ, IL-17F, IL-21, IL-23, IL-4, and IL-31 levels were observed in pSS patients in comparison with control subjects. PCA analysis showed three groups. The severe group was characterized by higher cytokine concentrations as well as an increase in clinical parameters such as antibody levels, damage index score, and others. The moderate group presented intermediate severity; meanwhile, the mild group presented the lowest severity. CONCLUSION: Cluster analysis revealed three groups that were different in cytokine levels and clinical parameters in which the mild group was defined by lower severity, the moderate group with intermediate severity, and the severe group with higher severity. This analysis could help subclassify the primary Sjögren syndrome patients for a better understanding of the clinical phenotype that impacts the treatment approach.

Downregulation of Inflammatory Cytokine Release from IL-1ß and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor.

The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1ß stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1ß and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1ß signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1ß-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1ß induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1ß-stimulated PBMC.

Appetite-regulating hormones and anthropometric indicators of infants according to the type of feeding.

It has been accepted that satiety- and appetite-stimulating hormones play a role in the regulation of food intake and body composition during and after the lactation stage. Therefore, the purpose was to demonstrate that serum appetite-regulating hormones in infants differ according to anthropometric indicators and type of feeding. In a nonrandom cohort study, 169 mother-newborn dyads whose pregnancy and birth were attended at the Hospital Civil de Guadalajara were enrolled. According to the type of feeding, infants were classified as full breastfeeding (FBF), partial breastfeeding (PBF), and infants receiving human milk substitutes (HMS). Serum concentrations of ghrelin (pg/ml), leptin (ng/ml), peptide YY (pg/ml), and glucagon-like peptide-1 (GLP-1) (pM) were measured. Anthropometric measurements including weight, length, cephalic, arm circumference, tricipital, and subscapular skinfolds were obtained. Weight/age, weight/height, height/age, and BMI Z-score indexes were estimated. We performed one-way ANOVA, unpaired Student's t test, post hoc Tukey test, and Pearson correlation tests. The ANOVA comparison of the three feeding types showed significant differences in most anthropometric indicators (z-scores), especially between infants receiving FBF versus HMS and particularly on indicators of adiposity; no differences were observed in length and cephalic circumference z-scores at 8th and 16th weeks. Further, significant correlations were found between most of the adiposity indicators with ghrelin, leptin, and GLP-1, especially in infants who received FBF. There were differences in anthropometric and body composition parameters among infants receiving FBF, PBF, and HMS. There were significant correlations between body composition indicators with ghrelin, leptin, and GLP-1 mainly in infants receiving FBF.

Relationship between TNF-α, MMP-8, and MMP-9 levels in gingival crevicular fluid and the subgingival microbiota in periodontal disease.

Periodontitis is modulated by a complex dysbiotic microbiota, these species stimulate upward the production of pro-inflammatory cytokines such as TNF-α, which, in turn, upregulates the production of bone resorption molecules. Enzymes such as MMP-8 and 9 have been associated with the destructive disease. This study evaluated the composition of periodontal microbiota with the checkerboard hybridization technique and its correlation with TNF-α, MMP-8, and MMP-9 evaluated with ELISA, of 80 patients (45 healthy, and 35 with chronic periodontitis). The frequency of the 18 species evaluated was higher in patients with bone loss compared with control group. TNF-α in gingival crevicular fluid was significantly higher in bone loss group (p < 0.01); MMP-8 (p = 0.34) by MMP-9 (p < 0.05) in bone loss group obtained lower values than in control group. Positive correlation of TNF-α was obtained with Aggregatibacter actinomycetemcomitans (rho = 0.38; p < 0.01), Fusobacterium nucleatum (rho = 0.25; p < 0.05) and Porphyromonas gingivalis (rho = 0.26; p < 0.05); negative correlation of MMP-8 with A. actinomycetemcomitans (rho = 0.26; p < 0.01), Capnocytophaga sputigena (rho = 0.33; p < 0.01), and F. nucleatum (rho = 0.21; p < 0.05); also negative correlation of MMP-9 with F. nucleatum (rho = 0.23; p < 0.05), P. gingivalis (rho = 0.23; p < 0.05), and Tannerella forsythia (rho = 0.26; p < 0.01). TNF-α increased due to the increase in each count of A. actinomycetemcomitans (ß = 0.57; p = 0.00). The presence of A. actinomycetemcomitans (ß = 1.88; p = 0.00), Campylobacter rectus (ß = 0.78; p = 0.01), F. nucleatum (ß = 0.65; p = 0.04), and P. gingivalis (ß = 0.65; p = 0.04) significantly increases TNF-α levels. TNF-α in gingival crevicular fluid, despite the minimal amounts collected, is a good biomarker of periodontal disease; since levels of TNF-α increases with the increase of the most harmful species to the periodontium.

Concentration of ghrelin and leptin in serum and human milk in nursing mothers according to the type of feeding / Concentración de grelina y leptina en suero y leche humana en madres lactantes según el tipo de alimentación

Objective: we assessed the relationship between serum and human foremilk and hindmilk concentrations of ghrelin and leptin in nursing mothers according to the type of feeding. Methods: this cohort design was carried out on 131 mother-newborn dyads admitted to a physiological puerperium ward. The independent variables were the type of feeding, full breastfeeding (FBF, 56.5%) and partial breastfeeding (PBF, 43.5%). The dependent variables were the concentration of total ghrelin (pg/ml) and leptin (ng/ml) in serum, foremilk and hindmilk at eight and 16 weeks. Fasting blood samples were obtained from the nursing mothers at four months for serum assays. Unpaired Student's t-test, Mann-Whitney U test, Pearson's correlation tests, coefficient of determination and linear regression were used. Results: the concentration of ghrelin and leptin in hindmilk was higher than that of foremilk in both groups at eight and 16 weeks. The concentration of ghrelin and leptin was higher in serum than in foremilk in both groups. These values showed a direct and significant linear correlation with the exception of ghrelin in the FBF group. The serum concentration of leptin in mothers explained 32% of the variance of its concentration in foremilk in the FBF and 13% in the PBF groups. Conclusion: the hindmilk/foremilk gradient suggests an intake regulating mechanism during the fed. The concentration of ghrelin and leptin was higher in the serum than in foremilk and its correlation and determination coefficients could suggest plasma-milk transfer in addition to synthesis regulation by the mammary gland, adipose tissue or other organs

Objetivo: evaluar la relación entre la concentración de suero y la leche materna y la concentración de grelina y leptina en leche materna en madres lactantes según el tipo de alimentación. Métodos: diseño de cohorte realizado en 131 diadas madre-lactante que ingresaron en una sala de puerperio fisiológico. Variables independientes: tipo de alimentación, lactancia materna completa (LMC, 56,5%) y lactancia materna parcial (LMP, 43,5%). Variables dependientes: concentración sérica de grelina total (pg/ml) y leptina (ng/ml), leche humana pre-tetada y pos-tetada a las ocho y 16 semanas. Se utilizaron pruebas no pareadas t de Student, U de Mann-Whitney, correlación de Pearson, coeficiente de determinación y regresión linear. Resultados: la concentración de grelina y leptina en leche humana pre-tetada fue mayor que en leche humana pos-tetada en ambos grupos a las ocho y 16 semanas. La concentración de grelina y leptina fue mayor en suero que en leche humana en ambos grupos; estos valores mostraron una correlación lineal directa y significativa con la excepción de la grelina en el grupo de LMC. La concentración sérica de leptina en las madres explicó el 32% de la varianza de su concentración en leche humana en LMC y el 13% en madres en LMP. Conclusión: el gradiente de leche humana pre-tetada/pos-tetada sugiere un mecanismo de regulación e ingestión de leche. La concentración de grelina y leptina fue mayor en suero que en leche humana y los coeficientes de determinación sugieren una transferencia de suero-leche, además de una regulación de la síntesis por la glándula mamaria, el tejido adiposo u otros órganos