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1.
Am J Hypertens ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38488616

ABSTRACT

BACKGROUND: Arterial stiffness has been confirmed to be associated with cognitive impairment. Carotid-femoral pulse wave velocity (cfPWV) is widely regarded as the gold standard for assessing arterial stiffness, yet it is not readily accessible. In response, the use of estimated pulse wave velocity (ePWV) has been proposed as a more accessible and cost-effective alternative. ePWV not only offers ease of calculation but also covers a broader spectrum of vascular aging processes, some of which may be distinct from those detected by cfPWV. The aim of our study was to investigate the association between ePWV and cognitive outcomes in SPRINT-MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension). METHODS: This study was a post-hoc analysis of the SPRINT-MIND. The primary endpoint was a composite outcome including probable dementia and mild cognitive impairment (MCI). The calculation of ePWV was based on age and mean blood pressure. The association between ePWV and cognitive outcomes was assessed using Cox regression analysis. The response of ePWV to antihypertensive treatment at 12 months was used to define treatment efficacy. RESULTS: 8563 patients were enrolled. The ePWV was found to be independently associated with risk of probable dementia (Tertile 3 vs. Tertile 1: HR, 95% CI: 1.70, 1.08-2.68, P = 0.023, P for trend = 0.013), MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.35, 1.71-3.23, P < 0.001, P for trend < 0.001), and the composite outcome of probable dementia or MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.17, 1.65-2.86, P < 0.001, P for trend < 0.001). The combined effect of treatment allocation and the response of ePWV to treatment exhibited that intensive/ePWV responders had the lowest risk of the primary outcome (Log-rank P = 0.002). CONCLUSION: EPWV demonstrated independent predictive value for cognitive outcomes in SPRINT-MIND.

2.
Sci Total Environ ; 922: 171151, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38395160

ABSTRACT

Per- and polyfluoroalkyl substances (PFASs) are widely used due to their unique structure and excellent performance, while also posing threats on ecosystem, especially long-chain perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). As the control of conventional PFASs, fluoroalkylether substances (ether-PFASs) as alternatives are constantly emerging. Subsequently, the three representative ether-PFASs, chlorinated polyfluoroalkyl ether sulfonic acid (F-53B), hexafluoropropylene oxide-dimer acid (HFPO-DA), and 4,8-Dioxa-3H-perfluorononanoicacid (ADONA) are discovered and have received more attention in the environment and ecosystem. But their security is now also being challenged. This review systematically assesses their security from six dimensions including environmental occurrence in water, soil and atmosphere, as well as bioaccumulation and risk in plants, animals and humans. High substitution level is observed for F-53B, whether in environment or living things. Like PFOS or even more extreme, F-53B exhibits high biomagnification ability, transmission efficiency from maternal to infant, and various biological toxicity effects. HFPO-DA still has a relatively low substitution level for PFOA, but its use has emerged in Europe. Although it is less detected in human bodies and has a higher metabolic rate than PFOA, the strong migration ability of HFPO-DA in plants may pose dietary safety concerns for humans. Research on ADONA is limited, and currently, it is detected in Germany frequently while remaining at trace levels globally. Evidently, F-53B has shown increasing risk both in occurrence and toxicity compared to PFOS, and HFPO-DA is relatively safe based on available data. There are still knowledge gaps on security of alternatives that need to be addressed.


Subject(s)
Alkanesulfonic Acids , Caprylates , Fluorocarbons , Propionates , Water Pollutants, Chemical , Animals , Humans , Bioaccumulation , Ecosystem , Fluorocarbons/analysis , Ethers , Ethyl Ethers , Water Pollutants, Chemical/analysis , China , Environmental Monitoring
3.
Int J Cardiol ; 395: 131588, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37989451

ABSTRACT

BACKGROUND: Atherosclerotic cardiovascular disease (ASCAD) is recognized as a chronic subclinical systemic inflammatory condition. The platelet-albumin ratio (PAR) has shown promise in prognosticating various inflammation-related disorders. Our study aimed to assess the connection between PAR and major adverse cardiovascular events (MACE) in percutaneous coronary intervention (PCI)-treated patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: PAR, derived from platelet and albumin counts, categorized participants into four quartiles. The primary outcome was composite MACE, encompassing all-cause mortality, non-fatal myocardial infarction (MI), and ischemia-driven revascularization. Secondary outcomes comprised individual MACE components. Multivariate Cox regression evaluated PAR's independent impact on adverse events. The non-linear relationship between the PAR value and MACE was explored using a restricted cubic spline (RCS). Receiver operating characteristic (ROC) analysis was conducted and the area under the curve (AUC) was calculated. Subgroup analysis was used to determine the effect of PAR on MACE in different subgroups. RESULTS: Enrolling 1391 NSTE-ACS patients, high PAR quartiles were correlated with elevated MACE rates (quartile 4 vs. quartile 1: 33.5% vs. 10.2%, p < 0.001). PAR was revealed to be independently related to an increased risk of MACE (quartile 4 vs. quartile 1: HR, 2.04 [95% CI, 1.34-3.08], p = 0.001). RCS indicated a positive PAR-MACE relationship. The AUC of PAR for the 3-year MACE was 0.659 (95% CI: 0.626-0.677, P<0.001). Subgroup analysis showed no significant interactions across subsets. CONCLUSION: PAR independently predicted MACE risk in PCI-treated NSTE-ACS patients.


Subject(s)
Acute Coronary Syndrome , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/surgery , Acute Coronary Syndrome/drug therapy , Percutaneous Coronary Intervention/adverse effects , Prognosis , Myocardial Infarction/etiology , Risk Factors , Treatment Outcome
4.
Foods ; 12(13)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37444255

ABSTRACT

Cellulase has been widely used in many industrial fields, such as feed and food industry, because it can hydrolyze cellulose to oligosaccharides with a lower degree of polymerization. Endo-ß-1,4-glucanase is a critical speed-limiting cellulase in the saccharification process. In this study, endo-ß-1,4-glucanase gene (CelA257) from Myxococcus sp. B6-1 was cloned and expressed in Escherichia coli. CelA257 contained carbohydrate-binding module (CBM) 4-9 and glycosyl hydrolase (GH) family 6 domain that shares 54.7% identity with endoglucanase from Streptomyces halstedii. The recombinant enzyme exhibited optimal activity at pH 6.5 and 50 °C and was stable over a broad pH (6-9.5) range and temperature < 50 °C. CelA257 exhibited broad substrate specificity to barley ß-glucan, lichenin, CMC, chitosan, laminarin, avicel, and phosphoric acid swollen cellulose (PASC). CelA257 degraded both cellotetrose (G4) and cellppentaose (G5) to cellobiose (G2) and cellotriose (G3). Adding CelA257 increased the release of reducing sugars in crop straw powers, including wheat straw (0.18 mg/mL), rape straw (0.42 mg/mL), rice straw (0.16 mg/mL), peanut straw (0.16 mg/mL), and corn straw (0.61 mg/mL). This study provides a potential additive in biomass saccharification applications.

5.
Qual Life Res ; 32(9): 2463-2476, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37119354

ABSTRACT

PURPOSE: Preference-based measures have been increasingly recommended to measure health outcomes for economic evaluation. However, none of existing cardiovascular disease (CVD)-specific health-related quality of life (HRQoL) instruments are preference-based. This study aimed to develop the descriptive system of preference-based HRQoL instrument for Chinese patients with CVDs under the Initiative of China Health Related Outcomes Measures (CHROME). METHODS: Qualitative face-to-face interviews were conducted with Chinese patients with CVDs. Content analysis was employed to generate candidate items for the instrument. Then expert consultation and cognitive debriefing interviews were conducted to guide further selection and revision of the items. RESULTS: We interviewed 127 CVD patients with 67.7% being male and 63.8% living in the urban area. A hierarchical code book comprised of four themes, 20 categories, 62 sub-categories, and 207 codes, was developed. Candidate items were selected based on the criteria set by the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology and ISPOR PRO guidance. An online survey and meeting with an expert advisory panel (n = 15) followed by cognitive debriefing interviews with 20 patients and 13 physicians were conducted to further select and revise the candidate items. The descriptive system of CHROME-CVD consists of 14 items, namely frequency and severity of chest pain, chest tightness, palpitation, shortness of breath, dizziness, fatigue, appetite, sleeping, mobility, daily activities, depression, worry, and social relationship. Four or five level responses were selected based on cognitive debriefing results to each item. CONCLUSION: The current study developed the descriptive system (items and response options) of CHROME-CVD, the future CVD-specific preference-based HRQoL instrument for Chinese CVD patients.


Subject(s)
Cardiovascular Diseases , Quality of Life , Humans , Male , Female , Quality of Life/psychology , East Asian People , Surveys and Questionnaires , Qualitative Research
6.
J Oleo Sci ; 71(9): 1337-1348, 2022.
Article in English | MEDLINE | ID: mdl-36047241

ABSTRACT

In this study, lipase A from Candida antarctica (CALA) was immobilized onto the macroporous resin NKA-9. Immobilization conditions (pH, time and CALA concentration) were studied, enzymatic activity and immobilization efficiency (IE) up to 968.89 U/g and 53.19% were respectively obtained under optimal conditions (immobilization pH 5.0, time 5 h and CALA concentration at 30 mg/mL). Then, the NKA-9 supported CALA (CALA@NKA-9) samples were used to catalyze glycerolysis in solvent-free system. With 0.25 g of the present CALA@NKA-9 (soybean oil 3.52 g and glycerol 0.184 g) and after 12 h reaction at 50 °C, diacylglycerols (DAG) content up to 64.37% and triacylglycerols (TAG) conversion at 83.33% were obtained. The relationship between temperature and TAG conversion was LnV 0 = 13.9310-6.4212/T for CALA@NKA-9. Meanwhile, the activation energy (Ea) of CALA@NKA-9 was calculated to be 53.39 kJ/mol. In addition, reusability in the glycerolysis reaction was also evaluated, and 57.82% of the initial glycerolysis activity was retained after 9 consecutive applications. Furthermore, the CALA@NKA-9 was also used to catalyze the esterification (esterification of fatty acids with glycerol), however, the present CALA@NKA-9 cannot initiate the esterification. Therefore, the present CALA@NKA-9 is shown to be potential for DAG production through glycerolysis reaction.


Subject(s)
Enzymes, Immobilized , Lipase , Basidiomycota , Diglycerides/chemistry , Enzymes, Immobilized/chemistry , Esterification , Fungal Proteins/chemistry , Glycerol , Lipase/chemistry , Triglycerides
7.
JACC Heart Fail ; 10(1): 27-37, 2022 01.
Article in English | MEDLINE | ID: mdl-34969494

ABSTRACT

OBJECTIVES: The authors sought to determine whether global longitudinal strain (GLS) is independently associated with the natural history of patients with heart failure (HF) with improved ejection fraction (HFimpEF). BACKGROUND: Left ventricular (LV) ejection fraction (EF) often improves in patients with reduced EF. The clinical course of patients with HFimpEF, however, is quite variable. GLS, a sensitive indicator of LV systolic function, could help predict risk of future events in this population. METHODS: Retrospective analysis of HF patients with LVEF >40% on index echocardiogram who had LVEF <40% on initial study and improvement of ≥10%. GLS was assessed by 2-dimensional speckle-tracking software on index echocardiography. Primary outcome was time to first occurrence of cardiovascular mortality or HF hospitalization/emergency treatment. RESULTS: Of the 289 patients with HFimpEF, median absolute values of GLS (aGLS) and LVEF from index echocardiography were 12.7% (IQR: 10.8%-14.7%) and 52% (IQR: 46%-58%), respectively. Over 53 months following index echocardiography, the primary endpoint occurred less frequently in patients with aGLS above the median than below it (21% vs 34%; P = 0.014); HR of 0.51; 95% CI: 0.33-0.81; P = 0.004. When assessed as a continuous variable, each 1% increase in aGLS on index echocardiogram was associated with a lower likelihood of the composite endpoint; HR of 0.86; 95% CI: 0.79-0.93; P < 0.001, an association that persisted after multivariable adjustment; HR 0.90; 95% CI: 0.82-0.97; P = 0.01. Lower aGLS was associated with increased likelihood of deterioration in LVEF. CONCLUSIONS: In patients with HFimpEF, GLS is a strong predictor for future HF events and deterioration in cardiac function.


Subject(s)
Heart Failure , Ventricular Dysfunction, Left , Humans , Prognosis , Retrospective Studies , Stroke Volume , Ventricular Function, Left
8.
Eur J Heart Fail ; 23(1): 58-67, 2021 01.
Article in English | MEDLINE | ID: mdl-32964537

ABSTRACT

AIMS: Whether risk of worsening renal function (WRF) during acute heart failure (AHF) hospitalization or the association between in-hospital WRF and post-discharge outcomes vary according to left ventricular ejection fraction (LVEF) is uncertain. We assessed incidence of WRF, factors related to its development and impact of WRF on post-discharge outcomes across the spectrum of LVEF in patients enrolled in RELAX-AHF-2. METHODS AND RESULTS: A total of 6112 patients who had LVEF measured on admission and renal function determined prospectively during hospitalization were included. WRF, defined as a rise in serum creatinine ≥0.3 mg/dL from baseline through day 5, occurred in 1722 patients (28.2%). Incidence increased progressively from lowest to highest LVEF quartile (P < 0.001). After baseline adjustment, WRF risk in Q4 (LVEF >50%) remained significantly greater than in Q1 (LVEF ≤29%; hazard ratio 1.2, 95% confidence interval 1-1.43; P = 0.050). Age and comorbidity burden including chronic kidney disease increased as LVEF increased. Neither admission haemodynamic abnormalities, extent of diuresis during hospitalization nor residual congestion explained the increased incidence of WRF in patients with higher LVEF. Serelaxin treatment and diuretic responsiveness were associated with reduced risk of WRF in all LVEF quartiles. WRF in patients in the upper three LVEF quartiles increased risk of post-discharge events. CONCLUSIONS: Worsening renal function incidence during AHF hospitalization increases progressively with LVEF. Greater susceptibility of patients with higher LVEF to WRF appears more related to their advanced age and worse underlying kidney function rather than haemodynamic or treatment effects. WRF is associated with increased risk of post-discharge events except in patients in the lowest LVEF quartile.


Subject(s)
Heart Failure , Relaxin , Acute Disease , Aftercare , Humans , Patient Discharge , Prognosis , Recombinant Proteins , Stroke Volume , Ventricular Function, Left
10.
J Oleo Sci ; 69(4): 347-358, 2020.
Article in English | MEDLINE | ID: mdl-32249262

ABSTRACT

In this study, Lecitase® Ultra (LU) was immobilized onto the parent and the amino-functionalized SBA-15. The immobilization conditions were studied and the activity of the parent SBA-15 supported LU (SBA-15-LU) was found to be at 2177.78 ± 101.84 U/g. After 3-aminopropyl and n-(2-aminoethyl)-3-aminopropyl groups functionalization, enzymatic activity was increased to 3555.56 ± 200.21 and 3444.44 ± 346.41 U/g respectively. The immobilized LU samples were then used to catalyze glycerolysis. The possibility for diacylglycerols (DAG) and monoacylglycerols (MAG) production was evaluated and it was found only suitable for DAG production. In addition, the glycerolysis activity of the immobilized LU was impaired by the tert-pentanol and solvent-free was found suitable. Similar DAG content over 50 wt% could be obtained from glycerolysis by the three immobilized LU samples. The reusability in glycerolysis was evaluated, and 9.79 % of the initial glycerolysis activity was remained from the SBA-15-LU after 5 cycles of reuse. Encouragingly, after 3-aminopropyl and n-(2-aminoethyl)-3-aminopropyl groups functionalization, 62.93 and 83.91% of their initial activity was respectively remained after 5 cycles of reuse.


Subject(s)
Enzymes, Immobilized/chemistry , Glycerol/chemical synthesis , Silicon Dioxide/chemistry , Catalysis , Glycerol/chemistry
11.
Eur J Heart Fail ; 22(4): 726-738, 2020 04.
Article in English | MEDLINE | ID: mdl-32141161

ABSTRACT

AIMS: Although left ventricular ejection fraction (LVEF) is routinely used to categorize patients with heart failure (HF), whether it predicts outcomes after hospitalization for acute heart failure (AHF) is uncertain. Consequently, we assessed the relationship between LVEF and cardiovascular (CV) outcomes in a large, well characterized cohort of patients hospitalized for AHF. METHODS AND RESULTS: The 6128 patients from the RELAX-AHF-2 trial who had LVEF measured during AHF hospitalization were separated into LVEF quartiles and the relationship between LVEF and a composite of CV mortality and rehospitalization for HF or renal failure through 180 days was assessed. We found progressively lower risk for this composite outcome as LVEF increased (hazard ratio 0.95, 95% confidence interval 0.93-0.98 per 5% LVEF increase, P < 0.001) that was driven predominantly by decreased risk for rehospitalization. The smoothed spline curve depicting risk remained stable as LVEF decreased until reaching approximately 40%, at which point risk increased progressively with further reductions in LVEF. Significant differences between LVEF quartiles for post-discharge CV risk were seen in patients with an ischaemic aetiology or with a history of HF preceding index hospitalization, but were less robust in patients with non-ischaemic aetiology and absent in those with de novo HF. CONCLUSION: In patients hospitalized with AHF, CV events over 180 days were more frequent in patients with lower LVEF. This was due predominantly to a significant increase in risk for HF/renal failure rehospitalization but not in either CV or all-cause mortality. LVEF had greater prognostic value in patients with ischaemic aetiology or pre-existing HF.


Subject(s)
Aftercare , Heart Failure , Heart Failure/drug therapy , Heart Failure/epidemiology , Hospitalization , Humans , Patient Discharge , Stroke Volume , Ventricular Function, Left
12.
Toxicology ; 423: 105-111, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31158416

ABSTRACT

BACKGROUND/AIMS: Patients with doxorubicin (Dox) treatment have a high risk of developing vascular toxicity with an unknown mechanism. l-arginine is a substrate for nitric oxide (NO). The decreased level of arginine-NO metabolite in Dox-treated cancer patients was associated with increased level of vascular damage, which promoted us to investigate the mechanism of Dox-induced vascular dysfunction and verify whether l-arginine supplement could alleviate this vasculotoxic effect. METHOD: Within a mouse model of Dox injection (5 mg/kg i.p., 2 or 4 weeks), we measured vascular relaxation, blood pressure, vascular NO generation, apoptosis, and oxidative stress. We tested the efficacy of l-arginine (1.5 mg/g/day, 4 weeks) on Dox-induced vascular relaxation, blood pressure, vascular NO generation, apoptosis, as well as oxidative stress. RESULTS: Dox induced endothelium-dependent vascular dysfunction, which was associated with increased reactive oxidative stress (ROS) production and reduced NO generation in the vessel. ROS was required for Dox-induced apoptosis of both smooth muscle cells and endothelial cells. Dox treatment in mice increased blood pressure, but had no effect on vascular inflammation and fibrosis. L-aringine restored Dox-induced vascular dysfunction via enhancing vascular NO production and alleviating ROS-mediated apoptosis. CONCLUSION: We for the first time demonstrated l-arginine was effectively in suppressing Dox-induced vascular dysfunction, by attenuating vascular NO release and apoptosis. Our results provide a therapeutic target or a circulating marker for assessing vascular dysfunction which response to Dox treatment, and advance our understanding of the mechanisms of Dox-induced vascular dysfunction.


Subject(s)
Antibiotics, Antineoplastic/toxicity , Aorta, Thoracic/drug effects , Arginine/pharmacology , Doxorubicin/toxicity , Endothelium, Vascular/drug effects , Nitric Oxide/metabolism , Protective Agents/pharmacology , Animals , Aorta, Thoracic/metabolism , Aorta, Thoracic/physiology , Apoptosis/drug effects , Blood Pressure/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiology , Male , Mice, Inbred C57BL , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism
13.
Int J Cardiol ; 232: 171-175, 2017 Apr 01.
Article in English | MEDLINE | ID: mdl-28109576

ABSTRACT

BACKGROUND: Cardiac rupture (CR) is a catastrophic complication that occurs after acute myocardial infarction (MI) and, at present, there are no effective pharmacological strategies for preventing this condition. The objective of this meta-analysis was to assess the effect of beta-blockers on CR in patients with acute MI. METHODS: An extensive search of the PUBMED, EMBASE, ISI Web of Science, MEDLINE and Cochrane was performed to retrieve the studies of beta-blockers treatment in patients with acute MI. Data were combined using a random effects model. A meta-analysis was performed using Review Manager 5.3. RESULTS: Four randomized controlled trials (RCTs) involving 68, 842 patients, 603 of whom occurred CR, were met criteria. Meta analysis showed that beta-blockers caused a statistically and clinically significant decrease in the incidence of CR of 32% (RR: 0.68, 95% CI: 0.47 to 0.99, P=0.04). CONCLUSIONS: The findings of this meta-analysis confirmed that the early use of beta-blockers is associated with decreased incidence of CR, suggesting some beneficial effects of beta-blockers on infarct healing after acute MI.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Heart Rupture, Post-Infarction/prevention & control , Myocardial Infarction/drug therapy , Randomized Controlled Trials as Topic , Heart Rupture, Post-Infarction/etiology , Humans , Myocardial Infarction/complications
14.
Mol Cancer Ther ; 8(3): 665-71, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19240160

ABSTRACT

The standard treatment for advanced, androgen-responsive prostate cancer is androgen deprivation therapy with or without a nonsteroidal antiandrogen, such as bicalutamide. Although maximal androgen blockade exhibits favorable responses in the majority of patients, prostate cancer eventually progresses to an androgen-refractory stage. The mechanism underlying bicalutamide resistance in the course of prostate cancer progression is incompletely understood. However, interleukin-6 (IL-6) plays a critical role in the development and progression of CRPC. Herein, we explored an association between IL-6 and bicalutamide resistance. To study this, series of lower and higher passages of LNCaP cell sublines generated by long-term exposure to IL-6 were used. The cells from higher passages of LNCaP treated with IL-6 developed resistance to bicalutamide treatment compared with parental LNCaP cells. The levels of transcriptional intermediary factor 2 (TIF2) in IL-6-treated LNCaP cells were found to be significantly higher than parental LNCaP cells. Down-regulation of TIF2 expression via short hairpin RNA in IL-6-treated LNCaP cells sensitized these cells to bicalutamide treatment, whereas overexpression of TIF2 in the parental LNCaP cells increased resistance to bicalutamide. Furthermore, overexpression of IL-6 attenuated bicalutamide-mediated blockage of androgen-induced androgen receptor nuclear translocation and recruitment. These results show that overexpression of IL-6 increases the resistance of prostate cancer cells to bicalutamide via TIF2. Overexpression of IL-6 not only plays an important role in prostate cancer progression but also contributes to bicalutamide resistance. Our studies suggest that bicalutamide-IL-6-targeted adjunctive therapy may lead to a more effective intervention than bicalutamide alone.


Subject(s)
Anilides/pharmacology , Drug Resistance, Neoplasm/genetics , Interleukin-6/physiology , Nitriles/pharmacology , Nuclear Receptor Coactivator 2/physiology , Prostatic Neoplasms/genetics , Tosyl Compounds/pharmacology , Androgens/pharmacology , Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Disease Progression , Drug Resistance, Neoplasm/drug effects , Gene Expression Regulation, Neoplastic/physiology , Humans , Interleukin-6/genetics , Interleukin-6/pharmacology , Male , Neoplasms, Hormone-Dependent/genetics , Neoplasms, Hormone-Dependent/pathology , Nuclear Receptor Coactivator 2/genetics , Prostatic Neoplasms/pathology , Tumor Cells, Cultured , Up-Regulation/drug effects , Up-Regulation/genetics
15.
Cardiovasc Pathol ; 18(6): 323-31, 2009.
Article in English | MEDLINE | ID: mdl-19150247

ABSTRACT

NK4 may be a promising agent to inhibit tumor invasion and metastasis. To observe the effects of NK4 on the cardiovascular system with pathological injury and to discuss the mechanism, we established an experimental model of viral myocarditis (VCM) by coxsackievirus B3 infection in Balb/c mice on Day 0 and administered NK4 twice daily to the VCM and control mice from Day 20 to Day 45. We then evaluated the cardiac function by means of ultrasonic inspection. Hepatocyte growth factor, TNF (tumor necrosis factor)-alpha, and angiotensin II levels in the myocardial tissue were measured with enzyme-linked immunosorbent assay. Myocardium histopathology was examined with hematoxylin and eosin stain. Collagen deposition of the myocardium was detected through Masson staining. Microvessel staining with the RECA antibody and apoptosis detection with terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling were performed in the myocardium. The changes in MMP3 (matrix metalloproteinase 3), MMP9, TIMP1 (tissue inhibitor of metalloproteinase 1), and TGF (transforming growth factor)-beta1 expression in the myocardium were measured by reverse-transcriptase polymerase chain reaction. We found that NK4 intervention increased TGF-beta and angiotensin II expression, suppressed MMPs, improved the activities of TIMPs, and then promoted collagen deposition in the myocardium. NK4 intervention also decreased the microvessels' density and increased the apoptotic cell count in the myocardia of VCM mice. However, we did not observe the obvious changes in the myocardia of control mice after NK4 intervention. These data suggest that NK4 made negative impacts on the restoration of cardiac function and the recovery from VCM in the experimental mice.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Myocarditis/drug therapy , Myocarditis/pathology , Animals , Apoptosis/drug effects , Coxsackievirus Infections/drug therapy , Coxsackievirus Infections/pathology , Cytokines/biosynthesis , Echocardiography , Enzyme-Linked Immunosorbent Assay , Hepatocyte Growth Factor/metabolism , In Situ Nick-End Labeling , Male , Matrix Metalloproteinases/drug effects , Matrix Metalloproteinases/metabolism , Mice , Mice, Inbred BALB C , Myocardium/pathology , Reverse Transcriptase Polymerase Chain Reaction
16.
Prostate ; 69(2): 126-32, 2009 Feb 01.
Article in English | MEDLINE | ID: mdl-18819102

ABSTRACT

BACKGROUND: Aberrant activation of androgen receptor (AR) plays an important role in the progression of castration resistant prostate cancer. Interleukin-4 (IL-4) enhances AR activation in the absence of androgen and stimulates castration resistant growth of androgen-sensitive prostate cancer cells. However, the mechanism of IL-4 mediated AR activation has not yet been revealed. METHODS: The effect of IL-4 on CBP/p300 expression was examined by Western blot analysis. The effect of IL-4 on the interactions of AR and CBP/p300 was examined by co-immunoprecipitation and ChIP assays. CBP/p300 siRNA was used to knockdown CBP/p300 expression to examine the role of CBP/p300 expression on IL-4 mediated AR activation. RESULTS: We found that IL-4 increases CBP/p300 protein expression and enhances interaction of AR with CBP/p300 proteins through an increase in the recruitment of CBP/p300 protein to the androgen responsive elements in the promoters of androgen responsive genes. Down regulation of CBP/p300 expression using CBP/p300 specific siRNA abolished IL-4 mediated AR activation, suggesting that CBP/p300 is responsible for AR activation induced by IL-4. Furthermore, AR activation can be enhanced by AR acetylation induced by IL-4 in prostate cancer cells. The IL-4 mediated AR acetylation can be blocked by knocking down CBP/p300 expression using CBP/p300 specific siRNA. CONCLUSION: These results suggest that IL-4 activates AR through enhanced expression of CBP/p300 and its histone acetyltransferase activity.


Subject(s)
Cell Nucleus/physiology , Interleukin-4/pharmacology , Receptors, Androgen/physiology , p300-CBP Transcription Factors/physiology , Binding Sites , Cell Line, Tumor , Cell Nucleus/drug effects , Consensus Sequence , Gene Expression Regulation, Neoplastic/drug effects , Histone Acetyltransferases/genetics , Humans , Male , Prostatic Neoplasms , Receptors, Androgen/drug effects , Receptors, Androgen/genetics
17.
Int J Cardiol ; 127(3): 442-3, 2008 Jul 21.
Article in English | MEDLINE | ID: mdl-18495274

ABSTRACT

OBJECTIVE: To study the potential mechanisms of hepatocyte growth factor (HGF) mediating improvement of the cardiac function of dilated cardiomyopathy mice (DCM). METHODS AND RESULTS: We established experimental model of dilated cardiomyopathy by repetitive coxsickievirus B3 (CVB3) infection in Balb/c mice and half of the experimental group mice were injected 0.2 microg recombinated human HGF through tail vein every 2 days starting from the 5th month. At the 5th month, dilated cardiomyopathy occurred in experimental group mice. The HGF level and N-cadherin expression in myocardium of experimental group was downregulated. At the 7th month, after HGF supplement, the HGF level and N-cadherin expression in the myocardium of the mice were increased, the fibrosis of myocardial and cells apoptosis were ameliorated and cardiac function was improved. In vitro experiment, we found that N-cadherin expression was increased in cultured myocardial cells treated with rHGF. CONCLUSION: Increasing in N-cadherin expression may be one of the potential mechanisms of HGF mediating Improvement of cardiac function of dilated cardiomyopathy mice.


Subject(s)
Cadherins/physiology , Cardiomyopathy, Dilated/physiopathology , Hepatocyte Growth Factor/therapeutic use , Animals , Atrial Function/drug effects , Atrial Function/physiology , Cadherins/antagonists & inhibitors , Cadherins/biosynthesis , Cardiomyopathy, Dilated/drug therapy , Cells, Cultured , Hepatocyte Growth Factor/administration & dosage , Humans , Male , Mice , Mice, Inbred BALB C , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Ventricular Function/drug effects , Ventricular Function/physiology
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