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1.
Hypertens Res ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632456

RESUMO

Data on the prognosis of clinically undiagnosed hypertensive patients who are aldosterone-to-renin ratio (ARR) positive are still scarce. Therefore, we investigated the clinical characteristics of clinically undiagnosed hypertensive patients who were ARR-positive and the influence of their different treatments on the occurrence and development of complications. A total of 285 hypertensive patients data with ARR ≥ 3.8 in the Second People's Hospital of Huai'an from January 2019 to December 2021 were collected, and 135 undiagnosed hypertensive patients were ultimately included in the analysis. According to their treatment strategy in various clinical departments, 135 patients were divided into the operation, spironolactone and control groups. Then, the clinical characteristics and the occurrence and development of complications in the three groups were compared. The results suggested that: (1) Only 34 (11.9%) of 285 hypertensive patients with ARR ≥ 3.8 were clearly diagnosed with Primary aldosteronism (PA) through functional tests, and the blood pressure (BP) compliance rate was only 50.30% during follow-up. (2) Based on exclusion criteria, 135 undiagnosed hypertensive patients were eventually included in the analysis. Patients in the surgery group had lower blood potassium levels and higher aldosterone levels than those in the other two groups, and their risk of new cerebrovascular complications was lower than that of the patients in the spironolactone group. (3) The risk of new cerebrovascular complications in the spironolactone group was 9.520 times higher than that of the control group, and this risk mainly occurred in patients with ARR values of 3.8-5.7. On the whole, surgery remains a good option for hypertensive patients with severe hyperaldosteronism and hypokalemia and those unable to undergo confirmatory tests; however, spironolactone therapy in patients with clinically undiagnosed hypertension, especially those with 3.8 ≤ ARR < 5.7, confered a higher risk of new cerebrovascular complications.

2.
Mol Cell Endocrinol ; 584: 112164, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38262527

RESUMO

Branched-chain amino acid (BCAA) metabolism is associated with triglyceride (TG) metabolism and the development of cardiovascular disease (CVD). However, the underlying mechanism remains uncertain. This study included 1302 subjects and followed for 4-5 years. A hyperbranched-chain aminoacidemia rat model was induced by high fructose diet (HFTD). The relationship between BCAAs and TG level and its regulatory mechanism was investigated in vitro. As results, as baseline BCAA percentile increased, subjects had higher prevalence and incidence of T2DM, NAFLD, and CVD risk (P < 0.05). In animal model, the accumulation of BCAAs and TG and betatrophin expression were significantly elevated in the HFTD group when comparing with those in the SD group(P < 0.05). Immunofluorescence and Masson's trichrome staining revealed that the area of interstitial fibrosis was significantly increased in the HFTD group compared with control group. Met treatment significantly decreased TG levels and betatrophin expression and reversed myocardial fibrosis (P < 0.05). In vitro, LO2 cells, stimulated with 0.1-5 mM BCAAs, displayed a significant dose-dependent increase in betatrophin expression (P < 0.05). And 5 mM BCAAs stimulation significantly increased the p-mTOR and SREBP-1 expression (P < 0.05). However, this effect could be reversed by using the corresponding inhibitor or siRNAs. In conclusions, BCAAs promote occurrence and development of cardiovascular disease dependent on TG metabolism via activation of the mTOR/SREBP-1/betatrophin pathway. The study provides a new theory for the pathogenesis of CVD caused by amino acid metabolism disorders.


Assuntos
Aminoácidos de Cadeia Ramificada , Doenças Cardiovasculares , Humanos , Ratos , Animais , Aminoácidos de Cadeia Ramificada/metabolismo , Proteína 8 Semelhante a Angiopoietina , Proteína de Ligação a Elemento Regulador de Esterol 1 , Serina-Treonina Quinases TOR/metabolismo , Triglicerídeos
3.
Endocr Connect ; 12(10)2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37522853

RESUMO

Previous studies have shown that the elevated levels of circulating branched-chain amino acids (BCAAs) are associated with the development of insulin resistance and its complications, including obesity, type 2 diabetes, cardiovascular disease and some cancers. However, animal models that can mimic the metabolic state of chronically elevated BCAAs in humans are rare. Therefore, the aim of this study was to establish the above animal model and analyse the metabolic changes associated with high BCAA levels. Sixteen 8-week-old Sprague-Dawley (SD) rats were randomly divided into two groups and given either a high fructose diet or a normal diet. BCAA levels as well as blood glucose and lipid levels were measured at different time points of feeding. The mRNA expression levels of two key enzymes of BCAA catabolism, ACAD (acyl-CoA dehydrogenase) and BCKDH (branched-chain α-keto acid dehydrogenase), were measured by qPCR, and the protein expression levels of these two enzymes were analysed by immunohistochemistry. Finally, the metabolite expression differences between the two groups were analysed by Q300 metabolomics technology. Our study confirms that defects in the catabolic pathways of BCAAs lead to increased levels of circulating BCAAs, resulting in disorders of glucose and lipid metabolism characterized by insulin resistance by affecting metabolic pathways associated with amino acids and bile acids.

4.
Arch. endocrinol. metab. (Online) ; 67(3): 306-313, June 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1429759

RESUMO

ABSTRACT Objective: Intrathyroidal injection using an insulin pen filled with a mixture of lidocaine and triamcinolone acetonide is a therapy for subacute thyroiditis (SAT) reported by us previously. We aimed to evaluate the clinical efficacy of ultrasound-guided intrathyroidal injection in the treatment of SAT. Subjects and methods: A total of 93 patients with SAT completed the study. All patients were evaluated via a history and clinical examination followed by thyroid function tests and ultrasonography of the thyroid. After ultrasound-guided intrathyroidal injection, the patients were followed up with respect to the injection frequency, treatment duration, and patient satisfaction. The visual numerical rating scale was used as a pain questionnaire for a given interval. Results: Thyroid pain instantly decreased to scores below 3.0 following the first injection. Sixty-three patients (67.74%) avoided relapse of thyroid pain within 3 injections, which occurred within only 3 days after the first injection. The pain in 27 patients (29.03%) disappeared completely after 4-6 injections. Only 3 patients (3.23%) were found to need more than 6 injections, with 10 cited as the maximum number of injections, the injection took only 17 days altogether. The mean treatment cycle of the intrathyroidal injection was 3.98 days. There were no other associated complications with the novel therapy except infrequent small subcutaneous hematomas, which could be prevented with skilled practice. The average patient satisfaction score was as high as 9.0. Conclusion: Intrathyroidal injection of lidocaine and triamcinolone acetonide using an insulin pen was found to be an advantageous and satisfactory treatment for SAT.

5.
Endocrinol Diabetes Nutr (Engl Ed) ; 70(2): 124-129, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36925229

RESUMO

INTRODUCTION: circRNA LRP6 participates in high-glucose-regulated cellular behaviours, while its role in gestational diabetes mellitus (GDM) is unclear. Our preliminary sequencing analysis revealed the altered expression of LRP6, suggesting its potential involvement in GDM and possible clinical value. This study explored the involvement of LRP6 in GDM. METHODS: In this study, a total of 300 pregnant women were enrolled and followed up until delivery. The occurrence of GDM and adverse outcomes was recorded. These 300 participants were grouped into high and low LRP6 level groups (n=150; cutoff=median). Occurrence of GDM and adverse outcomes were compared between the two groups. ROC curve analysis was conducted to explore the role of LRP6 expression on the day of admission in predicting GDM. Associations between LRP6 expression and adverse outcomes were analysed with the Chi-squared test. RESULTS: We observed that participants in the high LRP6 level group experienced a higher incidence of GDM during follow-up (33/150) compared to those in the low LRP6 level group (10/150). Compared to participants who developed GDM during follow-up, participants who did not develop GDM showed lower expression levels of LRP6 in plasma. ROC curve analysis showed that high expression levels of LRP6 on the day of admission effectively distinguished potential GDM patients from other participants. Interestingly, LRP6 was only closely associated with foetal malformation and intrauterine death, but not premature delivery, hypertension, macrosomia, intrauterine distress, miscarriage and intrauterine infection in all participants. CONCLUSION: Therefore, increased expression levels of LRP6 in GDM predicts foetal malformation and intrauterine death.


Assuntos
Diabetes Gestacional , Doenças do Recém-Nascido , Recém-Nascido , Gravidez , Feminino , Humanos , Resultado da Gravidez , RNA Circular , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade
6.
Arch Endocrinol Metab ; 67(3): 306-313, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36468926

RESUMO

Objective: : Intrathyroidal injection using an insulin pen filled with a mixture of lidocaine and triamcinolone acetonide is a therapy for subacute thyroiditis (SAT) reported by us previously. We aimed to evaluate the clinical efficacy of ultrasound-guided intrathyroidal injection in the treatment of SAT. Subjects and methods: A total of 93 patients with SAT completed the study. All patients were evaluated via a history and clinical examination followed by thyroid function tests and ultrasonography of the thyroid. After ultrasound-guided intrathyroidal injection, the patients were followed up with respect to the injection frequency, treatment duration, and patient satisfaction. The visual numerical rating scale was used as a pain questionnaire for a given interval. Results: Thyroid pain instantly decreased to scores below 3.0 following the first injection. Sixty-three patients (67.74%) avoided relapse of thyroid pain within 3 injections, which occurred within only 3 days after the first injection. The pain in 27 patients (29.03%) disappeared completely after 4-6 injections. Only 3 patients (3.23%) were found to need more than 6 injections, with 10 cited as the maximum number of injections, the injection took only 17 days altogether. The mean treatment cycle of the intrathyroidal injection was 3.98 days. There were no other associated complications with the novel therapy except infrequent small subcutaneous hematomas, which could be prevented with skilled practice. The average patient satisfaction score was as high as 9.0. Conclusion: Intrathyroidal injection of lidocaine and triamcinolone acetonide using an insulin pen was found to be an advantageous and satisfactory treatment for SAT.


Assuntos
Insulinas , Tireoidite Subaguda , Humanos , Lidocaína/uso terapêutico , Triancinolona Acetonida/uso terapêutico , Triancinolona Acetonida/efeitos adversos , Anestésicos Locais/uso terapêutico , Dor/induzido quimicamente , Dor/tratamento farmacológico , Resultado do Tratamento , Insulinas/uso terapêutico
7.
Hepatol Int ; 16(6): 1424-1434, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35849258

RESUMO

BACKGROUND: To reveal the role of branched-chain amino acids (BCAAs) in the development and progression of nonalcoholic fatty liver disease (NAFLD) and the effect on the incidence of subsequent cardiovascular disease. METHODS: A total of 1302 subjects in the cohort study of the Huai'an Diabetes Prevention Program were divided into two groups according to whether NAFLD was present at baseline. The group without NAFLD at baseline was only followed up, and the group with NAFLD at baseline received diet and exercise interventions. Anthropometric and biochemical examinations were performed at baseline and at the end of 4 years for all subjects. Serum BCAA (leucine, isoleucine, and valine) levels were measured by hydrophilic interaction chromatography-tandem mass spectrometry. The associations of baseline serum BCAA levels with the risk for NAFLD, coronary heart disease (CHD), and cardiovascular events (CVEs) after 4 years were further evaluated. RESULTS: (1) At baseline and after the 4-year follow-up, baseline serum leucine, valine, and total BCAAs in the NAFLD group were significantly higher than those in the non-NAFLD group (p < 0.05). (2) According to whether NAFLD was present at baseline and after follow-up, all subjects were divided into four groups, including the control group, new case group, improvement group, and unchanged group. There was no significant difference in baseline BCAAs levels between the new case group and the improvement group (p > 0.05). (3) Risk factors for the occurrence and development of NAFLD were analysed by a multiple logistic regression model according to whether NAFLD existed at baseline. Serum leucine (OR = 1.058, 95% CI 1.005-1.114, p = 0.033) and total BCAAs (OR = 1.023, 95% CI 1.001-1.046, p = 0.045) were independent risk factors for new-onset NAFLD. Serum valine (OR = 1.131, 95% CI 1.043-1.226, p = 0.003), and total BCAAs (OR = 1.040, 95% CI 1.003-1.078, p = 0.035) were independent risk factors showing that NAFLD could not be reversed. (4) The cross-table Chi-square test showed that the incidence of both CHD and CVEs was significantly highest in the new case group (p < 0.05). (5) After adjusting for confounding factors, baseline isoleucine, valine, and BCAA levels were independently associated with new-onset CHD in subjects with or without NAFLD at baseline (p < 0.05). CONCLUSIONS: High BCAA levels exacerbate the risk of CHD and CVEs by influencing the occurrence and progression of NAFLD. However, lifestyle interventions could reverse the risk of NAFLD, CHD and CVEs associated with BCAAs.


Assuntos
Doenças Cardiovasculares , Hepatopatia Gordurosa não Alcoólica , Humanos , Aminoácidos de Cadeia Ramificada/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos de Coortes , Isoleucina , Leucina , Valina
8.
Ann Med ; 53(1): 1316-1326, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34382495

RESUMO

OBJECTIVE: This study aimed to investigate the effects of PPM1K rs1440581 and rs7678928 single nucleotide polymorphisms (SNPs) on the serum branched-chain amino acids (BCAAs) levels and cardiovascular disease (CVD) risk. METHODS: Anthropometric and biochemical examinations were performed at baseline and the end of 4 years in 234 individuals who were randomly recruited from the Diabetes Prevention Programme in Huai'an and received lifestyle intervention and follow up for 4 years. Serum BCAAs (leucine, isoleucine and valine (Val)) levels were measured by hydrophilic interaction chromatography-tandem mass spectrometric method and the PPM1K rs1440581 and rs7678928 were detected by high-throughput SNP genotyping at baseline. The associations of rs1440581 and rs7678928 with serum BCAA levels and risk for CVD after 4 years were further evaluated. RESULTS: The distribution frequencies of PPM1K rs1440581 and rs7678928 met the Hardy-Weinberg equilibrium (p> .05). The baseline serum levels of Val (p = .022) and total BCAAs (p = .026) in subjects with rs1440581 CC genotype were higher than in those with TT genotype. There were no significant differences in the serum levels of BCAAs among subjects with different genotypes of rs7678928. After 4-year follow-up, the subjects with rs1440581 CC genotype had higher systolic blood pressure (SBP) (p = .027), diastolic blood pressure (DBP) (p = .019), triglycerides (TGs) (p = .019) and lower high-density lipoprotein cholesterol (HDL-c) (p = .008) than those with TT genotype, and had higher AST level than those with TT (p = .030) or TC (p = .003) genotype; the subjects with rs7678928 TT genotype had higher SBP (p = .039) and DBP (p = .019) and lower HDL-c than those with CC (p = .017) genotype. Lifestyle intervention had little influence on the serum levels of fasting plasma glucose (FPG), TG, HDL-c, alanine aminotransferase (ALT), AST and creatinine (CREA) in subjects with rs1440581 CC genotype or rs7678928 TT genotype (p> .05). The incidences of CVD and non-alcoholic fatty liver disease (NAFLD) in subjects with rs1440581 CC genotype were higher than in those with TT genotype; the incidence of CVD in subjects with rs7678928 TT genotype was higher than in those with CC (p < .05) genotype. CONCLUSIONS: Allele C of PPM1K rs1440581 was associated with elevated serum Val, total BCAAs and CVD risks. rs1440581 CC genotype may be a better marker than baseline serum BCAAs in predicting the risk for CVD. TRIAL REGISTRATION: Diabetes Prevention Programme in Huai'an of Huai'an Second People's Hospital, ChiCTR-TRC-14005029.KEY MESSAGEAllele C of PPM1K rs1440581 was relevant to elevated serum Val and total BCAAs.PPM1K rs1440581 CC and rs7678928 TT genotypes were associated with CVD risk.PPM1K rs1440581 CC genotype carriers were more likely to have liver injury and develop NAFLD.


Assuntos
Aminoácidos de Cadeia Ramificada/sangue , Doenças Cardiovasculares/epidemiologia , Proteína Fosfatase 2C/genética , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/genética , China/epidemiologia , HDL-Colesterol , Diabetes Mellitus Tipo 2/sangue , Feminino , Genótipo , Humanos , Incidência , Isoleucina/sangue , Leucina/sangue , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Polimorfismo de Nucleotídeo Único , Proteína Fosfatase 2C/metabolismo , Valina/sangue
10.
Ann Endocrinol (Paris) ; 81(6): 561-566, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32987003

RESUMO

OBJECTIVE: The aim of the study was to analyze the correlation between income and non-alcoholic fatty liver disease (NAFLD) in a Chinese population. METHOD: subjects were divided into three groups according to liver fat content (LFC). (1) normal: LFC < 9.15%, 197 cases; (2) low LFC: LFC 9.15-20%, 532 cases; and (3) high LFC: LFC > 20%, 201 cases. Participants' clinical and social background were collected, including a routine fasting test to assess the relevant indices. Intergroup differences were compared on 1-way ANOVA, to analyze the relation between income and each index on Pearson correlation, and independent factors for LFC were identified on binary logistic regression. RESULTS: (1) In retired persons, prevalence of NAFLD was greater in females (81.2%) than males (75%), but fell with age: the highest prevalence was between 40 and 49 years of age (87.5%), and the lowest above 70 years (68%). (2) Income correlated positively with triglyceride and serum uric acid levels and LFC (P < 0.05) and negatively with alanine aminotransferase (P = 0.01). (3) As income increased from level I to V, prevalence of NAFLD increased progressively (P < 0.05). In the study, LFC was taken as the dependent variable, and the traditional NAFLD risk factors and income level (I-V) were taken as independent variables. Income emerged as an independent risk factor for NAFLD. Risk in group V was 1.964-fold higher than in group I. CONCLUSION: Prevalence of NAFLD was closely related to socio-economic level. Demographic risk factors include female gender, age 40-49 years, and monthly income > 5,000 RMB. Thus, if income is increased without improving educational level and health awareness, NAFLD prevalence will rise.


Assuntos
Povo Asiático/estatística & dados numéricos , Renda/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Tecido Adiposo/patologia , Adulto , Idoso , Alanina Transaminase/sangue , China/epidemiologia , Feminino , Humanos , Estilo de Vida , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/patologia , Fatores de Risco , Triglicerídeos/sangue , Ácido Úrico/sangue
11.
Lipids Health Dis ; 18(1): 155, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315681

RESUMO

OBJECTIVE: This study was to analyse the prevalence of type 2 diabetes mellitus (T2DM) in premenopausal and postmenopausal women. METHODS: A total of 3227 women met the requirements from June to December in 2014, including 207 cases of premenopausal women and 3020 cases of postmenopausal women. The prevalence of T2DM and the associated risk factors in the two groups were analysed. RESULTS: The prevalence of premenopausal women with T2DM was 12.1%, while the prevalence in postmenopausal women was 19.4% (P < 0.05). Total serum protein (TP) (OR = 1.164 95% CI = 1.023-1.324) (P = 0.021) is a major risk factor for premenopausal women with T2DM. The prevalence of T2DM increased with the increase in TP. In postmenopausal groups, the prevalence of T2DM was associated with age (OR = 1.037 95% CI = 1.024-1.051) (P < 0.001), BMI (OR = 1.076 95% CI = 1.044-1.109) (P < 0.001), blood pressure (OR = 1.521 95% CI = 1.234-1.875) (P < 0.001), triglycerides (TG) (OR = 1.106 95% CI = 1.027-1.190) (P = 0.008), blood urea nitrogen (BUN) (OR = 1.065 95% CI = 1.004-1.129) (P = 0.036), alanine aminotransferase (ALT) (OR = 1.009 95% CI = 1.003-1.016) (P = 0.004) and TP (OR = 1.031 95% CI = 1.005-1.057) (P = 0.018). CONCLUSIONS: Postmenopausal women have a higher rate of type 2 diabetes than premenopausal women. TP is a major risk factor for premenopausal women with T2DM. TP, ALT, and BUN are postmenopausal risk factors in addition to traditional risk factors such as obesity, lipidaemia and blood pressure. We should monitor risk factors and take early prevention and intervention measures to reduce the prevalence of diabetes and improve the quality of life of postmenopausal women. TRIAL REGISTRATION: ChiCTR, ChiCTR-TRC-14005029. Registered 29 July 2014, http://www.chictr.org.cn/showproj.aspx?proj=4545.


Assuntos
Proteínas Sanguíneas/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Idoso , Alanina Transaminase/sangue , Nitrogênio da Ureia Sanguínea , China/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , Prevalência , Fatores de Risco , Triglicerídeos/sangue
12.
Diabetes Ther ; 10(4): 1357-1368, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172456

RESUMO

OBJECTIVE: This study aimed to explore the association of obstructive sleep apnea-hypopnea syndrome (OSAHS) hypoxia indicators with early renal injury and serum fibroblast growth factor 21 (FGF21) in obese type 2 diabetic patients. METHODS: A total of 109 obese patients with type 2 diabetes mellitus (T2DM) were recruited, including 70 males and 39 females, with an average age of 52.77 ± 13.57 years and average BMI of 29.08 ± 4.36 kg/m2. Overnight sleep monitoring was performed with a portable monitor to record respiratory parameters [apnea-hypopnea index (AHI), oxygen desaturation index (ODI), lowest oxygen saturation (LSaO2), mean oxygen saturation (MSaO2/MPO2) and cumulative time of oxygen saturation < 90% (CT < 90%)]. Ultrasonography was done to detect the quantitative liver fat content (LFC). The urine microalbumin and creatinine ratio (ACR) were determined by immunoturbidimetry. FGF21 was measured at baseline by enzyme-linked immunosorbent assay. Patients were divided into the proteinuria group (n = 42) and non-proteinuria group (n = 67). Correlation analysis and multivariate linear regression analysis were used to analyze the related data. In addition, patients were divided into the T2DM without OSAHS group (n = 16) and T2DM with OSAHS group (n = 93) according to the AHI value. The correlation analysis was used to assess the relationship between FGF21 and clinical variables. RESULTS: (1) ACR positively correlated with waist circumference (WC), AHI, ODI, CT < 90% and LFC, but negatively with MSaO2 and LSaO2. (2) AHI, ODI, CT < 90% and LFC were independent risk factors for ACR, LSaO2 and MSaO2 was a protective factor. (3) Serum FGF21 decreased in the OSAHS group compared with the non-OSAHS group. After adjustment for age, WC and TG, FGF21 correlated negatively with AHI, but positively with MSaO2. CONCLUSIONS: AHI, ODI, CT < 90% and LFC are independent risk factors for ACR. FGF21 is associated with hypoxia indicators, and improving OSAHS status and reducing liver fat content may be helpful for the prevention and treatment of early diabetic nephropathy (DN). CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15006225.

13.
Int J Biol Macromol ; 118(Pt B): 2163-2175, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30030077

RESUMO

Polysaccharides from Dendrobium officinale (PDO) have been found to elicit significant benefits for patients with fibrotic diseases. However, there are no reports on treatment of idiopathic pulmonary fibrosis (IPF) using PDO. The aim of this paper was to investigate the therapeutic effects of PDO on IPF and its underlying mechanisms. Our data showed that PDO significantly ameliorated indices for both pulmonary inflammation and fibrosis in a bleomycin (BLM)-induced pulmonary fibrosis model in rats, which was associated with inactivation of transforming growth factor ß1 (TGFß1)-Smad2/3 signaling pathway. Moreover, PDO effectively blocked TGFß1-induced transformation of rat alveolar epithelial type II cells into myofibroblasts, with the inhibition of total Smad2/3, pSmad2/3, collagen I and fibronectin protein expression in a dose-dependent manner in vitro. Therefore, PDO may represent as a promising candidate biomacromolecule drug for the safe and effective therapy of IPF.


Assuntos
Dendrobium/química , Polissacarídeos/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Bleomicina , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Hidroxiprolina/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Polissacarídeos/farmacologia , Fibrose Pulmonar/sangue , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Proteínas Smad/genética , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/genética
14.
Carbohydr Polym ; 176: 152-159, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28927593

RESUMO

The purpose of this paper was to investigate the anti-inflammatory and anti-angiogenic activities of a purified polysaccharide (CCPSn) from flesh of Cipangopaludina chinensis in lipopolysaccharide (LPS) activated RAW264.7 macrophages and human umbilical vein endothelial cells (HUVECs), respectively. Anti-inflammatory results showed that CCPSn not only greatly decreased the pro-/anti-inflammatory cytokine secretion ratios, including TNF-α/IL-10, IL-6/IL-10 and IL-1ß/IL-10, but also reduced release levels of nitric oxide (NO) and prostaglandin E2 (PGE2), and suppressed expressions of cyclooxygenase2 (COX2) and inducible nitric oxide synthase (iNOS). The results from anti-angiogenic activities revealed that proliferation, migration, tube formation and vascular endothelial growth factor (VEGF) of HUVECs were significantly inhibited by CCPSn treatment. Even more remarkable was the fact that anti-inflammatory and anti-angiogenic activities of CCPSn exhibited a clear dose-response manner, and these activities were irrelevant to the cytotoxicities of CCPSn to RAW264.7 macrophages and HUVECs. These results indicated that CCPSn possessed strong anti-inflammatory and anti-angiogenic activities.


Assuntos
Inibidores da Angiogênese/farmacologia , Anti-Inflamatórios/farmacologia , Gastrópodes/química , Polissacarídeos/farmacologia , Animais , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
Front Immunol ; 8: 905, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824631

RESUMO

Morinda officinalis is beneficial for the treatment of inflammatory bowel disease (IBD). The hairy root with higher genetic and biochemical stability cultured from M. officinalis might have similar effects to treat IBD. In this study, the main chemical composition of the root extracts of M. officinalis (MORE) native plant and the hairy root extract of M. officinalis (MOHRE) was compared by quantitative HPLC. The difference of their therapeutic effects and potential mechanism was evaluated using 3% dextran sodium sulfate-induced chronic colitis in mice and T lymphocytes in vitro. The results found that MOHRE possesses many specific peaks unobserved in the chromatogram of native plant. The content of iridoids in the MORE (3.10%) and MOHRE (3.01%) is somewhat similar but quite different for their anthraquinones's content (0.14 and 0.66%, respectively). Despite all this, treatment with both MORE and MOHRE significantly attenuated the symptoms of colitis, including diarrhea, body weight loss, colon shortening, histological damage, and decreased inflammatory cytokine levels. In addition, they dose-dependently increased the apoptosis of T lymphocyte in vivo and in vitro. And, the differences for treatment effects on ulcerative colitis (UC) between them both in this study were mostly insignificant. The results demonstrated that the effects of MORE and MOHRE for the treatment of UC are similar, although there are a few difference on their chemical composition, indicating the hairy root cultured from M. officinalis might be able to replace its native plant on treatment of UC. The successful derivation of a sustainable hairy root culture provides a model system to study the synthetic pathways for bioactive metabolites, which will make the use of bioreactors to largely produce traditional medicine become reality.

16.
BMC Nephrol ; 18(1): 192, 2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28610620

RESUMO

BACKGROUND: Association between metabolic syndrome (MS) and mildly reduced estimated glomerular filtration rates (eGFRs) remains unclear. Therefore, we aimed to evaluate the association between MS and a mildly reduced eGFR in Chinese adults. METHODS: Anthropometric and biochemical examinations were performed in 2992 individuals. The eGFR was calculated from the creatinine level. MS was defined according to the Adult Treatment Panel III criteria as the presence of three or more risk factors. Mildly reduced eGFR was defined as a value between 60 and 90 mL/min/1.73 m2. Multiple linear regression and multiple logistic regression analysis were used to evaluate association between metabolic syndrome and estimate glomerular filtration rate. RESULTS: After adjusting for several potential confounders, the participants with MS showed a 1.29-fold increased odds ratio for a mildly reduced eGFR compared with those without MS. Additionally, the odds ratios (and 95% confidence intervals (CIs)) for mildly reduced eGFR in participants with elevated triglycerides (TG), decreased high-density lipoprotein (HDL), obesity and elevated fasting blood glucose (FPG) after multivariable adjustment were 1.25 (1.05-1.49), 1.23 (1.03-1.48), 1.22 (1.03-1.45) and 0.64 (0.52-0.78), respectively. The odds ratios (95% CIs) for hyperfiltration in participants with elevated FPG and HbA1c levels after multivariable adjustment were 1.53 (1.30-1.81) and 2.86 (2.00-4.09), respectively. CONCLUSIONS: MS is associated with an increased risk of a mildly reduced eGFR in the Chinese population, and several individual components of MS have different impacts on eGFR levels. MS had dual roles on renal damage. TRIAL REGISTRATION: ChiCTR-TRC- 14005029 . Registered 28 July 2014.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Adulto , Fatores Etários , Idoso , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Fatores de Risco , Triglicerídeos/sangue
17.
PLoS One ; 12(1): e0170758, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28125672

RESUMO

OBJECTIVE: This study aimed to investigate the association of serum betatrophin with the status and progression of nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 249 subjects who received ultrasonic examination of liver fat content (LFC) were recruited. Anthropometric and biochemical examinations were performed. Serum betatrophin was measured by ELISA. RESULTS: Compared with control group, serum betatrophin significantly increased in NAFLD group (P < 0.05). There was significant difference in serum betatrophin among control, low liver fat content (LLFC), and high liver fat content (HLFC) groups (P < 0.01). After adjustment for gender, age, BMI, FPG and HbA1c, the betatrophin positively correlated with LFC (r = 0.185, P < 0.01) and TG (r = 0.195, P < 0.01). Stepwise multiple regression analysis indicated serum betatrophin was independently related to LFC (P < 0.05). Multivariate logistic regression analysis revealed subjects in the highest tertile of serum betatrophin had higher odds of having NAFLD after adjustment for traditional NAFLD risk factors (OR = 2.88, 95%CI: 1.15-7.19) (P<0.05). CONCLUSION: Serum betatrophin is an independent risk factor for NAFLD and potential non-invasive marker for its progression. Serum betatrophin may be helpful for the early diagnosis of NAFLD and improvement of its prognosis.


Assuntos
Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hormônios Peptídicos/sangue , Proteína 8 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Povo Asiático , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Progressão da Doença , Jejum/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Fígado/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etnologia , Hepatopatia Gordurosa não Alcoólica/patologia , Fatores de Risco
18.
Int J Biol Macromol ; 92: 278-281, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27381587

RESUMO

The purpose of this paper was to investigate the protective effects of polysaccharides from (PGL) Ganoderma lucidum on bleomycin-induced pulmonary fibrosis in rats. Our study demonstrated that treatment with PGL of 100-300mg/kg for 28 days led to significant reduction in the pulmonary index, inflammatory cell infiltration and collagen deposition in rats with bleomycin-induced pulmonary fibrosis, which was associated with increased levels of glutathione, glutathione peroxidase, catalase and superoxide dismutase and decreased contents of malondialdehyde and hydroxyproline in the lung. These results indicated that PGL played a positive protective role in the pulmonary fibrosis and its possible mechanism was to improve lung antioxidant ability.


Assuntos
Polissacarídeos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Reishi/química , Animais , Bleomicina , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hidroxiprolina/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/patologia , Masculino , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia , Substâncias Protetoras/farmacologia , Fibrose Pulmonar/enzimologia , Fibrose Pulmonar/patologia , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
19.
BMC Endocr Disord ; 15: 47, 2015 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-26363801

RESUMO

BACKGROUND: To examine whether elevated glycosylated hemoglobin A1c (HbA1c) is associated with hyperfiltration in a middle-aged and elderly Chinese population. METHODS: Anthropometric and biochemical examinations were performed in 2491 individuals from the general population, aged 40-79 years, who participated in the Huaian Diabetes Prevention Program. The estimated glomerular filtration rate (eGFR) was calculated from creatinine levels using the CKD-EPI formula. Hyperfiltration was defined as eGFR >90(th) percentile. RESULTS: After adjustment [for age, gender, waistline, body mass index, blood pressure, smoking, alcohol consumption, cholesterol, log(triglycerides), high-density lipoprotein, low-density lipoprotein, serum uric acid, sodium intake, hypertension, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers], HbA1c and fasting plasma glucose (FPG) were found to be independently positively associated with eGFR. Additionally, after multivariate adjustment, the odds ratios (95 % CI) for hyperfiltration calculated for a 1-unit increase in HbA1c and FPG were 1.396 (1.089-1.790) and 1.306 (1.117-1.526), respectively. Compared with participants with HbA1c levels <5.7%, the odds ratios (95 % CI) for hyperfiltration were 2.344 (1.025-5.364) in participants with HbA1c levels of 6.21-6.49%, and 2.965 (1.537-5.720) in those with HbA1c levels ≥ 6.5%. CONCLUSION: Elevated HbA1c (≥ 6.21%) is associated with an increased odds of hyperfiltration in middle-aged and elderly Chinese. Longitudinal studies are needed to explore whether hyperfiltration increases the odds of diabetic nephropathy in individuals with prediabetes.


Assuntos
Glicemia/metabolismo , Creatinina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Taxa de Filtração Glomerular , Hemoglobinas Glicadas/metabolismo , Estado Pré-Diabético/metabolismo , Adulto , Idoso , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances
20.
Int J Clin Exp Med ; 8(6): 9730-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26309649

RESUMO

OBJECTIVE: This study aimed to investigate the correlation between serum copeptin and glomerular filtration rate (GFR) in type 2 diabetes mellitus (T2DM) patients and to investigate the role of serum copeptin in the diagnosis of early DN in T2DM patients. METHODS: 120 T2DM inpatients were recruited and divided into 2 groups according to 24-h urine albumin excretion (UAE): normal UAE group (UAE<30 mg/24 h) and microalbuminuria group (30 mg/24 h≤UAE≤300 mg/24 h). RESULTS: Decline in GFR was found in 6.1% of patients in normal UAE group and 26.4% in microalbuminuria group. However, serum copeptin was comparable between two groups. Serum copeptin was negatively related to GFR (r=-0.586, P<0.001). Multivariate logistic regression analysis showed, after adjustment for age and gender, the OR of copeptin, 24-h UAE was 1.234 (95% CI: 1.003-1.456) (P<0.05) and 1.068 (95% CI: 1.005-1.187) (P<0.05), respectively. Univariate analysis of ROC showed the sensitivity of copeptin and 24-h UAE was 78.9% and 63.2%, respectively and the specificity was 88.9% and 89.7%, respectively in the diagnosis of DN, but the area under ROC of copeptin in combination with 24-h UAE was 0.90 (95% CI: 0.82-0.99) with the sensitivity of 80.9% and specificity of 91.1%. CONCLUSION: Serum copeptin is an independent risk factor of decline in renal function of T2DM patients. Copeptin in combination with 24-h UAE are helpful for the early diagnosis of DN. The causative relationship between serum copeptin and GFR is required to be further studied in long-term follow up.

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