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1.
Lett Appl Microbiol ; 77(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38755018

RESUMO

Our study aimed to identify markers of enterococci's virulence potential by evaluating the properties of strains of different sites of isolation. Enterococcal strains were isolated as commensals from faeces and as invasive strains from the urine and blood of patients from the University Clinical Centre, Gdansk, Poland. Changes in monocytes' susceptibility to the cytotoxic activity of isolates of different origins and their adherence to biofilm were evaluated using a flow cytometer. The bacterial protein profile was estimated by matrix assisted laser desorption ionization-time of flight mass spectrometer. The cytotoxicity of biofilm and monocytes' adherence to it were the most accurate factors in predicting the prevalence of the strain in the specific niche. Additionally, a bacterial protein with mass-to-charge ratio (m/z) 5000 was found to be responsible for the increased bacterial cytotoxicity, while monocytes' decreased adherence to biofilm was linked with the presence of proteins either with m/z 3330 or 2435. The results illustrate that monocytes' reaction when exposed to the bacterial biofilm can be used as an estimator of pathogens' virulence potential. The observed differences in monocytes' response are explainable by the bacterial proteins' profile. Additionally, the results indicate that the features of both bacteria and monocytes impact the outcome of the infection.


Assuntos
Biofilmes , Monócitos , Biofilmes/crescimento & desenvolvimento , Monócitos/microbiologia , Humanos , Virulência , Aderência Bacteriana , Infecções por Bactérias Gram-Positivas/microbiologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Enterococcus/patogenicidade , Polônia , Fezes/microbiologia
2.
Int J Mol Sci ; 25(6)2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38542357

RESUMO

Rheumatoid arthritis (RA) is a chronic, autoimmune disease with a complex outset. Besides the genetic susceptibility in its pathogenesis, various environmental factors also participate. Of these, in recent years, there have been increasing reports of the involvement of bacteria in the disease's outset and development, especially gut microbiota and oral pathogens. Most recent reports about bacteria participation in RA pathogenesis focus on Prevotella copri and Porphyromonas gingivalis. There are also reports about the involvement of respiratory and urinary tract pathogens. The exact mechanisms leading to RA development used by bacteria are not well known; however, some mechanisms by which bacteria can interact with the immune system are known and can potentially lead to RA development. The aim of this study is to provide a comprehensive review of the potential bacteria participating in RA development and the mechanism involved in that process.


Assuntos
Artrite Reumatoide , Doenças Transmissíveis , Microbioma Gastrointestinal , Humanos , Porphyromonas gingivalis , Doenças Transmissíveis/complicações , Predisposição Genética para Doença
3.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36769212

RESUMO

We have shown before that at least one intracellular proteolytic system seems to be at least as abundant in the peripheral blood lymphocytes of centenarians as in the same cells of young individuals (with the cells of the elderly population showing a significant dip compared to both young and centenarian cohorts). Despite scarce published data, in this review, we tried to answer the question how do different types of cells of longevous people-nonagenarians to (semi)supercentenarians-maintain the quality and quantity of their structural and functional proteins? Specifically, we asked if more robust proteodynamics participate in longevity. We hypothesized that at least some factors controlling the maintenance of cellular proteomes in centenarians will remain at the "young" level (just performing better than in the average elderly). In our quest, we considered multiple aspects of cellular protein maintenance (proteodynamics), including the quality of transcribed DNA, its epigenetic changes, fidelity and quantitative features of transcription of both mRNA and noncoding RNAs, the process of translation, posttranslational modifications leading to maturation and functionalization of nascent proteins, and, finally, multiple facets of the process of elimination of misfolded, aggregated, and otherwise dysfunctional proteins (autophagy). We also included the status of mitochondria, especially production of ATP necessary for protein synthesis and maintenance. We found that with the exception of the latter and of chaperone function, practically all of the considered aspects did show better performance in centenarians than in the average elderly, and most of them approached the levels/activities seen in the cells of young individuals.


Assuntos
Centenários , Longevidade , Idoso , Idoso de 80 Anos ou mais , Humanos , Longevidade/genética
4.
Eat Weight Disord ; 27(7): 2759-2773, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35691007

RESUMO

BACKGROUND: One of the environmental factors contributing to abnormal weight changes in children may be maternal exposure to adverse environmental factors during pregnancy, which in previous studies led to inconclusive results showing both overweight or obesity and underweight in children. The aim of the study was to assess the influence of prenatal stress on the BMI status and cut-off points for the percentage of fat content. METHODS: The cohort study included 254 girls and 276 boys. Information on prenatal stress was collected retrospectively with a questionnaire on objective adverse events completed by a parent/guardian of a 6-12-year-old child. We examined the body weight of children and performed an electrical bioimpedance analysis of their body composition. We assessed the BMI status according to the International Obesity Task Force (IOTF) criterion and on the basis of body fat according to McCarthy criterion. RESULTS: The results of our study show that the prenatal stress was related to increased risk of overweight (OR 2.14, 95% CI: 1.25-3.65) diagnosed on the basis of body fat cut-off points, but not when the BMI was a diagnostic criterion (OR 1.03, 95% CI: 0.58-1.83). CONCLUSION: The method of diagnosis based on the fat content appears to be an indicator of the occurrence of abnormalities in body composition due to prenatal stress more sensitive than that based on the BMI. LEVEL OF EVIDENCE: Level III evidence obtained from well-designed cohort or case-control analytic studies.


Assuntos
Sobrepeso , Obesidade Infantil , Tecido Adiposo , Índice de Massa Corporal , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Sobrepeso/epidemiologia , Prevalência , Estudos Retrospectivos
5.
Eat Weight Disord ; 27(5): 1751-1763, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34661883

RESUMO

PURPOSE: The aim of the study was to test the hypothesis that adverse childhood experiences (ACEs) are related to both obesity and underweight from childhood, and that the association of ACEs with weight abnormalities is modulated by type of ACEs, sex and socioeconomic status (SES) indices. METHODS: The relations between ACEs (0 vs ≥ 1), ACE accumulation and ACE type with weight status and z scores BMI were assessed in 503 children aged 6-12 years from Poznan, Poland. The effects of interaction of ACEs with sex and SES on z scores BMI were included in the analyses. RESULTS: ACEs were significantly related to both obesity and underweight, in unadjusted analysis, and when sex and SES indices, such as size of place of residence, people per room in household, and parental education were controlled. The relation of ACEs with z scores BMI was modulated by ACE type, parental subjective assessment of economic situation of a family and parental education. ACE accumulation was not related to an increase of obesity or underweight rate, or z scores BMI. CONCLUSION: The study implicates the need for both obesity and underweight prevention in individuals with adverse experiences as early as in childhood. LEVEL OF EVIDENCE: III: evidence obtained from well-designed cohort study.


Assuntos
Experiências Adversas da Infância , Criança , Estudos de Coortes , Escolaridade , Humanos , Obesidade , Magreza
6.
Mediators Inflamm ; 2021: 3639441, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35110971

RESUMO

BACKGROUND: The use of easily accessible biomarkers for assessing young patients' health is weighty. This cohort study is aimed at measuring stress/immune biomarkers in the saliva of healthy school-age children and comparing subgroups according to age, sex, and stress perception. Material and Methods. 503 children under 12 years old (8.7 ± 1.3) were included with anthropometric evaluation (height, waist, hip circumference, body weight, and body mass index (BMI)). Levels of opiorphin (OPI), free cortisol, alpha-amylase (sAA), and secreted immunoglobulin (sIgA) were determined by quantitative assays (ELISA) in unstimulated saliva. Unpaired t-test, Welch test, and Mann-Whitney U test were applied for appropriate group comparisons, and the correlation between variables was analyzed with Spearman's rank coefficient. Results were considered significant at p < 0.05. RESULTS: sIgA and sAA exhibited significant differences depending on age and sex: IgA (ng/mL): 86 ± 68.6 vs. 104.9 ± 72.1 for (6-7 y.o.) and (8-11 y.o.), respectively, and 108.1 ± 80.1 vs. 94.6 ± 62.2 for male and females, respectively; sAA (U/mL): 78.9 ± 54.4 vs. 100.5 ± 81.2 for (6-7 y.o.) and (8-11 y.o.). No difference related to age or sex between groups was observed for cortisol and OPI. However, OPI levels were higher and correlated to prior stress exposure in children (0.31 ± 0.4 vs. 0.26 ± 0.5 ng/mL, p = 0.031). sAA was negatively correlated to low mood self-declaration in children in the last two weeks (r = -0.10, p = 0.045). CONCLUSIONS: sIgA and sAA can be used as sex- and age-related biomarkers in children 6-12 y.o., which is not the case for free cortisol and opiorphin. However, OPI reflected previous exposure to stress, suggesting its use for evaluating stress-related changes in children.


Assuntos
Amilases , Hidrocortisona , Biomarcadores/análise , Criança , Estudos de Coortes , Feminino , Humanos , Hidrocortisona/análise , Imunoglobulina A , Masculino , Oligopeptídeos , Percepção , Estudos Prospectivos , Saliva/química , Proteínas e Peptídeos Salivares , Estresse Psicológico
7.
Cent Eur J Immunol ; 46(3): 405-417, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764816

RESUMO

Mammalian target of rapamycin (mTOR) inhibitors inclusive regimens are associated with increased risk of pulmonary toxicity, but the underlying mechanism has not been elucidated so far. We present the case of a 68-year-old man, after deceased-donor kidney transplantation (KTx), maintained on de novo everolimus (EVR) based immunosuppression, who developed Achromobacter denitrificans pneumonia 3 months after KTx. There was clinical improvement with antibiotic treatment, but without a radiological resolution. An additional reduction of the EVR dose resulted only in partial resolution of radiological abnormalities. We performed a functional analysis of peripheral blood neutrophils and monocytes. The ability of phagocytosis and oxidative burst generation against A. denitrificans and Escherichia coli was significantly decreased on EVR treatment as compared to the control healthy person, and significantly improved after 3 weeks of EVR absence. Additionally, these processes were significantly affected by increasing doses of EVR in vitro in the control healthy donor in a dose-dependent manner. EVR discontinuation, with no additional antibiotic treatment, resulted in complete recovery and resolution of pulmonary infiltrates. Our findings suggest that dose-dependent impairment of neutrophil/monocyte phagocytic activity and oxidative burst generation might be a potential mechanism for EVR pulmonary toxicity.

8.
Cent Eur J Immunol ; 45(4): 488-493, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33613097

RESUMO

Alterations in composition of human gut microbiome can lead to its dysbiosis. It is associated with gastrointestinal side effects during anti-cancer treatment, antibiotics administration, or infectious agents. There are studies confirming positive effect of consuming Lactobacillus plantarum 299v on intestinal microflora. This review summarizes the current knowledge about the role of L. plantarum 299v in supporting treatment of selected diseases, such as cancer, irritable bowel syndrome (IBS), and Clostridium difficile infection. The immunomodulating properties of L. plantarum 299v include an increase in the level of anti-inflammatory cytokines, which reduce the risk of cancer and improve the efficacy of regimens. The intake of L. plantarum 299v provides benefits for IBS patients, mainly due to normalization of stool and relief of abdominal pain, which significantly improves the quality of life of IBS patients. In addition, the intake of L. plantarum 299v prevents C. difficile-associated diarrhea among patients receiving antibiotic treatment. Due to the limited possibilities of treating these diseases and numerous complications of cancer treatment, there is a need for new therapeutic strategies. The administration of L. plantarum 299v seems to be useful in these cases.

9.
Cytokine ; 116: 128-133, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30711852

RESUMO

Autoimmune thyroid disease (ATD) is a chronic autoimmune thyroiditis with a complex pathogenesis including environmental factors, genetic background and immune system actions. Despite the large-scale research and discovery of new subpopulations of lymphocytes, cytokines, chemokines and their functions in the human body, the ethiology of ATD in many aspects remains a mystery. This article tries to summarize mostly the immunological aspects of this disease, including the roles of different cells types (dendritic cells, B cells, CD4+ and CD8+ T cells, NK cells and regulatory T cells) and of different cytokines (secreted by Th1/Th2/Th17/Th22 lymphocyte subpopulations and other, including the IL-23 and CXCL10). We describe the role of immunological abnormalities in the ATD pathogenesis and show that for some cells and cytokines their respective roles are not clear, and bi-directional action is possible. Finally, we propose a network of interactions between the immune cells and thyrocytes in the course of ATD.


Assuntos
Citocinas/imunologia , Células Dendríticas/imunologia , Doença de Hashimoto/imunologia , Linfócitos/imunologia , Células Epiteliais da Tireoide/imunologia , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Citometria de Fluxo , Doença de Hashimoto/patologia , Humanos , Células Matadoras Naturais/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia
10.
Pediatr Endocrinol Rev ; 16(3): 383-400, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30888128

RESUMO

Thirty-one scientists met at Aschauhof, Germany to discuss the role of beliefs and self-perception on body size. In view of apparent growth stimulatory effects of dominance within the social group that is observed in social mammals, they discussed various aspects of competitive growth strategies and growth adjustments. Presentations included new data from Indonesia, a cohort-based prospective study from Merida, Yucatan, and evidence from recent meta-analyses and patterns of growth in the socially deprived. The effects of stress experienced during pregnancy and adverse childhood events were discussed, as well as obesity in school children, with emphasis on problems when using z-scores in extremely obese children. Aspects were presented on body image in African-American women, and body perception and the disappointments of menopause in view of feelings of attractiveness in different populations. Secular trends in height were presented, including short views on so called 'racial types' vs bio-plasticity, and historic data on early-life nutritional status and later-life socioeconomic outcomes during the Dutch potato famine. New tools for describing body proportions in patients with variable degrees of phocomelia were presented along with electronic growth charts. Bio-statisticians discussed the influence of randomness, community and network structures, and presented novel tools and methods for analyzing social network data.

11.
Cytokine ; 97: 1-13, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28551592

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of cytokine concentrations in sera and mononuclear cell supernatants in order to examine inter- and intra-individual cytokine variations in undifferentiated arthritis progressing to rheumatoid arthritis and healthy control groups. METHODS: Patients with UA (undifferentiated arthritis) developing RA (rheumatoid arthritis) (UA→RA) (n=16) and healthy controls (n=16) were enrolled into the study. UA→RA patients were followed up for six months since the final RA diagnosis. Cytokines IFN-γ, IL-10, TNF, IL-17A, IL-6, IL-1ß, IL-2 in sera and mononuclear cell supernatants in 72h and 120h culture variants with- and without anti-CD3 stimulations were assayed using flow cytometric bead array. RESULTS: The cytokine profile of UA→RA differs from the healthy individual cytokine profile. It is possible to observe specific cytokine pattern characterizing each patient, which alters during course of disease. Specifically, we can distinguish three UA→RA cohorts: the group of patients susceptible to the therapy, characterized by the drop of cytokine levels between 1st and 3rd visit with visible decrease of cytokines in 2nd visit and then secondary slighter increase in 3rd visit; the group of patients refractory or clinically worsening on the therapy, characterized by the highest cytokine levels at 2nd visit with secondary decrease in 3rd visit; and the group of patients with variable responses to the therapy without any specific common cytokine pattern. The cytokine patterns in supernatants of PBMC stimulated anti-CD3 for 72h and 120h are very similar. CONCLUSIONS: The personal profile including multiplexed cytokine patterns in serum and supernatant may be potentially used for optimization of therapy introduction and monitoring.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Artrite/imunologia , Citocinas/análise , Citocinas/sangue , Adulto , Artrite/tratamento farmacológico , Artrite/fisiopatologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Biomarcadores/análise , Biomarcadores/sangue , Células Cultivadas , Meios de Cultura , Progressão da Doença , Feminino , Humanos , Interferon gama/análise , Interferon gama/sangue , Interleucina-10/análise , Interleucina-10/sangue , Interleucina-17/análise , Interleucina-17/sangue , Interleucina-2/análise , Interleucina-2/sangue , Interleucina-6/análise , Interleucina-6/sangue , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Medicina de Precisão
12.
Postepy Hig Med Dosw (Online) ; 71(1): 797-810, 2017 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-28894040

RESUMO

Witamina D, poza istotna rola w utrzymaniu homeostazy wapnia i metabolizmie kostnym, odgrywa wazna role w funkcjonowaniu ukladu odpornosciowego. Niedobór witaminy D wiaze sie z wieloma niekorzystnymi dla zdrowia skutkami, wlaczajac w to m.in. oslabienie odpornosci, czego skutkiem jest zwiekszona podatnosc na zakazenia wirusowe, bakteryjne oraz grzybicze. W artykule opisano podstawy metabolizmu witaminy D oraz jej role fizjologiczna, ze szczególnym uwzglednieniem wplywu na komórki ukladu odpornosciowego. Ze wzgledu na jej istotna role w regulacji odpowiedzi zapalnej oraz wytwarzaniu cytokin zwraca sie uwage na jej role w rozwoju chorób o podlozu autoimmunologicznym, takich jak cukrzyca typu 1, toczen rumieniowaty, reumatoidalne zapalenie stawów, stwardnienie rozsiane, nieswoiste zapalenia jelit, luszczyca, bielactwo, czy twardzina, w których witamina D ma potencjalne szerokie zastosowanie zarówno w prewencji, jak i wspomaganiu dzialan terapeutycznych.


Assuntos
Doenças Autoimunes , Vitamina D , Humanos , Vitaminas
13.
Cent Eur J Immunol ; 42(3): 259-268, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29204090

RESUMO

INTRODUCTION: Currently used clinical scale and laboratory markers to monitor patients with early rheumatoid arthritis (RA) seem to be not sufficient. It has been demonstrated that disease- related cytokines may be elevated very early in RA development and cytokines are considered as the biomarkers potentially useful for RA monitoring. MATERIAL AND METHODS: The group of patients with undifferentiated arthritis (UA) developing RA (UA→RA) was identified from a total of 121 people with arthralgia. UA→RA (n = 16) and healthy control (n = 16) subjects underwent clinical and laboratory evaluation, including acute phase reactants (APRs) and autoantibodies. Cytokines IFN-γ, IL-10, TNF, IL-17A, IL-6, IL-1b, IL-2 in sera were assayed using flow cytometric bead array test. RESULTS: 34.5% of patients with UA developed RA. DAS28 reduced as early as 3 months after initiation of treatment. No DAS28 difference between groups of autoantibody (RF, anti-CCP, ANA-HEp-2) -positive and -negative patients was observed, however, comparing groups of anti-CCP and RF-double negative and -double positive patients, the trend of sooner clinical improvement was visible in the second abovementioned group. After the treatment introduction, the ESR level reduced significantly, while CRP level reduction was not significant. Serum cytokine levels of IL-10, IL-6 and IL-17A reduced after 6 months since introduction of treatment. The positive correlations between ESR, CRP and specific cytokine levels were observed. CONCLUSIONS: The autoantibody and APR profile is poorly connected with the RA course. The serum cytokine profile change in the course of RA and may be potentially used for optimization of RA monitoring.

14.
Cytokine ; 76(2): 527-536, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26321413

RESUMO

Rheumatoid arthritis (RA), as a common chronic disease leading to severe disability, requires early diagnosis and introduction of proper treatment. Deregulation in the cytokine network plays an undoubtedly crucial role in the pathogenesis of RA. The understanding of the role of cytokines in RA can be used for patients' benefit. Technological advances had already allowed introduction of the tailor-made cytokine-targeted therapies (so far anti-TNF, anti-IL-1 and anti-IL-6) into clinical practice. This type of treatment is currently developing very fast. Moreover, cytokines are considered to be potential powerful biomarkers of RA with roles predicted to grow in the future. Detailed understanding of the cytokine balance in RA may assist both the diagnostic process and therapy.


Assuntos
Artrite Reumatoide/fisiopatologia , Biomarcadores/metabolismo , Citocinas/fisiologia , Medicina de Precisão , Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos
15.
Inflamm Res ; 63(2): 99-103, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24189710

RESUMO

OBJECTIVE: Immunodeficiency of end-stage renal disease (ESRD) is caused by several factors including uremic toxins and biocompatibility reactions due to the repeated hemodialysis (HD) procedure. It has also been suggested that poor T cell responses could be associated with the increased number of regulatory T cells (Tregs) which are necessary to limit the function of activated T cells. The aim of the study was to determine the proportion of CD4(+)CD25(+) cells (activated T cells) to CD4(low)CD25(high) cells (Tregs) within the CD4(+) population in ESRD patients. PATIENTS AND METHODS: Two groups of ESRD patients, predialysis patients treated conservatively and patients undergoing hemodialysis (HD), as well as healthy controls were included in the study. Percentages of activated and regulatory T cells were determined ex vivo with flow cytometry based on the expression of CD4 and CD25 antigens. RESULTS AND CONCLUSIONS: HD patients showed an increased percentage of CD4(+)CD25(+) cells when compared with healthy controls, while there was no difference in the percentage of CD4(low)CD25(high) cells between the patient groups. In our opinion, the repeated hemodialysis procedure significantly disturbs the balance between activated T cells and regulatory T cells in ESRD patients. Lack of Treg mobilization and chronic stimulation of T cells may contribute to the immune deficiency observed in these patients.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Falência Renal Crônica/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Linfócito CD4 , Feminino , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Masculino , Pessoa de Meia-Idade , Diálise Renal , Adulto Jovem
16.
Nutrients ; 16(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474814

RESUMO

The gut microbiome may contribute to the development of autoimmune diseases, such as autoimmune thyroiditis (AIT). Diet has a critical impact on the gut microbiome, and it has been shown that a gluten-free diet can negatively affect its composition. A gluten-free diet is popular among patients, and therefore the aim of this study was to check whether it affects thyroid function and gut microbiome composition in AIT. Thirty-one women with AIT complied with a gluten-free diet for 8 weeks. After the first 4 weeks, participants were divided into two groups: the first group received gluten in capsules and the other one-rice starch (placebo). Blood and stool samples were examined before diet (T0), after 4 weeks (T1) and after 8 weeks of diet (T2). The only significant difference in blood parameters was observed between T1 and T2 in the placebo group for the thyroid peroxidase antibody level. After the first 4 weeks, a significant increase in Desulfobacterota, Proteobacteria, Prevotella and Parasutterella and a significant decrease in Actinobacteriota, Coriobacteriaceae and Bifidobacterium were observed. The detected microbiome alterations may indicate increasing inflammation; however, further research is required, and for now, a gluten-free diet should be used cautiously in AIT.


Assuntos
Microbioma Gastrointestinal , Doença de Hashimoto , Tireoidite Autoimune , Humanos , Feminino , Dieta Livre de Glúten , Glutens
17.
J Clin Immunol ; 33(3): 661-5, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23180360

RESUMO

Recombinant human erythropoietin (rhEPO) treatment of hemodialyzed (HD) patients normalizes the altered phenotype of CD4(+) lymphocytes and restores the balance of Th1/Th2 cytokines. We decided to test how the presence of rhEPO in cell culture modulates cytokine production of CD4(+) lymphocytes in HD patients with stable hemoglobin level and expression of activation antigens of stimulated CD4(+) lymphocytes similar to those observed in healthy individuals. We also tested whether the presence of rhEPO in cell culture protects stimulated CD4(+) lymphocytes of HD patients from apoptosis. Peripheral blood mononuclear cells (PBMC) of HD patients were stimulated with an immobilized anti-CD3 antibody with or without addition of rhEPO. The percentage of apoptotic CD4(+) lymphocytes and the level of Th1/Th2 cytokines in culture supernatants were measured with flow cytometry. HD patients showed a decrease in the percentage of apoptotic CD4(+) cells after stimulation with the anti-CD3 antibody combined with rhEPO. The level of IFN-γ and IL-10 was increased while the level of TNF-α was decreased in the presence of rhEPO in cell culture from HD patients. These results confirm the role of rhEPO signaling in T lymphocytes of HD patients.


Assuntos
Apoptose/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Citocinas/biossíntese , Eritropoetina/farmacologia , Diálise Renal , Idoso , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes
18.
Immun Ageing ; 10(1): 27, 2013 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-23835405

RESUMO

BACKGROUND: Ubiquitous system of regulatory, calcium-dependent, cytoplasmic proteases - calpains - and their endogenous inhibitor - calpastatin - is implicated in the proteolytic regulation of activation, proliferation, and apoptosis of many cell types. However, it has not been thoroughly studied in resting and activated human lymphocytes yet, especially in relation to the subjects' ageing process. The CALPACENT project is an international (Polish-Italian) project aiming at verifying the hypothesis of the role of calpains in the function of peripheral blood immune cells of Polish (Pomeranian) and Italian (Sicilian) centenarians, apparently relatively preserved in comparison to the general elderly population. In this preliminary report we aimed at establishing and comparing the baseline levels of expression of µ- and m-calpain and calpastatin in various, phenotypically defined, populations of human peripheral blood lymphocytes for healthy elderly Sicilians and Poles, as compared to these values observed in young cohort. RESULTS: We have found significant differences in the expression of both µ- and m-calpain as well as calpastatin between various populations of peripheral blood lymphocytes (CD4+, CD8+ and CD19+), both between the age groups compared and within them. Interestingly, significantly higher amounts of µ- and m-calpains but not of calpastatin could be demonstrated in the CD4+CD28- and CD8+CD28- lymphocytes of old subjects (but not in the cells of young individuals), as compared to their CD28+ counterparts. Finally, decreased expression of both calpains in the elderly T cells is not related to the accumulation of effector/memory (CD45RO+) cells in the latter, as the expression of both calpains does not differ significantly between the naïve and memory T cells, while is significantly lower for elderly lymphocytes if both populations are taken separately. CONCLUSIONS: Observed differences in the amounts of CCS member proteins between various populations of lymphocytes of young and elderly subjects may participate in the impaired proliferative activity of these cells in the elderly.

19.
J Physiol Anthropol ; 42(1): 29, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066615

RESUMO

BACKGROUND: Overweight and obesity among children have become significant global health concerns. Previous studies have highlighted the potential role of genetic factors, particularly polymorphisms in the FTO and MC4R genes, as well as environmental factors in the development of childhood obesity. This study aimed to investigate the relationships between genetic, socioeconomic and perinatal factors, adverse childhood events (ACEs), and lifestyle, and their impact on overweight, obesity and body composition parameters in children. Additionally, we explored potential interactions between genetic factors and ACEs. METHODS: Four hundred fifty-six children aged 6-12 years participated in our study. Information on the socioeconomic status, perinatal factors, ACEs and lifestyle of the children was collected with a questionnaire completed by their parents/guardians. We examined the children's body weight and conducted an electrical bioimpedance analysis. Overweight and obesity were diagnosed based on the International Obesity Task Force and McCarthy criteria. We genotyped two selected polymorphisms in the FTO and MC4R genes using the TaqMan SNP allelic discrimination method. RESULTS: Higher BMI (Body Mass Index) z scores were related to higher paternal BMI and lower maternal age at the child's birth. Higher FMI (Fat Mass Index) z scores were associated with higher paternal BMI, increased gestational weight, lower maternal education and the presence of the FTO risk allele. Higher FatM (fat mass in kg) z scores were linked to lower maternal education, lower maternal age at the child's birth, higher maternal body weight gain, paternal BMI and the presence of the FTO risk allele. Moreover, interaction effects were observed on BMI z scores between ACE and FTO AA, and on FMI z scores and FatM z scored between ACE and MC4R CC. CONCLUSIONS: The contribution of environmental factors is more strongly related to changes in body composition than genetic ones. Additionally, the presence of the risk allele combined with unfavourable environmental factors like ACEs leads to visible interaction effects, resulting in increased BMI z scores and FMI z scores in children.


Assuntos
Adiposidade , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Índice de Massa Corporal , Sobrepeso , Obesidade Infantil , Criança , Feminino , Humanos , Gravidez , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Predisposição Genética para Doença , Genótipo , Sobrepeso/epidemiologia , Sobrepeso/genética , Obesidade Infantil/epidemiologia , Obesidade Infantil/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 4 de Melanocortina/genética , Adiposidade/genética
20.
Sci Rep ; 13(1): 12148, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37500688

RESUMO

The FTO gene rs9936909 polymorphism is one of the well-documented single nucleotide polymorphisms in the context of increased risk of obesity, including in children. Few studies have tested the association of the FTO gene with cognitive functions. Deficits of "cool" executive functions (EFs) are considered a potential risk factor for excessive weight. The aims of our study were to investigate whether cool EFs are associated with the Body Mass Index, the Fat Mass Index and the risk of excess body mass and overfatness in neurotypically school-aged children, and whether the FTO gene polymorphism is involved in development of this possible association. The sample consisted of 553 children aged 6-12 years old. A body composition analysis, a neuropsychological assessment of EFs, and FTO polymorphism genotyping were performed in the children studied. The study found a significant association of an interference effect in theStroop Color-Word Interference Task and the risk of excessive body fatness, but not excessive body mass. There were no explicit associations between the FTO genotype and EFs deficits. Environmental factors, and particularly low maternal education, appeared to be the strongest contributors to the increased risk of obesity.


Assuntos
Adiposidade , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Função Executiva , Criança , Humanos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Obesidade Infantil/genética
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