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1.
Geroscience ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720047

RESUMO

Emerging evidence indicates an association between blood pressure and inflammation, yet this relationship remains unclear in older adults, despite the elevated prevalence of hypertension. We investigated the association between blood pressure, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and white blood cell (WBC) count in a cohort of 3571 older adults aged 65 and above, and 587 middle-aged participants (55-59 years old). In women aged 65 and above, the relationship between inflammatory markers and blood pressure was consistent, with hs-CRP and WBC emerging as predictors of high blood pressure. For hs-CRP, the adjusted odds ratio (OR) was 1.5 (95% CI, 1.07 to 2.10, P = 0.02), and for WBC, the adjusted OR was 1.41 (95% CI, 1.02 to 1.94, P = 0.04), comparing the highest to the lowest quartiles. In men, only the WBC count was significantly associated with an increased OR for high BP (adjusted OR 1.49, 95% CI, 1.09 to 2.02, P = 0.01) across quartiles. Across the entire study population, in a fully adjusted model, all inflammatory markers were modestly associated with blood pressure levels, while the effect of being over 65 years was the most significant predictor of high blood pressure (OR 1.84, 95% CI, 1.50 to 2.25, P < 0.001). The link between key inflammation markers and blood pressure in older adults varies by sex and biomarker type and may differ from the relationship observed in younger individuals. These relationships are likely to be affected by factors linked to age.

2.
Int J Mol Sci ; 25(10)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38791098

RESUMO

The similarity of the clinical picture of metabolic syndrome and hypercortisolemia supports the hypothesis that obesity may be associated with impaired expression of genes related to cortisol action and metabolism in adipose tissue. The expression of genes encoding the glucocorticoid receptor alpha (GR), cortisol metabolizing enzymes (HSD11B1, HSD11B2, H6PDH), and adipokines, as well as selected microRNAs, was measured by real-time PCR in adipose tissue from 75 patients with obesity, 19 patients following metabolic surgery, and 25 normal-weight subjects. Cortisol levels were analyzed by LC-MS/MS in 30 pairs of tissues. The mRNA levels of all genes studied were significantly (p < 0.05) decreased in the visceral adipose tissue (VAT) of patients with obesity and normalized by weight loss. In the subcutaneous adipose tissue (SAT), GR and HSD11B2 were affected by this phenomenon. Negative correlations were observed between the mRNA levels of the investigated genes and selected miRNAs (hsa-miR-142-3p, hsa-miR-561, and hsa-miR-579). However, the observed changes did not translate into differences in tissue cortisol concentrations, although levels of this hormone in the SAT of patients with obesity correlated negatively with mRNA levels for adiponectin. In conclusion, although the expression of genes related to cortisol action and metabolism in adipose tissue is altered in obesity and miRNAs may be involved in this process, these changes do not affect tissue cortisol concentrations.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1 , Hidrocortisona , MicroRNAs , Obesidade , Receptores de Glucocorticoides , Humanos , Hidrocortisona/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Obesidade/metabolismo , Obesidade/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Tecido Adiposo/metabolismo , Gordura Intra-Abdominal/metabolismo , Regulação da Expressão Gênica , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Desidrogenases de Carboidrato
3.
Proc Natl Acad Sci U S A ; 121(22): e2310864121, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38781213

RESUMO

IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals and that single-nucleotide polymorphisms in IL33 and IL1RL1 were associated with pneumococcal pneumonia in humans. The effect of IL-33 on S. pneumoniae infection was mediated by negative regulation of IL-22 production in innate lymphoid cells (ILCs) but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33's influence on IL-22-dependent antibacterial defense was dependent on housing conditions of the mice and mediated by IL-33's modulatory effect on the gut microbiota. Collectively, we provide insight into the bidirectional crosstalk between the innate immune system and the microbiota. We conclude that both genetic and environmental factors influence the gut microbiota, thereby impacting the efficacy of antibacterial immune defense and susceptibility to pneumonia.


Assuntos
Imunidade Inata , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina 22 , Interleucina-33 , Interleucinas , Streptococcus pneumoniae , Animais , Interleucina-33/imunologia , Interleucina-33/genética , Interleucina-33/metabolismo , Interleucinas/metabolismo , Interleucinas/imunologia , Interleucinas/genética , Camundongos , Streptococcus pneumoniae/imunologia , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/imunologia , Humanos , Camundongos Knockout , Microbiota/imunologia , Camundongos Endogâmicos C57BL , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/microbiologia , Microbioma Gastrointestinal/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Polimorfismo de Nucleotídeo Único
4.
Geriatrics (Basel) ; 9(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38247989

RESUMO

Frailty is a major geriatric problem leading to an increased risk of disability and death. Prevention, identification, and treatment of frailty are important challenges in gerontology and public health. The study aimed to estimate the prevalence of the frailty phenotype (FP) among the oldest-old Polish Caucasians and investigate the relationship between the FP and mortality. Baseline data were collected from 289 long-lived individuals, including 87 centenarians and 202 subjects aged 94-99. Mortality was obtained from population registers over the following 5 years. Sixty percent of subjects were classified as frail, 33% as prefrail, and 7% as robust. Frailty was more common in women than men and among centenarians than nonagenarians. During the 5-year observation period, 92.6% of the frail women and all frail men died, while mortality rates were lower among prefrail, 78.8% and 66.7%, and robust individuals, 60% and 54.5%, respectively. In the survival analysis, frailty was the strongest negative risk factor: HR = 0.328 (95% CI: 0.200-0.539). The inability to perform handgrip strength measurement was an additional predictor of short survival. In conclusion, the FP is prevalent in nonagenarians and centenarians and correlates with lower survivability. Future studies should address differences between unavoidable age-associated frailty and reversible disability in long-lived individuals.

5.
Int J Mol Sci ; 24(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38139276

RESUMO

The advanced glycosylation end-product receptor (AGER) is involved in the development of metabolic inflammation and related complications in type 2 diabetes mellitus (T2DM). Tissue expression of the AGER gene (AGER) is regulated by epigenetic mediators, including a long non-coding RNA AGER-1 (lncAGER-1). This study aimed to investigate whether human obesity and T2DM are associated with an altered expression of AGER and lncAGER-1 in adipose tissue and, if so, whether these changes affect the local inflammatory milieu. The expression of genes encoding AGER, selected adipokines, and lncAGER-1 was assessed using real-time PCR in visceral (VAT) and subcutaneous (SAT) adipose tissue. VAT and SAT samples were obtained from 62 obese (BMI > 40 kg/m2; N = 24 diabetic) and 20 normal weight (BMI = 20-24.9 kg/m2) women, while a further 15 SAT samples were obtained from patients who were 18 to 24 months post-bariatric surgery. Tissue concentrations of adipokines were measured at the protein level using an ELISA-based method. Obesity was associated with increased AGER mRNA levels in SAT compared to normal weight status (p = 0.04) and surgical weight loss led to their significant decrease compared to pre-surgery levels (p = 0.01). Stratification by diabetic status revealed that AGER mRNA levels in VAT were higher in diabetic compared to non-diabetic women (p = 0.018). Elevated AGER mRNA levels in VAT of obese diabetic patients correlated with lncAGER-1 (p = 0.04, rs = 0.487) and with interleukin 1ß (p = 0.008, rs = 0.525) and resistin (p = 0.004, rs = 0.6) mRNA concentrations. In conclusion, obesity in women is associated with increased expression of AGER in SAT, while T2DM is associated with increased AGER mRNA levels and pro-inflammatory adipokines in VAT.


Assuntos
Diabetes Mellitus Tipo 2 , RNA Longo não Codificante , Humanos , Feminino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/complicações , Obesidade/genética , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Adipocinas/genética , Adipocinas/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Gordura Subcutânea/metabolismo
6.
Biomedicines ; 11(12)2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38137455

RESUMO

Lymphedema is often complicated by chronic inflammation, leading to fibrosis, fat deposition, and inhibition of lymphangiogenesis. This study aimed to verify whether lymphedema itself or together with commensal bacterial flora infection contributes to the severity of local inflammation. Edema was induced by interruption of the lymph flow in the rat's hind limb. Immune cell infiltrates were examined by flow cytometry and immunohistochemistry. Nine-day edema alone did not affect immune cell content in the skin but resulted in a decrease in CD4+ T helper lymphocytes and monocytes in the draining popliteal lymph nodes. In turn, local saprophytic Staphylococcus epidermidis infection of the edematous limb resulted in dense infiltrates of CD68+ macrophages and monocytes, MHC class II antigen-presenting cells, CD90+ stem cells, thymocytes, and immature B cells in the skin, accompanied by a simultaneous reduction in density of CD4+ T helper lymphocytes and monocytes, OX62+ dendritic cells, CD68+ macrophages and monocytes, HiS48+ granulocytes, CD90+ stem cells, thymocytes, and immature B cells in the draining popliteal lymph nodes. These results indicate that the combination of edema and saprophytic bacteria infection induces severe inflammation in the peripheral tissues and results in a delay of antibacterial protection processes in neighboring lymphatic organs.

7.
Adv Clin Exp Med ; 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37676098

RESUMO

Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.

8.
Biomedicines ; 11(6)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37371754

RESUMO

Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5mC), first to 5-hydroxymethylcytosine (5hmC), then to 5-formylcytosine (5fC), and finally to 5-carboxycytosine (5caC). Evidence suggests that changes in TET expression may impact cell function and the phenotype of aging. Proliferation, apoptosis, markers of autophagy and double-strand DNA break repair, and the expression of Fibulin 5 were assessed by flow cytometry in TET1 and TET2-overexpressing fibroblasts isolated from sun-unexposed skin of young (23-35 years) and age-advanced (75-94 years) individuals. In cells derived from young individuals, TET1 overexpression resulted in the inhibition of proliferation and apoptosis by 37% (p = 0.03) and 24% (p = 0.05), respectively, while the overexpression of TET2 caused a decrease in proliferation by 46% (p = 0.01). Notably, in cells obtained from age-advanced individuals, TETs exhibited different effects. Specifically, TET1 inhibited proliferation and expression of autophagy marker Beclin 1 by 45% (p = 0.05) and 28% (p = 0.048), respectively, while increasing the level of γH2AX, a marker of double-strand DNA breaks necessary for initiating the repair process, by 19% (p = 0.04). TET2 inhibited proliferation by 64% (p = 0.053) and increased the level of γH2AX and Fibulin 5 by 46% (p = 0.007) and 29% (p = 0.04), respectively. These patterns of TET1 and TET2 effects suggest their involvement in regulating various fibroblast functions and that some of their biological actions depend on the donor's age.

9.
Front Med (Lausanne) ; 10: 1100547, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36968815

RESUMO

Introduction: The study aimed to estimate the cut-off value for homeostatic model assessment for insulin resistance (HOMA-IR) discriminating the insulin resistance based on the sex hormones binding globulin (SHBG) level in women with polycystic ovary syndrome (PCOS). Materials and methods: Data from medical records of 854 Caucasian women diagnosed with PCOS were analyzed. Anthropometric data, fasting plasma glucose, insulin and SHBG levels were measured. HOMA-IR was calculated with a standard formula. The cut-off value was calculated using receiver-operating characteristics. Results: Circulating SHBG levels below the normal range (26.1 nmol/L) were found in 25.4% of study participants. This subgroup had a significantly higher BMI, fasting glucose and insulin concentrations and HOMA-IR values. Empirical optimal cut-off values for HOMA-IR corresponding to low SHBG levels was ≥2.1 [area under the curve (AUC) 0.73, accuracy 0.65, sensitivity 72.3%, specificity 63.1%, positive predictive value (PPV) 40.0%, negative predictive value (NPV) 87.0%]. Conclusions: Our study suggests that the cut-off point for HOMA-IR discriminating the insulin resistance based on the SHBG level, in young Caucasian women with polycystic ovary syndrome is 2.1, and is consistent with the cut-off value adopted by the European Group for the Study of Insulin Resistance (above 2.0).

10.
Int J Mol Sci ; 24(4)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36834766

RESUMO

Vitiligo is a chronic pigmentary disease with complex etiology, the signs of which are caused by the destruction of melanocytes in the epidermis, leading to the lack of melanin pigment responsible for skin coloration. The treatment of vitiligo, which aims at repigmentation, depends both on the clinical characteristics of the disease as well as on molecular markers that may predict the response to treatment. The aim of this review is to provide an overview of the clinical evidence for vitiligo cell-based therapies taking into account the required procedures and equipment necessary to carry them out as well as their effectiveness in repigmentation, assessed using the percentage of repigmentation of the treated area. This review was conducted by assessing 55 primary clinical studies published in PubMed and ClinicalTrails.gov between 2000 and 2022. This review concludes that the extent of repigmentation, regardless of the treatment method, is highest in stable localized vitiligo patients. Moreover, therapies that combine more than one cell type, such as melanocytes and keratinocytes, or more than one method of treatment, such as the addition of NV-UVB to another treatment, increase the chances of >90% repigmentation. Lastly, this review concludes that various body parts respond differently to all treatments.


Assuntos
Hipopigmentação , Vitiligo , Humanos , Vitiligo/terapia , Melanócitos , Epiderme , Queratinócitos , Resultado do Tratamento
11.
Nutrients ; 14(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36364882

RESUMO

Obesity is associated with an increased risk of morbidity and mortality; however, data suggest that in old age, obesity is not detrimental. The study's objective was to verify whether obesity frequency still increases in Polish Caucasian seniors and to verify the "obesity paradox". Five thousand and fifty-seven community-dwelling individuals aged ≥ 65 years completed a detailed medical questionnaire, underwent measurements of the body mass index (BMI) and the waist circumference (WC), and an evaluation of physical and cognitive performances. Over a decade, general obesity increased by 2.1%, mostly due to a 3.9% increase in men. Abdominal obesity increased by 1.0%, mainly due to males, in whom it increased by 3.9%. Obesity increased the risk of several aging-related diseases, but this effect was less pronounced in the oldest-old. Obesity did not adversely affect the physical and cognitive functioning or mortality. Through a multivariable analysis, the BMI and WC remained the independent predictors of the Katz Activities of Daily Living score (p < 0.001 and p < 0.05, respectively) and Mini-Mental State Examination score (both p < 0.001). The Kaplan−Meier survival curves revealed that overweight and obesity classes 1 and 2 were associated with the lowest mortality. Through a multivariable analysis, overweight, class 1 obesity, and abdominal obesity remained the independent predictors of a decreased mortality (all p < 0.001). In conclusion, we found that overweight and obesity are not detrimental in seniors, including the oldest-old. We suggest that the anthropometric values defining obesity should be modified for age-advanced people.


Assuntos
Obesidade Abdominal , Sobrepeso , Masculino , Humanos , Idoso de 80 Anos ou mais , Obesidade Abdominal/complicações , Sobrepeso/complicações , Atividades Cotidianas , Circunferência da Cintura , Índice de Massa Corporal , Obesidade/complicações , Fatores de Risco
12.
PLoS One ; 17(8): e0272045, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35994462

RESUMO

INTRODUCTION: To determine the prevalence of treated and untreated thyroid dysfunction and to identify factors associated with increased risk of undiagnosed thyroid dysfunction in older adults. METHODS: The population of 5987 community-dwelling Polish Caucasian seniors aged 60 years and above who participated in the PolSenior 2 study (2018-2019). Population-based cross-sectional multidisciplinary study in design. Data from structured questionnaires, geriatric tests, and scales were obtained from all study participants who underwent anthropometric and blood pressure measurements during three home visits. Assessment of thyroid function was based on TSH serum measurements. RESULTS: The prevalence of thyroid dysfunction in the Polish population aged 60 years or above was estimated at 15.5% (21.5% in women and 7.2% in men), with 3.2% of undiagnosed individuals among them. The prevalence of hypothyroidism and hyperthyroidism in the studied group was 13.9% (19.4% in women and 6.3% in men) and 1.6% (2.1% in women and 0.9% in men) respectively, untreated hypothyroidism was revealed in 21.9% (in 160 out of 732 subjects) and untreated hyperthyroidism in 34.2% of subjects (in 41 out of 120 participants). In multiple regression analysis independent risk factors for thyroid disorders being untreated were older age (> 75 years), male sex, a low education level (primary or lower), and low utilization of medical services. CONCLUSIONS: One-fifth of Polish Caucasian seniors with hypothyroidism and one-third with hyperthyroidism are untreated. Older, poorly educated and rarely utilizing medical services seniors, especially men, are more frequently untreated for thyroid dysfunction and some of them do not benefit from contemporary achievements in medicine.


Assuntos
Hipertireoidismo , Hipotireoidismo , Doenças da Glândula Tireoide , Idoso , Estudos Transversais , Feminino , Humanos , Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Masculino , Prevalência , Fatores de Risco , Inquéritos e Questionários , Doenças da Glândula Tireoide/epidemiologia , Tireotropina
13.
Drug Dev Res ; 83(6): 1419-1424, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35774024

RESUMO

With increased life expectancies in developed countries, cancer rates are becoming more common among the elderly. Cancer is typically driven by a combination of germline and somatic mutations accumulating during an individual's lifetime. Yet, many centenarians reach exceptionally old age without experiencing cancer. It was suggested that centenarians have more robust DNA repair and mitochondrial function, allowing improved maintenance of DNA stability. In this study, we applied real-time quantitative PCR to examine the expression of ATM in lymphoblastoid cell lines (LCLs) from 15 healthy female centenarians and 24 younger female donors aged 21-88 years. We observed higher ATM mRNA expression of in LCLs from female centenarians compared with both women aged 21-48 years (FD = 2.0, p = .0016) and women aged 56-88 years (FD = 1.8, p = .0094. Positive correlation was found between ATM mRNA expression and donors age (p = .0028). Levels of hsa-miR-181a-5p, which targets ATM, were lower in LCLs from centenarians compared with younger women. Our findings suggest a role for ATM in protection from age-related diseases, possibly reflecting more effective DNA repair, thereby reducing somatic mutation accumulation during aging. Further studies are required for analyzing additional DNA repair pathways in biosamples from centenarians and younger age men and women.


Assuntos
Envelhecimento , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Centenários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Linhagem Celular , Feminino , Humanos , RNA Mensageiro/genética
14.
Int J Mol Sci ; 23(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35682668

RESUMO

Estrogen affects adipose tissue function. Therefore, this study aimed at assessing changes in the transcriptional activity of estrogen receptor (ER) α and ß genes (ESR1 and ESR2, respectively) in the adipose tissues of obese individuals before and after weight loss and verifying whether epigenetic mechanisms were involved in this phenomenon. ESR1 and ESR2 mRNA and miRNA levels were evaluated using real-time PCR in visceral (VAT) and subcutaneous adipose tissue (SAT) of 78 obese (BMI > 40 kg/m2) and 31 normal-weight (BMI = 20−24.9 kg/m2) individuals and in 19 SAT samples from post-bariatric patients. ESR1 and ESR2 methylation status was studied using the methylation-sensitive digestion/real-time PCR method. Obesity was associated with a decrease in mRNA levels of both ERs in SAT (p < 0.0001) and ESR2 in VAT (p = 0.0001), while weight loss increased ESR transcription (p < 0.0001). Methylation levels of ESR1 and ESR2 promoters were unaffected. However, ESR1 mRNA in the AT of obese subjects correlated negatively with the expression of hsa-miR-18a-5p (rs = −0.444), hsa-miR-18b-5p (rs = −0.329), hsa-miR-22-3p (rs = −0.413), hsa-miR-100-5p (rs = −0.371), and hsa-miR-143-5p (rs = −0.289), while the expression of ESR2 in VAT correlated negatively with hsa-miR-576-5p (rs = −0.353) and in SAT with hsa-miR-495-3p (rs = −0.308). In conclusion, obesity-associated downregulation of ER mRNA levels in adipose tissue may result from miRNA interference.


Assuntos
MicroRNAs , Receptores de Estrogênio , Tecido Adiposo/metabolismo , Epigênese Genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Obesidade/genética , Obesidade/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Redução de Peso/genética
15.
Biomedicines ; 10(5)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35625758

RESUMO

In individuals with lymphedema, diabetic foot, or other diseases, infections with saprophytes are common. The response of major cell subpopulations in the draining lymph nodes to skin infection with Staphylococcus epidermidis was assessed using the rat model. After massive subepidermal infection, a cytometric evaluation showed an increase in cytotoxic and helper T lymphocytes and major subpopulations of the innate immune response. Three weeks later, signs of inflammation reduction with an increase in the content of memory T helper lymphocytes and effector memory T cytotoxic lymphocytes were observed. After skin re-infection, a rapid response of cytotoxic, helper, and memory T lymphocytes, memory B lymphocytes and plasmablasts, and macrophages was detected. In addition, a reduction in the number of naïve B lymphocytes, activated MHC class II+ cells, and some cells of the innate immune system was observed. T regulatory lymphocyte response after the initial and secondary S. epidermidis skin infection was not detected. The morphometric evaluation showed significant changes in the main cell subpopulations in each functional zone of the node and then confirmed the efficient elimination of the administered antigen, as evidenced by the observations on day 28. Notably, after re-infection, the cellular response did not exceed the level after the initial infection and was reduced in many cell subpopulations. Understanding how the lymph nodes eliminate S. epidermidis can provide valuable insights into creating immunological therapies against infections with saprophytes.

16.
Int J Endocrinol ; 2022: 6498768, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35140785

RESUMO

OBJECTIVE: Decreased synthesis of sex hormone-binding globulin (SHBG) related to hyperinsulinemia is one of the disturbances characteristic of polycystic ovary syndrome (PCOS). Hyperinsulinemia is a compensatory mechanism for liver insulin resistance (IR); thus, SHBG may be considered as a surrogate marker of liver IR. Therefore, this study aimed to assess the prediction of IR and impaired fasting glucose (IFG) based on SHBG levels in women with PCOS. METHODS: This analysis included data retrieved from medical records of 854 patients with PCOS hospitalized in the Gynecological Endocrinology Clinic from 2012 to 2019. Data including anthropometric parameters, fasting plasma glucose, insulin, and SHBG levels were analyzed. BMI and HOMA-IR were calculated with standard formulas. RESULTS: IFG and IR assessed based on HOMA-IR values > 2.0 were found in 19.5% and 47.8% of the study group, respectively. Empirical optimal cutoff values for SHBG levels were ≤41.5 nmol/L typical for IR (AUC 0.711, sensitivity 61.1%, specificity 71.6%, positive predictive value (PPV) 70.7%, and negative predictive value (NPV) 62.1%). The probability of insulin resistance occurrence for SHBG concentration 26.1 nmol/L (the lower normal range) was 61.6% (95% CI: 57.4%-65.8%). The SHBG concentration of 36.4 nmol/L and 8.1 nmol/L was related to a 10% and 20% probability of IFG, respectively. CONCLUSION: In conclusion, this is the first study estimating the probability of liver IR and IFG occurrence based on SHBG levels in women with PCOS. Despite the low sensitivity, SHBG level below 42 nmol/L should cause closer monitoring for the fatty liver and prediabetes.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35162054

RESUMO

Polypharmacy is a challenging issue in geriatrics. The aim of the study was to characterize correlates of polypharmacy in the PolSenior project. The PolSenior project, was a comprehensive survey in a large and longitudinal representative sample of thePolish older population. The project was conducted by the International Institute of Molecular and Cell Biology in Warsaw between 2008 and 2011. All medications consumed during the week preceding the survey were evaluated for each participant (n = 4793, including 2314 females (48.3%)). Thereafter, the percentage of those with polypharmacy (at least 5 medications) and excessive polypharmacy (at least 10 medications) was calculated, and their correlates were determined. The average number of medications used by participants was 5.1 ± 3.6, and was higher in females than in males (5.5 ± 3.5 vs. 4.8 ± 3.5; p < 0.001). Polypharmacy characterized 2650 participants (55.3%) and excessive polypharmacy-532 of them (11.1%). The independent correlates associated withpolypharmacy were: age over 70 years, female sex, higher than primary education, living in an urban area, comorbidities, any hospitalization during past five years, and visiting general practicioners at least yearly. As for correlates with excessive polypharmacy, they were: age 80-84 years, female sex, living in an urban area, diagnosis of at least four chronic diseases, and at least two hospitalizations in the last five years. This study serves as a starting place to understand patient characteristics associated with polypharmacy, excessive polypharmacy, and identify targeted interventions.


Assuntos
Polimedicação , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Polônia
18.
Front Endocrinol (Lausanne) ; 13: 1081157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36605940

RESUMO

Background: In young women, hypothyroidism is associated with impaired fertility, increased risk of pregnancy loss, premature delivery, and impaired infant neurodevelopment, justifying the need to recognize the risk of hypothyroidism in women of reproductive age. Thus, this study aimed at assessing the frequency of occurrence of antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb) in young Caucasian women in connection with various confounders. Methods: The cross-sectional study involved 366 women aged 18-40 years without a diagnosis of thyroid disease. The personal and family medical history was collected, body mass and height were measured and an ultrasound examination of the thyroid gland was performed. Thyrotropin (TSH), free thyroxine, and free triiodothyronine levels, as well as TPOAb and TGAb titers, were determined by ECLIA. Results: Two cases of hyperthyroidism (0.5%) and 6 cases (1.6%) of subclinical hypothyroidism were detected. TPOAb was detected in 21 (5.7%) and TGAb in 31 (8.6%) and any of the antibodies in 42 (11.6%) women. Antibodies were more frequent in the subgroup with TSH levels ≥ 2.5 mIU/L than in the subgroup with lower TSH levels (15.5% vs 6.9%, respectively, p<0.05). Any anti-thyroid antibodies were also detected more frequently in the subgroup with TSH levels ≥ 2.5 mIU/L (18.3% vs 10.0%, respectively, p<0.05). Women with the presence of TGAb or seropositive for either TGAb or TPOAb or TPOAb and TGAb antibodies were more likely to have higher TSH levels (OR = 2.48 and OR = 2.02; respectively, p < 0.05 for both). A family history of any thyroid diseases increased the risk of any anti-thyroid antibodies positivity (OR = 1.94; p < 0.05). Conclusions: The results of our study suggest that TSH ≥ 2.5 mIU/L and a family history of any thyroid diseases justify screening for anti-thyroid antibodies in women of reproductive age, although the occurrence of these antibodies in the majority of cases is not related to thyroid dysfunction.


Assuntos
Hipertireoidismo , Hipotireoidismo , Doenças da Glândula Tireoide , Feminino , Humanos , Estudos Transversais , Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/diagnóstico , Tireotropina
19.
Cells ; 10(11)2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34831371

RESUMO

Aging affects all tissues and organs. Aging of the immune system results in the severe disruption of its functions, leading to an increased susceptibility to infections, an increase in autoimmune disorders and cancer incidence, and a decreased response to vaccines. Lymph nodes are precisely organized structures of the peripheral lymphoid organs and are the key sites coordinating innate and long-term adaptive immune responses to external antigens and vaccines. They are also involved in immune tolerance. The aging of lymph nodes results in decreased cell transport to and within the nodes, a disturbance in the structure and organization of nodal zones, incorrect location of individual immune cell types and impaired intercellular interactions, as well as changes in the production of adequate amounts of chemokines and cytokines necessary for immune cell proliferation, survival and function, impaired naïve T- and B-cell homeostasis, and a diminished long-term humoral response. Understanding the causes of these stromal and lymphoid microenvironment changes in the lymph nodes that cause the aging-related dysfunction of the immune system can help to improve long-term immune responses and the effectiveness of vaccines in the elderly.


Assuntos
Envelhecimento/patologia , Imunossenescência , Linfonodos/patologia , Linfonodos/fisiopatologia , Animais , Microambiente Celular , Humanos , Modelos Biológicos , Neutrófilos/patologia
20.
Cells ; 10(8)2021 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-34440936

RESUMO

Vitamin B12, folate, iron deficiency (IDA), chronic kidney disease (CKD), and anemia of inflammation (AI) are among the main causes of anemia in the elderly. WHO criteria of nutritional deficiencies neglect aging-related changes in absorption, metabolism, and utilization of nutrients. Age-specific criteria for the diagnosis of functional nutritional deficiency related to anemia are necessary. We examined the nationally representative sample of Polish seniors. Complete blood count, serum iron, ferritin, vitamin B12, folate, and renal parameters were assessed in 3452 (1632 women, 1820 men) participants aged above 64. Cut-off points for nutritional deficiencies were determined based on the WHO criteria (method-A), lower 2.5 percentile of the studied population (method-B), and receiver operating characteristic (ROC) analysis (method-C). Method-A leads to an overestimation of the prevalence of vitamin B12 and folate deficiency, while method-B to their underestimation with over 50% of unexplained anemia. Based on method-C, anemia was classified as nutritional in 55.9%. In 22.3% of cases, reasons for anemia remained unexplained, the other 21.8% were related to CKD or AI. Mild cases were less common in IDA, and more common in non-deficiency anemia. Serum folate had an insignificant impact on anemia. It is necessary to adopt the age-specific criteria for nutrient deficiency in an old population.


Assuntos
Anemia/etiologia , Anemia/metabolismo , Anemia Ferropriva/complicações , Anemia Ferropriva/metabolismo , Feminino , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/metabolismo , Humanos , Inflamação/complicações , Inflamação/metabolismo , Masculino , Polônia , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/metabolismo
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