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.
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.
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.
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.
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.
•Flaxseed supplementation may improve glycemic control in prediabetes and type 2 diabetes mellitus.•Flaxseed supplementation may improve insulin concentrations and insulin resistance in prediabetes and type 2 diabetes mellitus.•Further studies are needed to address methodological aspects, such as the administration, dosage, and the combined effect with other treatments.
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)-1β 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-1β 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 (
< 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (
< 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-1β induced a sustained cytokine production (
< 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC.
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.
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.
Principal component analysis of 14 cytokines was realized to determine the cytokine groups in primary Sjögren´s syndrome patients. The mild group was characterized by less severity of the disease with low cytokine levels and fewer clinical parameters; the moderate group included patients with intermediate severity, presented higher cytokine levels than the mild group but less than severe group. Patients of the severe group showed higher severity, higher cytokine levels, and clinical parameters.
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.
Summary of key results from this study. (1) “Linkage disequilibrium was identified between ‐173 G>C and STR‐794 CATT5‐8 polymorphisms (D′ value = 0.62, r2 = 0.17, p < 0.001, Figure 1). (2) “the ‐173 CC genotype was associated with high MIF serum levels ". (3) "The ‐173 GC genotype and the 6C haplotype of the MIF polymorphisms are associated with susceptibility to PP in the Mexican population". (4) "overproduction of MIF may be important in mediating pathogenic effects in psoriasis".
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-1β, 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.
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
(
β
= 0.57;
p
= 0.00). The presence of
A. actinomycetemcomitan
s (
β
= 1.88;
p
= 0.00),
Campylobacter rectus
(
β
= 0.78;
p
= 0.01),
F. nucleatum
(
β
= 0.65;
p
= 0.04), and
P. gingivalis
(
β
= 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.
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.
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
and
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
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
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
variant was found in any of the studied populations.
Introduction
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, ...IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity.
Methodology
This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI).
Results
The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (
p
< 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (
p
< 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices.
Conclusions
Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity.
Key Points
• IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease.
• RF, anti-CCP, and anti-MCV had higher levels in early than established RA.
• IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker.
• Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15.
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