Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39
Filtrar
1.
Heliyon ; 9(4): e15438, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37123982

RESUMO

There is a significant increase in the literature on learning resources in Higher Education (HE) but very limited evidence of studies that have taken a global overview of the context, range, and emerging trends from the previous research. This study aims to conduct a Scientometric analysis of research articles to accommodate a global overview and research trends under the theme of learning resources in HE. 4489 scientific articles were obtained as the dataset from the Web Of Science database between 1970 and 2022. Network maps and critical data were obtained by conducting co-authorship analysis for authors, organisations and countries and co-occurrence analysis for keywords from the VOSviewer software. The study revealed that the USA had a significant research input, and Salamin, N. from the University of Lausanne was recognised as the most frequently published author. The University of Illinois, USA, has the highest contribution to research articles, and the most popular research hotspots and trends were e-learning, Education, Academic libraries, Learning resources, and Cloud computing. However, the most critical finding from the study is that there needs to be real collaboration within the research theme and suggests ways to improve collaborations to enhance learning resources in HE. This study may be the first to conduct a scientometric analysis of Learning Resources in Higher education. This study offers valuable insight to academics, academic institutions, researchers, policymakers and pedagogical statutory bodies to understand the current context of learning resources in HE and recognise further develop research, collaborations and policies by considering critical findings from the study.

2.
Environ Technol ; 44(2): 197-210, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34380379

RESUMO

Oil interceptors are traditional SuDS devices used in highway runoff treatment to remove both floatable impurities (leaves, oil) and total suspended solids (TSS). This paper presents the results of an examination of the performance of an oil interceptor based on particle size distribution (PSD) and TSS during three rainfall events. The interceptor is situated on one of the busiest motorways in the UK (where peak traffic flow is 30,000 vehicles per hour). Although the overall data collected for this study provided evidence that the interceptor removed, in most cases, 70% of TSS, the data for particle size distribution (PSD) showed that the interceptor did not always cope with particle separation for particles of less than 25 µm diameter.


Assuntos
Chuva , Movimentos da Água , Monitoramento Ambiental/métodos
3.
Environ Sci Pollut Res Int ; 30(9): 24088-24100, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36334206

RESUMO

The role of nanozinc source (nanohydrozincite: nHZ; nanozinc oxide: nZO) on the performance of alkali-activated slag (AAS) was explored for the first time in the present work. The results showed that nHZ with different contents (0.5, 1.0, and 1.5 wt%) retards the early hydration rate of AAS, whereas nZO showed the lowest retardation effect. Zn(OH)2 is the main retarder inside AAS-nZO and AAS-nHZ, which consumes the dissolved Ca2+ (responsible for the early hardening of AAS) from slag to yield calcium zincate hydrate (CZH). The high retardation rate of nHZ is originated from its high affinity to consume much Ca2+ through the formation of additional pirssonite (Na2CO3.CaCO3.2H2O) double salt. Although adding nHZ induced the drying shrinkage of AAS, it improved the later compressive strengths (28 to 365 days), especially at low nHZ content (0.5 wt%), via the formation of CASH with lower Ca/Si ratio and higher binding capacity compared to that formed inside AAS and AAS-nZO. A further research is needed to reduce the drying shrinkage and to accelerate the early strength of AAS containing nHZ.


Assuntos
Álcalis , Cálcio , Força Compressiva , Dessecação , Óxidos
4.
Materials (Basel) ; 15(22)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36431551

RESUMO

The findings of an extensive experimental research study on the usage of nano-sized cement powder and other additives combined to form cement-fine-aggregate matrices are discussed in this work. In the laboratory, dry and wet methods were used to create nano-sized cements. The influence of these nano-sized cements, nano-silica fumes, and nano-fly ash in different proportions was studied to the evaluate the engineering properties of the cement-fine-aggregate matrices concerning normal-sized, commercially available cement. The composites produced with modified cement-fine-aggregate matrices were subjected to microscopic-scale analyses using a petrographic microscope, a Scanning Electron Microscope (SEM), and a Transmission Electron Microscope (TEM). These studies unravelled the placement and behaviour of additives in controlling the engineering properties of the mix. The test results indicated that nano-cement and nano-sized particles improved the engineering properties of the hardened cement matrix. The wet-ground nano-cement showed the best result, 40 MPa 28th-day compressive strength, without mixing any additive compared with ordinary and dry-ground cements. The mix containing 50:50 normal and wet-ground cement exhibited 37.20 MPa 28th-day compressive strength. All other mixes with nano-sized dry cement, silica fume, and fly ash with different permutations and combinations gave better results than the normal-cement-fine-aggregate mix. The petrographic studies and the Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) analyses further validated the above findings. Statistical analyses and techniques such as correlation and stepwise multiple regression analysis were conducted to compose a predictive equation to calculate the 28th-day compressive strength. In addition to these methods, a repeated measures Analysis of Variance (ANOVA) was also implemented to analyse the statistically significant differences among three differently timed strength readings.

6.
Environ Sci Pollut Res Int ; 29(31): 47209-47224, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35182335

RESUMO

This study represents the sustainable/safe consumption of lead glass sludge (LGS) in the fabrication of thermally insulating foamed glass via sintering (750-950º C) and chlorination processes. The impact of selected additives including calcium chloride (CaCl2) and sodium hydroxide (NaOH) on the foaming efficiency and Pb-stabilization has been deeply investigated. LGS is mainly lead silicate material with considerable content of calcium carbonate, which acts as foaming agent during sintering process. The newly developed foamed-materials exhibited thermal conductivity of 0.054-0.136 W/m.K, density of 0.23-1.10 g/cm3, porosity of 63.3-92.6%, and compressive strength of 0.10-2.69 MPa. X-ray diffraction proved that the immobilization mechanism was attributed to the transformation of free Pb within LGS into insoluble ganomalite Pb9Ca5MnSi9O33 phase. Adding NaOH enhanced the foaming process accompanied by a significant reduction in Pb-leaching. Incorporating CaCl2 has resulted in a retardation in Pb-leaching, which associated with Pb-stabilization and Pb-vaporization. In an attempt to reduce CO2-emission, the potential use of alkali-rich-wastewater (AW) as eco-friendly alkali source in lieu of NaOH was studied. Regardless of the variation in Pb-concentrations in leachates, all samples recorded Pb-concentrations lower than the safe limit (≤ 5 mg/l), achieving Pb-immobilization of 95.98-99.87%. The significantly reduced thermal conductivity and enhanced Pb-immobilization efficiency along with the reasonable compressive strength summarize the major innovation presented in this study.


Assuntos
Chumbo , Esgotos , Álcalis , Cloreto de Cálcio , Hidróxido de Sódio
7.
Environ Technol ; 43(11): 1732-1744, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33180680

RESUMO

Although highway runoff has historically been extensively studied, the increasing complexity of stormwater management means that there are still significant gaps regarding the reduction of soluble metals. The work reported in this paper addresses these challenges by analysing the presence and behaviour of iron, copper and zinc in runoff from junction 24 of the M1 motorway in the UK (peak traffic flow: 30,000 vehicles per hour) and comparing it with other urban sources of metals found in the same catchment (a local brook and sewage treatment works). The sampling site included an interceptor and a treatment lagoon and the event monitoring indicated a trend by which the metals did not change their concentration or particulate soluble proportion immediately, hence showing that pre- and post-storm conditions are important factors when analysing the solubility of metals and their behaviour. The data provided further evidence of the important influence of storm characteristics on metal concentrations in highway runoff, in particular the effects of an antecedent dry weather period (ADWP). In addition, this study also helped us to better understand how the release of sodium the application of de-icer for road maintenance in winter affects the availability of zinc.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Cobre/análise , Poeira/análise , Monitoramento Ambiental , Metais/análise , Metais Pesados/análise , Chuva , Movimentos da Água , Poluentes Químicos da Água/análise , Zinco/análise
8.
Funct Imaging Model Heart ; 12738: 273-284, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34263263

RESUMO

Accurate and efficient quantification of cardiac motion offers promising biomarkers for non-invasive diagnosis and prognosis of structural heart diseases. Cine cardiac magnetic resonance imaging remains one of the most advanced imaging tools to provide image acquisitions needed to assess and quantify in-vivo heart kinematics. The majority of cardiac motion studies are focused on human data, and there remains a need to develop and implement an image-registration pipeline to quantify full three-dimensional (3D) cardiac motion in mice where ideal image acquisition is challenged by the subject size and heart rate and the possibility of traditional tagged imaging is hampered. In this study, we used diffeomorphic image registration to estimate strains in the left ventricular wall in two wild-type mice and one diabetic mouse. Our pipeline resulted in a continuous and fully 3D strain map over one cardiac cycle. The estimation of 3D regional and transmural variations of strains is a critical step towards identifying mechanistic biomarkers for improved diagnosis and phenotyping of structural left heart diseases including heart failure with reduced or preserved ejection fraction.

9.
Cells ; 10(4)2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807406

RESUMO

Dilated cardiomyopathy (DCM) is characterized by pathologic cardiac remodeling resulting in chambers enlargement and impaired heart contractility. Previous reports and our in-silico analysis support the association of DCM phenotype and impaired tissue angiogenesis. Here, we explored whether the modulation in cardiac angiogenesis partly intervenes or rescues the DCM phenotype in mice. Here, a DCM mouse model [α-tropomyosin 54 (α-TM54) mutant] was crossbred with microRNA-210 transgenic mice (210-TG) to develop microRNA-210 (miR-210) overexpressing α-TM54 mutant mice (TMx210). Contrary to wild-type (WT) and 210-TG mice, a significant increase in heart weight to body weight ratio in aged mixed-gender TMx210 and DCM mice was recorded. Histopathological analysis revealed signs of pathological cardiac remodeling such as myocardial disarray, myofibrillar loss, and interstitial fibrosis in DCM and TMx210 mice. Contrary to WT and DCM, a significant increase in angiogenic potential was observed in TMx210 and 210-TG mice hearts which is reflected by higher blood vessel density and upregulated proangiogenic vascular endothelial growth factor-A. The echocardiographic assessment showed comparable cardiac dysfunction in DCM and TMx210 mice as compared to WT and 210-TG. Overall, the present study concludes that miR-210 mediated upregulated angiogenesis is not sufficient to rescue the DCM phenotype in mice.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Neovascularização Fisiológica , Regulação para Cima , Animais , Cardiomiopatia Dilatada/genética , Modelos Animais de Doenças , Coração/fisiopatologia , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/metabolismo , Mutação/genética , Neovascularização Fisiológica/genética , Fenótipo , Transdução de Sinais , Tropomiosina/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-33129971

RESUMO

BACKGROUND: Left-sided ablation, targeting left inferior AV nodal extensions, is thought to be necessary for success in a small proportion of atrioventricular nodal re-entrant tachycardia (AVNRT) ablations; however Indian data are scarce in this regard. METHODS: Consecutive cases of AVNRT undergoing slow pathway ablation in a single centre over an 18-month period were retrospectively analyzed. Left-sided ablation at the posteroseptal mitral annulus was performed if right-sided ablation failed to abolish AVNRT. RESULTS: From January 2017 to June 2018, out of 215 consecutive supraventricular tachycardia (SVT) cases, 154 (71.6%) were AVNRT (47.1 ± 13.1 years, 46.1% male). Trans-septal ablation was required in 5 (3.2%) cases (mean age 48.8 ± 9.4 years; 4 female, 1 male); all with typical (slow-fast) form of AVNRT. Compared with cases needing only right-sided ablation, radiofrequency time (50.8 ± 16.9 vs. 9.9 ± 8.5 min; p = 0.005) and procedure time (166.0 ± 35.0 vs 79.6 ± 35.9 min; p = 0.004) were significantly longer for trans-septal cases, while baseline intervals and tachycardia cycle length were not significantly different. Junctional ectopy was seen in only 2 of the 5 cases during left-sided ablation, but acute success (non-inducibility) was obtained in 3 cases. There were no instances of AV block. Over mean follow-up of 12.2 ± 4.0 months, clinical recurrence of AVNRT occurred in one case, while others remained arrhythmia-free without medication. CONCLUSION: Left-sided ablation was required in a small proportion of AVNRT ablations. Trans-septal approach targeting the posteroseptal mitral annulus was safe and yielded good mid-term clinical success.

11.
Biophys Rev ; 12(4): 1065-1084, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32656747

RESUMO

Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease characterized by ventricular enlargement, diastolic dysfunction, and increased risk for sudden cardiac death. Sarcomeric genetic defects are the predominant known cause of HCM. In particular, mutations in the myosin-binding protein C gene (MYBPC3) are associated with ~ 40% of all HCM cases in which a genetic basis has been established. A decade ago, our group reported a 25-base pair deletion in intron 32 of MYBPC3 (MYBPC3Δ25bp) that is uniquely prevalent in South Asians and is associated with autosomal dominant cardiomyopathy. Although our studies suggest that this deletion results in left ventricular dysfunction, cardiomyopathies, and heart failure, the precise mechanism by which this variant predisposes to heart disease remains unclear. Increasingly appreciated, however, is the contribution of secondary risk factors, additional mutations, and lifestyle choices in augmenting or modifying the HCM phenotype in MYBPC3Δ25bp carriers. Therefore, the goal of this review article is to summarize the current research dedicated to understanding the molecular pathophysiology of HCM in South Asians with the MYBPC3Δ25bp variant. An emphasis is to review the latest techniques currently applied to explore the MYBPC3Δ25bp pathogenesis and to provide a foundation for developing new diagnostic strategies and advances in therapeutics.

12.
Int J Prev Med ; 11: 10, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089810

RESUMO

BACKGROUND: To explore the essence of game changing on applying joint venture (JV) approach for healthcare system improvement in developing countries. METHODS: This is cross-sectional study exploring the factors influencing the successful implementation of JV for the healthcare services in low- and middle-income countries (LMICs). The study included: Qatar Statistical Authority, CIA fact book, Ministry of Health Annual Report, Hamad Medical Corporation Annual Report, Organization for Economic Cooperation and Development information, and Qatar's healthcare system history. RESULTS: The research indicated that the LMIC healthcare system would benefit from affiliation with leading technology partner for healthcare reform. The findings support the view of LMIC healthcare systems' needs to incorporate joint venture approach in implementing JV concept for process improvement and knowledge transfer to contribute in country economic growth, development, and stability. Current study explored evidence supporting decision maker and management control of JV trends in different ways in comparison with developed countries. JV can also help the organization to share the risk and cost of large capital investment. CONCLUSIONS: The present study supports observations on expending the use of JVs as approach for improvement in LMIC healthcare system. The current study confirmed the advantages of JV which include helping businesses grow faster, increasing productivity, and generating greater profits, both parties sharing the risks and costs, accessing new markets and distribution networks.

13.
J Orthop Surg (Hong Kong) ; 27(3): 2309499019867006, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31470760

RESUMO

PURPOSE: Tibial bowing in valgus knees with arthritis can lead to component malplacement during total knee arthroplasty (TKA). Incidence of valgus knees with medial tibial bowing, its effect on tibial component placement during primary TKA and methods to improve accuracy of the component placement were studied. METHODS: Full-length weight-bearing alignment radiograph was taken in 117 patients (149 knees) with valgus deformity undergoing TKA. In these cases, the proximal tibial reference for extramedullary jig placement was planned preoperatively with reference to the tibial spines and classified as four zones. RESULTS: The mean preoperative hip-knee-ankle (HKA) angle was 192.9° (180.3-234.5°). Bowing >3° was considered significant (p < 0.001) and at this level of bowing, the proximal tibial reference was shifted from centre to medial. Tibial bowing <3° was considered straight and >3° as tibia valga. Tibia was bowed in 70 knees (46.97%). Severity of valgus deformity had strong positive correlation with the tibia valga (p < 0.001). The post-operative medial proximal tibial angle (MPTA) and HKA angle were 91.63° (87.9-95.7°) and 182.6° (178.1-189.7°), respectively. The mean MPTA and post-operative HKA angle in bowed and straight tibiae were 90.35° versus 89.78° (p = 0.547) and 181.5° versus 180.7° (p = 0.5716), respectively, and the difference was not statistically significant. CONCLUSION: Medial tibial bowing is very common in valgus knees. Tibia valga has a strong positive correlation with the severity of valgus deformity. Accurate tibial component placement can be achieved with a medialized reference point for extramedullary tibial cutting jig in knees with significant tibia valga. The study has been registered in clinical trials registry - India (CTRI/2018/03/012283).


Assuntos
Artrite/cirurgia , Artroplastia do Joelho , Geno Valgo/complicações , Genu Varum/epidemiologia , Adulto , Idoso , Artrite/diagnóstico por imagem , Artrite/etiologia , Feminino , Geno Valgo/diagnóstico por imagem , Geno Valgo/cirurgia , Genu Varum/complicações , Genu Varum/diagnóstico por imagem , Genu Varum/cirurgia , Humanos , Incidência , Índia , Masculino , Pessoa de Meia-Idade , Radiografia , Suporte de Carga
14.
J Am Heart Assoc ; 8(15): e012089, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31315484

RESUMO

Background Myocardial infarction results in a large-scale cardiomyocyte loss and heart failure due to subsequent pathological remodeling. Whereas zebrafish and neonatal mice have evident cardiomyocyte expansion following injury, adult mammalian cardiomyocytes are principally nonproliferative. Despite historical presumptions of stem cell-mediated cardiac regeneration, numerous recent studies using advanced lineage-tracing methods demonstrated that the only source of cardiomyocyte renewal originates from the extant myocardium; thus, the augmented proliferation of preexisting adult cardiomyocytes remains a leading therapeutic approach toward cardiac regeneration. In the present study we investigate the significance of suppressing cell cycle inhibitors Rb1 and Meis2 to promote adult cardiomyocyte reentry to the cell cycle. Methods and Results In vitro experiments with small interfering RNA-mediated simultaneous knockdown of Rb1 and Meis2 in both adult rat cardiomyocytes, isolated from 12-week-old Fischer rats, and human induced pluripotent stem cell-derived cardiomyocytes showed a significant increase in cell number, a decrease in cell size, and an increase in mononucleated cardiomyocytes. In vivo, a hydrogel-based delivery method for small interfering RNA-mediated silencing of Rb1 and Meis2 is utilized following myocardial infarction. Immunofluorescent imaging analysis revealed a significant increase in proliferation markers 5-ethynyl-2'-deoxyuridine, PH3, KI67, and Aurora B in adult cardiomyocytes as well as improved cell survivability with the additional benefit of enhanced peri-infarct angiogenesis. Together, this intervention resulted in a reduced infarct size and improved cardiac function post-myocardial infarction. Conclusions Silencing of senescence-inducing pathways in adult cardiomyocytes via inhibition of Rb1 and Meis2 results in marked cardiomyocyte proliferation and increased protection of cardiac function in the setting of ischemic injury.


Assuntos
Ciclo Celular/fisiologia , Proteínas de Homeodomínio/genética , Infarto do Miocárdio , Miócitos Cardíacos/citologia , Proteínas de Ligação a Retinoblastoma/genética , Fatores de Transcrição/genética , Ubiquitina-Proteína Ligases/genética , Fatores Etários , Animais , Proteínas de Homeodomínio/fisiologia , Humanos , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Ratos , Ratos Endogâmicos F344 , Proteínas de Ligação a Retinoblastoma/fisiologia , Fatores de Transcrição/fisiologia , Ubiquitina-Proteína Ligases/fisiologia
15.
PLoS Negl Trop Dis ; 13(4): e0007302, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30951526

RESUMO

BACKGROUND: With the introduction of new interventions to prevent leprosy, such as post-exposure prophylaxis (PEP) given to contacts of leprosy patients, it is necessary to update our understanding of knowledge and perception of leprosy among the populations where these interventions will be introduced, in order to tailor communication optimally to the current situation. This study is a baseline study of the PEP++ project and aimed to assess the knowledge, attitudes and practices regarding leprosy in Fatehpur, India. METHODOLOGY: The study used a community-based cross-sectional design with a mixed-methods approach. We assessed knowledge, attitudes, and practices with the KAP measure, and stigma with the Explanatory Model Interview Catalogue community stigma scale (EMIC-CSS) and the Social Distance Scale (SDS). In addition, semi-structured interviews and focus group discussions were conducted with all participant groups. The quantitative data were analysed using stepwise multivariate regression. The qualitative data were analysed using open, inductive coding and content analysis. FINDINGS: A total of 446 participants were included in the study: 100 persons affected by leprosy, 111 close contacts, 185 community members and 50 health care workers. In addition, 24 in-depth interviews were conducted and 35 people were included in focus group discussions. 12.5% of the participants had adequate knowledge of leprosy, while 22% had poor knowledge. Knowledge on cause (answered correctly by 10% of the participants), mode of transmission (5%) and symptoms of leprosy (16%) was especially poor. The mean EMIC-CSS score was 15.3 (95%CI 14.6-16.0) and mean SDS score 7.2 (95%CI 6.6-7.8). Better knowledge of leprosy was associated with lower levels of social distance towards persons affected by leprosy. CONCLUSION: This study revealed poor knowledge regarding leprosy and high levels of stigma and fear and desire to keep social distance towards persons affected by leprosy. Community education that takes cultural beliefs, knowledge gaps and fears into consideration could improve knowledge, reduce misconceptions and positively influence the perception of leprosy.


Assuntos
Erradicação de Doenças , Conhecimentos, Atitudes e Prática em Saúde , Hanseníase/prevenção & controle , Percepção Social , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pesquisa Participativa Baseada na Comunidade , Estudos Transversais , Feminino , Educação em Saúde , Pessoal de Saúde/psicologia , Humanos , Índia/epidemiologia , Hanseníase/epidemiologia , Masculino , Pessoa de Meia-Idade , Estigma Social , Inquéritos e Questionários , Adulto Jovem
16.
Am J Physiol Heart Circ Physiol ; 317(1): H168-H180, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31026178

RESUMO

In this study, we investigated the role of DNA methylation [5-methylcytosine (5mC)] and 5-hydroxymethylcytosine (5hmC), epigenetic modifications that regulate gene activity, in dilated cardiomyopathy (DCM). A MYBPC3 mutant mouse model of DCM was compared with wild type and used to profile genomic 5mC and 5hmC changes by Chip-seq, and gene expression levels were analyzed by RNA-seq. Both 5mC-altered genes (957) and 5hmC-altered genes (2,022) were identified in DCM hearts. Diverse gene ontology and KEGG pathways were enriched for DCM phenotypes, such as inflammation, tissue fibrosis, cell death, cardiac remodeling, cardiomyocyte growth, and differentiation, as well as sarcomere structure. Hierarchical clustering of mapped genes affected by 5mC and 5hmC clearly differentiated DCM from wild-type phenotype. Based on these data, we propose that genomewide 5mC and 5hmC contents may play a major role in DCM pathogenesis. NEW & NOTEWORTHY Our data demonstrate that development of dilated cardiomyopathy in mice is associated with significant epigenetic changes, specifically in intronic regions, which, when combined with gene expression profiling data, highlight key signaling pathways involved in pathological cardiac remodeling and heart contractile dysfunction.


Assuntos
Cardiomiopatia Dilatada/genética , Metilação de DNA , Epigênese Genética , Íntrons , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Animais , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Proteínas de Transporte/genética , Ilhas de CpG , Redes Reguladoras de Genes , Predisposição Genética para Doença , Hidroxilação , Masculino , Camundongos Mutantes , Mutação , Fenótipo , Regiões Promotoras Genéticas , Transcriptoma , Função Ventricular Esquerda/genética
17.
Hypertens Res ; 42(8): 1099-1113, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30867575

RESUMO

Essential hypertension (EH) is a multifactorial disease of the cardiovascular system that is influenced by the interplay of genetic, epigenetic, and environmental factors. The molecular dynamics underlying EH etiopathogenesis is unknown; however, earlier studies have revealed EH-associated genetic variants. Nevertheless, this finding alone is not sufficient to explain the variability in blood pressure, suggesting that other risk factors are involved, such as epigenetic modifications. Therefore, this review highlights the potential contribution of well-defined epigenetic mechanisms in EH, specifically, DNA methylation, post-translational histone modifications, and microRNAs. We further emphasize global and gene-specific DNA methylation as one of the most well-studied hallmarks among all epigenetic modifications in EH. In addition, post-translational histone modifications, such as methylation, acetylation, and phosphorylation, are described as important epigenetic markers associated with EH. Finally, we discuss microRNAs that affect blood pressure by regulating master genes such as those implicated in the renin-angiotensin-aldosterone system. These epigenetic modifications, which appear to contribute to various cardiovascular diseases, including EH, may be a promising research area for the development of novel future strategies for EH prevention and therapeutics.


Assuntos
Metilação de DNA , Epigênese Genética , Hipertensão Essencial/etiologia , Animais , Hipertensão Essencial/metabolismo , Código das Histonas , Humanos , MicroRNAs/metabolismo
18.
J Mol Med (Berl) ; 95(12): 1369-1385, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28948298

RESUMO

An innovative approach for cardiac regeneration following injury is to induce endogenous cardiomyocyte (CM) cell cycle re-entry. In the present study, CMs from adult rat hearts were isolated and transfected with cel-miR-67 (control) and rno-miR-210. A significant increase in CM proliferation and mono-nucleation were observed in miR-210 group, in addition to a reduction in CM size, multi-nucleation, and cell death. When compared to control, ß-catenin and Bcl-2 were upregulated while APC (adenomatous polyposis coli), p16, and caspase-3 were downregulated in miR-210 group. In silico analysis predicted cell cycle inhibitor, APC, as a direct target of miR-210 in rodents. Moreover, compared to control, a significant increase in CM survival and proliferation were observed with siRNA-mediated inhibition of APC. Furthermore, miR-210 overexpressing C57BL/6 mice (210-TG) were used for short-term ischemia/reperfusion study, revealing smaller cell size, increased mono-nucleation, decreased multi-nucleation, and increased CM proliferation in 210-TG hearts in contrast to wild-type (NTG). Likewise, myocardial infarction (MI) was created in adult mice, echocardiography was performed, and the hearts were harvested for immunohistochemistry and molecular studies. Compared to NTG, 210-TG hearts showed a significant increase in CM proliferation, reduced apoptosis, upregulated angiogenesis, reduced infarct size, and overall improvement in cardiac function following MI. ß-catenin, Bcl-2, and VEGF (vascular endothelial growth factor) were upregulated while APC, p16, and caspase-3 were downregulated in 210-TG hearts. Overall, constitutive overexpression of miR-210 rescues heart function following cardiac injury in adult mice via promoting CM proliferation, cell survival, and angiogenesis. KEY MESSAGES: MiRNA-210 transfected adult rat CMs show proliferation and reduced cell death in vitro. Cell cycle inhibitor APC is a target of miR-210. MiR-210 overexpressing (210-TG) mouse hearts show CMs cell cycle re-entry and survival post myocardial injury. 210-TG mice show significant neovascularization and angiogenic potential post myocardial infarction. 210-TG hearts show reduced infarct size following ischemic injury.


Assuntos
MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Neovascularização Fisiológica , Regeneração , Proteína da Polipose Adenomatosa do Colo/metabolismo , Envelhecimento , Animais , Sequência de Bases , Morte Celular , Proliferação de Células , Sobrevivência Celular , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos
19.
Pharm Biol ; 54(4): 674-85, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26510692

RESUMO

CONTEXT: Thymoquinone (TQ), an active component of Nigella sativa L. (Ranunculaceae), possesses anti-inflammatory and anti-oxidative properties. Polycystic ovary syndrome exhibits chronic inflammatory behavior, thus might involve nuclear factor kappa B (NF-κB) signaling and related molecular factors. OBJECTIVE: The objective of the present study is to investigate and validate the effect of TQ in polycystic ovary (PCO) rat. MATERIALS AND METHODS: To validate the effect of TQ (1 µM/ml), NF-κB activation, COX2 (cyclooxygenase-2) expression and reactive oxygen species (ROS) induction were studied in the KK1 cell line. To evaluate the effect of TQ (2 mg/200 µl olive oil/rat; sc) with an in vivo system, ovulation rate, levels of key ovulation mediators, and ovarian gelatinases activity were compared in superovulated, PCO, and RU486 + TQ-treated Wistar rats. RESULTS: In vitro studies showed that NF-κB nuclear translocation, COX2, and ROS expression were repressed via TQ supplementation in RU486-treated KK1 cells. Pretreatment of TQ in the PCO rat model induced significant restoration of normal physio-molecular behavior of ovary, such as reduced cysts formation, increased ovulation rate, and normalization of key ovarian factors [like TNF-α-stimulated gene/protein 6, hyaluronan, hyaluronan-binding protein 1, COX2, matrix metalloproteinases (membrane type 1-matrix metalloproteinase, MMP9 and MMP2)], tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2), and gelatinases (like MMP9 and -2) activity during follicular maturation. DISCUSSION AND CONCLUSION: Overall, most of the above molecular changes are regulated via NF-κB pathway, thus TQ, due to its modulatory effect on the NF-κB signaling, could elevate normal ovarian phenotype and physiological function in the PCO model, indicating its remarkable potential as a remedy for rat PCO.


Assuntos
Benzoquinonas/uso terapêutico , Modelos Animais de Doenças , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Animais , Benzoquinonas/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Feminino , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Wistar
20.
Nat Prod Res ; 29(12): 1166-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25922109

RESUMO

This study was carried out to assess the spermicidal action of hexane extract from the fruits of Piper longum Linn. The sperm immobilisation studies showed that 20 mg/mL of hexane extract was able to immobilise sperms completely within 20 s. The sperm revival test revealed that the effects were spermicidal as sperm immobilisation effect was irreversible. There was also a significant reduction in sperm viability in the treated group in comparison to the control. The hypo-osmotic swelling of these sperms was significantly reduced, indicating that the hexane extract may probably cause injury to the sperm plasma membrane. Hence, this study showed that the hexane extract of P. longum possesses potential contraceptive spermicidal activity in vitro.


Assuntos
Piper/química , Extratos Vegetais/farmacologia , Espermicidas/farmacologia , Espermatozoides/efeitos dos fármacos , Hexanos , Humanos , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA