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1.
J Clin Endocrinol Metab ; 109(2): 333-343, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-37708356

RESUMO

OBJECTIVE: Placenta-derived inflammation plays a vital role in the pathophysiology of gestational diabetes mellitus (GDM). IL-32 is a novel pro-inflammatory cytokine and metabolic regulator involved in the development of metabolic disease. We investigated the effect of IL-32 in GDM. MATERIALS AND METHODS: First-trimester C-reactive protein (CRP) level was monitored in a case-control study of 186 women with GDM and 186 women without. Placental tissue was lysed and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Circulating level of inflammatory cytokines IL-32, IL-6, and TNF-α were measured by ELISA kits. The expression of placenta-derived macrophages, inflammatory cytokines, and related pathway proteins were assessed by reverse transcriptase-quantitative PCR, western blot, immunohistochemistry, or immunofluorescence. RESULTS: First-trimester CRP level in peripheral blood was closely associated with glucose and insulin resistance index and was an independent correlation with the development of GDM. High-resolution liquid chromatography-tandem mass spectrometry revealed that placenta-derived CRP expression was dramatically elevated in women with GDM. Interestingly, the expression of placenta-derived IL-32 was also increased and located in the macrophages of placental tissue. Meanwhile, the expression of IL-6, TNF-α, and p-p38 were up-regulated in the placental tissues with GDM. Either IL-6 or TNF-α was colocated with IL-32 in the placental tissue. Importantly, circulating IL-32 throughout pregnancy was increased in GDM and was related to placental-derived IL-32 expression, circulating IL-6, and TNF-α, glucose and insulin resistance index. CONCLUSION: Increased circulating IL-32 throughout pregnancy was closely associated with placenta macrophage-derived IL-32 expression and GDM. First trimester IL-32 level in peripheral blood may serve to predict the development of GDM.


Assuntos
Diabetes Gestacional , Resistência à Insulina , Gravidez , Feminino , Humanos , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Estudos de Casos e Controles , Placenta/metabolismo , Citocinas , Insulina , Glucose
2.
J Diabetes ; 16(3): e13508, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38036859

RESUMO

BACKGROUND: Diabetic kidney disease (DKD) is the most frequent complication in patients with type 2 diabetes mellitus (T2DM). It causes a chronic and progressive decline in kidney function, and ultimately patients require renal replacement therapy. To date, an increasing number of clinical studies have been conducted to explore the potential and novel biomarkers, which can advance the diagnosis, estimate the prognosis, and optimize the therapeutic strategies at the early stage of DKD. In the current study, we sought to investigate the association of plasma myoglobin with DKD. METHODS: A total of 355 T2DM patients with DKD and 710 T2DM patients without DKD were enrolled in this study. Laboratory parameters including blood cell count, hemoglobin A1c, biochemical parameters, and plasma myoglobin were recorded. Patients were classified on admission according to the tertile of myoglobin and clinical parameters were compared between the groups. Pearson correlation analysis, linear regression, logistic regression, receiver operating characteristics (ROC) analysis, and spline regression were performed. RESULTS: Plasma myoglobin significantly increased in patients with DKD and was associated with renal function and inflammatory parameters. Plasma myoglobin was an independent risk factor for the development of DKD. The area under ROC curve of myoglobin was 0.831. Spline regression showed that there was a significant linear association between DKD incidence and a high level of plasma myoglobin when it exceeded 36.4 mg/mL. CONCLUSIONS: This study shows that elevated plasma myoglobin level is closely associated with the development of kidney injury in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Mioglobina , Taxa de Filtração Glomerular , Rim
3.
Front Public Health ; 11: 1102509, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36935678

RESUMO

Background: To compare whether the general population, especially those without characteristic symptoms, need spirometry screening for chronic obstructive pulmonary disease (COPD). Methods: Residents aged > 40 years old in Minhang, Shanghai, China, filled out screening questionnaires and underwent spirometry. The structured questionnaire integrating COPD population screening and COPD screening questionnaire was designed to obtain data on demographic characteristics, risk factors of COPD, respiratory symptoms, lifestyle habits, and comorbidities. We assessed the correlations between variables and COPD and the impact factors of FEV1% predicted. Results: A total of 1,147 residents were included with a newly diagnosed mild to moderate COPD prevalence of 9.4% (108/1,147); half of the patients (54/108) were asymptomatic. Multivariate analysis did not reveal any significant differences in symptoms or lifestyle factors between newly diagnosed COPD patients and non-COPD participants. However, according to the generalized linear model, older age (ß = -0.062, p < 0.001), male sex (ß = -0.031, p = 0.047), and respiratory symptoms (ß = -0.025, p = 0.013) were associated with more severe airflow limitation. Conclusion: Newly diagnosed COPD patients had few differences compared with the general population, which suggests that a targeted case finding strategy other than general screening was currently preferred. More attention should be paid to respiratory symptoms when making a diagnosis and exploring new therapies and interventions for COPD in the early stage.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Adulto , China/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Pulmão , Comorbidade , Fatores de Risco
4.
Cell Immunol ; 384: 104659, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36608372

RESUMO

Autoimmune thyroiditis (AIT), characterized by an endless inflammatory process of self-destruction, ultimately leads to chronic swelling of the thyroid gland and its dysfunction. Here, we investigated the involvement of the NLR pyrin domain-containing 3 (NLRP3) inflammasome in AIT development. We found that NLRP3 is significantly upregulated in the thyroid of AIT patients and mice with experimental autoimmune thyroiditis (EAT). Pharmacological suppression of NLRP3 using its inhibitor MCC950 suppressed the progression of EAT in vivo. Furthermore, MCC950 treatment significantly reduced the numbers of infiltrating CD4+ and CD8+ T cells in the thyroid. Moreover, MCC950 significantly lowered the amounts of T helper 1 cells, T helper 17 cells, interferon gamma, and interleukin-17A; however, it significantly increased regulatory-T-cell numbers and interleukin-10 levels. These results suggest that suppression of NLRP3 inflammasome activation reverses AIT by inhibiting Th1- and Th17-cell responses and promoting Treg cell responses. Hence, the NLRP3 inflammasome is a promising therapeutic and theragnostic target in AIT. inhibits Th1- and Th17-cell responses and promotes Treg cell responses.


Assuntos
Indenos , Tireoidite Autoimune , Animais , Camundongos , Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sulfonamidas/farmacologia , Humanos
5.
Diabetologia ; 65(8): 1398-1411, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35587276

RESUMO

AIMS/HYPOTHESIS: IgM is the primary antibody produced by B cells and we hypothesise that IgM antibodies to gut microbiota may play a role in immunometabolism in obesity and type 2 diabetes. To test our hypothesis, we used B6 mice deficient in activation-induced cytidine deaminase (Aid-/- [also known as Aicda-/-]) which secrete only IgM antibodies, and human faecal samples. METHODS: We studied the immunometabolic effects and gut microbial changes in high-fat-diet-induced obesity (HFDIO) in Aid-/- B6 mice compared with wild-type mice. To determine similarities between mice and humans, human stool samples were collected from children and adolescents who were obese with normal glucose tolerance (NGT), obese with glucose intolerance (IGT), or obese and newly diagnosed with type 2 diabetes, for faecal microbiota transplant (FMT) into germ-free (GF) B6 mice and we assessed IgM-bound bacteria and immune responses. RESULTS: Compared with wild-type mice, Aid-/- B6 mice developed exacerbated HFDIO due to abundant levels of IgM. FMT from Aid-/- B6 to GF B6 mice promoted greater weight gain in recipient mice compared with FMT using wild-type mouse faecal microbiota. Obese youth with type 2 diabetes had more IgM-bound gut bacteria. Using the stools from the obese youth with type 2 diabetes for FMT to GF B6 mice, we observed that the gut microbiota promoted body weight gain and impaired glucose tolerance in the recipient GF B6 mice. Importantly, some clinical features of these obese young individuals were mirrored in the GF B6 mice following FMT. CONCLUSIONS/INTERPRETATION: Our results suggest that IgM-bound gut microbiota may play an important role in the immuno-pathogenesis of obesity and type 2 diabetes, and provide a novel link between IgM in obesity and type 2 diabetes in both mice and humans. DATA AVAILABILITY: The 16s rRNA sequencing datasets supporting the current study have been deposited in the NCBI SRA public repository ( https://www.ncbi.nlm.nih.gov/sra ; accession no. SAMN18796639).


Assuntos
Diabetes Mellitus Tipo 2 , Adolescente , Animais , Bactérias/genética , Criança , Dieta Hiperlipídica , Humanos , Imunoglobulina M , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/microbiologia , RNA Ribossômico 16S/genética , Aumento de Peso
6.
Int Arch Allergy Immunol ; 183(2): 225-234, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34544076

RESUMO

BACKGROUND: Intestinal flora is associated with Graves' disease (GD). This study explored the association of serum 25(OH)D with the diversity of the intestinal flora and serum IL-17 in GD patients. METHODS: Patients newly diagnosed with GD at 2 centers between 2018 and 2021 were consecutively included. According to their 25(OH)D levels, they were divided into the deficiency group, the insufficiency group, and the sufficiency group. Some patients with vitamin D deficiency or insufficiency were randomly selected and were matched with healthy volunteers (normal control [NC]) in terms of sex, age, and case number. The diversity and differential species of the intestinal flora and serum IL-17 levels were compared. RESULTS: Serum 25(OH)D negatively correlated with serum IL-17, the platelet/lymphocyte ratio, and TSH receptor antibody. The diversity of the intestinal flora decreased in the GD group, with noticeable differences in the composition of the intestinal flora when compared with the NC group. At the phylum level, the GD group exhibited a significantly lower abundance of Firmicutes but a higher abundance of Actinobacteria. At the genus level, the GD group exhibited higher relative abundances of Bifidobacterium, Collinsella, and Pediococcus but lower abundances of Roseburia and Dialister. CONCLUSIONS: The changes in the vitamin D level and the composition of the intestinal flora may partially contribute to the development of GD.


Assuntos
Microbioma Gastrointestinal/imunologia , Doença de Graves/sangue , Doença de Graves/etiologia , Interleucina-17/sangue , Deficiência de Vitamina D/complicações , Adulto , Biodiversidade , Biomarcadores , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Doença de Graves/diagnóstico , Humanos , Masculino , Metagenoma , Metagenômica/métodos , Pessoa de Meia-Idade , Testes de Função Tireóidea , Vitamina D/sangue , Deficiência de Vitamina D/sangue
7.
J Clin Endocrinol Metab ; 107(1): 192-204, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478541

RESUMO

CONTEXT: The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. OBJECTIVE: Here, we investigated the potential effect of monocytes in GDM. METHODS: Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages, and their products were measured. RESULTS: Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and was closely associated with glucose level, insulin resistance, and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia both in the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level, and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 109/L. Notably, CD206 and interleukin 10 (IL-10) were significantly lower, whereas CD80, CD86, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) were higher both in GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α, and IL-6. CONCLUSION: Decreased monocyte count throughout pregnancy was closely associated with the development of GDM, macrosomia, and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.


Assuntos
Diabetes Gestacional/epidemiologia , Macrossomia Fetal/epidemiologia , Monócitos/imunologia , Adulto , Peso ao Nascer/imunologia , Glicemia/análise , Estudos de Casos e Controles , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/imunologia , Feminino , Macrossomia Fetal/imunologia , Humanos , Incidência , Recém-Nascido , Inflamação/sangue , Inflamação/epidemiologia , Inflamação/imunologia , Contagem de Leucócitos , Gravidez , Primeiro Trimestre da Gravidez/sangue , Medição de Risco/métodos , Fatores de Risco , Adulto Jovem
8.
Endocr Connect ; 10(12): 1513-1521, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34727090

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effect of TFR2 on iron storage in type 2 diabetes. METHODS: A cross-sectional study was conducted among 1938 participants from the Jiangchuan Community of Shanghai. A total of 784 participants with T2DM and 1154 normal participants (non-T2DM) were enrolled in this study. Serum ferritin, fasting blood glucose, postprandial blood glucose, and HbA1C (glycated hemoglobin A1c) levels were determined. Eighteen Wistar male rats were randomly assigned into three groups (n = 6/group): rats in a high-fat diet streptozotocin (HFD+STZ) group were fed with HFD for 4 weeks and intraperitoneally injected with streptozotocin (STZ); rats in a control group were fed with a standard diet for 4 weeks and intraperitoneally injected with buffer; rats in an STZ group were fed with a standard diet for 4 weeks and intraperitoneally injected with streptozotocin. Glucose tolerance test was performed at the end of the study. Blood samples and liver tissues were assessed for liver TFR2, blood glucose, serum ferritin, and iron levels. RESULTS: The mean serum ferritin level of T2DM participants was significantly higher than that of the control group (227 (140-352) vs 203.5 (130.5-312) ng/mL, P < 0.05). Serum ferritin level was an independent risk factor for T2DM (high ferritin group vs low ferritin group, 1.304 (1.03-1.651), P < 0.05). Diabetic rats showed reduced liver TFR2 levels, with increased serum ferritin levels. CONCLUSION: T2DM participants exhibited iron disorder with elevated serum ferritin levels. Elevated serum ferritin levels in diabetic rats were accompanied by reduced liver TFR2 levels.

9.
Diabetes Metab Syndr Obes ; 14: 4557-4567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815682

RESUMO

PURPOSE: Diabetic kidney disease (DKD) is an inflammatory disease. This study aimed to investigate the association of fibrinogen to albumin ratio (FAR) with DKD. PATIENTS AND METHODS: A total of 1022 type 2 diabetes mellitus (T2DM) patients with DKD and 1203 T2DM patients without DKD were enrolled in this study. Laboratory values including blood cell count, hemoglobin A1c, biochemical parameters, and fibrinogen and albumin creatinine ratio were recorded. Patients were classified according to tertile of admission FAR. Clinical parameters were compared between groups. Logistic regression, linear regression, ROC analysis and spline regression were carried out. RESULTS: FAR in the DKD group was significantly higher than that in the non-DKD group. FAR had the highest odds ratio as an independent risk factor for the development of DKD and the highest area under ROC curve for predicting DKD compared with albumin (ALB) or fibrinogen (FIB) alone. Simple linear regression analyses revealed a significant and linear correlation of FAR with neutrophil and neutrophil-to-lymphocyte ratio. FAR was an independent risk factor for development of DKD. Spline regression showed that there was a significant linear association between DKD incidence and continuous FAR value when it exceeded 67.3mg/g. CONCLUSION: FAR is a stronger independent predictor of DKD than FIB and ALB. FAR is an independent risk factor for DKD development when it exceeded 67.3mg/g. FAR might be one of novel diagnostic biomarkers to predict and prevent DKD progression. However, a prospective study to validate the prognostic model is still needed.

10.
J Clin Lab Anal ; 35(11): e24014, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34545629

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) is considered to be an inflammatory disease. This study aimed to investigate the association of monocyte to high-density lipoprotein cholesterol ratio (MHR) with PTC. METHODS: Clinical parameters from 300 patients with PTC and 552 patients with benign thyroid nodule were compared. Serum renal function and liver enzymes, fasting plasma glucose, lipid profile, and blood cell count were measured. RESULTS: Patients with PTC had a higher MONO (p < 0.001) and MHR (p < 0.001). There was a step-wise increase in the prevalence of PTC (p = 0.003) with the tertile of MHR. Logistic regression analysis revealed that MHR could be considered an independent risk factor (p < 0.001) in the case-control study and the cohort study. Pearson correlation analysis and simple linear regression analysis indicated that MHR was positively associated with neutrophil (NEU) and lymphocyte (LYM) count as well as neutrophil-to-lymphocyte ratio (NLR). Area under the curve (AUC) was 0.711. The optimal cutoff of MHR was 0.33 × 109 /mmol. CONCLUSION: This study identifies novel evidence that patients with PTC have a higher MHR. MHR is an independent risk factor for PTC. These findings support the application of MHR to predict, diagnose, and evaluate the occurrence of PTC.


Assuntos
HDL-Colesterol/sangue , Monócitos/citologia , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Câncer Papilífero da Tireoide/sangue , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/fisiopatologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/fisiopatologia
11.
J Int Med Res ; 48(8): 300060520952973, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32867566

RESUMO

OBJECTIVE: The aim of our study was to explore the association between serum cystatin C (CysC) and euthyroid Hashimoto's thyroiditis. METHODS: There were 119 female euthyroid Hashimoto's thyroiditis patients and 225 healthy controls who were recruited. Serum CysC, thyroid function, thyroid autoantibodies, fasting glucose, liver enzymes, and lipid profile were determined. Clinical parameters were compared between two groups. RESULTS: Serum CysC levels were significantly higher in euthyroid Hashimoto's thyroiditis patients compared with controls. In the lowest, middle, and highest tertile groups of CysC, the percentage of Hashimoto's thyroiditis was 15.9%, 34.2%, and 53.5%, respectively. The percentage of Hashimoto's thyroiditis was significantly higher in the highest tertile than in the lowest and middle tertiles. Spearman's correlation analysis showed that serum CysC levels were negatively correlated with free triiodothyronine (FT3), and positively correlated with serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb). Logistic regression analysis showed that serum CysC was independently related to the status of euthyroid Hashimoto's thyroiditis. CONCLUSIONS: The present study shows the first evidence suggesting that serum CysC levels are positively correlated with TPOAb and TGAb. Serum CysC might underlie the pathophysiologic features of euthyroid Hashimoto's thyroiditis.


Assuntos
Cistatina C , Doença de Hashimoto , Adulto , Autoanticorpos , China , Feminino , Humanos
12.
Endocr Connect ; 9(8): 858-863, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32880377

RESUMO

The aim of our study was to explore the diagnostic value of prealbumin to fibrinogen ratio (PFR) for predicting prognosis with the optimal cut-off value in diabetic peripheral neuropathy (DPN) patients. A total of 568 type 2 diabetes mellitus (T2DM) patients were enrolled in this study. The values including Toronto clinical neuropathy score (TCNS), nerve conduction velocity (NCV), vibration perception threshold (VPT), blood cells count, biochemical parameters, fibrinogen and PFR were recorded. The patients were divided into tertiles based on admission PFR value. First, clinical parameters were compared among the groups. Secondly, a logistic regression and ROC analysis were performed as the statistical model. The percentage of DPN, TCNS and VPT were significantly higher in the lowest PFR tertile than in the middle PFR tertile and the highest PFR tertile (P < 0.01-0.001). NCV was significantly lower in lowest PFR tertile than in the middle PFR tertile and the highest PFR tertile (P < 0.01-0.001). The Spearman correlation analysis showed that PFR was negatively correlated with TCNS and VPT (P < 0.001), while PFR was positively correlated with median motor NCV (P < 0.001), peroneal motor NCV (P < 0.001), median sensory NCV (P < 0.001), and peroneal sensory NCV (P < 0.001). After adjusting these potentially related factors, PFR was independently related to DPN (P = 0.007). The area under ROC curve was 0.627. This study finds the first evidence to suggest PFR may be the key component associated with DPN in T2DM, while PFR might underlie the pathophysiologic features of DPN.

13.
Diabetes ; 69(7): 1401-1410, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32332157

RESUMO

Chronic low-grade inflammation plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). To investigate the ability of different inflammatory blood cell parameters in predicting the development of GDM and pregnancy outcomes, 258 women with GDM and 1,154 women without were included in this retrospective study. First-trimester neutrophil count outperformed white blood cell count and the neutrophil-to-lymphocyte ratio in the predictability for GDM. Subjects were grouped based on tertiles of neutrophil count during their first-trimester pregnancy. The results showed that as the neutrophil count increased, there was a stepwise increase in GDM incidence as well as in glucose and glycosylated hemoglobin levels, HOMA for insulin resistance (HOMA-IR), macrosomia incidence, and newborn weight. Neutrophil count was positively associated with prepregnancy BMI, HOMA-IR, and newborn weight. Additionally, neutrophil count was an independent risk factor for the development of GDM, regardless of the history of GDM. Spline regression showed that there was a significant linear association between GDM incidence and the continuous neutrophil count when it was >5.0 × 109/L. This work suggested that the first-trimester neutrophil count is closely associated with the development of GDM and adverse pregnancy outcomes.


Assuntos
Diabetes Gestacional/etiologia , Neutrófilos/fisiologia , Adulto , Peso ao Nascer , Índice de Massa Corporal , Feminino , Humanos , Resistência à Insulina , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Estudos Retrospectivos
14.
J Diabetes Res ; 2019: 4251829, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31871946

RESUMO

The correlation between serum 25-hydroxy vitamin D (25(OH)D) levels and lower extremity atherosclerotic disease and the predictive value of 25(OH)D for early-stage lower extremity atherosclerotic disease in patients with type 2 diabetes mellitus (T2DM) were explored. In total, 620 subjects (590 T2DM patients and 30 healthy subjects) completed a questionnaire. All subjects were divided into four groups according to serum 25(OH)D concentration quartile: Q1 (<12.18 ng/ml), Q2 (12.18~20.65 ng/ml), Q3 (20.65~31.97 ng/ml), and Q4 (>31.97 ng/ml). Participants were also divided into four groups based on the degree of lower extremity arteriostenosis: A1 (T2DM), A2 (T2DM with mild lower extremity vascular lesions (LEVL)), A3 (T2DM with moderate LEVL), and A4 (T2DM with severe LEVL). The incidence of lower extremity artery plaque was significantly higher in groups Q1 and Q2 than in group Q4 (both P < 0.05). The concentration of 25(OH)D was significantly lower in group A4 than in groups A1 and A2. Pearson correlation analysis revealed that the degree of lower extremity vascular stenosis was positively correlated with age, smoking, and HbA1c, CRP, and LDL-C levels and negatively correlated with 25(OH)D concentrations. Logistic regression analysis demonstrated that 25(OH)D concentrations exerted a protective effect against LEVL in T2DM patients. Serum 25(OH)D concentrations may be correlated with the incidence of macrovascular disease in T2DM patients. A low serum 25(OH)D concentration is an independent risk factor for lower extremity vascular pathological changes and acts as a prognostic index for lower extremity atherosclerotic disease.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/etiologia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , China/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Medição de Risco , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
15.
Int J Chron Obstruct Pulmon Dis ; 14: 2081-2088, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564855

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by incomplete reversible airflow limitation, which is associated with emphysema and chronic inflammation. Oxidative/antioxidant imbalance is one of the mechanisms of the current pathogenesis of COPD and several recent studies have attempted to uncover genetic causes of COPD and its progression. GST, HO-1, and SOD-3 are important susceptibility genes related to COPD. Methods: A total of 300 blood samples were included in two groups: Control group and COPD group. We genotyped 4 single nucleotide polymorphisms (SNPs) from these 3 genes in 150 COPD patients and 150 controls to analyze genetic polymorphisms and interactions with COPD-related quantitative traits using correlation analysis and multivariate logistic regression analysis. Results: The results indicated that genotype distributions and allele frequencies of GSTP1, HO-1, and SOD-3 were significantly different between the COPD and the control group, while there is no correlation between the polymorphism of GSTP1, HO-1, SOD3, and the different stages of COPD. Furthermore, multivariate logistic regression analysis indicated that COPD GSTP1-exon5 SNP and HO-1 (GT)n SNP are high-risk factors for COPD and there was interaction between GSTP1 exon5 SNPS and HO-1 (GT)n SNP. More important, the genotypes, AG, GG of GSTP1 exon5 and L/M*S, L/L of HO-1 (GT)n associated with increased 8-iso-prostaglandin F (2 alpha) (8-iso-PGF2) and malondialdehyde (MDA) concentration and decreased catalase (CAT) activity. Conclusion: Collectively, this study shows that genetic polymorphisms of GSTP1, HO-1, and SOD-3 are associated with COPD susceptibility.


Assuntos
Glutationa S-Transferase pi/genética , Heme Oxigenase-1/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Superóxido Dismutase/genética , Idoso , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/enzimologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Capacidade Vital
16.
Endocr Pract ; 25(11): 1158-1165, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414906

RESUMO

Objective: Macrosomia is closely associated with gestational diabetes mellitus (GDM) but its relationship with maternal intermediate state gestational blood glucose (ISGBG; normal fasting blood glucose and 7.8 mmol/L <1 hour blood glucose [BG] <10 mmol/L or 6.7 mmol/L <2 hour BG <8.5 mmol/L) is unclear. Here, we analyzed the clinical characteristics and pregnancy outcomes and explored risk factors for macrosomia in women with ISGBG. Methods: A total of 847 women with normal glucose tolerance gestation, 330 with ISGBG, and 99 with GDM were included. Maternal and fetal clinical data were collected and 3-point BG following oral glucose tolerance test, fasting insulin, glycated hemoglobin, and blood lipids profile were measured. Results: The incidence rate of macrosomia among the neonates of women with ISGBG was as high as 10.9%. In the ISGBG group, prepregnancy body mass index (BMI), gestational weight gain (GWG) and the proportion of women with excessive GWG (eGWG) were significantly higher in women with macrosomia compared with those who delivered a normal weight neonate. In women with ISGBG, neonate weight was positively correlated with maternal prepregnancy weight (r = 0.183, P<.01), prepregnancy BMI (r = 0.135, P<.01), and GWG (r = 0.255, P<.01), and negatively correlated with high-density lipoprotein cholesterol (r = -0.172, P<.01). Nonetheless, only eGWG was an independent risk factor (odds ratio = 3.18, 95% confidence interval = 1.26 to 7.88, P<.05) for macrosomia. The risk of macrosomia in pregnant women with prepregnancy BMI <25 kg/m2 or BMI ≥25 kg/m2 and eGWG was 3.39 and 3.27 times, respectively. Conclusion: The incidence rate of macrosomia is increased in women with ISGBG and eGWG is the strongest independent risk factor. In order to reduce the risk for macrosomia, timely lifestyle intervention to promote appropriate weight gain during pregnancy deserves evaluation. Abbreviations: AUC = area under the curve; BG = blood glucose; 1 hour BG = 1 hour blood glucose after OGTT; 2 hour BG = 2 hour blood glucose after OGTT; BMI = body mass index; CI = confidence interval; eGWG = excessive gestational weight gain; FBG = fasting blood glucose; FINS = fasting insulin; GDM = gestational diabetes mellitus; HbA1c = glycated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance index; ISGBG = intermediate state gestation blood glucose; LDL-C = low-density lipoprotein cholesterol; Ln = natural logarithm; MLBW = mature low birth weight; NGTG = normal glucose tolerance gestation; OGTT = oral glucose tolerance test; OR = odds ratio; SD = standard deviation.


Assuntos
Diabetes Gestacional , Macrossomia Fetal , Ganho de Peso na Gestação , Peso ao Nascer , Glicemia , Índice de Massa Corporal , Feminino , Humanos , Recém-Nascido , Gravidez , Fatores de Risco
17.
Endocr J ; 65(1): 75-82, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29033409

RESUMO

Ferritin is a universal intracellular protein that acts as an iron carrier. Several studies have indicated that iron deficiency affects thyroid function in non-pregnant women. Our objective was to assess the relationship between serum ferritin levels and thyroid function in pregnant women during the second trimester. Pregnant women with sufficient iodine intake and normal antithyroid antibodies during the second trimester were recruited from the obstetric outpatient department of the Fifth People's Hospital of Fudan University. Serum ferritin (SF) levels, thyroid function, anti-thyroid antibodies and vitamin B12 were determined by electrochemiluminescence immunoassay kit. Maternal serum iron (Fe), unsaturated iron binding capacity (UIBC), hemoglobin (Hb), creatinine (Cr), fasting blood glucose (FBG), and alanine aminotransferase (ALT) were also evaluated. Stepwise regressions performed to evaluate the associations between SF and other maternal parameters. In the second trimester, 11.4% pregnant women had a SF concentration less than 12 µg/L, and 7.6% pregnant women were anemic. SF levels were negatively correlated with serum TSH levels (r = -0.219, p < 0.05), and positively correlated with FT4 levels (r = 0.203, p < 0.05). Linear regression analysis showed only SF, age, week of gestation were significant predictors of regression with TSH as the dependent variable (ß: -0.007, -0.059, and 0.118 respectively; all p < 0.05). However consistent relation between the SF levels and FT4 was not observed in stepwise linear regression. Maternal iron status is a determinant of TSH concentrations during pregnancy in pregnant women during the second trimester.


Assuntos
Anemia Ferropriva/fisiopatologia , Ferritinas/sangue , Hipotireoidismo/etiologia , Fenômenos Fisiológicos da Nutrição Materna , Complicações na Gravidez/etiologia , Glândula Tireoide/fisiopatologia , Saúde da População Urbana , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/etnologia , Doenças Assintomáticas/epidemiologia , China/epidemiologia , Feminino , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/etnologia , Hipotireoidismo/fisiopatologia , Fenômenos Fisiológicos da Nutrição Materna/etnologia , Testes para Triagem do Soro Materno , Estado Nutricional/etnologia , Adeno-Hipófise/metabolismo , Adeno-Hipófise/fisiopatologia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etnologia , Complicações na Gravidez/fisiopatologia , Terceiro Trimestre da Gravidez , Fatores de Risco , Glândula Tireoide/fisiologia , Tireotropina/sangue , Tireotropina/metabolismo , Tiroxina/sangue , Saúde da População Urbana/etnologia , Adulto Jovem
18.
Oncotarget ; 8(33): 54227-54235, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903336

RESUMO

The expression and potential biological functions of G protein-coupled receptor kinase 6 (GRK6) in human glioma are tested in this study. We show that protein and mRNA expression of GRK6 in human glioma tissues was significantly higher than that in the normal brain tissues. Further immunohistochemistry assay analyzing total 118 human glioma tissues showed that GRK6 over-expression was correlated with glioma pathologic grade and patients' Karnofsky performance status (KPS) score. At the molecular level, in the GRK6-low H4 glioma cells, forced over-expression of GRK6 promoted cell proliferation. Reversely, siRNA-mediated knockdown of GRK6 in the U251MG (GRK6-high) cells led to proliferation inhibition and cell cycle arrest. Intriguingly, GRK6 could also be an important temozolomide resistance factor. Temozolomide-induced cytotoxicity was prominent only in GRK6-low H4 glioma cells. On the other hand, knockdown of GRK6 by targeted siRNA sensitized U251MG cells (GRK6-high) to temozolomide. Thus, GRK6 over-expression in glioma is important for cell proliferation and temozolomide resistance.

19.
Respir Res ; 18(1): 155, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28806967

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an obstinate pulmonary disease, causing irreversible alveoli collapse and increasing the risk for cardiovascular disease. Accumulating evidence has shown that the dysregulation of miRNAs is crucially involved in the pathogenesis and development of COPD. However, the effects and role of microRNA-181c (miR-181c) have not been investigated in a murine model of COPD. METHODS: miR-181c expression was detected in human lung tissue samples of 34 patients, an in vivo murine model of CS exposure, and primary human bronchial epithelial cells (HBECs) by qRT-PCR. Degeneration of lung tissue, necrosis, infiltration and neutrophil cells were assessed with H&E and flow cytometry. Interleukin (IL)-6 and IL-8 levels were determined by an enzyme-linked immunosorbent assay and qRT-PCR. Luciferase reporter assay and correlation analyses were used to confirm and measure the levels between miR-181c and its target CCN1. RESULTS: We showed that miR-181c was significantly down-regulated in lung tissues from patients with COPD compared to individuals who had never smoked (p < 0.01). We also observed a down-regulation of miR-181c in HBECs and a mouse model after cigarette smoke (CS) exposure. Functional assays demonstrated that miR-181c over-expression decreased the inflammatory response, neutrophil infiltration, reactive oxygen species (ROS) generation, and inflammatory cytokines induced by CS, while its down-regulation produced the opposite effects. Subsequent investigation found that CCN1 was a direct target of miR-181c. CCN1 expression was increased in lung tissues of COPD patients, and was negatively correlated with miR-181c expression in human COPD samples (p < 0.01). CONCLUSIONS: Taken together, our data suggest the critical roles of miR-181c and its target CCN1 in COPD development, and provide potential therapeutic targets for COPD treatment.


Assuntos
Proteína Rica em Cisteína 61/biossíntese , Pulmão/metabolismo , MicroRNAs/fisiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fumar/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Administração por Inalação , Idoso , Idoso de 80 Anos ou mais , Animais , Proteína Rica em Cisteína 61/genética , Feminino , Expressão Gênica , Humanos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , Distribuição Aleatória , Fumar/efeitos adversos , Fumar/patologia
20.
Chin J Integr Med ; 2016 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-27896586

RESUMO

OBJECTIVE: To assess the effects of berberine (BBR) on high-molecular weight (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high-fat (HF) diet fed rats. METHODS: Forty Wistar male rats were randomly assigned into a normal diet fed group and three HF diet (fat for 45% calories) fed groups (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks feeding, rats in the two of three HF diet fed groups were treated with 150 mg·kg-1·day-1 BBR (HF+LBBR group) and 380 mg·kg-1·day-1 BBR (HF+HBBR group) by gavage once a day respectively for the next 8 weeks while the rats in other groups treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were observed and recorded on daily basis. At the end of 12 weeks, the blood, liver, epididymal fat tissues and quadriceps femoris muscles were collected. Fasting insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin and HMW adiponectin levels were measured by enzyme linked immunosorbent assay method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine the insulinsensitizing. Meanwhile the homeostasis model assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The expressions of adipoR1, adipoR2 and adenosine monophophate activated protein kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were detected by Western blot. Liver and kidney toxicity were evaluated during treatment. RESULTS: The body weight of rats in high- or low-dose BBR group reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels decreased compared with HF+Veh group (P<0.05). BBR also increased the ratio of HMW to total adiponectin in high fat-fed rats compared with rats in the HF+Veh group. High- and low-dose BBR increased adipoR1 expression in skeletal muscle by over 6- and 2-fold (P<0.05), respectively, and high-dose BBR also increased adipoR2 expression in liver tissue by over 2-fold (P<0.05). BBR significantly increased AMPK phosphorylation in HF diet rats compared with normal diet rats (P<0.05). The ratio of HMW to total adiponectin was inversely correlated with HOMA-IR (r=-0.52, P=0.001). Meantime, no liver and kidney toxicity was found in high fat-fed rats that treated by BBR. CONCLUSION: Berberine may improve insulin resistance by increasing the expression of adiponectin receptors and the ratio of HMW to total adiponectin.

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