Miracle-dz/UniFAR-FTUs huggingface dataset:
The cytotoxicity and cellular stress by temperature‐fabricated polyshaped gold nanoparticles using marine macroalgae, Padina gymnospora

Bioreduction of metal ions for the synthesis of stable nanoparticles (NPs) in physiological environment has been a great challenge in the field of nanotechnology and its application. In the present study, well‐defined biofunctionalized gold nanoparticles (AuNPs) were developed following a biomimetic approach for an enhanced anticancer activity. The fucoxanthins‐capped crystalline AuNPs showed a particle size of 14 nm. The temperature‐mediated biosynthesized NPs were characterized by UV–vis, dynamic light scattering, high‐resolution transmission electron microscopy, and energy‐dispersive X‐ray spectroscopy. The cytotoxicity of the NPs was analyzed on liver (HepG2) and lung (A549) cancerous cells. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay infers that the biofunctionalized polyshaped AuNPs synthesized with an aqueous macroalgae extract showed a satisfactory anticancer effect on the cell lines, as evaluated by changes in cell morphology, cell viability, and metabolic activity. An altered cellular function and the morphology of cancer cell lines suggest a potential for in vivo application of AuNPs and the need to understand the interactions between nanomaterials, biomolecules, and cellular components. With continued improvements, these NPs may prove to be potential drug delivery vehicles for cancer therapy.
Medical Error Reporting System Design: Multiple User Considerations and their Implications

The purpose of this paper is to examine the differences between the preferences of physicians and clinical assistants for the design of a statewide medical error reporting system. The study employed a series of separate focus groups composed of physicians and clinical assistants. The focus groups covered a wide range of relevant topics based on the previous literature on error reporting both in and outside of healthcare. Focus group transcripts were subject to a content analysis resulting in a total of 86 major and minor themes. While physicians and clinical assistants shared similar preferences and beliefs surrounding error reporting such as its educational potential and fear of punitive repercussions, they differed as well. Some of the differences uncovered included the rules and regulations governing the use of the system, the medium of reporting, and aspects of the organization that may affect reporting levels. The design implications for considering these issues are discussed.
Captopril reduces deposition of collagen in lamina propria and muscular layers of the bladder and ureter in neonatal dogs with partial urethral obstruction

Objective. It has been recognized that most boys with posterior urethral valve ablation have varying degrees of ureteral dilation and abnormal bladder function. It has been shown that deposition of collagen in the bladder layers increases the intravesical pressure that is transmitted to the pelvicalyceal system. The purpose of this study was to evaluate, using stereological methods, the effect of captopril on prevention of collagen formation in different layers of the ureter and bladder under conditions of partial urethral obstruction (PUO). Material and methods. PUO was induced in 10 neonatal dogs. These animals were then divided into two equal groups: the experimental group received captopril (35 mg/kg/day) and the positive control group received no treatment. After 6 weeks, the neonatal dogs underwent left nephroureterectomy and cystectomy. The ureter and bladder volumes, the volume fraction and absolute volume of the histological parameters of the ureter and bladder, the collagen content of the lamina propria, muscular and adventitial layers, and the muscle content of the muscular layer were estimated using stereological methods. Results. The ureter and bladder volumes, the volumes of the layers including mucosa, lamina propria and muscular layer adventitia, the muscle content of the muscular layer and the collagen content of the adventitial layer did not show any significant differences between the groups. The collagen content (absolute volume) of lamina propria and muscular layer in the experimental group was lower than that in the positive control group for both the ureter and bladder. Conclusion. Administration of captopril decreases the collagen content of the lamina propria and muscular layer in the ureter and bladder of neonatal dogs with PUO.
ULTRASOUND‐MEDIATED MICROBUBBLE DESTRUCTION ENHANCES THE EFFICACY OF BONE MARROW MESENCHYMAL STEM CELL TRANSPLANTATION AND CARDIAC FUNCTION

1 Application of ultrasound (US) to intravascular microbubble (MB) contrast agents causes small capillary ruptures. The purpose of the present study was to examine the effects of US‐mediated MB destruction on bone marrow mesenchymal stem cell (BMSC) transplantation into the infarcted myocardium and to evaluate whether this approach could improve cardiac function. 2 Ultrasound was applied to the anterior chest of rabbits after intravenous injection of MB followed by infusion of BMSC. There were four groups investigated: (i) a control group, in which neither US nor MB were used prior to infusion of BMSC; (ii) one group subjected to US alone prior to infusion of BMSC; (iii) another group injected with MB prior to infusion of BMSC; and (iv) a group in which US was applied to MB prior to the infusion of BMSC. Cardiac function was evaluated by echocardiography 24 h and 4 weeks after cell transplantation. All rabbits were killed to enable histological and immunochemical examination. 3 Echocardiography 24 h after infusion of BMSC indicated no difference in cardiac function between any of the groups, as assessed by left ventricular ejection fraction (LVEF), left ventricular end‐diastolic dimensions (LVDD), left ventricular systolic diameter (LVSD) and fractional shortening (FS%; all P > 0.05). However, 4 weeks after BMSC transplantation, there was a significant improvement in LVEF in the group subjected to US plus MB compared with the control, US alone and MB alone groups (59.5 ± 3.5, 52.5 ± 5.5, 52.8 ± 5.2 and 51.1 ± 3.5%, respectively; all P < 0.05). In addition, treatment with US plus MB significantly reduced LVDD and LVSD and increased capillary density in the infarcted area. 4 In conslusion, the results of the present study indicate that using US‐mediated MB destruction prior to BMSC transplantation into the infarcted myocardium improves the effectiveness of cardiac cell therapy and cardiac function in rabbits.
MicroRNA‐320 EXPRESSION IN MYOCARDIAL MICROVASCULAR ENDOTHELIAL CELLS AND ITS RELATIONSHIP WITH INSULIN‐LIKE GROWTH FACTOR‐1 IN TYPE 2 DIABETIC RATS

1 The aim of the present study was to determine the role of myocardial microvascular endothelial cells (MMVEC) in impaired angiogenesis of type 2 diabetic Goto‐Kakizaki (GK) rats. 2 A microRNA (miRNA) microarray was used to assess miRNA expression in MMVEC from GK and Wistar rats. Upregulation of miRNA‐320 was observed in MMVEC from GK rats using real‐time reverse transcription–polymerase chain reaction (RT‐PCR). 3 So far, nine miRNAs have been reported to target angiogenic factors and/or receptors, including kinase insert domain containing receptor (Flk‐1), insulin‐like growth factor 1 (IGF‐1) and insulin‐like growth factor 1 receptor (IGF‐1R). The predicted genes targeted by miR‐320 include Flk‐1, IGF‐1 and IGF‐1R. Western blot analysis and RT‐PCR were used to analyse the protein and mRNA expression, respectively, of the putative genes IGF‐1 and IGF‐1R. The expression of IGF‐1 and IGF‐1R proteins decreased significantly in diabetic MMVEC. However, the expression of IGF‐1 mRNA increased rather than decreased. The mRNA expression of IGF‐1R did not differ significantly between diabetic and control MMVEC. 4 Transfection of an miR‐320 inhibitor into MMVEC from GK rats confirmed that miR‐320 impaired angiogenesis. The proliferation and migration of diabetic MMVEC improved after transfection of the miR‐320 inhibitor. In addition, the miR‐320 inhibitor significantly increased the expression of IGF‐1 protein, but had no effect on the expression of IGF‐1R. 5 Eleven miRNAs were upregulated in MMVEC from GK rats compared with those in Wistar rats: let‐7e, miR‐129, miR‐291‐5p, miR‐320, miR‐327, mir‐333, miR‐363–5p, miR‐370, miR‐494, miR‐503 and miR‐664. 6 The results indicate that upregulation of miR‐320 in MMVEC from GK rats may be responsible for the inconsistency between the expression of IGF‐1 protein and mRNA and therefore related to impaired angiogenesis in diabetes. Transfection of an miR‐320 inhibitor may be a therapeutic approach for the treatment of impaired angiogenesis in diabetes.
Mechanomyogram signal detection and decomposition: conceptualisation and research design

The primary purpose of the present study is to construct behavioural modelling of the detection and analysis of the Mechanomyogram (MMG) signal for different muscles using virtual muscle model. Mechanomyography is the superficial recording of low frequency vibrations detected over contracting muscles. In this study, a MEMS based accelerometer model is used. Three decomposition techniques which are Discrete Wavelet Transform, Principle Component Analysis and empirical mode decomposition are applied on the MMG for the purpose of feature extraction which could be used for the diagnosis process. A comparison between results of the different techniques as well as hybrid techniques is studied to reach the best one.
Algal Biofuels: A Credible Prospective?

Global energy use has reached unprecedented levels and increasing human population, technological integration, and improving lifestyle will further fuel this demand. Fossil fuel based energy is our primary source of energy and it will remain to be in the near future. The effects from the use of this finite resource on the fate of our planet are only now being understood and recognised in the form of climate change. Renewable energy systems may offer a credible alternative to help maintain our lifestyle sustainably and there are a range of options that can be pursued. Biofuels, especially algae based, have gained significant publicity recently. The concept of making biofuels, biochemicals, and by-products works well theoretically and at small scale, but when considering scaleup, many solutions can be dismissed on either economical or ecological grounds. Even if an (cost-) effective method for algae cultivation is developed, other input parameters, namely, fixed nitrogen and fresh water, remain to be addressed. Furthermore, current processing routes for harvesting, drying, and extraction for conversion to subsequent products are economically unattractive. The strategies employed for various algae-based fuels are identified and it is suggested that ultimately only an integrated algal biorefinery concept may be the way forward.
Different pharmacological properties of the optical isomers of MN9202, a novel 1,4‐dihydropyridine Ca2+ channel modulator, in rat ventricular myocytes

1. We have shown previously that 1,4‐dihydro‐2,6‐dimethyl‐4‐(3‐nitrophenyl)‐3,5‐pyridinedicarboxylic acid pentyl methyl ester (MN9202), a new 1,4‐dihydropyridine Ca2+ channel modulator, has significant hypotensive effects and favourable pharmacokinetic characteristics. As a chiral molecule, MN9202 has two optical isomers. The aim of the present study was to evaluate the pharmacological properties of the two enantiomers.
Promovendo o auto-cuidado: treinamento e assistência de enfermagem a pacientes portadores de bexiga neurogênica

Neste trabalho, as autoras fazem algumas consideracoes sobre a execucao da assistencia de enfermagem especificamente a pacientes portadores de Bexiga Neurogenica. A individualidade de cada paciente e considerada para que os mesmos adquiram independencia no auto-cuidado e convivam da melhor maneira possivel com as suas limitacoes, facilitando, desta forma, sua reintroducao na vida familiar e social. Apresentam uma sonda de vidro confeccionada no Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, utilizada somente para pacientes do sexo feminino, tentando estabelecer e desenvolver um programa de orientacao ao auto-cateterismo intermitente.
Celecoxib, but not rofecoxib or naproxen, attenuates cardiac hypertrophy and fibrosis induced in vitro by angiotensin and aldosterone

1. Cyclo‐oxygenase (COX)‐2 inhibitors and other non‐steroidal anti‐inflammatory drugs (NSAIDs) have been implicated in increased cardiovascular events. However, the direct effects of these drugs on cardiac function have not been explored extensively. Given the important role of the renin–angiotensin–aldosterone system (RAAS) in cardiac remodelling, we sought to determine the effect of COX‐2 inhibitors and non‐specific (NS‐) NSAIDs on RAAS‐induced cardiac hypertrophy and fibrosis in neonatal rat cardiac myocytes (NCM) and fibroblasts (NCF) isolated from 1–2‐day‐old Sprague‐Dawley rat pups.
Physiologically based pharmacokinetic (PBPK) modelling tools: how to fit with our needs?

In 2005, a survey compared a number of commercial PBPK software available at the time, mainly focusing on ‘ready to use’ modelling tools. Since then, these tools and software have been further developed and improved to allow modellers to perform WB‐PBPK modelling including ADME processes at a high level of sophistication. This review presents a comparison of the features, values and limitations of both the ‘ready to use’ software and of the traditional user customizable software that are frequently used for the building and use of PBPK models, as well as the challenges associated with the various modelling approaches regarding their current and future use. PBPK models continue to be used more and more frequently during the drug development process since they represent a quantitative, physiologically realistic platform with which to simulate and predict the impact of various potential scenarios on the pharmacokinetics and pharmacodynamics of drugs. The ‘ready to use’ PBPK software has been a major factor in the increasing use of PBPK modelling in the pharmaceutical industry, opening up the PBPK approach to a broader range of users. The challenge is now to educate and to train scientists and modellers to ensure their appropriate understanding of the assumptions and the limitations linked both to the physiological framework of the ‘virtual body’ and to the scaling methodology from in vitro to in vivo (IVIVE). Copyright © 2012 John Wiley & Sons, Ltd.
Predicting human hepatic clearance from in vitro drug metabolism and transport data: a scientific and pharmaceutical perspective for assessing drug–drug interactions

Membrane transporters and metabolism are major determinants of the hepatobiliary elimination of drugs. This work investigates several key questions for drug development. Such questions include which drugs demonstrate transporter‐based clearance in the clinic, and which in vitro methods are most suitable for drug classification, i.e. transporter‐ vs metabolism‐dependent compound class categories. Additional questions posed are: what is the expected quantitative change in exposure in the presence of a transporter‐ and/or metabolism‐inhibiting drug, and which criteria should trigger follow‐up clinical drug–drug interaction studies.
NADA Ear Acupuncture for Breast Cancer Treatment–Related Hot Flashes and Night Sweats: An Observational Study

Abstract Background: Hot flashes and night sweats (HF&NS) are major side-effects of adjuvant hormonal treatments for breast cancer. Objective: The aim of this study was to evaluate the feasibility of the National Acupuncture Detoxification Association (NADA) five-point ear acupuncture protocol to reduce HF&NS and improve physical and emotional well-being for women receiving adjuvant treatments for breast cancer. Design: This trial was a single-arm observational study that used before-and-after measurements. Setting: The trial was conducted at a National Health Service cancer treatment center in southern England. Patients: The subjects included women with early breast cancer, ≥35 years old, ≥6 months post–active cancer treatment, receiving tamoxifen ≥6 months, and self-reporting ≥4 HF&NS incidents/24-hours for ≥3 months. Intervention: Fifty participants completed weekly NADA treatment for 8 weeks in small groups of ≤5 patients. Main Outcome Measures: The factors examined were changes in scores at end of tr.
Disposition of d‐penicillamine, a promising drug for preventing alcohol‐relapse. Influence of dose, chronic alcohol consumption and age: studies in rats

Pharmacokinetic studies concerning d‐penicillamine (an acetaldehyde sequestering agent) are scarce and have not evaluated the influence of chronic ethanol consumption and age on its disposition. Since recent preclinical studies propose d‐penicillamine as a promising treatment for alcohol relapse, the main aim of the present work was to evaluate the influence of these two factors on d‐penicillamine disposition in order to guide future clinical studies on the anti‐relapse efficacy of this drug in alcoholism. Additionally, the effect of the administered dose was also evaluated. To this end, three studies were carried out. Study 1 assessed the influence of dose on d‐penicillamine disposition, whereas studies 2 and 3 evaluated, respectively, the influence of chronic alcohol consumption and age. Rapid intravenous administrations of 2, 10 and 30 mg/kg of d‐penicillamine were performed using young or adult ethanol‐naïve rats or adult ethanol‐experienced (subjected to a long‐term ethanol self‐administration protocol) rats. Pharmacokinetic parameters were derived from the biexponential model. Statistical analysis of CL, normalized AUC0∞, V1 and k10 revealed that disposition, in the range plasma concentrations assayed, is non‐linear both in young ethanol‐naïve and in adult ethanol‐experienced rats. Notably, no significant changes in t1/2 were detected. Chronic ethanol consumption significantly reduced CL values by 35% without affecting t1/2. d‐Penicillamine disposition was equivalent in young and adult animals. In conclusion, although DP pharmacokinetics is non‐linear, the lack of significant alterations of the t1/2 would potentially simplify the clinical use of this drug. Chronic consumption of ethanol also alters d‐penicillamine disposition but, again, does not modify t1/2. Copyright © 2014 John Wiley & Sons, Ltd.
Characterization of preclinical in vitro and in vivo ADME properties and prediction of human PK using a physiologically based pharmacokinetic model for YQA‐14, a new dopamine D3 receptor antagonist candidate for treatment of drug addiction

YQA‐14 is a novel and selective dopamine D3 receptor antagonist, with potential for the treatment of drug addiction. However, earlier compounds in its structural class tend to have poor oral bioavailability. The objectives of this study were to characterize the preclinical absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK) of YQA‐14, then to simulate the clinical PK of YQA‐14 using a physiologically based pharmacokinetics (PBPK) model to assess the likelihood of developing YQA‐14 as a clinical candidate. For human PK prediction, PBPK models were first built in preclinical species, rats and dogs, for validation purposes. The model was then modified by input of human in vitro ADME data obtained from in vitro studies. The study data showed that YQA‐14 is a basic lipophilic compound, with rapid absorption (Tmax ~ 1 h) in both rats and dogs. Liver microsomal clearances and in vivo clearances were moderate in rats and dogs consistent with the moderate bioavailability observed in both species. The PBPK models built for rats and dogs simulated the observed PK data well in both species. The PBPK model refined with human data predicted that YQA‐14 would have a clearance of 8.0 ml/min/kg, a volume distribution of 1.7 l/kg and a bioavailability of 16.9%. These acceptable PK properties make YQA‐14 an improved candidate for further research and development as a potential dopamine D3R antagonism for the treatment of drug addiction in the clinic. Copyright © 2014 John Wiley & Sons, Ltd.
Aldosterone induces p21‐regulated apoptosis via increased synthesis and secretion of tumour necrosis factor‐α in human proximal tubular cells

Aldosterone has been shown to mediate p21‐dependent cellular senescence in rat kidney proximal tubules in vivo and in cultured human proximal tubular cells. The p21‐induced senescent cells express higher levels of apoptotic cytokines, such as tumour necrosis factor (TNF)‐α compared with non‐senescent cells. The aim of the present study was to investigate the hypothesis that aldosterone increases proximal tubular apoptosis by increasing the secretion of apoptosis–inducing factors through a p21‐dependent mechanism. Human proximal tubular cells were incubated with aldosterone (10 nmol/L) and cell senescence was detected by senescence‐associated β‐galactosidase staining and expression of p21. Apoptosis was analysed by terminal deoxyribonucleotidyl transferase‐mediated dUTP–digoxigenin nick end‐labelling and annexin/propidium iodide staining, whereas p21 localization was determined by immunofluorescence. Exposure of cells to aldosterone for 3 or 5 days increased senescence–associated β‐galactosidase staining, p21 and TNF‐α mRNA expression and secretion of TNF‐α into the culture medium. These changes were abolished by gene silencing of p21. Aldosterone failed to increase the number of apoptotic cells on day 3, but did increase them on day 5. A neutralizing antibody against TNF‐α prevented the aldosterone‐induced apoptotic changes. Aldosterone did not affect localization of p21. These findings indicate that aldosterone increases TNF‐α synthesis and secretion in proximal tubular cells via p21/senescence–dependent cell phenotypic changes and that the TNF‐α secreted plays an important role as a paracrine factor in mediating cell apoptosis, indicating a possible involvement in aldosterone‐induced renal damage.