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1.
Pediatr Res ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38570557

ABSTRACT

While perinatal medicine advancements have bolstered survival outcomes for premature infants, bronchopulmonary dysplasia (BPD) continues to threaten their long-term health. Gene-environment interactions, mediated by epigenetic modifications such as DNA methylation, histone modification, and non-coding RNA regulation, take center stage in BPD pathogenesis. Recent discoveries link methylation variations across biological pathways with BPD. Also, the potential reversibility of histone modifications fuels new treatment avenues. The review also highlights the promise of utilizing mesenchymal stem cells and their exosomes as BPD therapies, given their ability to modulate non-coding RNA, opening novel research and intervention possibilities. IMPACT: The complexity and universality of epigenetic modifications in the occurrence and development of bronchopulmonary dysplasia were thoroughly discussed. Both molecular and cellular mechanisms contribute to the diverse nature of epigenetic changes, suggesting the need for deeper biochemical techniques to explore these molecular alterations. The utilization of innovative cell-specific drug delivery methods like exosomes and extracellular vesicles holds promise in achieving precise epigenetic regulation.

2.
Materials (Basel) ; 16(20)2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37895799

ABSTRACT

Increasing the water-cement ratio and water-reducer dosage of cement slurry enhances its fluidity. However, a high water-cement ratio diminishes the beneficial effects of water reducers on fluidity. The stone content of the slurry decreases as the water-reducer dosage increases. Additionally, the water-cement ratio significantly affects stone content. However, when the water-cement ratio exceeds a threshold value, stone content decreases. Furthermore, the threshold value of the water-cement ratio decreases with increasing water-reducer dosage. Without the addition of the water reducer, as the water-cement ratio increases the overall integrity of the grout stone decreases. The addition of the water reducer alters the surface pore distribution, wherein "uniform small pores" change to "localized large pores." Based on the multi-objective optimization of Matlab, the recommended optimal mix composition for a slow-setting cement slurry is a water-cement ratio of 0.25 and water-reducer dosage of 1.5%. With the use of this optimized mix composition, the stone content and compressive strength increase by 7.8% and 145.6%, respectively, compared to those obtained using the recommended mix ratio in the specifications. Additionally, all relevant performance parameters meet the requirements specified by previous standards.

3.
Sci Rep ; 13(1): 9312, 2023 Jun 08.
Article in English | MEDLINE | ID: mdl-37291240

ABSTRACT

Climate warming leads to frequent extreme precipitation events, which is a prominent manifestation of the variation of the global water cycle. In this study, data from 1842 meteorological stations in the Huang-Huai-Hai-Yangtze River Basin and 7 climate models of CMIP6 were used to obtain the historical and future precipitation data using the Anusplin interpolation, BMA method, and a non-stationary deviation correction technique. The temporal and spatial variations of extreme precipitation in the four basins were analysed from 1960 to 2100. The correlation between extreme precipitation indices and their relationship with geographical factors was also analysed. The result of the study indicates that: (1) in the historical period, CDD and R99pTOT showed an upward trend, with growth rates of 14.14% and 4.78%, respectively. PRCPTOT showed a downward trend, with a decreasing rate of 9.72%. Other indices showed minimal change. (2) Based on SSP1-2.6, the intensity, frequency, and duration of extreme precipitation changed by approximately 5% at SSP3-7.0 and 10% at SSP5-8.5. The sensitivity to climate change was found to be highest in spring and autumn. The drought risk decreased, while the flood risk increased in spring. The drought risk increased in autumn and winter, and the flood risk increased in the alpine climate area of the plateau in summer. (3) Extreme precipitation index is significantly correlated with PRCPTOT in the future period. Different atmospheric circulation factors significantly affected different extreme precipitation indices of FMB. (4) CDD, CWD, R95pD, R99pD, and PRCPTOT are affected by latitude. On the other hand, RX1day and RX5day are affected by longitude. The extreme precipitation index is significantly correlated with geographical factors, and areas above 3000 m above sea level are more sensitive to climate change.


Subject(s)
Climate Change , Droughts , Seasons , Floods , China
4.
Materials (Basel) ; 16(7)2023 Apr 04.
Article in English | MEDLINE | ID: mdl-37049166

ABSTRACT

Affected by the erosive environment, tunnel lining concrete in the long-term service zprocess often exhibits engineering diseases such as concrete corrosion degradation and loss of strength, decreasing the stability of the tunnel lining structure and the traffic safety. Based on HTG tunnel project, the basic distribution rule of tunnel lining corrosion and macro mechanical properties of corroded concrete were explored in this paper through engineering disease site investigation. Then, on this basis, aiming at large-scale corrosion of tunnel lining structure, two reinforcement and repair schemes are proposed, corrugated steel plate reinforcement method and channel steel reinforcement method. Indoor component tests are carried out on the two reinforcement schemes. The failure characteristics and stress and deformation law of tunnel lining members after reinforcement and repair were verified. The analysis showed that the failure process of the reinforced specimens on the tensile side could be divided into the non-cracking stage and the working stage with cracks, and the cracking load and failure load of the specimens were significantly increased. The bearing capacity of the reinforced specimens was divided into the ultimate bearing capacity against cracking and the ultimate bearing capacity during failure. Finally, the calculation methods of the bearing capacity of the channel steel reinforcement method and the corrugated steel plate reinforcement method were derived. Comparative analysis shows that the results of numerical simulation, experimental testing and theoretical simplification methods are close to each other, and the maximum deviation is less than 8%. The established method for calculating the bearing capacity of corroded components after reinforcement is reliable and can be used for the design calculation of corroded lining reinforcement.

5.
Sci Rep ; 12(1): 20592, 2022 Nov 29.
Article in English | MEDLINE | ID: mdl-36446822

ABSTRACT

The drilling and blasting method is widely used in tunnel engineering. The accompanying airblast may damage structures and annoy nearby occupants. The prediction of airblast overpressure (poa) outside the tunnel is necessary to improve the safety of blasting works. A study of propagation characteristics of airblasts induced by tunnel blasting was carried out through experimental and numerical studies. The results indicate that the distributions of the poa outside the tunnel were anisotropic, which does not conform to the decay law of an explosion in free-field. The propagation of airblasts induced by tunnel blasting is related to the airblast shape. The phenomenon that the poa along the axial direction of the tunnel was higher than along other directions can be explained by the numerical results of the process of airblasts. The airblasts outside the tunnel traveled as a spherical wave, but the pressure was not uniformly distributed. After an airblast plane wave with high speed and high pressure inside the tunnel was transmitted out of the tunnel, its inertia strengthened the pressure in the axial direction. The airblast outside the tunnel is related to the propagation distance Rout, the angle from the measurement to the tunnel axis α, and the pressure intensity p0 at the tunnel portal. Subsequently, an ellipsoidal contour curve of the poa outside the tunnel was plotted, and therefore a new prediction equation was validated by numerical results and field data. Finally, the newly proposed methodology guided the blast design.

6.
Materials (Basel) ; 15(13)2022 Jun 23.
Article in English | MEDLINE | ID: mdl-35806560

ABSTRACT

The present study explored the degradation law and service life prediction of tunnel lining concrete with different mineral admixtures under coupled actions of sulfate attack (SA) and drying−wetting (DW) cycles. The deterioration resistance coefficient (DRC) of compressive strength and influence coefficients of sulfate concentration, mineral admixture content, water/binder (w/b) ratio, and curing regime on DRC were studied. After that, a new service life prediction model based on damage mechanics was developed and analyzed. Results show that, by increasing the DW cycles, the DRC first increases and then decreases. DRCs of Ordinary Portland cement (OPC), fly ash (FA), and ground granulated blast-furnace slag (GGBS) concrete linearly decrease with the increase of sulfate concentration, while the silica fume (SF) concrete displays a two-stage process; by increasing the admixture content, the DRCs of FA and GGBS concrete exhibit two distinct stages, while the SF concrete depicts a three-stage process; increasing the w/b ratio linearly decreases the DRC; the DRC of curing regime was sequenced as standard curing (SC) > fog curing (FC) > water curing (WC) > same condition curing (SCC). Based on the experimental results, the service life prediction model is applied and validated. The validation results show that the proposed model can accurately predict the lifetime of concrete with different mix proportions. Furthermore, it is found that the mineral admixture can effectively improve the lifetime of concrete, and the composite mineral admixture is more effective than a single mineral admixture in improving the lifetime of concrete.

7.
Medicine (Baltimore) ; 100(38): e22571, 2021 Sep 24.
Article in English | MEDLINE | ID: mdl-34559092

ABSTRACT

BACKGROUND: There are few reports on the chest computed tomography (CT) imaging features of children with coronavirus disease 2019 (COVID-19), and most reports involve small sample sizes. OBJECTIVES: To systematically analyze the chest CT imaging features of children with COVID-19 and provide references for clinical practice. DATA SOURCES: We searched PubMed, Web of Science, and Embase; data published by Johns Hopkins University; and Chinese databases CNKI, Wanfang, and Chongqing Weipu. METHODS: Reports on chest CT imaging features of children with COVID-19 from January 1, 2020 to August 10, 2020, were analyzed retrospectively and a meta-analysis carried out using Stata12.0 software. RESULTS: Thirty-seven articles (1747 children) were included in this study. The heterogeneity of meta-analysis results ranged from 0% to 90.5%. The overall rate of abnormal lung CT findings was 63.2% (95% confidence interval [CI]: 55.8%-70.6%), with a rate of 61.0% (95% CI: 50.8%-71.2%) in China and 67.8% (95% CI: 57.1%-78.4%) in the rest of the world in the subgroup analysis. The incidence of ground-glass opacities was 39.5% (95% CI: 30.7%-48.3%), multiple lung lobe lesions was 65.1% (95% CI: 55.1%-67.9%), and bilateral lung lesions was 61.5% (95% CI: 58.8%-72.2%). Other imaging features included nodules (25.7%), patchy shadows (36.8%), halo sign (24.8%), consolidation (24.1%), air bronchogram signs (11.2%), cord-like shadows (9.7%), crazy-paving pattern (6.1%), and pleural effusion (9.1%). Two articles reported 3 cases of white lung, another reported 2 cases of pneumothorax, and another 1 case of bullae. CONCLUSIONS: The lung CT results of children with COVID-19 are usually normal or slightly atypical. The lung lesions of COVID-19 pediatric patients mostly involve both lungs or multiple lobes, and the common manifestations are patchy shadows, ground-glass opacities, consolidation, partial air bronchogram signs, nodules, and halo signs; white lung, pleural effusion, and paving stone signs are rare. Therefore, chest CT has limited value as a screening tool for children with COVID-19 and can only be used as an auxiliary assessment tool.


Subject(s)
COVID-19/diagnostic imaging , Lung/diagnostic imaging , Thorax/diagnostic imaging , Tomography, X-Ray Computed/statistics & numerical data , Adolescent , Blister/diagnostic imaging , Blister/epidemiology , Blister/virology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Data Management , Female , Humans , Incidence , Infant , Lung/pathology , Lung/virology , Male , Pleural Effusion/diagnostic imaging , Pleural Effusion/epidemiology , Pleural Effusion/virology , Pneumothorax/diagnostic imaging , Pneumothorax/epidemiology , Retrospective Studies , SARS-CoV-2/genetics , Solitary Pulmonary Nodule/diagnostic imaging , Solitary Pulmonary Nodule/epidemiology , Solitary Pulmonary Nodule/virology , Tomography, X-Ray Computed/methods , Tomography, X-Ray Computed/trends
9.
Polymers (Basel) ; 13(5)2021 Feb 25.
Article in English | MEDLINE | ID: mdl-33668865

ABSTRACT

The far-infrared ray (FIR) is one kind of electromagnetic wave employed for numerous bio-interactive applications such as body thermoregulation, infrared therapy, etc. Tuning the FIR-emitting property of the functional textile surface can initiate a new horizon to utilize this property in sportswear or even smart textiles. Ceramic particles were studied for their unique ability to constantly emit FIR rays. The purpose of this research is to characterize the FIR emission properties and the thermogravimetric analysis of ceramic-embedded polyurethane films. For this purpose, ceramic particles such as aluminum oxide, silicon dioxide, and titanium dioxide were incorporated (individually) with water-based polyurethane (WPU) binder by a sonication technique to make a thin layer of film. Significant improvement in FIR emissive property of the films was found when using different ceramic particles into the polyurethane films. Reflection and transmission at the FIR range were measured with a gold integrating sphere by Fourier-transform infrared (FTIR) spectrometer. The samples were also characterized by thermogravimetric analysis (TGA). Different physical tests, such as tensile strength and contact angle measurements, were performed to illustrate the mechanical properties of the films. The study suggested that the mechanical properties of the polyurethane films were significantly influenced by the addition of ceramic particles.

10.
J Nutr Educ Behav ; 53(2): 130-141, 2021 02.
Article in English | MEDLINE | ID: mdl-33189586

ABSTRACT

OBJECTIVE: To explore intergenerational differences on key factors of food parenting practices (FPPs) related to home eating behavior of schoolchildren. DESIGN: In-depth interviews with social recognition theory-based semistructured interviews conducted from December 2016 to January 2017. PARTICIPANTS: Primary caregivers of elementary schoolchildren from 23 households (16 parents, 14 grandparents) in 4 remote areas of Hualien, Taiwan. PHENOMENON OF INTEREST: Factors related to FPPs hindering micronutrient-dense food group consumption by schoolchildren in a remote area. SETTING: In-depth interviews were conducted at participants' houses. ANALYSIS: Interviews were audiorecorded and transcribed verbatim. Inductive thematic analysis was performed to elicit studied phenomenon. RESULTS: Routine family meals provided adequate staple, protein, and vegetables but inadequate whole grains, dairy, fruits, and nuts. More parents provided breakfast composed of pan-fried and semiprocessed products made of refined flour and sugary beverages. Both parents and grandparents had ambiguous nutrition concepts and inconsistent FPPs but in different aspects. They both reflected expectations for assistance from local schools for nutrition and FPPs education to shape up healthy eating behavior of children. CONCLUSIONS AND IMPLICATIONS: Study findings pinpoint the strength and barriers of FPPs for primary caregivers. Implementing integrated nutrition education programs tailored for empowering nutrition literacy and FPPs is suggested to enhance the healthy eating behavior of schoolchildren in a remote area.


Subject(s)
Grandparents , Parenting , Child , Diet , Feeding Behavior , Humans , Parents
11.
Eur J Pharmacol ; 880: 173125, 2020 Aug 05.
Article in English | MEDLINE | ID: mdl-32360347

ABSTRACT

Whether and how insulin counteracts the cytotoxic effects of hypoxia and improves cardiomyocyte viability remains unclear. To achieve this aim, cultured neonatal rat cardiomyocytes pretreated with vehicle or 1 µM insulin were exposed to either normoxic or hypoxia environment for up to 24 h. Cell viability was monitored and cellular apoptosis as well as necrosis, indexes of autophagy, endoplasmic reticular (ER) stress, and expressions of specific relevant mediators of the signaling pathways of autophagy were also assessed. Hypoxia impaired cell viability, induced autophagy, triggered apoptosis, activated ER stress pathway-associated apoptotic responses along with downstream pro-apoptotic transcriptional factor C/EBP homologous protein (CHOP), and increased apoptosis of myocardial cells. On the other hand, insulin pretreatment effectively ameliorated autophagy via PI3-K/Akt signaling pathway, suppressed ER stress, and prevented hypoxia-induced cellular apoptosis. In an ex vivo study, isolated rat hearts were pre-treated in some cases with insulin and subjected to proximal left coronary artery ligation to induce acute myocardial ischemia. Coronary ligation-induced acute ischemia upregulated glucose-related protein 78 (GRP78) and triggered cellular apoptosis in the jeopardized myocardium. Conversely, insulin pretreatment suppressed these hypoxia-related cytotoxic events and reduced myocardial infarct size by up to 15.2%. In conclusion, hypoxia impedes cell viability through triggering autophagy, ER stress and apoptosis, whereas insulin pretreatment effectively prevents these cytotoxic actions of hypoxia, preserves myocardial cell viability and reduces myocardial infarct size. These results indicated the cytoprotective mechanism of insulin against the insult of hypoxia may justify insulin as a therapeutic option for patients with acute myocardial infarction.


Subject(s)
Cell Hypoxia/drug effects , Insulin/pharmacology , Myocytes, Cardiac/drug effects , Animals , Apoptosis/drug effects , Autophagy/drug effects , Cells, Cultured , Cytoprotection , Endoplasmic Reticulum Stress/drug effects , Heat-Shock Proteins/metabolism , Male , Myocytes, Cardiac/metabolism , Rats, Sprague-Dawley , Transcription Factor CHOP/metabolism
12.
Materials (Basel) ; 11(12)2018 Dec 05.
Article in English | MEDLINE | ID: mdl-30563050

ABSTRACT

Functional finishing brings an alteration on the mechanical and surface properties of textile materials and henceforth influences the tactile properties. In this work, Kawabata evaluation systems (KES) for fabrics were utilized to notice the changes in the tactile properties of fabrics resulting from different finishing types such as inkjet printing, screen printing, and coating. The effects of functional finishing on the fabric's tactile property were inconsistent with reference to the course of decrease or increase being dependent on the types of finishes. The findings showed that KES can be employed as a promising tool to sort out the suitable functional finishing types in terms of tactile properties. Amongst the implemented finishing types, inkjet printing offered superior tactile properties with respect to tensile energy (softness), shear rigidity, compressional softness, bending stiffness (drapability), and surface properties. The KES results confirmed that low-stress mechanical properties are strongly associated with the tactile property and might assist as a quality profile data source for guaranteeing the production and development of a virtuous quality product. The result encourages further utilization of the KES for functional fabric tactile property evaluation.

13.
Aesthetic Plast Surg ; 37(4): 704-8, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23824058

ABSTRACT

UNLABELLED: An epicanthal fold is common in the eyelids of Orientals, weakening the aesthetic appearance of blepharoplasty. Many techniques have been designed to eliminate the epicanthal fold and create a beautiful palpebral fissure with less scarring produced in the medial canthus. However, many of these procedures were designed to correct the epicanthus completely and create an out-type of palpebral fold, which leaves a minor scar in the epicanthus and an unnatural eye appearance. Thus, based on dynamic mechanisms, a beautiful design of the epicanthus, and a double fold in most Asian people, a new modified Z-plasty procedure combined with blepharoplasty to create an in-type of palpebral fissure was performed for 873 patients in our hospital from September 2006 to November 2010. The procedure showed good and natural results in most Asian patients. No recurrence of the epicanthal fold and no scarring of the medial canthus were found during a 6-month follow-up period. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Subject(s)
Asian People , Blepharoplasty/methods , Surgical Flaps , Adolescent , Adult , Child , Eyelids/anatomy & histology , Eyelids/physiology , Female , Humans , Ligaments/surgery , Male , Young Adult
14.
Chin J Physiol ; 56(1): 11-7, 2013 Feb 28.
Article in English | MEDLINE | ID: mdl-23347011

ABSTRACT

In this study, C6 glioma cells were used to test the effects of 2-azafluorenone and its related compounds on membrane phosphatidylinositol (PI) and phosphatidylcholine (PC) turnover. An increase of [³H]-labeled inositol phosphate (IP1) formation by histamine (100 µM) or A23187 (100 nM) via the activation of phosphatidylinositol-specific phospholipase C (PI-PLC) to breakdown labeled substrate was observed, and this effect could be partially blocked by about half at 100 µM of 2-azafluorenones. Histamine induced the increase of IP1 formation, but failed to cause an increase in extracellularly releasing of [3H]choline metabolites, or intracellular accumulation of [³H]phosphscholine. However, platelet activation factor (PAF) from 0.2 to 1 µM, and phorbol 12-myristate-13-acetate (PMA) at 1 µM caused an increase in extracellularly releasing of [³H]choline metabolites, and intracellular accumulation of [³H]phosphocholine via the activation on phosphatidylcholine (PC)-PLC. These responses of PAF and PMA were not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at high concentration (10⁻4 M). A23187 induced an increase of intracellular [³H]choline release via the activation of PCphospholipase D (PLD). This increasing effect of 100 nM A23187 was not affected by 2-azafluorenone or 4-methyl-2-azafluorenone even at a high concentration of 10⁻4 M. In summary, the inhibitory effect of 2-azafluorenone and its related compound 4-methyl-2-azafluorenone was observed selectively on PIPLC, but not on PC-PLC or PC-PLD based on changes of products after the activation of these enzymes.


Subject(s)
Fluorenes/pharmacology , Phosphoinositide Phospholipase C/drug effects , Phospholipase D/drug effects , Type C Phospholipases/drug effects , Animals , Calcimycin , Cell Line, Tumor , Enzyme Activation/drug effects , Histamine , Phosphatidylcholines/metabolism , Phosphatidylinositols/metabolism , Phosphoinositide Phospholipase C/metabolism , Phospholipase D/metabolism , Platelet Activating Factor , Rats , Tetradecanoylphorbol Acetate , Tritium , Type C Phospholipases/metabolism
15.
Int J Mol Sci ; 11(11): 4526-38, 2010 Nov 12.
Article in English | MEDLINE | ID: mdl-21151454

ABSTRACT

Fengycin, a lipopeptide biosurfactant, was produced by indigenous Bacillus subtilis F29-3 isolated from a potato farm. Although inhibiting the growth of filamentous fungi, the fengycin is ineffective against yeast and bacteria. In this study, fengycin was isolated from fermentation broth of B. subtilis F29-3 via acidic precipitation (pH 2.0 with 5 N HCl) followed by purification using ultrafiltration and nanofiltration. The purified fengycin product was characterized qualitatively by using fast atom bombardment-mass spectrometer, Fourier transform infrared spectrometer, ultraviolet-visible spectrophotometer, (13)C-nuclear magnetic resonance spectrometer and matrix assisted laser desorption ionization-time of flight, followed by quantitative analysis using reversed-phase HPLC system. This study also attempted to increase fengycin production by B. subtilis F29-3 in order to optimize the fermentation medium constituents. The fermentation medium composition was optimized using response surface methodology (RSM) to increase fengycin production from B. subtilis F29-3. According to results of the five-level four-factor central composite design, the composition of soybean meal, NaNO(3), MnSO(4)·4H(2)O, mannitol-mannitol, soybean meal-mannitol, soybean meal-soybean meal, NaNO(3)-NaNO(3) and MnSO(4)·4H(2)O-MnSO(4)·4H(2)O significantly affected production. The simulation model produced a coefficient of determination (R(2)) of 0.9043, capable of accounting for 90.43% variability of the data. Results of the steepest ascent and central composite design indicated that 26.2 g/L of mannitol, 21.9 g/L of soybean meal, 3.1 g/L of NaNO(3) and 0.2 g/L of MnSO(4)·4H(2)O represented the optimal medium composition, leading to the highest production of fengycin. Furthermore, the optimization strategy increased the fengycin production from 1.2 g/L to 3.5 g/L.


Subject(s)
Bacillus subtilis/metabolism , Lipopeptides/chemistry , Bacillus subtilis/growth & development , Biotechnology/methods , Culture Media/chemistry , Fermentation , Lipopeptides/biosynthesis
16.
Eur J Pharmacol ; 644(1-3): 176-87, 2010 Oct 10.
Article in English | MEDLINE | ID: mdl-20655905

ABSTRACT

Cardiac toxicity remains a serious yet unsolved complication of doxorubicin. This study was designed to examine whether doxycycline, a tetracycline-derived synthetic antibiotic with potential cytoprotective properties, could ameliorate this complication of doxorubicin. Male mice at 4-week of age were administrated with vehicle, doxorubicin (3mg/kg intraperitoneally every other day at 3 doses), doxycycline (2.5mg/kg intraperitoneally every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1day post doxycycline). After 28days, left ventricular geometric and systolic parameters were measured by transthoracic echocardiography, and hearts were harvested for extensive analyses regarding oxidative stress and cellular apoptosis. At 28days, hearts of doxorubicin-treated mice were characterized by less weight compared with controls, also with remodeling and depressed systolic function of the left ventricle. Biochemical analyses disclosed that content of malondialdehyde was increased and activity of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, was decreased in these hearts. Both mitochondrion-dependent and endoplasmic reticulum stress-induced apoptotic pathways were also activated in the hearts of doxorubicin-treated mice as reflected by decreased Bcl-2/Bcl-(XL) and elevated Bax/Bad, p53/Apaf-1, endoplasmic reticulum glucose-related protein 78, C/EBP homologous protein, cytochrome c release from mitochondria, caspases-9/-3 cleavage, and cardiomyocyte apoptosis. In contrast, all the above left ventricular remodeling, systolic depressing, oxidative and pro-apoptotic actions of doxorubicin could be significantly alleviated by doxycycline pretreatment. Thus, doxycycline extensively counteracts multiple oxidative and apoptotic actions of doxorubicin in heart, hence may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.


Subject(s)
Antibiotics, Antineoplastic/toxicity , Doxorubicin/toxicity , Doxycycline/pharmacology , Oxidative Stress/drug effects , Animals , Antioxidants/metabolism , Apoptosis/drug effects , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Glutathione Peroxidase/drug effects , Glutathione Peroxidase/metabolism , Male , Malondialdehyde/metabolism , Mice , Mice, Inbred ICR , Mitochondria, Heart/drug effects , Mitochondria, Heart/metabolism , Superoxide Dismutase/drug effects , Superoxide Dismutase/metabolism , Ventricular Remodeling/drug effects
17.
Cardiovasc Res ; 80(2): 227-35, 2008 Nov 01.
Article in English | MEDLINE | ID: mdl-18632596

ABSTRACT

AIMS: The objective of this study was to investigate whether a cytoprotective herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial effect on doxorubicin-induced cardiac toxicity in vitro and in vivo. METHODS AND RESULTS: Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 microM), EGb761 (25 microg/mL), or EGb761 plus doxorubicin. After 24 h, doxorubicin upregulated p53 mRNA expression, disturbed Bcl-2 family protein balance, disrupted mitochondrial membrane potential, precipitated mitochondrion-dependent apoptotic signalling, induced apoptotic cell death, and reduced viability of cardiomyocytes, whereas EGb761 pretreatment suppressed all the actions of doxorubicin. Similarly, rats treated with doxorubicin [3 mg/kg intraperitoneally (i.p.) three doses every other day] displayed retarded growth of body and heart as well as elevated apoptotic indexes in heart tissue at both 7 and 28 days after exposure, whereas EGb761 pretreatment (5 mg/kg i.p. 1 day before each dose of doxorubicin) effectively neutralized the aforementioned gross and cellular adverse effects of doxorubicin. CONCLUSION: Doxorubicin impairs viability of cardiomyocytes at least partially by activating the p53-mediated, mitochondrion-dependent apoptotic signalling. EGb761 can effectively and extensively counteract this action of doxorubicin, and may potentially protect the heart from the severe toxicity of doxorubicin.


Subject(s)
Apoptosis/drug effects , Cardiovascular Agents/pharmacology , Heart Diseases/prevention & control , Mitochondria, Heart/drug effects , Myocytes, Cardiac/drug effects , Plant Extracts/pharmacology , Animals , Animals, Newborn , Caspase 3/metabolism , Cell Survival/drug effects , Cells, Cultured , Cytochromes c/metabolism , Cytoprotection , Disease Models, Animal , Doxorubicin , Ginkgo biloba , Heart Diseases/chemically induced , Heart Diseases/metabolism , Heart Diseases/pathology , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria, Heart/enzymology , Mitochondria, Heart/pathology , Myocytes, Cardiac/enzymology , Myocytes, Cardiac/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Sprague-Dawley , Time Factors , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
18.
Biochem Pharmacol ; 74(7): 969-80, 2007 Oct 01.
Article in English | MEDLINE | ID: mdl-17673183

ABSTRACT

Spermatogenic cells constitute one of the body tissues that are susceptible to doxorubicin-induced oxidative stress and apoptosis. To explore whether doxorubicin toxicity to these male germ cells could be prevented by adjuvant medication, this study was designed to examine the possible ameliorating action of doxycycline, an antibiotic with anti-oxidant property, on doxorubicin-induced oxidative and apoptotic effects in mouse testes. Male mice at 5-week of age were treated with vehicles, doxorubicin alone (3 mg/kg, i.p. every other day for 3 doses), doxycycline alone (2.5 mg/kg, i.p. every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1 day post-doxycycline). After 28 days, mice treated with doxorubicin alone displayed smaller body and testicular weights, reduced sperm counts, impaired spermatogenic capability (scarcer spermatids and spermatocytes), increased oxidative stress (malondialdehyde levels), decreased anti-oxidant activity (superoxide dismutase and glutathione peroxidase), and elevated apoptotic indexes (upregulation of Bax and Bad, downregulation of Bcl-2 and Bcl-xL, release of cytochrome c from mitochondria to cytosol, activation of caspase-3, and increase of cleaved caspase-3 abundance and TUNEL positive cells), while doxycycline pretreatment could effectively prevent nearly all of these abnormalities. These results provide firm evidence that doxycycline pretreatment would offset the oxidative and apoptotic impact imposed by doxorubicin, and imply doxycycline to be a promising adjuvant agent that may attenuate the toxicity of doxorubicin on testicular tissues in clinical practice.


Subject(s)
Apoptosis/drug effects , Doxorubicin/adverse effects , Doxycycline/pharmacology , Testis/cytology , Testis/drug effects , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents/adverse effects , Body Weight/drug effects , Caspase 3/metabolism , Cytochromes c/metabolism , Down-Regulation , Doxycycline/administration & dosage , Male , Mice , Mice, Inbred ICR , Organ Size/drug effects , Oxidative Stress , Spermatogenesis/drug effects , Up-Regulation
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