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J Inflamm (Lond) ; 17(1): 36, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33292270


BACKGROUND: Obesity, a risk factor for many chronic diseases, is a potential independent risk factor for iron deficiency. Evidence has shown that chronic intermittent hypobaric hypoxia (CIHH) has protective or improved effects on cardiovascular, nervous, metabolic and immune systems. We hypothesized that CIHH may ameliorate the abnormal iron metabolism in obesity. This study was aimed to investigate the effect and the underlying mechanisms of CIHH on iron metabolism in high-fat-high-fructose-induced obese rats. METHODS: Six to seven weeks old male Sprague-Dawley rats were fed with different diet for 16 weeks, and according to body weight divided into four groups: control (CON), CIHH (28-day, 6-h daily hypobaric hypoxia treatment simulating an altitude of 5000 m), dietary-induced obesity (DIO; induced by high fat diet and 10% fructose water feeding), and DIO + CIHH groups. The body weight, systolic arterial pressure (SAP), Lee index, fat coefficient, blood lipids, blood routine, iron metabolism parameters, interleukin6 (IL-6) and erythropoietin (Epo) were measured. The morphological changes of the liver, kidney and spleen were examined. Additionally, hepcidin mRNA expression in liver was analyzed. RESULTS: The DIO rats displayed obesity, increased SAP, lipids metabolism disorders, damaged morphology of liver, kidney and spleen, disturbed iron metabolism, increased IL-6 level and hepcidin mRNA expression, and decreased Epo compared to CON rats. But all the aforementioned abnormalities in DIO rats were improved in DIO + CIHH rats. CONCLUSIONS: CIHH improves iron metabolism disorder in obese rats possibly through the down-regulation of hepcidin by decreasing IL-6 and increasing Epo.

Front Physiol ; 11: 13, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32082187


Aim: Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) can confer hepatic protection by reducing endoplasmic reticulum stress (ERS) in high-fat-high-fructose induced metabolic syndrome (MS) rats. It is known that there is a functional coupling between autophagy and ERS. This study aimed to investigate the effect of CIHH on autophagy function and adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin (AMPKα-mTOR) signaling pathway in hepatic tissue of MS rats. Main Methods: 6-week old male Sprague-Dawley rats were randomly divided into: control (CON), CIHH (treated with hypobaric hypoxia simulating 5000-m altitude for 28 days, 6 h daily), MS (induced by 16-week high fat diet and 10% fructose water feeding), and MS + CIHH groups (exposed to CIHH after 16-week MS model). Food and water intakes, body weight, Lee's index, fat coefficient, systolic arterial pressure, blood biochemicals, and histopathology of liver were measured, the expression of phosphorylated (p)-AMPK, p-mTOR, autophagy-related and ERS-related proteins were assayed in hepatic tissue. Key Findings: The MS rats displayed obesity, hypertension, polydipsia, glucose and lipids metabolism disorders, increased inflammatory cytokine, hepatic tissue morphological and functional damage, and the up-regulated expressions of ERS-related, autophagy-related proteins and p-mTOR, and the down-regulated expression of p-AMPKα. All aforementioned abnormalities in MS rats were ameliorated in MS + CIHH rats. Significance: In conclusion CIHH confers hepatic protection through activating AMPK-mTOR signaling pathway and the autophagy function, thus inhibiting ERS in hepatic tissue.

Life Sci ; 205: 145-154, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29733850


AIMS: The study aimed to investigate the protective effect of chronic intermittent hypobaric hypoxia (CIHH) on endothelium function and relaxation of mesenteric artery in metabolism syndrome (MS) rats. MAIN METHODS: Male adult Sprague-Dawley rats were randomly divided into control (CON), CIHH (treated with 28-days hypobaric hypoxia simulating an altitude of 5000 m, 6 h daily), MS (induced by high fat diet and 10% fructose water feeding), and MS + CIHH groups. Body weight, systolic arterial pressure, blood biochemical and the endothelium dependent relaxation (EDR) of mesenteric arteries were measured. The expression of phosphor-endothelial nitric oxide synthase (p-eNOS), endoplasmic reticulum (ER) stress-related proteins and autophagy-related proteins in mesenteric arteries was assayed. KEY FINDINGS: The MS rats displayed hypertension, obesity, metabolic abnormity and insulin resistance, EDR was attenuated, p-eNOS expression was down-regulated, the expressions of ER stress-related proteins were up-regulated, and autophagy dysfunction occurred. All aforementioned abnormalities in MS rats were ameliorated in MS + CIHH rats. Furthermore, the improvement of CIHH on EDR and p-eNOS was cancelled by the ER stress inducer, and the autophagy inhibitor. SIGNIFICANCE: In conclusion CIHH protects endothelium function and enhances relaxation in mesenteric arteries of MS rats through improving autophagy function, reducing ER stress and up-regulating p-eNOS.

Autofagia , Endotélio Vascular/patologia , Hipóxia/patologia , Síndrome Metabólica/patologia , Síndrome Metabólica/terapia , Pressão do Ar , Animais , Pressão Arterial , Peso Corporal , Dieta Hiperlipídica , Estresse do Retículo Endoplasmático , Masculino , Artérias Mesentéricas/patologia , Óxido Nítrico Sintase Tipo III/biossíntese , Ratos , Ratos Sprague-Dawley
Nan Fang Yi Ke Da Xue Xue Bao ; 38(4): 490-495, 2018 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-29735453


OBJECTIVE: To explore the relationship between fasting C-peptide (F-CP) and serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 347 hospitalized patients with T2DM were stratified according to F-CP level to analyze the impact of increased F-CP levels on SUA level and the incidence of hyperuricemia (HUA). The patients with an elevated SUA level (>420 µmol/L) and a normal SUA level (≤420 µmol/L) were compared for general data, fasting C-peptide and other clinical indexes. Pearson or Spearman correlation analysis was used to analyze the correlation of SUA level with F-CP levels and other parameters. The risk factors of elevated SUA were analyzed by binary logistic regression, multiple regression analysis and hierarchical interaction analysis. The ROC curve was used to analyze the independent risk factors of elevated SUA and determine the corresponding cut-off values. RESULTS: Compared with those with a normal SUA level, patients with elevated SUA had higher body mass index (BMI), waist-to-hip ratio, F-CP, postprandial 2hC peptide (2hP-CP), triglyceride (TG), homocysteine (HCY), serum creatinine (SCr) level (P<0.05), and a greater percentage of drinking (44.8% vs 32.6%, P=0.006), but had significantly lowered levels of HbA1c, high-density lipoprotein (HDL), and estimated glomerular filtration rate (eGFR) (P<0.05). SUA was found to be positively correlated with F-CP, 2hP-CP, BMI, waist-to-hip ratio, diastolic blood pressure, TG, HCY, SCr, smoking and drinking (P<0.05), and was negatively correlated with gender, age, age of disease onset, HbA1c, HDL and eGFR (P<0.05). SUA level and the incidence of hyperuricemia increasea significantly with F-CP level (P<0.05). F-CP was identified as an independent risk factor for elevated SUA, and gender did not affect the relationship between F-CP and SUA. ROC curve analysis showed that a F-CP level >1.260 ng/mL was associated with a significantly increased risk of hyperuricemia in T2DM patients. CONCLUSION: F-CP is closely related with SUA and may be an independent risk factor of elevated SUA in patients with T2DM.

Peptídeo C/sangue , Diabetes Mellitus Tipo 2/sangue , Hiperuricemia/diagnóstico , Ácido Úrico/sangue , Jejum , Humanos , Fatores de Risco
Exp Ther Med ; 12(3): 1934-1938, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27602099


Tacrolimus (TAC) has been shown to improve remission from proteinuria in patients with refractory IgA nephropathy (IgAN); however, the efficacy and safety of TAC in such patients have not been fully explored. Therefore, the present study was conducted to evaluate the tolerance to and efficacy of TAC combined with low-dose corticosteroids in patients with refractory IgAN. This was a single-center retrospective study. A total of 28 patients with refractory IgAN were randomly included and received TAC plus corticosteroid; 26 patients received TAC and prednisone, and 2 patients received TAC and methylprednisolone. In addition, all patients were treated with an angiotensin inhibitor. Total urinary protein excretion, serum albumin, blood glucose, complete remission (CR), partial remission (PR), cholesterol, low-density lipoprotein (LDL), serum creatinine (Scr) and estimated GFR (eGFR) were tested at baseline and at 3, 6 and 12 months after the initiation of treatment in all patients. The primary endpoints were CR and PR. Secondary endpoints included changes of Scr, eGFR, clinical data and adverse events. After 12 months, CR was achieved in 40.1% of patients and PR in 43.4%, yielding a total response rate of 83.5%, and the total urinary protein excretion, serum albumin, cholesterol and LDL results were improved significantly compared with those at baseline. Proteinuria and serum albumin results were significantly improved by month 3 of treatment. Two patients relapsed during months 3-6 of follow-up. At the 12-month follow-up, renal function was improved compared with the baseline level as evidenced by eGFR and Scr, respectively. The blood glucose level was stable. One case of pneumococcal pneumonia developed in a patient treated with TAC plus low-dose methylprednisolone and one case of upper gastrointestinal hemorrhage was found in a patient treated with TAC plus low-dose prednisone; both cases completely recovered after treatment. In conclusion, TAC combined with low-dose corticosteroids may be an effective and safe therapeutic option for the treatment of refractory IgAN. However, given the small number of patients in this study, further prospective randomized controlled trials are required with a larger sample of participants and longer follow-up period.

Kaohsiung J Med Sci ; 31(1): 42-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25600919


The tolerance of mycophenolate mofetil (MMF; Shanghai Roche, China) in Lee Classes III, IV, and V immunoglobulin A nephropathy (IgAN) remains unclear. This article reports nine cases of severe pneumonia (SP), including pneumocystis pneumonia (PCP) and cytomegalovirus (CMV) pneumonia, and its risk factors in MMF plus low-dose corticosteroid-treated patients with Lee Classes III, IV, and V IgAN. Fifty-three patients with IgAN were included in this single-center study. The treatment regimen was MMF (1-1.5 g/d) plus low-dose corticosteroids (0.5 mg/kg/d). SP was defined as diffuse bilateral lung infiltrate with respiratory failure. PCP was diagnosed by detecting the organisms in the sputum and bronchoalveolar lavage. CMV infection was diagnosed through serum screening for CMV-IgG and IgM antibodies and CMV-DNA testing by a real-time polymerase chain reaction assay. The risk factors of SP were analyzed. Nine cases (16.9%) of SP occurred in this study. All SP developed at approximately the 10(th)-14(th) week after the initiation of the regimen: PCP was diagnosed in four cases and CMV infection in two cases. Renal function impairing was more serious in patients with SP than in those without SP, as evidenced by estimated glomerular filtration rate (p = 0.019) and serum creatinine level (p = 0.016). Six of the nine SPs occurred in MMP plus low-dose methylprednisolone group, which was statistically higher than that in the MMF plus low-dose prednisone group (p = 0.000). The incidence of SP in this study was 16.9%. Chronically impaired renal function and the use of methylprednisolone may be the risk factors for SP.

Corticosteroides/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Pneumonia/tratamento farmacológico , Corticosteroides/efeitos adversos , Adulto , Feminino , Glomerulonefrite por IGA/metabolismo , Humanos , Imunoglobulina A/metabolismo , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Pneumonia por Pneumocystis/tratamento farmacológico , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco