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1.
BMC Endocr Disord ; 21(1): 228, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781943

RESUMO

BACKGROUND: The outbreak of severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide. SARS-CoV-2 has been found to cause multiple organ damage; however, little attention has been paid to the damage to the endocrine system caused by this virus, and the subsequent impact on prognosis. This may be the first research on the hypothalamic-pituitary-thyroid (HPT) axis and prognosis in coronavirus disease 2019 (COVID-19). METHODS: In this retrospective observational study, 235 patients were admitted to the hospital with laboratory-confirmed SARS-CoV-2 infection from 22 January to 17 March 2020. Clinical characteristics, laboratory findings, and treatments were obtained from electronic medical records with standard data collection forms and compared among patients with different thyroid function status. RESULTS: Among 235 patients, 17 (7.23%) had subclinical hypothyroidism, 11 (4.68%) severe non-thyroidal illness syndrome (NTIS), and 23 (9.79%) mild to moderate NTIS. Composite endpoint events of each group, including mortality, admission to the ICU, and using IMV were observed. Compared with normal thyroid function, the hazard ratios (HRs) of composite endpoint events for mild to moderate NTIS, severe NTIS, subclinical hypothyroidism were 27.3 (95% confidence interval [CI] 7.07-105.7), 23.1 (95% CI 5.75-92.8), and 4.04 (95% CI 0.69-23.8) respectively. The multivariate-adjusted HRs for acute cardiac injury among patients with NTF, subclinical hypothyroidism, severe NTIS, and mild to moderate NTIS were 1.00, 1.68 (95% CI 0.56-5.05), 4.68 (95% CI 1.76-12.4), and 2.63 (95% CI 1.09-6.36) respectively. CONCLUSIONS: Our study shows that the suppression of the HPT axis could be a common complication in COVID-19 patients and an indicator of the severity of prognosis. Among the three different types of thyroid dysfunction with COVID-19, mild to moderate NTIS and severe NTIS have a higher risk of severe outcomes compared with subclinical hypothyroidism.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Síndromes do Eutireóideo Doente/etiologia , Hipertensão/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores Sexuais
2.
Front Endocrinol (Lausanne) ; 12: 727419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589058

RESUMO

Background: Blood parameters, such as neutrophil-to-lymphocyte ratio, have been identified as reliable inflammatory markers with diagnostic and predictive value for the coronavirus disease 2019 (COVID-19). However, novel hematological parameters derived from high-density lipoprotein-cholesterol (HDL-C) have rarely been studied as indicators for the risk of poor outcomes in patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Here, we aimed to assess the prognostic value of these novel biomarkers in COVID-19 patients and the diabetes subgroup. Methods: We conducted a multicenter retrospective cohort study involving all hospitalized patients with COVID-19 from January to March 2020 in five hospitals in Wuhan, China. Demographics, clinical and laboratory findings, and outcomes were recorded. Neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), and platelet to HDL-C ratio (PHR) were investigated and compared in both the overall population and the subgroup with diabetes. The associations between blood parameters at admission with primary composite end-point events (including mechanical ventilation, admission to the intensive care unit, or death) were analyzed using Cox proportional hazards regression models. Receiver operating characteristic curves were used to compare the utility of different blood parameters. Results: Of 440 patients with COVID-19, 67 (15.2%) were critically ill. On admission, HDL-C concentration was decreased while NHR was high in patients with critical compared with non-critical COVID-19, and were independently associated with poor outcome as continuous variables in the overall population (HR: 0.213, 95% CI 0.090-0.507; HR: 1.066, 95% CI 1.030-1.103, respectively) after adjusting for confounding factors. Additionally, when HDL-C and NHR were examined as categorical variables, the HRs and 95% CIs for tertile 3 vs. tertile 1 were 0.280 (0.128-0.612) and 4.458 (1.817-10.938), respectively. Similar results were observed in the diabetes subgroup. ROC curves showed that the NHR had good performance in predicting worse outcomes. The cutoff point of the NHR was 5.50. However, the data in our present study could not confirm the possible predictive effect of LHR, MHR, and PHR on COVID-19 severity. Conclusion: Lower HDL-C concentrations and higher NHR at admission were observed in patients with critical COVID-19 than in those with noncritical COVID-19, and were significantly associated with a poor prognosis in COVID-19 patients as well as in the diabetes subgroup.


Assuntos
COVID-19/sangue , HDL-Colesterol/sangue , Diabetes Mellitus/sangue , Idoso , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , China , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucócitos/citologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
3.
Cell Stem Cell ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34582804

RESUMO

Adult stem cells maintain regenerative tissue structure and function by producing tissue-specific progeny, but the factors that preserve their tissue identities are not well understood. The small and large intestines differ markedly in cell composition and function, reflecting their distinct stem cell populations. Here we show that SATB2, a colon-restricted chromatin factor, singularly preserves LGR5+ adult colonic stem cell and epithelial identity in mice and humans. Satb2 loss in adult mice leads to stable conversion of colonic stem cells into small intestine ileal-like stem cells and replacement of the colonic mucosa with one that resembles the ileum. Conversely, SATB2 confers colonic properties on the mouse ileum. Human colonic organoids also adopt ileal characteristics upon SATB2 loss. SATB2 regulates colonic identity in part by modulating enhancer binding of the intestinal transcription factors CDX2 and HNF4A. Our study uncovers a conserved core regulator of colonic stem cells able to mediate cross-tissue plasticity in mature intestines.

4.
Diabetes Metab Syndr Obes ; 14: 2561-2571, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135608

RESUMO

Purpose: Changes in transition from metabolically healthy overweight/obesity (MHO) to metabolically unhealthy overweight/obesity (MUO) are associated with the risk for cardiometabolic complications. This study aims to investigate the effects of short-term dynamic changes in body mass index (BMI) and metabolic status on the risk of type 2 diabetes (T2D) and to identify biological predictors for the MHO-to-MUO transition. Patients and Methods: A total of 4604 subjects from the REACTION study were included for a 3-year follow-up. Subjects were categorized based on their BMI and metabolic syndrome status. Overweight/obesity was defined as BMI ≥ 24 kg/m2. Metabolically healthy was defined as having two or fewer of the metabolic syndrome components proposed by the Chinese Diabetes Society. Thus, subjects were divided into four groups: metabolically healthy normal weight (MHNW), MHO, metabolically unhealthy normal weight (MUNW), and MUO. Results: Compared with MHNW, MHO was not predisposed to an increased risk for T2D (OR 1.08, 95% CI 0.64-1.83, P = 0.762). However, a 3-year transition probability of 20.6% was identified for subjects who shifted from MHO to MUO; this conversion increased the risk of T2D by 3-fold (OR 3.04, 95% CI 1.21-7.68, P = 0.018). The fatty liver index independently predicted the MHO-to-MUO transition with an OR 3.14 (95% CI 1.56-7.46, P = 0.002) when comparing the fourth quartile to the first quartile. Conclusion: This study reveals that metabolic changes affect the short-term susceptibility to T2D in the overweight/obese Chinese population, and the fatty liver index is an efficient clinical parameter for identifying those with a metabolic deterioration risk.

5.
Epidemiol Infect ; 149: e144, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33397542

RESUMO

The coronavirus disease 2019 (COVID-19) epidemic is spreading globally. Studies revealed that obesity may affect the progression and prognosis of COVID-19 patients. The aim of the meta-analysis is to identify the prevalence and impact of obesity on COVID-19. Studies on obese COVID-19 patients were obtained by searching PubMed, Cochrane Library databases and Web of Science databases, up to date to 5 June 2020. And the prevalence rate and the odds ratio (OR) of obesity with 95% confidence interval (CI) were used as comprehensive indicators for analysis using a random-effects model. A total of 6081 patients in 11 studies were included. The prevalence of obesity in patients with COVID-19 was 30% (95% CI 21-39%). Obese patients were 1.79 times more likely to develop severe COVID-19 than non-obese patients (OR 1.79, 95% CI 1.52-2.11, P < 0.0001, I2 = 0%). However obesity was not associated with death in COVID-19 patients (OR 1.05, 95% CI 0.65-1.71, P = 0.84, I2 = 66.6%). In dose-response analysis, it was estimated that COVID-19 patients had a 16% increased risk of invasive mechanical ventilation (OR 1.16, 95% CI 1.10-1.23, P < 0.0001) and a 20% increased risk of admission to ICU (OR 1.20, 95% CI 1.11-1.30, P < 0.0001) per 5 kg/m2 increase in BMI. In conclusion, obesity in COVID-19 patients is associated with severity, but not mortality.


Assuntos
COVID-19/complicações , Obesidade/complicações , Índice de Massa Corporal , COVID-19/epidemiologia , COVID-19/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença
6.
BMC Complement Med Ther ; 20(1): 373, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298044

RESUMO

BACKGROUND: 4-Hydroxyisoleucine (4-HIL) is an active ingredient extracted from Trigonella foenum-graecum L., a Chinese traditional herbal medicine, which exerts the efficacy of anti-obesity and anti-diabetes. We previously reported that 4-HIL potentiates anti-inflammatory and anti-insulin resistance effects through down-regulation of TNF-α and TNF-α converting enzyme (TACE) in 3 T3-L1 adipocytes and HepG2 cells. In the present study, we further investigate the effects and mechanisms of 4-HIL on obesity-induced inflammation in RAW264.7 macrophages and 3 T3-L1 adipocytes co-culture system. METHODS: RAW264.7 macrophages and 3 T3-L1 adipocytes were co-cultured to mimic the microenvironment of adipose tissue. siRNA-iRhom2 transfection was performed to knockdown iRhom2 expression in RAW264.2 macrophages. The mRNA and protein expression of iRhom2 and TACE were measured by real-time quantitative PCR (RT-qPCR) and western blotting. The production of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), IL-6 and IL-10 were evaluated by ELISA. The ratio of M2/M1 was detected by flow cytometry. RESULTS: 4-HIL significantly repressed the mRNA and protein levels of iRhom2 and TACE in RAW264.7 macrophages after LPS stimulated. Meanwhile, the levels of pro-inflammatory cytokines, including TNF-α, MCP-1, and IL-6, were substantially suppressed by 4-HIL in the co-culture system. Moreover, the level of anti-inflammatory cytokine IL-10 was increased significantly by 4-HIL in the co-culture system after LPS stimulation. Additionally, the ratio of M2/M1 was also increased by 4-HIL in the co-culture system after LPS stimulation. Finally, these effects of 4-HIL were largely enhanced by siRNA-iRhom2 transfection. CONCLUSION: Taken together, our results indicated that obesity-induced inflammation was potently relieved by 4-HIL, most likely through the iRhom2-dependent pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Isoleucina/análogos & derivados , Medicina Tradicional Chinesa/métodos , Células 3T3-L1 , Animais , Técnicas de Cocultura , Isoleucina/farmacologia , Lipopolissacarídeos , Camundongos , Células RAW 264.7
7.
Biomed Res Int ; 2020: 4138657, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381554

RESUMO

Background: Associations between iodine intake and thyroid nodules (TNs) were not consistent. We aimed to illustrate the relationship between urinary iodine concentration (UIC) and TNs. Methods: A total of 12,698 participants were enrolled in analysis. All of the participants filled out questionnaires and underwent physical examinations, laboratory tests, and thyroid ultrasonography. UIC, serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) were measured in the central laboratory. Results: The prevalence of TNs was 16.00%, and the median UIC was 206.1 µg/L. TNs and UIC were negatively related when UIC was less than 527 µg/L (adjusted OR = 0.87; 95% CI, 0.80, 0.94), and the relationship between UIC and TNs was not statistically significant when UIC was greater than 527 µg/L (adjusted OR = 1.25; 95% CI, 0.98, 1.60). In women, UIC was negatively associated with risk for TNs (adjusted OR 0.95; 95% CI, 0.91, 0.99). Conclusion: The relationship between TNs and UIC differed between men and women. The risk of TNs decreased with the elevation of UIC in men when UIC was lower than 527 µg/L, while UIC and the presence of TNs were negatively correlated in women. In the future, cohort studies or other studies that can explain causality must be conducted to explore the relationship between iodine status and TNs.


Assuntos
Iodo/urina , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/urina , Adulto , Autoanticorpos/sangue , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônios Tireóideos/sangue
8.
Biomed Pharmacother ; 132: 110818, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33053509

RESUMO

Diabetic retinopathy(DR) is an expanding global health problem, the exact mechanism of which has not yet been clarified clearly, new insights into retinal physiology indicate that diabetes-induced retinal dysfunction may be viewed as an impairment of the retinal neurovascular unit, including retinal ganglion cells, glial cells, endothelial cells, pericytes, and retinal pigment epithelium. Different retinal cells have unique structure and functions, while the interactions among which are less known. Cells are the basic unit of organism structure and function, their impairment could lead to abnormal physiological functions and even organ disorder. Considering the body is multi-dimension and the complexity of DR, one point or a single type of cell can't be used to illustrate the mechanism of occurrence and development of DR. In this review, we provided a systematic and comprehensive elaboration of the cells that are involved in the process of DR. We underlined the importance of considering the neurovascular unit, not just retinal vascular and neural cells, in understanding the pathophysiology of DR. Our studies provided a better understanding of the pathological process in DR and provide a theoretical basis for further research.


Assuntos
Retinopatia Diabética/fisiopatologia , Retina/citologia , Animais , Células Endoteliais/citologia , Humanos , Retina/patologia , Células Ganglionares da Retina/citologia , Epitélio Pigmentado da Retina/citologia , Vasos Retinianos/citologia
9.
Life Sci ; 258: 118222, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768577

RESUMO

AIMS: We previously reported that fenugreek-derived 4-hydroxyisoleucine ameliorates insulin resistance via regulation of TNF-α converting enzyme (TACE) expression. In the present study, we further investigate the effects and mechanisms of fenugreek on obesity-induced inflammation and insulin signaling in the high-fat diet (HFD)-challenged obese mice. MAIN METHODS: After 12 weeks of HFD intervention, mice were treated with the low or high dosages of fenugreek. Serum levels of glucose, insulin, lipid profile, inflammation cytokines, and adipokines were detected. Macrophage infiltration and adipose tissue morphology were observed. Western blot was conducted to investigate the expressions of inactive rhomboid 2 (iRhom2) and TACE as well as other signaling pathways in subcutaneous adipose tissue. KEY FINDINGS: We showed that fenugreek significantly suppressed body weight gain and fat accumulation in HFD-challenged obese mice. Meanwhile, fasting glucose, insulin, and HOMA-IR in fenugreek-treated mice were remarkably decreased, which were properly explained by fenugreek-induced activation of the insulin receptor signaling pathway. Moreover, the anti-inflammatory properties of fenugreek were shown by the decrease of systemic and local expressions of pro-inflammatory cytokines as well as reduced macrophage infiltration into adipose tissue. Additionally, fenugreek markedly deactivated NF-κB and JNK pathways. Finally, we demonstrated that fenugreek strikingly repressed the transcriptions and expressions of iRhom2 and TACE. SIGNIFICANCE: Fenugreek shows an encouraging and promising property in ameliorating insulin resistance and suppressing inflammation in obesity, which might be realized by fenugreek-mediated inhibition of iRhom2/TACE axis-facilitated TNF-α release from adipocytes.


Assuntos
Proteína ADAM17/antagonistas & inibidores , Proteínas de Transporte/antagonistas & inibidores , Mediadores da Inflamação/antagonistas & inibidores , Resistência à Insulina/fisiologia , Obesidade/tratamento farmacológico , Trigonella , Proteína ADAM17/sangue , Animais , Proteínas de Transporte/sangue , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Inflamação/sangue , Inflamação/tratamento farmacológico , Mediadores da Inflamação/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sementes
10.
Artigo em Inglês | MEDLINE | ID: mdl-32754119

RESUMO

Background: Diabetes correlates with poor prognosis in patients with COVID-19, but very few studies have evaluated whether impaired fasting glucose (IFG) is also a risk factor for the poor outcomes of patients with COVID-19. Here we aimed to examine the associations between IFG and diabetes at admission with risks of complications and mortality among patients with COVID-19. Methods: In this multicenter retrospective cohort study, we enrolled 312 hospitalized patients with COVID-19 from 5 hospitals in Wuhan from Jan 1 to Mar 17, 2020. Clinical information, laboratory findings, complications, treatment regimens, and mortality status were collected. The associations between hyperglycemia and diabetes status at admission with primary composite end-point events (including mechanical ventilation, admission to intensive care unit, or death) were analyzed by Cox proportional hazards regression models. Results: The median age of the patients was 57 years (interquartile range 38-66), and 172 (55%) were women. At the time of hospital admission, 84 (27%) had diabetes (and 36 were new-diagnosed), 62 (20%) had IFG, and 166 (53%) had normal fasting glucose (NFG) levels. Compared to patients with NFG, patients with IFG and diabetes developed more primary composite end-point events (9 [5%], 11 [18%], 26 [31%]), including receiving mechanical ventilation (5 [3%], 6 [10%], 21 [25%]), and death (4 [2%], 9 [15%], 20 [24%]). Multivariable Cox regression analyses showed diabetes was associated increased risks of primary composite end-point events (hazard ratio 3.53; 95% confidence interval 1.48-8.40) and mortality (6.25; 1.91-20.45), and IFG was associated with an increased risk of mortality (4.11; 1.15-14.74), after adjusting for age, sex, hospitals and comorbidities. Conclusion: IFG and diabetes at admission were associated with higher risks of adverse outcomes among patients with COVID-19.


Assuntos
Glicemia/metabolismo , Infecções por Coronavirus/mortalidade , Complicações do Diabetes/mortalidade , Diabetes Mellitus/fisiopatologia , Intolerância à Glucose/complicações , Hiperglicemia/complicações , Pneumonia Viral/mortalidade , Adulto , Idoso , Betacoronavirus/isolamento & purificação , COVID-19 , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/virologia , Diabetes Mellitus/virologia , Jejum , Feminino , Seguimentos , Intolerância à Glucose/virologia , Mortalidade Hospitalar , Hospitalização , Humanos , Hiperglicemia/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Taxa de Sobrevida
12.
Diabetes Obes Metab ; 22(10): 1897-1906, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32469464

RESUMO

AIM: To evaluate the association between different degrees of hyperglycaemia and the risk of all-cause mortality among hospitalized patients with COVID-19. MATERIALS AND METHODS: In a retrospective study conducted from 22 January to 17 March 2020, 453 patients were admitted to Union Hospital in Wuhan, China, with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Patients were classified into four categories: normal glucose, hyperglycaemia (fasting glucose 5.6-6.9 mmol/L and/or HbA1c 5.7%-6.4%), newly diagnosed diabetes (fasting glucose ≥7 mmol/L and/or HbA1c ≥6.5%) and known diabetes. The major outcomes included in-hospital mortality, intensive care unit (ICU) admission and invasive mechanical ventilation (IMV). RESULTS: Patients with newly diagnosed diabetes constituted the highest percentage to be admitted to the ICU (11.7%) and require IMV (11.7%), followed by patients with known diabetes (4.1%; 9.2%) and patients with hyperglycaemia (6.2%; 4.7%), compared with patients with normal glucose (1.5%; 2.3%), respectively. The multivariable-adjusted hazard ratios of mortality among COVID-19 patients with normal glucose, hyperglycaemia, newly diagnosed diabetes and known diabetes were 1.00, 3.29 (95% confidence interval [CI] 0.65-16.6), 9.42 (95% CI 2.18-40.7) and 4.63 (95% CI 1.02-21.0), respectively. CONCLUSION: We showed that COVID-19 patients with newly diagnosed diabetes had the highest risk of all-cause mortality compared with COVID-19 patients with known diabetes, hyperglycaemia and normal glucose. Patients with COVID-19 need to be kept under surveillance for blood glucose screening.


Assuntos
Doenças Assintomáticas/mortalidade , COVID-19/mortalidade , COVID-19/terapia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/terapia , Idoso , Doenças Assintomáticas/terapia , Glicemia/fisiologia , COVID-19/complicações , COVID-19/epidemiologia , China/epidemiologia , Diabetes Mellitus/diagnóstico , Feminino , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Hiperglicemia/mortalidade , Hiperglicemia/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/fisiologia
13.
EMBO Mol Med ; 12(7): e12421, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32428990

RESUMO

Progression to severe disease is a difficult problem in treating coronavirus disease 2019 (COVID-19). The purpose of this study is to explore changes in markers of severe disease in COVID-19 patients. Sixty-nine severe COVID-19 patients were included. Patients with severe disease showed significant lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, and D-dimer was found in most severe cases. Baseline interleukin-6 (IL-6) was found to be associated with COVID-19 severity. Indeed, the significant increase of baseline IL-6 was positively correlated with the maximal body temperature during hospitalization and with the increased baseline of CRP, LDH, ferritin, and D-dimer. High baseline IL-6 was also associated with more progressed chest computed tomography (CT) findings. Significant decrease in IL-6 and improved CT assessment was found in patients during recovery, while IL-6 was further increased in exacerbated patients. Collectively, our results suggest that the dynamic change in IL-6 can be used as a marker for disease monitoring in patients with severe COVID-19.


Assuntos
Infecções por Coronavirus/patologia , Interleucina-6/análise , Pneumonia Viral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Biomarcadores/análise , Proteína C-Reativa/análise , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Feminino , Humanos , Linfopenia/etiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
15.
Addiction ; 114(3): 436-449, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30326548

RESUMO

AIM: To assess the causality between alcohol intake, diabetes risk and related traits. DESIGN: Mendelian randomization (MR) study. Subgroup analysis, standard instrumental variable analysis and local average treatment effect (LATE) methods were applied to assess linear and non-linear causality. SETTING: China. PARTICIPANTS: A total of 4536 participants, including 721 diabetes cases. FINDINGS: Carriage of an ALDH2 rs671 A allele reduced alcohol consumption by 44.63% [95% confidence interval (CI) = -49.44%, -39.37%]. In males, additional carriage of an A allele was significantly connected to decreased diabetes risk for the overall population [odds ratio (OR) = 0.716, 95% CI = 0.567-0.904, P = 0.005] or moderate drinkers (OR = 0.564, 95% CI = 0.355-0.894, P = 0.015). In instrumental variable (IV) analysis, increasing alcohol consumption by 1.7-fold was associated with an incidence-rate ratio of 1.32 (95% CI = 1.06-1.67, P = 0.014) for diabetes risk, and elevated alcohol intake was causally connected to natural log-transformed fasting, 2-hour post-load plasma glucose (ß = 0.036, 95% CI = 0.018-0.054; ß = 0.072, 95% CI = 0.035-0.108) and insulin resistance [homeostatic model assessment for IR (HOMA-IR] (ß = 0.104, 95% CI = 0.039-0.169), but was not associated with beta-cell function (HOMA-beta). In addition, the LATE method did not identify significant U-shaped causality between alcohol consumption and diabetes-related traits. In females, the effects of alcohol intake on all the outcomes were non-significant. CONCLUSION: Among men in China, higher alcohol intake appears to be causally associated with increased diabetes risk and worsened related traits, even for moderate drinkers. This study found no significant U-shaped causality between alcohol consumption and diabetes-related traits.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Diabetes Mellitus/epidemiologia , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , China/epidemiologia , Feminino , Humanos , Resistência à Insulina , Células Secretoras de Insulina , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Fatores Sexuais
16.
Endocr Connect ; 7(12): 1507-1517, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30521481

RESUMO

Objective: To explore the influence by not performing an oral glucose tolerance test (OGTT) in Han Chinese over 40 years. Design: Overall, 6682 participants were included in the prospective cohort study and were followed up for 3 years. Methods: Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2h-PG), FPG and 2h-PG (OGTT), and HbA1c testing using World Health Organization (WHO) or American Diabetes Association (ADA) criteria were employed for strategy analysis. Results: The prevalence of diabetes is 12.4% (95% CI: 11.6-13.3), while the prevalence of prediabetes is 34.1% (95% CI: 32.9-35.3) and 56.5% (95% CI: 55.2-57.8) using WHO and ADA criteria, respectively. 2h-PG determined more diabetes individuals than FPG and HbA1c. The testing cost per true positive case of OGTT is close to FPG and less than 2h-PG or HbA1c. FPG, 2h-PG and HbA1c strategies would increase costs from complications for false-positive (FP) or false-negative (FN) results compared with OGTT. Moreover, the least individuals identified as normal by OGTT at baseline developed (pre)diabetes, and the most prediabetes individuals identified by HbA1c or FPG using ADA criteria developed diabetes. Conclusions: The prevalence of isolated impaired glucose tolerance and isolated 2-h post-load diabetes were high, and the majority of individuals with (pre)diabetes were undetected in Chinese Han population. Not performing an OGTT results in underdiagnosis, inadequate developing risk assessment and probable cost increases of (pre)diabetes in Han Chinese over 40 years and great consideration should be given to OGTT in detecting (pre)diabetes in this population. Further population-based prospective cohort study of longer-term effects is necessary to investigate the risk assessment and cost of (pre)diabetes.

17.
Front Immunol ; 9: 1775, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123216

RESUMO

The thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) axis is involved in multiple inflammatory immune diseases, including coronary artery disease (CAD). To explore the causal relationship between this axis and CAD, we performed a three-stage case-control association analysis with 3,628 CAD cases and 3,776 controls using common variants in the genes TSLP, interleukin 7 receptor (IL7R), and TSLPR. Three common variants in the TSLP/TSLPR axis were significantly associated with CAD in a Chinese Han population [rs3806933T in TSLP, Padj = 4.35 × 10-5, odds ratio (OR) = 1.18; rs6897932T in IL7R, Padj = 1.13 × 10-7, OR = 1.31; g.19646A>GA in TSLPR, Padj = 2.04 × 10-6, OR = 1.20]. Reporter gene analysis demonstrated that rs3806933 and rs6897932 could influence TSLP and IL7R expression, respectively. Furthermore, the "T" allele of rs3806933 might increase plasma TSLP levels (R2 = 0.175, P < 0.01). In a stepwise procedure, the risk for CAD increased by nearly fivefold compared with the maximum effect of any single variant (Padj = 6.99 × 10-4, OR = 4.85). In addition, the epistatic interaction between TSLP and IL33 produced a nearly threefold increase in the risk of CAD in the combined model of rs3806933TT-rs7025417TT (Padj = 3.67 × 10-4, OR = 2.98). Our study illustrates that the TSLP/TSLPR axis might be involved in the pathogenesis of CAD through upregulation of mRNA or protein expression of the referenced genes and might have additive effects on the CAD risk when combined with IL-33 signaling.


Assuntos
Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Citocinas/genética , Epistasia Genética , Regulação da Expressão Gênica , Interleucina-33/genética , Receptores de Citocinas/genética , Idoso , Alelos , Estudos de Casos e Controles , China , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Citocinas/sangue , Citocinas/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-33/metabolismo , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Receptores de Citocinas/metabolismo , Receptores de Interleucina-7/genética , Transdução de Sinais
18.
J Diabetes ; 10(9): 708-714, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29437292

RESUMO

BACKGROUND: Dyslipidemia predicts the development and progression of diabetes. A higher non-high-density lipoprotein cholesterol (HDL-C): HDL-C ratio is reportedly associated with metabolic syndrome and insulin resistance, but its relationship with glycemic levels and diabetes remains unclear. METHODS: In all, 4882 subjects aged ≥40 years without diabetes and not using lipid-lowering drugs were enrolled in the study. The non-HDL-C: HDL-C ratio was log10 transformed to achieve normal distribution. Multivariate logistic regression was used to investigate the association between the log10 -transformed non-HDL-C: HDL-C ratio and diabetes. Stratified analyses of the association by age, gender, and body mass index (BMI) were also performed. RESULTS: After 3 years of follow-up, 704 participants developed diabetes. After adjustment for age, gender, current smoking, current drinking, physical activity, BMI, systolic blood pressure, and family history of diabetes, each 1-SD increase in the log(non-HDL-C: HDL-C ratio) was associated with higher fasting blood glucose (FPG) levels (ß = 0.1; 95% confidence interval [CI] 0.1-0.1), 2-h postload plasma glucose levels (2-h glucose; ß = 0.2; 95% CI 0.1-0.2), and risk of diabetes (odds ratio [OR] 1.1; 95% CI 1.0-1.2). In a multivariate model, subjects in the top quartile of non-HDL-C: HDL-C ratio had higher FPG (ß = 0.2; 95% CI 0.2-0.3), 2-h glucose (ß = 0.5; 95% CI 0.3-0.7) and HbA1c (ß = 0.1; 95% CI 0.1-0.2) levels, and a 40% increased risk of diabetes (OR 1.4; 95% CI 1.1-1.8) than participants in the bottom quartile. CONCLUSIONS: The non-HDL-C: HDL-C ratio was found to be an independent risk factor for diabetes.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colesterol/sangue , Diabetes Mellitus/sangue , Glicemia/análise , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
20.
Exp Biol Med (Maywood) ; 242(3): 297-304, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27190252

RESUMO

Catch-up growth in adult, is increasingly recognized as an important causative factor for the extremely prevalent insulin resistance-related diseases especially in developing countries/territories. We aimed to investigate the alteration of bile acids level, phosphorylation and sumoylation of its interacting protein, bile acid receptor/farnesoid X receptor and their downstream signaling pathway, as well as insulin sensitivity and lipid profile in catch-up growth in adult rats. Male Sprague-Dawley rats were randomly allocated into four groups for two sampling points: caloric restriction group, catch-up growth in adult refed with normal chow and their normal chow controls for four or eight weeks (N4, N8 individually).We found that total serum bile acids and farnesoid X receptor phosphorylation increased without significant changes in farnesoid X receptor sumoylation and its downstream small heterodimer partner expression at the end of caloric restriction stage, while the visceral fat decreased and insulin resistance never occurred in these animals; After refeeding, total serum bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as Cyp7a1, SREBP-1c mRNA levels were higher with significant decrease in small heterodimer partner expression, which is associated fat accumulation, and drastic insulin resistance in whole body and skeletal muscle. Our findings demonstrated that the fat accumulation and insulin resistance are associated with increases of bile acids, alteration of farnesoid X receptor phosphorylation, and sumoylation and its downstream signaling pathway. These changes of bile acids, farnesoid X receptor phosphorylation and sumoylation, as well as their downstream signaling might be of importance in the etiology of fat accumulation and insulin resistance in catch-up growth in adult.


Assuntos
Ácidos e Sais Biliares/metabolismo , Restrição Calórica , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/fisiologia , Fígado/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Ácidos e Sais Biliares/sangue , Glicemia/fisiologia , Colesterol 7-alfa-Hidroxilase/genética , Masculino , Fosforilação , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Sumoilação , Triglicerídeos/sangue
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