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1.
Diagnostics (Basel) ; 10(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007898

RESUMO

This study aimed to investigate the diagnostic performance of semi-quantitative parameters of thallium-201 myocardial perfusion imaging (MPI) for coronary artery disease (CAD). From January to December 2017, patients were enrolled who had undergone Tl-201 MPI and received cardiac catheterization for coronary artery disease within three months of MPI. Receiver operating characteristics (ROC) analysis was used to determine the optimal cutoff values of semi-quantitative parameters. A comparison of the sensitivity and specificity of these parameters based on different subgroupings was further performed. A total of 130 patients were enrolled for further analysis. Among the collected parameters, the stress total perfusion deficit (sTPD) had the highest value of the area under curve (0.813) under the optimal cutoff value of 3.5%, with a sensitivity and specificity of 73.5% and 74.5%, respectively (p = 0.0000), for the diagnosis of CAD. With further subgrouping analysis based on history of diabetes or dyslipidemia, the sensitivity and specificity showed similar results. Based on the currently collected data and image acquisition conditions, the sTPD parameter has a clinical role for the diagnosis of CAD with a cutoff value of 3.5%.

2.
J Bone Miner Metab ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32876727

RESUMO

INTRODUCTION: Bone turnover markers (BTMs) can be used to monitor bone metabolism, while the actual clinical changing in hip fracture had not been certified to evaluate the changes of BTMs during the healing process after surgery of elderly hip fractures; and to get the effects of operation type, gender, serum 25(OH)D level, and age on bone turnover markers. MATERIALS AND METHODS: A total of 100 elderly cases with hip fracture were selected, including 74 females and 26 males, and the patients were followed to 180-230 days after surgery. Serum levels of N-propeptide of type 1 collagen (P1NP), C-terminal crosslinking telopeptides of type 1 collagen (CTX), Osteocalcin (OC), and 25 hydroxy vitamin D (25OHD) were investigated. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry (DXA). RESULTS: (1) P1NP and CTX showed peak time at 30-60 days after operation, while OC keep going even at 180-230 days; P1NP showed less than 4 times elevation during healing, CTX and OC only had less than 2 times rise. (2) Female had higher serum CTX and OC than male, intramedullary nailing for intertrochanteric fracture patients had higher P1NP than hip replacement for femoral neck fracture patients, and both the degrees of increase were less than 50%. (3) Serum average 25(OH)D level had no effect on BTMs during the fracture healing; different from the young old (65-84 years), serum OC level of eldest older patients(≥ 85 years) decreased early in the process of fracture healing. CONCLUSIONS: BTMs reached the peak level in 30-60 days after surgery, P1NP showed less than 4 times elevation, and CTX and OC had less than 2 times rise. It was not necessary to take gender into account when observing P1NP, and it was not necessary to take fracture and operation type into account when observing CTX and OC.

3.
Adv Exp Med Biol ; 1250: 125-140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32601942

RESUMO

In the tissue engineering research field, nanobiomaterials highlight the impact of novel bioactive materials in both current applications and their potentials in future progress for tissue engineering and regenerative medicine. Tissue engineering is a well-investigated and challenging biomedical field, with promising perspectives to improve and support quality of life for the patient. To assess the response of those extracellular matrices (ECMs), induced by biomedical materials, this review will focus on cell response to natural biomaterials for biocompatibility.


Assuntos
Materiais Biocompatíveis , Engenharia Tecidual , Materiais Biocompatíveis/normas , Células/imunologia , Matriz Extracelular/imunologia , Humanos , Qualidade de Vida , Medicina Regenerativa , Engenharia Tecidual/métodos
4.
Chin J Integr Med ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32418178

RESUMO

OBJECTIVE: To investigate the effect of early intervention of Tongxinluo (, TXL) on right ventricular function (RVF) of rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). METHODS: A total of 30 adult male Sprague-Dawley rats were assigned to 5 groups with complete random experiment design: Sham group (Sham), MCT group, TXL group, sildenafil (SIL) group and combination group (TXL+SIL), 6 rats in each group. Rats were injected with 50 mg/kg MCT solution for inducing PAH model except for those in the sham group. From the day of modeling, rats of TXL, SIL and TXL+SIL groups were given TXL (1.2 g/kg), SIL (10 mg/kg) and combination solution (TXL:1.2 g/kg, SIL: 10 mg/kg) respectively, and rats in Sham and MCT groups were given normal saline (5 mL/kg). The samples were collected and tested after 21 consecutive days of intragastric administration. Echocardiography was used to measure the related indices of RVF, including pulmonary arterial flow spectrum, pulmonary artery diameter (PAD), right ventricular wall thickness (RVWT), right ventricular diameter (RVD), tricuspidannular plane systolic excursion (TAPSE), right atrium transverse diameter (RAT), and inferior vena cava diameter (IVCD). Elastic Verhoeff-Van Gieson staining was adopted to measure the percentage of wall thickness (WT%) of pulmonary arteriols. Hematoxylin-eosin staining was used to measure the cross-sectional area (CSA) of right ventricular cardiomyocytes. RESULTS: MCT-induced PAH rat model was successfully established. In MCT group the wall of pulmonary arterioles exhibited a prominent-increase thickness, PAD, RVWT, RVD, RAT, IVCD, WT%, right ventricular hypertrophy index (RVHI) as well as CSA of RV cardiomyocyte significantly increased (all P<0.01), and TAPSE markedly decreased (P<0.01). At the same time, TXL prominently improved all of the above indices (all P<0.01). In comparison with SIL, TXL significantly reduced RVD (P<0.05) and decreased CAS of RV cardiomyocytes (P<0.01), but TAPSE in SIL group was much larger than in TXL group (P<0.01). Moreover, TAPSE in TXL+SIL group was larger than that in TXL group (P<0.01), while the two groups performed equally well in terms of the other indices. CONCLUSION: Early intervention of TXL could inhibit pulmonary arterioles remodeling, and improve RVF by attenuating right ventricular hypertrophy, and TXL has a stronger effect on inhibiting right ventricular remodeling than SIL.

5.
Aging (Albany NY) ; 12(3): 2530-2544, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32023551

RESUMO

Circular RNA (circRNA) is a novel class of noncoding RNAs, and the roles of circRNAs in the development of cardiac hypertrophy remain to be explored. Here, we investigate the potential roles of circRNAs in cardiac hypertrophy. By circRNA sequencing in left ventricular specimens collected from 8-week-old mice with isoproterenol hydrochloride-induced cardiac hypertrophy, we found 401 out of 3323 total circRNAs were dysregulated in the hypertrophic hearts compared with the controls. Of these, 303 circRNAs were upregulated and 98 were downregulated. Moreover, the GO and KEGG analyses revealed that the majority of parental gene of differentially expressed circRNAs were not only related to biological process such as metabolic process and response to stimulus, but also related to pathway such as circulatory system and cardiovascular diseases. On the other hand, total 1974 miRNAs were predicted to binding to these differentially expressed circRNAs, and the possible target mRNAs of those miRNAs were also predicted and analyzed in terms of functional annotation. Finally, we identified that ANF and miR-23a are downstream targets of circRNA wwp1, suggesting that circRNA wwp1 exerts inhibitory roles of cardiac hypertrophy via down-regulation of ANF and miR-23a, which underlying the potential mechanisms whereby circRNA regulates cardiac hypertrophy.

6.
Int Immunopharmacol ; 78: 105790, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31813830

RESUMO

Acute lung injury (ALI) is a complex clinical syndrome with high morbidity and mortality rates. Autophagy is an adaptive process that plays a complex role in ALI. The aim of this study was to investigate the effects of autophagy on lipopolysaccharide (LPS)-induced lung injury by establishing a rat ALI model and to further explore the possible mechanisms involved. Rats were pretreated with the autophagy inhibitor 3-methyladenine (3-MA) or the autophagy activator rapamycin before they were challenged with the intratracheal instillation of LPS (5 mg/kg). The level of autophagy in the lung tissue was detected. Lung injury and vascular permeability were assessed. The role of the mechanistic target of rapamycin (mTOR)-mediated Unc-51-like kinase 1 (ULK1) and the class III PI3 kinase VPS34 in autophagy regulation was examined. LPS challenge induced autophagy and rapamycin pretreatment enhanced autophagy activity in LPS-induced ALI rats. LPS caused severe lung injury and high pulmonary vascular permeability, which could be alleviated by enhancing autophagy. In addition, the inhibition of mTOR upregulated the expression of ULK1 and VPS34 and thus increased LPS-induced autophagy. Autophagy plays a protective role in LPS-induced ALI, and enhancing autophagy via the inhibition of mTOR alleviates lung injury and pulmonary barrier function. Moreover, mTOR negatively mediates ULK1 and VPS34 to regulate LPS-induced autophagy in rats.

7.
Clin Chim Acta ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31790698

RESUMO

BACKGROUND: Progesterone is one of the female steroid hormones and plays an important role in the menstrual cycle and during pregnancy. It is especially important in preparing the uterus for the implantation of the blastocyst and maintaining pregnancy. The concentration in human serum is measured to determine the ovarian function retroactively and the cause of abortion in early pregnancy. METHODS: A quantification assay based on isotope dilution mass spectrometry to determine the concentration of progesterone in human serum is reported. Incorporated with 13C3-progesterone, serum samples were subjected to progesterone extraction and clean-up by C4 solid-phase-extraction columns and hexane-based liquid/liquid extraction, respectively. The cleaned-up serum samples were then subjected to MALDI-TOF mass spectrometry for the quantification of progesterone. RESULTS: Progesterone and the internal standard, 13C3-progesterone, were measured in the selected reaction monitoring mode for the transitions m/z 315.4 to 108.9 and m/z 318.4 to 111.9, respectively. We calculated the peak area ratio of progesterone to 13C3-progesterone. The progesterone concentration in human serum was calculated by substituting the peak area ratio into an isotope dilution calibration curve, and then compared with the radioimmunoassay. CONCLUSIONS: In the study, the concentrations of serum progesterone were measured, and the recovered progesterone concentration determined by the assay showed good robustness and consistency in comparison to the conventional radioimmunologic assay. We concluded that the 13C3-progesterone-based quantification assay is a robust method for the measurement of serum progesterone.

8.
Chin J Integr Med ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227964

RESUMO

OBJECTIVE: To investigate the protective effects and mechanism of Chinese herbal compound Tongxinluo Capsule (, TXL) on the Parkin-mediated mitophagy and the ubiquitin-proteasome system in a rat model of myocardial ischemia-reperfusion injury (MIRI). METHODS: Seventy adult male Sprague-Dawley rats were randomly divided into 7 groups: sham group, MIRI group, low- and high-dose TXL (0.5 and 1 g·kg-1·d-1, respectively) groups, atorvastatin (ATV) group (7.2 g·kg-1·d-1), chloroquine (CQ) group (10 g·kg-1·d-1), and highdose TXL + CQ group. After pharmacological administration for 7 days, rats underwent left anterior descending artery ligation surgery to establish the MIRI models with 50 min ischemia followed by 4 h reperfusion. Blood was taken for cardiac troponin I (cTnI) detection and hearts were harvested for infarct staining and apoptosis detection. The autophagy or mitophagy proteins and ubiquitinated proteins were detected by Western blotting. RESULTS: Compared with the sham group, the MIRI group exhibited a larger infarcted area (27.13%±0.01%, P<0.01), a higher apoptotic index (34.33%±2.03% vs.1.81%±0.03%, P<0.01), and higher cTnI expression (14.18±1.01 vs. 7.96±0.32, P<0.01). The mitochondrial integrity was damaged in the MIRI group, while TXL and ATV alleviated the damage of MIRI. More autophagosomes were observed in the high-dose TXL group than in the MIRI group (7.00±0.58 vs. 4.33±1.15, P<0.05). More amounts of PTEN-induced putative kinase protein 1 (PINK1) and Parkin translocated onto the mitochondria were detected in the high-dose TXL group than in the MIRI group (P<0.05). The ubiquitin response was signifificantly downregulated in the high-dose TXL group relative to the MIRI group (P<0.05). CQ administration abolished the activation of autophagy flux and the PINK1/ Parkin pathway induced by high-dose of TXL. CONCLUSIONS: TXL ameliorates MIRI via activating Parkin-mediated mitophagy in rats. The downregulation of the ubiquitin-proteasome system is also involved.

9.
Toxicol Appl Pharmacol ; 378: 114607, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170416

RESUMO

Glycine N-methyltransferase is a protein with many functions. In addition to catalyzing the production of sarcosine in the one carbon metabolism pathway, it plays a role in the detoxification of environmental carcinogens such as benzo[a]pyrene, aflatoxin B1, and aristocholic acid. There is also increasing evidence suggesting a role of GNMT deficiency in liver carcinogenesis. In this review, we discuss the role of GNMT in the detoxification of xenobiotics and the mechanism of GNMT suppression during liver tumorigenesis. The protective role of GNMT in the liver allows GNMT to not only serve as a marker of liver disease, but also potentially be applied in the treatment of liver disorders and hepatocellular carcinoma. We describe the potential use of GNMT in gene therapy and we introduce the development of a GNMT promoter reporter assay that can be used to screen medicinal drugs and herbal libraries for natural compounds with anti-cancer properties.

10.
Stem Cell Res Ther ; 10(1): 118, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30987681

RESUMO

BACKGROUND: Adult stem cells exist in a quiescent state (G0) within the in vivo niche; the loss of quiescence often leads to a decrease in the number and function of adult stem cells, impairing tissue regeneration and repair. Endogenous repair by nucleus pulposus-derived stem cells has recently shown promising regenerative potential for the treatment of intervertebral disc degeneration (IDD). However, the number and function of nucleus pulposus stem cells (NPSCs) declined throughout the process of IDD. This effect may have a specific relationship with quiescence. However, the biology of the quiescent NPSCs has not been reported. METHODS: First, we established an in vitro model for NPSC quiescence with serum starvation. The induction of G0 was confirmed by flow cytometry analyses of dual staining with Hoechst 33342 and Pyronin Y, immunofluorescent staining with Ki67 and Western blot analysis of P27 expression. NPSCs were cultured under serum starvation conditions for a long time period (21 days). To examine the functional phenotype of quiescent NPSCs, the cells were reactivated with 10% serum and differentiated into osteogenic and chondrogenic lineages in vitro. The number of colony-forming units was also estimated. To elucidate the role of autophagy in the quiescence of NPSCs, we activated and inhibited autophagy in starved cells with rapamycin and chloroquine, respectively. Then, the expression of P27 was evaluated by Western blot analysis, and the immunofluorescence of Ki67 was assessed. Finally, we assessed the role of P27 siRNA in NPSC quiescence by flow cytometry analyses and 5-ethynyl-20-deoxyuridine incorporation assays under normal and serum-starved conditions. RESULTS: NPSC quiescence was induced by 48 h of serum starvation, and they maintained quiescence for up to 21 days. Upon reactivation with serum, the quiescent NPSCs re-entered the cell cycle and exhibited enhanced clonogenic self-renewal, osteogenic differentiation and chondrogenic differentiation potentials compared to control NPSCs under normal culture conditions. We also found that autophagy underlay serum starvation-induced NPSC quiescence. Further study demonstrated that autophagy mediated the quiescence of NPSCs by regulating P27. CONCLUSIONS: Serum starvation efficiently induces quiescence in NPSCs. Quiescent NPSCs maintain stem cell properties. Our study reveals that autophagy plays a role in maintaining NPSC quiescence and that autophagy mediates the quiescence of NPSCs by regulating P27. We conclude that the induction of quiescence in cultured NPSCs provides a useful model for the analysis of mechanisms that might be relevant to the biology of NPSCs in vivo.

11.
J Food Drug Anal ; 27(2): 551-564, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987727

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia in late life. It is difficult to precisely diagnose AD at early stages, making biomarker search essential for further developments. The objective of this study was to identify protein biomarkers associated with aluminum ions toxicity (AD-like toxicity) in a human neuroblastoma cell model, SH-SY5Y and assess potential prevention by NAP (NAPVSIPQ). Complete proteomic techniques were implemented. Four proteins were identified as up-regulated with aluminum ion treatment, CBP80/20-dependent translation initiation factor (CTIF), Early endosome antigen 1 (EEA1), Leucine-rich repeat neuronal protein 4 (LRRN4) and Phosphatidylinositol 3-kinase regulatory subunit beta (PI3KR2). Of these four proteins, EEA1 and PI3KR2 were down-regulated after NAP-induced neuroprotective activity in neuroblastoma cells. Thus, aluminum ions may increase the risk for neurotoxicity in AD, and the use of NAP is suggested as a treatment to provide additional protection against the effects of aluminum ions, via EEA1 and PI3KR2, associated with sorting and processing of the AD amyloid precursor protein (APP) through the endosomal system.

12.
J Food Drug Anal ; 27(2): 603-609, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987732

RESUMO

Glycine N-methyltransferase (GNMT) protein is highly expressed in certain tissues, such as liver, pancreas, and prostate. GNMT serves multiple roles which include a methyl group transfer enzyme and a liver tumor suppressor. Benzo(a)pyrene (BaP), a family member of polycyclic aromatic hydrocarbon (PAH), is a known environmental carcinogen found in coal tar, tobacco smoke, barbecued food and incomplete combustion of auto fuel. BaP recruits cytochrome P450 to transform itself into benzo(a)pyrene-7,8-diol-9,10-epoxide (B(a)PDE), which covalently interacts with DNA causing tumorigenesis. BaP can be detoxified through GNMT and induces GNMT translocation into the cellular nucleus. GNMT translocation is accompanied by phosphorylation, but the role of phosphorylation in GNMT remains to be explored. Using liquid chromatography coupled with tandem mass spectrometry, this study identified serine 9 of GNMT as the phosphorylation site upon BaP treatment. When serine 9 was mutated and lost the capability to be phosphorylated, the occurrence of BaP-induced GNMT nuclear translocation was dramatically decreased. Also, this mutant from of GNMT lost the ability of phosphorylation and increased cytochrome P450 1A1 (Cyp1a) expression upon BaP treatment. In addition, protein kinase C (PKC) and c-Jun NH2-terminal kinase (JNK) may be required for such phosphorylation. Further characterization of phosphorylated GNMT for its link to BaP may bring new insights into chemical detoxification.

13.
Bone ; 124: 62-68, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31004806

RESUMO

The purpose of this study was to investigate the differences in bone mineral density (BMD) and hip structure between femoral neck and trochanteric fractures in elderly Chinese individuals using quantitative computed tomography (QCT). A total of 625 Chinese patients (mean age 75.8 years) who sustained low-energy hip fractures (female: 293 femoral neck, 175 trochanteric; male: 82 femoral neck, 75 trochanteric) were recruited. Each patient underwent a hip QCT scan. The areal BMD (aBMD) of the contralateral normal hip was obtained using a computed tomography X-ray absorptiometry module. Using the bone investigation toolkit (BIT) module, the femoral neck was divided into four quadrants: supero-anterior (SA), infero-anterior (IA), infero-posterior (IP), and supero-posterior (SP). Estimated cortical thickness, cortical BMD, and trabecular BMD were measured in each quadrant. Using the hip structure analysis (HSA) function, several parameters were calculated. Stratified by sex, covariance analyses were applied to compare the femoral neck fractures group with trochanteric fractures group after adjustments for age, height, and weight. In women, trochanteric fractures exhibited lower trabecular BMD and estimated cortical thickness at three quadrants of the femoral neck (IA: P = 0.02, P < 0.01; IP: P < 0.01, P = 0.01; SP: P = 0.01, P < 0.01), and lower aBMD at the trochanter area (P < 0.01); femoral neck fractures exhibited lower cortical BMD and estimated cortical thickness at the SA quadrant (P = 0.04, P = 0.01). Differences in HSA parameters were not statistically significant. Among all parameters, the most valuable ones to discrimination of hip fracture type are estimated cortical thickness of the SA quadrant of femoral neck and the aBMD of the trochanter area. In men, only lower cortical BMD at the SP quadrant and aBMD at the trochanter were found in the trochanteric fractures (P = 0.02, P < 0.01). QCT outcomes indicate that spatial differences are helpful to explore the pathogenesis of different type of hip fractures. In women, trochanteric fractures are related to severer osteoporosis, whereas cortical fragility in the SA region of the femoral neck predominates in cases of femoral neck fractures. In men, trochanteric fractures are related to more bone loss of trochanter.

14.
Sci Rep ; 9(1): 2552, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30796242

RESUMO

Characterized with a high recurrence rate and low detection rate, prevention is the best approach to reduce mortality in hepatocellular carcinoma (HCC). The overexpression of Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2 (PREX2) is observed in various tumors, including HCC; and the frequent PREX2 mutations in melanoma are associated with invasiveness. We sought to identify somatic mutations and the functional changes in mutational signatures of PREX2. Genomic DNA sequencing was performed in 68 HCC samples with three types of hepatitis viral infection status: HBs Ag-positive, anti-HCV Ab-positive, and negative for any hepatitis B or C markers. Stabilities and interactions of proteins as well as cell proliferation and migration were evaluated. Fourteen non-silent point mutations in PREX2 were detected, with 16 of 68 HCC patients harboring at least one non-silent mutation. All mutant forms of PREX2, except for K400f, had an extended half-life compared with wild-type PREX2. Moreover, only the half-life of S1113R was twice that of the wild-type. PREX2 mutant-S1113R also promoted migration and activated the AKT pathway as well as impaired HectH9-mediated ubiquitination. Our study identified a gain-of-function mutation of PREX2 - S1113R in HCC. Such mutation enhanced PREX2 protein stability, promoted cell proliferation, and was associated with aggressiveness of HCC.

15.
Life Sci ; 219: 74-81, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30611784

RESUMO

AIMS: Progressive cardiac conduction disease (PCCD) is a rare heart disease that usually shows familial inheritance. Potential genetic risk factors for PCCD have been mostly limited to genes that encode ion channels, cardiac transcription factors, T-box transcription factors, gap junction proteins, energy metabolism regulators and structural proteins. MAIN METHODS: Subjects in the present study came from a family who exhibited the autosomal dominant inheritance of PCCD. The primary proband had syncope and an electrocardiogram typical for PCCD, which started in the left bundle branch block, and passed to the atrioventricular block. The patient received a permanent pacemaker in 2013. Pathogenic mutations in the proband's family were identified using whole-exome sequencing and Sanger sequencing. KEY FINDINGS: The results for the family members were verified using Sanger sequencing, while the results for healthy unrelated individuals were verified using SNaPShot. All patients in the family shared two adjacent missense mutations in the preprodynorphin (PDYN) gene (c.581A > T, c.580G > C; p.D194L). SIGNIFICANCE: The PDYN double mutation c.581A > T and c.580G > C (p.D194L) may be linked to the onset of familial PCCD. The effects of these mutations on electrophysiology require further investigation.


Assuntos
Doença do Sistema de Condução Cardíaco/genética , Dinorfinas/genética , Exoma/genética , Mutação de Sentido Incorreto/genética , Precursores de Proteínas/genética , Adulto , Doença do Sistema de Condução Cardíaco/fisiopatologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
16.
J Cell Physiol ; 234(8): 13252-13262, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30580435

RESUMO

Although cardiac hypertrophy is widely recognized as a risk factor that leads to cardiac dysfunction and, ultimately, heart failure, the complex mechanisms underlying cardiac hypertrophy remain incompletely characterized. The nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) is involved in the regulation of cardiac lipid metabolism. Here, we describe a novel PPARδ-dependent molecular cascade involving microRNA-29a (miR-29a) and atrial natriuretic factor (ANF), which is reactivated in cardiac hypertrophy. In addition, we identify a novel role of miR-29a, in which it has a cardioprotective function in isoproterenol hydrochloride-induced cardiac hypertrophy by targeting PPARδ and downregulating ANF. Finally, we provide evidence that miR-29a reduces the isoproterenol hydrochloride-induced cardiac hypertrophy response, thereby underlining the potential clinical relevance of miR-29a in which it may serve as a potent therapeutic target for heart hypertrophy treatment.


Assuntos
Fator Natriurético Atrial/metabolismo , Cardiomegalia/metabolismo , Regulação da Expressão Gênica/fisiologia , MicroRNAs/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Regulação para Baixo , Camundongos , Camundongos Endogâmicos ICR , Miócitos Cardíacos/metabolismo
17.
Pak J Pharm Sci ; 31(6): 2403-2410, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30473511

RESUMO

This study was design to investigate preventive function of Tongxinluo (TXL) capsule on micro vascular function and endothelial survival in rats model of intestine ischemia/reperfusion (I/R) injury. We randomly divided fifty male Sprague-Dawley rats into Sham group, I/R group, TXL0.4+I/R group, TXL0.8+I/R group, TXL1.6+I/R group (10 rats each). Rat intestine I/R injury was carried out using a model of acute superior mesenteric artery occlusion with 30 min ischemia followed by 60 min reperfusion. The distribution of endothelial apoptosis in intestine was determined by CD31+TUNEL immunofluorescent double staining analysis. VE-Cadherin, ANGPTL4, HMGB1 and NF-κB were determined by immunohistochemical analysis. I/R induced massively endothelial cell apoptosis, accompanied with reduced expression of adherens junction protein VE-Cadherin and up regulation of inflammatory mediator HMGB1 and NF-κB. TXL pretreatment groups (TXL0.4+I/R, TXL0.8+I/R and TXL1.6+I/R group) significantly attenuated endothelial cell apoptosis with a dose-dependent effect. TXL pretreatment could maintain the expression of VE-Cadherin and promote the expression of ANGPTL4 which help to maintain endothelial integrity. TXL pretreatment also exert great influence in inhibiting HMGB1 expression and NF-κB expression induced by I/R. It could be concluded from this study that micro vascular dysfunction and endothelial damage play a causal role in rat intestine I/R injury. TXL pretreatment could significantly prevent the I/R induced pathology of endothelial apoptosis, micro vascular integrity disruption and inflammatory reaction.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Mediadores da Inflamação/metabolismo , Intestinos/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Proteína 4 Semelhante a Angiopoietina/metabolismo , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Citoproteção , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Proteína HMGB1/metabolismo , Masculino , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
18.
Arch Pharm Res ; 41(11): 1074-1081, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30151611

RESUMO

Two new phenylpropanoids, retusiusines A (1) and B (2), and a pair of new phenylpropyl enantiomers, (±)-retusiusine C (3a and 3b), together with eight known compounds, dihydroconiferyl dihydro-p-coumarate (4), methyl 3-(4-hydroxyphenyl) propionate (5), 3-(4-hydroxyphenyl)-propanoic acid (6), dihydroferulic acid (7), methyl 3-(4-methoxyphenyl) propionate (8), 3-(3,4-dimethoxyphenyl)-2-propenal (9), trans-p-coumaric acid (10) and dihydroconiferyl alcohol (11), were isolated from the tubers of Bulbophyllum retusiusculum. The absolute configurations of the new compounds were determined by calculating their electronic circular dichroism (ECD), spectra and specific optical rotations and comparing the calculated values with the experimental data. Compound 2 exhibited potent antifungal activity against Candida albicans (16 µg/mL). Compound 3 showed moderate antibacterial activity against Bacillus subtilis (64 µg/mL).


Assuntos
Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Orchidaceae/química , Fenilpropionatos/isolamento & purificação , Tubérculos/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenilpropionatos/farmacologia , Plantas Medicinais , Estereoisomerismo
19.
Huan Jing Ke Xue ; 39(5): 2274-2282, 2018 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965528

RESUMO

The sludge conditioning performance of inorganic Al, Fe, and Ti coagulants were systematically compared in terms of specific resistance to filtration (SRF), the content of protein and polysaccharide in extracellular polymeric substances (EPS), the change in three-dimensional excitation emission matrix fluorescence (3D-EEM), the molecular weight of organic matter in EPS, and the floc size and surface morphology. The sludge conditioning ability and the mechanism were systematically analyzed. The results showed that the sludge conditioning ability of the three inorganic coagulants was in the order of polyaluminum chloride (PAC) > titanium xerogel coagulant (TXC) > polymeric ferric sulfate (PFS). After conditioning, the contents of protein and polysaccharide in the EPS were greatly reduced, especially in the loosely bound EPS (LB-EPS). The combined capacity for coagulation between TXC/PFS and organic matter was stronger than that of PAC. The content of polysaccharide in LB-EPS was the key factor affecting the sludge dewatering performance but not the coagulated floc size. The surface charge and the chelating ability with organic matter co-determined the sludge dewatering ability. The organic cationic polymer, polyacrylamide (PAM), made the sludge aggregate via charge neutralization. However, the use of PAM alone was not a good choice owing to the low dewatering ability and the loose sludge structure. The results here are helpful for the selection of suitable coagulants for sludge conditioning.


Assuntos
Filtração , Esgotos , Resinas Acrílicas , Alumínio , Floculação , Ferro , Polímeros , Polissacarídeos , Proteínas , Titânio
20.
Chin Med J (Engl) ; 131(13): 1527-1532, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29941705

RESUMO

Background: Imbalance of interferon-gamma (IFN-γ), interleukin (IL)-4, and IL-17 producing by T cells is confirmed to contribute to the pathogenesis of systemic lupus erythematosus (SLE). Autophagy is now emerging as a core player in the development and the function of the immune system. Therefore, we investigated the autophagic behavior in IFN-γ-, IL-4-, and IL-17-producing T cells from patients with SLE. Methods: Thirty patients with SLE and 25 healthy controls matched for gender and age were recruited between September 2016 and May 2017. The autophagic levels in IFN-γ+ T cells, IL-4+ T cells, and IL-17+ T cells from patients with newly diagnosed SLE and healthy controls were measured using flow cytometry. The plasma levels of IFN-γ were determined by enzyme-linked immunosorbent assay in SLE patients and healthy controls. Unpaired t-tests and the nonparametric Mann-Whitney U-test were used to compare data from patients with SLE and controls. Spearman's rank correlation coefficient was applied for calculation of the correlation between parallel variables in single samples. Results: Our results showed increased percentage of autophagy in IFN-γ+ T cells from patients with SLE and healthy controls ([8.07 ± 2.72]% vs. [3.76 ± 1.67]%, t = 5.184, P < 0.001), but not in IL-4+ T cells or IL-17+ T cells (P > 0.05) as compared to healthy donors. Moreover, the plasma levels of IFN-γ in SLE patients were significantly higher than those in healthy controls ([68.9 ± 29.1] pg/ml vs. [24.7 ± 17.6] pg/ml, t = 5.430, P < 0.001). Moreover, in SLE patients, the percentage of autophagy in IFN-γ+ T cells was positively correlated with the plasma levels of IFN-γ (r = 0.344, P = 0.046), as well as the disease activity of patients with SLE (r = 0.379, P = 0.039). Conclusion: The results indicate that autophagy in IFN-γ+ T cells from SLE patients is activated, which might contribute to the persistence of T cells producing IFN-γ, such as Th1 cells, and consequently result in the high plasma levels of IFN-γ, and then enhance the disease activity of SLE.


Assuntos
Autofagia , Interferon gama/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Células Th1/fisiologia , Adulto , China , Feminino , Humanos , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Masculino , Pessoa de Meia-Idade
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