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Léri-Weill dyschondrosteosis (LWD) has typical triad: short middle limbs, short stature, Madelung deformity of wrist, and increased body mass index. Short stature and high body mass index are risk factors for metabolic syndrome, type 2 diabetes, cardiovascular diseases, and autoimmune thyroid diseases. However, metabolic disorders and thyroid diseases in adult LWD patients have not been elucidated. This paper reports two adult patients with LWD presented to the Department of Endocrinology and metabolism. By introducing clinical characteristics, genetic variations, and diagnostic methods, physicians can deepen their understanding of LWD, improve diagnosis, and be aware of the comorbid metabolic diseases and thyroid disorders with a view of early prevention and treatment.
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Objective:We aimed to estimate the incidence of anxiety or depression in asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) patients and explore its related factors.Methods:Stable patients who were treated or followed up in the outpatient department of respiratory medicine in the First Hospital of China Medical University from March 2018 to March 2019 were enrolled, including 53 ACO patients, 74 asthma patients, and 138 patients with COPD. Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to evaluating the anxiety and depression status of the three groups of patients, and the risk factors of anxiety and/or depression in ACO patients were analyzed.Results:There were 33 cases (62.3%), 35 cases (47.3%) and 69 cases (50.0%) combined with anxiety in ACO, asthma and COPD group; there were 29 cases (54.7%), 25 cases (33.8%) and 58 cases (42.0%) combined with depression in ACO, asthma and COPD group, respectively. The patients with depression in ACO were significantly higher than those in asthma group ( P<0.05). There were 28 patients (52.8%), 24 patients (32.4%) and 52 patients (37.7%) combined with anxiety and depression in ACO, asthma and COPD group, respectively, with significant difference in ACO group and asthma group ( P<0.05). Multivariate logistic regression analysis showed that chronic obstructive pulmonary disease assessment test (CAT) score≥10 was associated with anxiety ( OR=15.00, P<0.01) or depression ( OR=8.667, P<0.01) in patients with ACO. Conclusions:Anxiety/depression is common in chronic airway disease. Compared with asthma, anxiety and/or depression is more frequent in the patients with ACO. ACO patients with high CAT scores should pay attention to screening for anxiety/depression.
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A multiple-stimuli-responsive drug-conjugated cross-linked micelles was prepared by radical copolymerization. The chemical structure, morphology, and size of the cross-linked micelles were characterized, and the drug loading of the micelle was calculated. The experimental results indicated that the hydrodynamic size of the drug-loaded micelles were about 100 nm, and the as prepared micelles could be degraded and swelled in presence of reducing glutathione (GSH). The low critical solution temperature (LCST) of the micelle was around 39.4℃. According to the experimental results, the micelles will shrink at temperature above the LCST. Subsequently, the accumulative drug release rate was up to 91.78% under acidic (pH 5.0), reductive (GSH 10 mmol/L) and high temperature (42.0℃) conditions mimicking the tumor microenvironment, while a relatively low release rate of 1.12% was observed without stimulation. The drug-conjugated cross-linked micelles showed a strong cell uptake behavior. In the cytotoxicity assay, the micelles exhibited effective anti-cancer activity and excellent biocompatibility. In brief, the experimental results show that the as-prepared drug-conjugated cross-linked micelle exhibits multiple stimuli-responsiveness, which holds great promise for anti-cancer drug delivery.
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The expression levels of serum tenascin-C, osteopontin(OPN), and transforming growth factor-β1(TGF-β1) in the patients of diabetic mellitus were measured by ELISA. With the increase of the UACR, the expression of tenascin-C, osteopontin, and transforming growth factor-β1 showed a trend of increase and hypertension will argument this phenomenon. Pearson correlation analysis showed that levels of tenascin-C were positively correlated with HbA1C , body mass index, systolic blood pressure, diastolic blood pressure, UACR, osteopontin, and transforming growth factor-β1.
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Objective:To observe the effect of Yizhi cream on vascular dementia in rats.Methods:The rat model of vascular de-mentia was established by the double thread ligation of bilateral common carotid artery. The rats in each dose group were intragastrically given Yizhi cream at high,medium and low dose for 30 days. Morris water maze was used to observe the effect of Yizhi cream on learn-ing and memory impairment in rats. The biochemical method was used to observe the levels of acetylcholine (Ach) and nitric oxide (NO),and the activity of nitric oxide synthase(NOS) in serum was measured. The brain index was calculated to evaluate the state of cerebral edema. HE staining was used to observe the pathological changes of brain tissue.Results: Compared with that in the model group,the escape latency in each Yizhi cream group was significantly shortened(P<0.05),the number of sites found in 3 min signif-icantly increased (P<0.05),the Ach content significantly increased (P<0.05),the NO content and NOS activity significantly de-creased (P<0.05),the brain index was significantly lowered (P<0.05), and the brain histopathology was significantly improved. Conclusion:Yizhi cream can significantly improve the learning and memory ability of vascular dementia rats,and notably improve the cerebral edema and brain histopathology in the rats with vascular dementia. The mechanism of action is related to reducing the serum NO content and NOS activity,enhancing the ability of oxidative damage prevention,reducing brain injury,increasing the Ach content and enhancing the function of cholinergic nerve.
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Objective To investigate the association of adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)with urinary albumin excretion rate in patients with type 2 diabetes mellitus (T2DM),and to explore the role of APPL1 in the development of diabetic kidney disease(DKD). Methods According to the urinary albumin/creatinine ratio(UACR),288 newly-diagnozed patients with T2DM were divided into normal albuminuria group(UACR<30 mg/g,n=116),microalbuminuria group(UACR 30 ~300 mg/g,n=95),and macroalbuminuria group(UACR>300 mg/g,n=77). 130 healthy subjects with matched sex and age were used as control group. Serum APPL1,tumor necrosis factor α(TNF-α),and adiponectin levels were measured by ELISA method. Results Serum APPL1 level in T2DM patients was significantly higher than that in control subjects (P<0.01), and increased with the rising of UACR. In patients with T2DM, serum APPL1 level was negatively correlated with estimated glomerular filtration rate(r=-0.246, P<0.01) while it was positively correlated with HbA1C, low density lipoprotein cholesterol, total cholesterol, triglycerides, insulin resistance index, serum creatinine,blood urea nitrogen, systolic blood pressure, TNF-α, and adiponectin(r=0. 119, 0. 167, 0. 209, 0.194,0.273,0.242,0.131,0.144,0.365, and 0.952, respectively, P<0.05 or P<0.01). Conclusion Serum APPL1 level in patients with T2DM was increased with the rising of UACR, suggesting that APPL1 may be involved in the development of DKD.
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267 newly-diagnosed patients with type 2 diabetes were divided into normoalbuminuria group [group N-UAlb, urinary albumin to creatinine ratio (UACR)300 mg/g, n=76). The control group(group NC) consisted of 114 healthy individuals. Serum betatrophin, adiponectin(APN), and interleukin-1β( IL-1β) levels were determined with ELISA methods and the parameters of body mass index (BMI), estimated glomerular filtration rate(eGFR), HbA1C, fasting plasma glucose(FPG), OGTT 2h plasma glucose(2hPG), fasting insulin(FINS), OGTT 2h postprandial insulin(2hPINS), fasting C-peptide(FCP), homeostasis model assessment insulin resistant index(HOMA-IR), and blood lipid were collected. Compared with group NC, the serum betatrophin levels in patients with type 2 diabetes were obviously increased. In patients with type 2 diabetes, betatrophin levels increased along with the increase of UACR and there were significant differences in betatrophin among the three groups(P<0. 01). Betatrophin positively correlated with UACR, HbA1C, FPG, 2hPG, FINS, 2hPINS, HOMA-IR, TC, LDL-C, and TG( r were 0. 785, 0. 225, 0. 136, 0. 241, 0. 386, 0. 223, 0. 411, 0.216,0.193,and0.298,allP<0.05),and betatrophin were also positively correlated with APN and IL-1β(rwere 0. 643 and 0. 710, both P<0. 01). Stepwise multiple regression analysis showed that UACR, HbA1C, FINS, and TG were independent relevant factors affecting betatrophin levels.
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Objective To investigate the expression levels of serum vasohibin-1(VASH-1)in type 2 diabetes mellitus(T2DM)patients at different stages of urinary albumin to creatinineratio(UACR)and to attempt to investigate the relationship between VASH-1 and inflammation and fibrosis in the pathogenesis of diabetic nephropathy(DN), one of the microvascular complications of T2DM. Methods 486 patients with T2DMwere divided into four groups:normal albuminuria [ UACR 300 mg/ g, n = 106 ], and clinical albuminuria hypertensive [ UACR > 300 mg/ g, with hypertension, n=124] groups. Age, course, serum levels ofVASH1, inflammation markers(CRP, ESR)and fibrosis marker( TGF-β1) with other biochemical indicators were measured, and 130 normal control subjects were also included. Results Compared with normal control group, the levels of UACR, HbA1C ,ESR, CRP, TGF-β1 and VASH-1 in groups ofnormal albuminuria, microalbuminuria, clinical albuminuria, and clinical albuminuria hypertensive were significantly higher(P<0. 05). Pearson correlation analysis showed that levels of VASH-1 were positively correlated with UACR, HbA1C ,ESR, CRPand TGF-β1( r = 0. 521, 0. 261, 0. 519, 0. 523, 0. 479, P<0. 001), while multivariate regression analysis showed that levels of UACR, HbA1C ,ESR, CRP and TGF-β1 were important factors affecting serum VASH-1 levels. Conclusion Serum levels of VASH-1 may become new biomarkers of early diagnosis of DN. Consequently, VASH-1 level may provide a new pattern and direction of inflammation and fibrosis for consideration in diabetic kidney damage.
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Objective To investigate the effects of low-dose,sustained release oral theophylline on the chronic obstructive pulmonary disease (COPD) patient.Methods Fifty-six patients with stable COPD were randomly divided into two group:theophylline group (n =35) that was treated with slow-release theophylline(100 mg,twice daily),and control group (n =21) that was given with placebo.A series of parameters including lung function,quality of life scores,body mass index,airflow obstruction,dyspnea,and exercise capacity index (BODE) score,exercise tolerance,exacerbations,satisfaction with treatments and adverse effects were tested before and 12 weeks after the treatments.Results Forty two patients completed the study,25 cases in the slow-release theophylline group,and 17 cases in the placebo group.The differences of two groups before the treatment were not prominent except the age (P ＞ 0.05).After treated with slow-release theophylline,the forced expiratory volume in one second (FEV1),forced vital capacity (FVC) and the symptom score were slightly increased,but there were no statistically significant differences (P ＞0.05).After theophylline therapy,the quality of life score,including activity ability score,disease activity score and total score,and BODE index score were significantly decreased(P ＜0.05),but 6 minutes walk test (6 MWT) differences were no significant (P ＞0.05).The differences in pulmonary function test,the quality of life score,BODE index score and 6 minutes walk test were no significant between before and after the treatment with the placebo (P ＞ 0.05).Compared to the cases who treated with the placebo group,the patients in slow-release theophylline group reduced the frequencies of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (3/25 vs 7/17,x2 =4.748,P ＜0.05),and increased the efficacy satisfaction (Z =-2.579,P ＜ 0.05).Slightly adverse reaction was observed in 3 cases in slow-release theophylline group,but it could relieve by oneself,and not affect the common treatment.There was no adverse reaction in the placebo group.Conclusions Low dose,sustained release oral theophylline was efficient in improvement of the quality of life scores and BODE index score.
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Objective To explore the roles of MircroRNA-217 ( Mir-217 ) , silent information regulator 1 (Sirt1), and hypoxia-inducible factor-1α(HIF-1α)in high glucose-induced inflammation and fibrosis in rat glomerular mesangial cells( RMCs) . Methods RMCs were pre-incubated with a Sirt1 activator resveratrol prior to high glucose treatment or transfected with Sirt1 small interfering RNA( siRNA) , HIF-1αsiRNA, and Mir-217 inhibitor. Real-time PCR was used to analyze the expressions of Mir-217, Sirt1 mRNA, and HIF-1α mRNA; Western blot was used to observe the protein expressions of Sirt1, HIF-1α, connective tissue growth factor(CTGF), endothelin-1(ET-1), and fibronectin( FN) . Enzyme-linked immunosorbent assay was applied to detect protein expression of transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF). Results High glucose increased Mir-217, HIF-1α, CTGF, ET-1, FN, TGF-β1, and VEGF expressions(all P<0. 01), while decreased Sirt1 expression. In addition, Mir-217 gene silencing or 25μmol/L resveratrol suppressed high glucose-stimulated expressions of HIF-1α, CTGF, endothelin-1, FN, TGF-β1, and VEGF(all P<0. 01). Conclusion Mir-217 mediates high glucose-induced inflammation and fibrosis in RMCs via Sirt1/HIF-1αsignal pathway. This study provides new evidence to clarify the protective mechanisms of Sirt1 in diabetic nephropathy.
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Objective To explore the associations of serum Mir-217 with silent information regulator 1 (Sirt1)and hypoxia-inducible factor-1α(HIF-1α)in type 2 diabetic patients with different urinary albumin excretion rates. Methods A total of 479 patients with type 2 diabetes were divided into normoalbuminuric(D1, n=181), microalbuminuric(D2, n=165), and macroalbuminuric(D3, n=133)subgroups. 192 normal subjects served as control group. Serum level of Mir-217 was detected by realtime PCR. Serum Sirt1, HIF-1α, and vascular endothelial growth factor ( VEGF ) levels were determined by enzyme-linked immunosorbent assay. Results Compared with control subjects, serum Mir-217 level was significantly increased in type 2 diabetic patients and gradually increased in D1, D2, and D3 groups(P<0. 01). The parameters of age, diabetes duration, body mass index, fasting plasma glucose, fasting insulin, homeostasis model assessment of insulin resistant index(HOMA-IR), HbA1C, low density lipoprotein-cholesterol( LDL-C) , total cholesterol ( TC ) , triglyceride ( TG ) , serum uric acid ( SUA ) , blood urea nitrogen(BUN), HIF-1α, VEGF, and Mir-217 all were positively correlated with ACR(all P<0. 05). High density lipoprotein-cholesterol(HDL-C)and Sirt1 were negatively correlated with ACR(both P<0. 05). VEGF, HIF-1α, Mir-217, BUN, diabetes duration, LDL-C, Sirt1, and SUA were independent factors that influenced ACR(all P<0. 01). Additionally, diabetes duration, HOMA-IR, HbA1C, ACR, LDL-C, TC, TG, SUA, BUN, HIF-1α, and VEGF were positively correlated with Mir-217(all P<0. 05), while Sirt1 was negatively correlated with Mir-217(P<0. 01). Conclusion Serum Mir-217, as a possible biomarker for early diagnosis of diabetic nephropathy, may be involved in the development of diabetic nephropathy by promoting chronic inflammatory reaction, renal fibrosis, and angiogenesis.
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Objective To investigate the anti-inflammatory effects of low-dose and sustained release oral theophylline on the chronic obstructive pulmonary disease (COPD) patients.Methods Thirty four patients with stable COPD were randomly divided into two groups:theophylline group (n =18) was treated with slow-release theophylline (100 mg,twice daily),and placebo group (n =16) was given with placebo.Healthy non-smokers (n =12) were taken as control.The course of treatment was 12 weeks both of theophylline group and placebo group.The percentages of Neu/Leu and Mφ/Leu in sputum were detected before and after treatment and the concentrations of interleukin (IL)-17,IL-8,and tumor necrosis factor-α (TNF-et) were detected with enzyme linked immunosobent assay (ELISA).Results (1) Compared to pretreatment with theophylline group,the Neu/Leu was increased [(89 ±4.14)％ vs (83.4 ±6.98)％,P ＜0.05] and the Mφ/Leu was decreased [(6.4 ± 4.11) ％ vs (12.3 ± 6.96) ％,P ＜ 0.05] in the post-treated theophylline group.No significant changes in both Neu/Leu and Mφ/Leu were observed before and after placebo-treatment (P ＞ 0.05).(2) Compared to the control group,the concentrations of TNF-α,IL-8,and IL-17 in the sputum supernatant were significantly increased in both pretreatment and posttreatment with the theophylline or the placebo.Sputum TNF-α,IL-8,and IL-17 levels were significantly decreased in COPD patients who were given theophylline.Compared to pre-treatment with placebo group,the IL-8 and IL-17 levels were significantly increased in the post-treated placebo group (P ＜0.01).There was no significant change in TNF~ level between before and after treatment with the placebo.(3) The concentrations of IL-17,IL-8,and TNF-α in the sputum supernatant were positively correlated with the Neu/Leu counts (r =0.471,0.652,0.466,respectively,all P ＜0.01),negatively correlated with the forced expiratory volume in one second (FEV1 ％) (r =-0.516,-0.652,-0.496,respectively,all P ＜ 0.01).Conclusions Low-dose and sustained-release oral theophylline was efficient in improving airway inflammatory cells and inflammatory mediators,which plays an anti-inflammatory effect.
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Objective To investigate changes of serum silent information regulator 1 (Sirt1) and inflammatory cytokines in type 2 diabetes patients with different stages of diabetic nephropathy.To explore the relationship between serum Sirt1 level and inflammatory cytokines in type 2 diabetic patients with different urinary albumin excretion rates.Methods A total of 436 cases with type 2 diabetes were divided into three groups:normoalbuminuric [D1,n =168],microalbuminuric [D2;n =152],and macroalbuminuric [D3,n =116].Serum Sirt1,hypoxia-inducible factor-1α (HIF-1α),early growth response protein 1 (EGR1),insulin-like growth factors-Ⅰ (IGF-Ⅰ),and monocyte chemotactic protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay (ELISA).Results The levels of serum Sirt1 in type 2 diabetes patients were significantly lower than that in control group,and with the increase of urinary protein excretion rate,the levels of serum Sirt1 in group D1,D2 and D3 were decreased gradually (P ＜ 0.01).Compared to control,serum inflammatory cytokines (HIF-1α,EGR1,IGF-Ⅰ,and MCP-1) levels were significantly increased in type 2 diabetic patients and gradually increased in the patients of D1,D2 and D3 groups (P ＜0.01).Furthermore,Serum Sirt1 was negatively correlated with the levels of inflammatory cytokines.Age,duration,fasting blood glucose (FBG),fasting insulin (FINS),homeostasis model assessment insulin resistance index (HOMA-IR),glycosylated hemoglobin (HbA1c),low density lipoprotein (LDL),total cholesterol (TC),triglyceride (TG),serum creatinine (Scr),blood urea nitrogen (BUN),uric acid (UA),HIF-1α,EGR1,IGF-Ⅰ,and MCP-1 were positively correlated with Ln Koc of urinary albumin to creatinine ratio [Ln(ACR)] (P ＜ 0.05);and Sirt1 were negatively correlated with Ln(ACR)(P ＜ 0.01).HIF-1α,MCP-1,IGF-Ⅰ,duration,BUN,Sirt1,UA,LDL,and EGR1 were independent factors that significantly influenced Ln (ACR) (P ＜ 0.05).Conclusions Serum Sirt1 might be a new target for the treatment of diabetic nephropathy.Enhancing serum Sirt1 levels might have a role in delaying the progression of diabetic nephropathy.
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[Summary] The aim of this study was to detect the levels of serum miR-130b expression in patients with type 2 diabetes mellitus and to analyze their correlation with diabetic renal damage. 243 patients with type 2 diabetes mellitus were divided into three groups according to urinary albumin/creatinine ratio ( UACR ): normoalbuminuria group (UACR300 mg/g, n=54). The levels of serum miR-130b were validated by realtime polymerase chain reaction. Serum transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α(TNF-α) were determined by enzyme-linked immunosorbent assay ( ELISA) in all patients and 59 healthy volunteers. Compared with control group, the level of serum miR-130b in the type 2 diabetes mellitus group were significantly decreased, gradually with the increases of UACR. The level of serum miR-130b was inversely correlated with blood urea nitrogen ( r=-0. 295, P<0.05), serum creatinine(r=-0. 316, P<0. 05), UACR(r=-0. 463, P<0. 05), but positively related to the estimated glomerular filtration rate(r=0. 367, P<0. 01). The level of serum miR-130b was also negatively correlated to homeostasis model assessment for insulin resistance, triglyceride, low density lipoprotein-cholesterol, TNF-α, and TGF-β1 (r=-0. 257,-0. 345,-0. 242,-0. 562,-0. 622, all P<0. 01). The present study indicates that serum miR-130b might be a potential new biomarker for early diagnosis of diabetic nephropathy. Serum miR-130b might be involved in the pathogenesis of diabetic nephropathy.
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Objective To investigate the value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of sarcoidosis.Methods Twenty-two cases of clinically suspected sarcoidosis underwent bronchoscopy and ultrasound bronchoscopy examination,including endobronchial biopsy (EBB),transbronchial lung biopsy (TBLB),and EBUS-TBNA.The biopsy samples of EBB,TBLB,and EBUS-TBNA were paraffin-embedded for hematoxylin eosin (HE) staining and acid-fast staining,respectively.Differences in the diagnosis of sarcoidosis were compared among EBB,TBLB,and EBUS-TBNA.The diagnostic performance of EBUS-TBNA was evaluated.Interventional pulmonology diagnostic strategy of sarcoidosis was analyzed.Results Among all the 22 patients with suspected sarcoidosis,20 cases were diagnosed as sarcoidosis,1 case was small cell lung cancer,and 1 case was lymphoma.The number of patients who were diagnosed by EBB,TBLB,and EBUS-TBNA was 6 cases,9 cases,and 16 cases,respectively;and their diagnostic yield was 30.0％,45.0％,and 80.0％,respectively.The diagnostic yield of EBUS-TBNA was significantly better than the other two (P =0.005).Combined EBB and EBUS-TBNA,the diagnostic yield was 85.0％.Combined TBLB and EBUS-TBNA,the diagnostic yield was 90.0％.Combined those three,the diagnostic yield was 95.0％.EBUS-TBNA diagnostic yield was affected by the location and size of lymph nodes.The diagnostic yield of subcarinal lymph nodes and paratracheal lymph nodes by EBUS-TBNA was significantly better than that of Hilar lymph nodes (x2 =4.29,P ＜0.05),EBUS-TBNA showed better diagnostic yield for the lymph nodes whose diameter was greater than 2cm (x2 =4.067,P ＜ 0.05).EBUS-TBNA had fewer complications.Most patients only had a little bleeding in puncture site.Conclusions EBUS-TBNA contributed to diagnose sarcoidosis,while TBLB and EBB had a complementary value in the diagnosis of sarcoidosis by EBUS-TBNA.
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Objective To examine whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation via mammalian target of rapamycin (mTOR) signaling.Methods The cell proliferation and cycle were determined by methylthiazoletetrazolium(MTT) assay and flow cytometry,respectively.The mRNA expression of AMP-activated protein kinase(AMPK) was detected by realtime PCR.The phosphorylation levels of protein kinase B (Akt),mTOR,eukaryotic translation initiation factor 4E binding protein 1 (4EBP1),and 70S6 kinase (p70S6K) were measured by Western blot.Results 0.25 mmol/L LA promoted high glucose-sitmulated rat mesangial cell proliferation(P＜0.01) and entry of cell cycle into S phase(P＜0.01),along with increased phosphorylation levels of Akt,mTOR,p70S6K,and 4EBP1 (P＜0.05).These effects of 0.25 mmol/L LA disappeared when Akt activity was inhibited.On the contrary,1.0 mmol/L LA inhibited high glucose-induced cell proliferation(P＜0.01) and entry of cell cycle into S phase(P＜0.01),with the decreased phosphorylation levels of mTOR,p70S6K,and 4EBP1 (P＜ 0.05) and the enhanced activity of AMPK(P＜0.01).These effects of 1.0 mmol/L LA were prevented when AMPK activity was inhibited.Conclusions LA dose-dependently regulates mesangial cell proliferation induced by glucose via mTOR signaling pathway.
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Objective To explore the changes in expression of Klotho, an aging-suppression protein, and neutrophil gelatinase associated lipocalin ( NGAL) and their relationship with rat mesangial cells ( RMCs) cultured with high glucose in vitro, and to explore the role played by Toll-like receptor-4 (TLR4) / nuclear factor-kB(NF-kB) p65 pathways in this process. Methods Three NGAL-siRNA sequences were designed and synthesized. The effective sequence in subsequent experiments was chosen. RMCs were preincubated with pyrrolidinedithiocarbamate (PDTC)or exogenously added Klotho prior to high glucose treatment. Realtime PCR was used to analyze Klotho, TLR4, NGAL mRNA expressions. Western blot was used to observe Klotho, TLR4,NF-kB p65, NGAL,fibronectin (FN), and connective tissue growth factor ( CTGF) protein expression. ELISA assay was used to detect monocyte chemoattractant protein-1 ( MCP-1) and CXCL5 secretions. Results High glucose suppressed Klotho expression significantly(P<0. 05) and activated TLR4 / NF-kB p65 pathway. Meanwhile,the levels of NGAL,FN,CTGF, MCP-1, and CXCL5 were highly expressed ( P < 0. 01). NGAL gene silencing obviously down-regulated the increased expressions of FN, CTGF, MCP-1, and CXCL5 ( P < 0. 01). After PDTC treatment the overexpression of NGAL protein was markedly lowered(P<0. 01). In addition, Klotho treatment significantly inhibited the activity of TLR4 /NF-kB p65 pathways and down-regulated the expressions of NGAL, FN, CTGF, MCP-1 and CXCL5 stimulated by high glucose(P<0. 01). Conclusion Klotho inhibits the activity of TLR4 / NF-kB p65 pathways and thus inhibits NGAL expression in RMCs cultured with high glucose in vitro. And then it suppresses the expressions of FN, CTGF, MCP-1, and CXCL5. This provides a new basis to illustrate the protection mechanism of the anti-aging protein Klotho in diabetic nephropathy, and may provide new ideas and therapeutic targets for prevention and treatment.
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A total of 175 patients with type 2 diabetes mellitus (T2DM) were composed of 69 with normoalbuminuria,60 with microalbuminuria,and 46 with macroalbuminuria.The control group consisted of 64 healthy individuals.Serum YKL-40 levels were determined with ELISA method and related metabolic data were collected.Serum YKL-40 levels were significantly higher in T2DM group than in control group(P＜0.01).Significant correlations of YKL-40 were found with the ratio of microalbuminuria to uric creatinine(r=0.677,P＜0.01),HbA1C (r =0.562,P＜0.01),systolic blood pressure (r =0.372,P =0.001),HOMA-IR (r =0.460,P =0.001),low density lipoprotein-cholesterol (r=0.304,P=0.012),age(r=0.260,P=0.015),blood uric acid (r=0.329,P=0.018),and high density lipoprotein-cholesterol (r=-0.247,P=0.032).YKL-40 may play a role in the occurrence and development of diabetic nephropathy.
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A total of 185 patients with type 2 diabetes mellitus (T2DM) were consisted of male group (n =95) and postmenopausal female group (n =90).The parameters of fasting plasma glucose,HbA1c,fasting insulin,fasting C peptide,homeostasis model assessment insulin resistant index (HOMA-IR) and β-cell function (HOMA-β),blood lipid,body mass index,and waist to hip ratio were collected and analyzed by Pearson correlation analysis and stepwise multiple regression analysis.The relationships between osteocalcin and these parameters were investigated.The results revealed that osteocalcin was negatively correlated with HbA1C (P＜0.05),and osteocalcin was an independent relevant factor affecting HbA1Clevels.Osteocalcin may be involved in the regulation of glucose metabolism in T2DM.
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A novel recombinant Bacille Calmette-Guerin (rBCG) vaccine co-expressed Eimeria tenella rhomboid and cytokine chicken IL-2 (chIL-2) was constructed, and its efficacy against E. tenella challenge was observed. The rhomboid gene of E. tenella and chIL-2 gene were subcloned into integrative expression vector pMV361, producing vaccines rBCG pMV361-rho and pMV361-rho-IL2. Animal experiment via intranasal and subcutaneous route in chickens was carried out to evaluate the immune efficacy of the vaccines. The results indicated that these rBCG vaccines could obviously alleviate cacal lesions and oocyst output. Intranasal immunization with pMV361-rho and pMV361-rho-IL2 elicited better protective immunity against E. tenella than subcutaneous immunization. Splenocytes from chickens immunized with either rBCG pMV361-rho and pMV361-rho-IL2 had increased CD4+ and CD8+ cell production. Our data indicate recombinant BCG is able to impart partial protection against E. tenella challenge and co-expression of cytokine with antigen was an effective strategy to improve vaccine immunity.