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1.
Cureus ; 16(3): e56438, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646299

RESUMO

The global adoption of remote thyroidectomy is increasing, with the transoral endoscopic thyroidectomy vestibular approach (TOETVA) and transareolar approach (TAA) emerging as predominant methods. However, existing meta-analyses comparing these approaches to operative surgeries and short-term postoperative complications have significant limitations. To address this gap, our meta-analysis provides a comprehensive comparison between the TOETVA and TAA, focusing on operation time, intraoperative blood loss, postoperative drainage, and hospital stay duration. It aims to offer robust insights into their relative efficacy and safety profiles. We searched SCOPUS, PubMed, Web of Science, MEDLINE, and Cochrane Library from June 2015 to January 2024 for studies comparing transoral endoscopic thyroidectomy with the vestibular approach and areolar thyroidectomy using keywords, including "transoral thyroidectomy" and "scarless thyroidectomy." Studies were included if they were randomized controlled trials, case-control studies, or prospective/retrospective cohort studies comparing the TOETVA and TAA. Exclusion criteria removed case series, cross-sectional studies, editorials, non-English language, animal studies, and irrelevant articles. Data on operative time, postoperative drainage, intraoperative blood loss, and hospital stay were extracted. The Newcastle-Ottawa Scale was used to assess study quality (all studies scored 7-8). The findings revealed that the operative time was longer among the TOETVA group, with less intraoperative blood loss (odds ratio (OR) = 13.31, 95% confidence interval (CI) = 4.44-22.19); OR = -1.61, 95% CI = -2.82 to -0.39, respectively). Regarding hospitalization duration and postoperative drainage, no discernible difference was observed between the endoscopic TAA (ETAA) and TOETVA (OR = -0.04, 95% CI = -0.24 to 0.16; OR = -6.74, 95% CI = -20.08 to 6.60, respectively). The TOETVA has advantages over the TAA in terms of intraoperative blood loss and shorter operation times. However, both approaches exhibited comparable outcomes in terms of hospital stay duration and postoperative drainage. Furthermore, extensive randomized trials are warranted.

2.
Dev Cell ; 58(19): 1967-1982.e8, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37734383

RESUMO

Neuroblastoma is the most common extracranial solid tumor in infants, arising from developmentally stalled neural crest-derived cells. Driving tumor differentiation is a promising therapeutic approach for this devastating disease. Here, we show that the CDK4/6 inhibitor palbociclib not only inhibits proliferation but induces extensive neuronal differentiation of adrenergic neuroblastoma cells. Palbociclib-mediated differentiation is manifested by extensive phenotypic and transcriptional changes accompanied by the establishment of an epigenetic program driving expression of mature neuronal features. In vivo palbociclib significantly inhibits tumor growth in mouse neuroblastoma models. Furthermore, dual treatment with retinoic acid resets the oncogenic adrenergic core regulatory circuit of neuroblastoma cells, further suppresses proliferation, and can enhance differentiation, altering gene expression in ways that significantly correlate with improved patient survival. We therefore identify palbociclib as a therapeutic approach to dramatically enhance neuroblastoma differentiation efficacy that could be used in combination with retinoic acid to improve patient outcomes.


Assuntos
Neuroblastoma , Piperazinas , Piridinas , Tretinoína , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Diferenciação Celular , Tretinoína/farmacologia , Neuroblastoma/tratamento farmacológico , Adrenérgicos/uso terapêutico
3.
Allergol Immunopathol (Madr) ; 51(4): 148-150, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37422791

RESUMO

BACKGROUND: While the link between foods and chronic spontaneous urticaria (CSU) is controversial, many immunological mechanisms have been proposed to establish a causal relationship. OBJECTIVE: To explore the potential benefit of avoiding immunoglobulin G (IgG)-mediated food hypersensitivity as a triggering factor in a case with CSU. HISTORY: The patient is a 50-year-old woman who complained of CSU for 1 and half year, which responded partially and temporarily to antihistamine medications. Of interest, it started 6 months after she followed an oat-rich diet. Her Urticaria Activity Score 7 was 23 out of 40. RESULTS: Specific immunoglobulin E responses to common food and inhalant allergens were negative. A food-specific IgG antibody test was conducted, and it was mainly elevated for chicken eggs, rye, sweet pepper, gluten, garlic, wheat, and pineapple. Avoiding these foods had a curative effect on the CSU over a 2-month period. CONCLUSION: To the best of our knowledge, this is the first case report of symptoms of CSU that resolved after identifying and avoiding food items with IgG antibodies. Furthermore, well-controlled studies are advocated to verify the potential role of IgG food hypersensitivity in the pathogenesis of CSU.


Assuntos
Urticária Crônica , Hipersensibilidade Alimentar , Urticária , Feminino , Humanos , Imunoglobulina G , Doença Crônica , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/complicações , Alérgenos
4.
Res Dev Disabil ; 134: 104424, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36638672

RESUMO

BACKGROUND: Although dyslexia is the most common learning disorder in children, it has not received adequate attention in Saudi Arabia. AIMS: This study aimed at determining the prevalence of dyslexia among Saudi students in Grades 3-6, exploring associations between severity of dyslexia, its behavioral indicators, gender and grade, and the moderating role of grade in the relationship between severity and behavioral indicators. METHODS AND PROCEDURES: The sample consisted of 2848 female students and 2647 male students in Zulfi governorate, Saudi Arabia. A survey-based mixed-methods design was chosen including a structured interview with teachers and three assessments using the Diagnostic Assessment Scale for Dyslexia, the Arabic Reading Test, and the Dyslexia Behavioral Indicators Scale. OUTCOMES AND RESULTS: Dyslexia was assessed in 5.86 % of the total sample. It was twice as prevalent among male students as among female students (6.54 % and 3.83 %, respectively). The mean score for behavioral indicators of dyslexia was also significantly higher for male than for female students. The correlation between dyslexia severity and behavioral indicators score was high and significant, with grade level as a significant moderator. CONCLUSIONS AND IMPLICATIONS: We found that, for children with dyslexia in Saudi Arabia, dyslexia was twice as prevalent among male students as among female students. Early dyslexia diagnosis and intervention services are suggested to reduce the risk for reading problems.


Assuntos
Dislexia , Deficiências da Aprendizagem , Criança , Humanos , Masculino , Feminino , Arábia Saudita/epidemiologia , Dislexia/diagnóstico , Dislexia/epidemiologia , Dislexia/complicações , Estudantes , Instituições Acadêmicas
5.
Front Cell Dev Biol ; 10: 942579, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263020

RESUMO

Neuroblastoma is believed to arise from sympathetic neuroblast precursors that fail to engage the neuronal differentiation programme, but instead become locked in a pro-proliferative developmental state. Achaete-scute homolog 1 (ASCL1) is a proneural master regulator of transcription which modulates both proliferation and differentiation of sympathetic neuroblast precursor cells during development, while its expression has been implicated in the maintenance of an oncogenic programme in MYCN-amplified neuroblastoma. However, the role of ASCL1 expression in neuroblastoma is not clear, especially as its levels vary considerably in different neuroblastoma cell lines. Here, we have investigated the role of ASCL1 in maintaining proliferation and controlling differentiation in both MYCN amplified and Anaplastic Lymphoma Kinase (ALK)-driven neuroblastoma cells. Using CRISPR deletion, we generated neuroblastoma cell lines lacking ASCL1 expression, and these grew more slowly than parental cells, indicating that ASCL1 contributes to rapid proliferation of MYCN amplified and non-amplified neuroblastoma cells. Genome-wide analysis after ASCL1 deletion revealed reduced expression of genes associated with neuronal differentiation, while chromatin accessibility at regulatory regions associated with differentiation genes was also attenuated by ASCL1 knock-out. In neuroblastoma, ASCL1 has been described as part of a core regulatory circuit of developmental regulators whose high expression is maintained by mutual cross-activation of a network of super enhancers and is further augmented by the activity of MYC/MYCN. Surprisingly, ASCL1 deletion had little effect on the transcription of CRC gene transcripts in these neuroblastoma cell lines, but the ability of MYC/MYCN and CRC component proteins, PHOX2B and GATA3, to bind to chromatin was compromised. Taken together, our results demonstrate several roles for endogenous ASCL1 in neuroblastoma cells: maintaining a highly proliferative phenotype, regulating DNA binding of the core regulatory circuit genes to chromatin, while also controlling accessibility and transcription of differentiation targets. Thus, we propose a model where ASCL1, a key developmental regulator of sympathetic neurogenesis, plays a pivotal role in maintaining proliferation while simultaneously priming cells for differentiation in neuroblastoma.

6.
ACS Omega ; 7(41): 36748-36761, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36278035

RESUMO

The Es4 s shale is taken as the main research object to understand and describe the reservoir characteristics in Boxing Sag, Dongying Depression. Through core observation, X-ray diffraction, thin section observation, field-emission scanning electron microscopy analysis, and low-pressure nitrogen gas adsorption experiment, the reservoir space of the Es4 s shale including pore types, pore size, and pore structure characteristics was elucidated. The study shows that the shale in the Boxing Sag has the following characteristics: (1) the reservoir space in the study area is diverse, with the development of inorganic pores, organic pores, and microfractures. The higher the content of calcite and organic matter, the more favorable the development of intergranular pores, dissolution pores, and organic matter pores and (2) complex pore structure. The average Barrett-Joyner-Halenda pore size of calcareous shale is 6.5-22.8 nm, and the Brunauer-Emmett-Teller cumulative specific surface area is 0.7588-4.744 m2/g. According to the morphological analysis of the adsorption and desorption curve, it is found that the shale samples in the target interval are mainly ink-bottle-shaped, cylindrical, and slit-shaped pores. The shale samples with relatively well-laminated intervals are mainly composed of ink-bottle-shaped and cylindrical pores, while the samples with relatively unlaminated intervals and high clay mineral content are mainly composed of slit-shaped pores. The contents of clay minerals and calcite are correlated with pore volume, specific surface area, and pore size, which further indicates the controlling effect of clay minerals and carbonate mineral components on pore structure parameters. This study not only helps us to understand the distribution of various micropores/nanopores in the lacustrine shale but also acts as a guiding note for the characterization of the shale oil reservoir, which ultimately offers a theoretical foundation for lacustrine shale oil exploration and development.

7.
Front Cell Dev Biol ; 10: 943924, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147741

RESUMO

Neuroblastoma is a pediatric tumour that accounts for more than 15% of cancer-related deaths in children. High-risk tumours are often difficult to treat, and patients' survival chances are less than 50%. Retinoic acid treatment is part of the maintenance therapy given to neuroblastoma patients; however, not all tumours differentiate in response to retinoic acid. Within neuroblastoma tumors, two phenotypically distinct cell types have been identified based on their super-enhancer landscape and transcriptional core regulatory circuitries: adrenergic (ADRN) and mesenchymal (MES). We hypothesized that the distinct super-enhancers in these different tumour cells mediate differential response to retinoic acid. To this end, three different neuroblastoma cell lines, ADRN (MYCN amplified and non-amplified) and MES cells, were treated with retinoic acid, and changes in the super-enhancer landscape upon treatment and after subsequent removal of retinoic acid was studied. Using ChIP-seq for the active histone mark H3K27ac, paired with RNA-seq, we compared the super-enhancer landscape in cells that undergo neuronal differentiation in response to retinoic acid versus those that fail to differentiate and identified unique super-enhancers associated with neuronal differentiation. Among the ADRN cells that respond to treatment, MYCN-amplified cells remain differentiated upon removal of retinoic acid, whereas MYCN non-amplified cells revert to an undifferentiated state, allowing for the identification of super-enhancers responsible for maintaining differentiation. This study identifies key super-enhancers that are crucial for retinoic acid-mediated differentiation.

8.
Biochim Biophys Acta Rev Cancer ; 1877(6): 188805, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36162542

RESUMO

Neuroblastoma is a solid, neuroendocrine tumor with divergent clinical behavior ranging from asymptomatic to fatal. The diverse clinical presentations of neuroblastoma are directly linked to the high intra- and inter-tumoral heterogeneity it presents. This heterogeneity is strongly associated with therapeutic resistance and continuous relapses, often leading to fatal outcomes. The development of successful risk assessment and tailored treatment strategies lies in evaluating the extent of heterogeneity via the accurate genetic and epigenetic profiling of distinct cell subpopulations present in the tumor. Recent studies have focused on understanding the molecular mechanisms that drive tumoral heterogeneity in pursuing better therapeutic and diagnostic approaches. This review describes the cellular, genetic, and epigenetic aspects of neuroblastoma heterogeneity. In addition, we summarize the recent findings on three crucial factors that can lead to heterogeneity in solid tumors: the inherent diversity of the progenitor cells, the presence of cancer stem cells, and the influence of the tumor microenvironment.


Assuntos
Neuroblastoma , Humanos , Neuroblastoma/genética , Neuroblastoma/patologia , Células-Tronco Neoplásicas/patologia , Microambiente Tumoral/genética
9.
BMC Genomics ; 23(1): 255, 2022 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-35366798

RESUMO

BACKGROUND: The pro-neural transcription factor ASCL1 is a master regulator of neurogenesis and a key factor necessary for the reprogramming of permissive cell types to neurons. Endogenously, ASCL1 expression is often associated with neuroblast stem-ness. Moreover, ASCL1-mediated reprogramming of fibroblasts to differentiated neurons is commonly achieved using artificially high levels of ASCL1 protein, where ASCL1 acts as an "on-target" pioneer factor. However, the genome-wide effects of enhancing ASCL1 activity in a permissive neurogenic environment has not been thoroughly investigated. Here, we overexpressed ASCL1 in the neuronally-permissive context of neuroblastoma (NB) cells where modest endogenous ASCL1 supports the neuroblast programme. RESULTS: Increasing ASCL1 in neuroblastoma cells both enhances binding at existing ASCL1 sites and also leads to creation of numerous additional, lower affinity binding sites. These extensive genome-wide changes in ASCL1 binding result in significant reprogramming of the NB transcriptome, redirecting it from a proliferative neuroblastic state towards one favouring neuronal differentiation. Mechanistically, ASCL1-mediated cell cycle exit and differentiation can be increased further by preventing its multi-site phosphorylation, which is associated with additional changes in genome-wide binding and gene activation profiles. CONCLUSIONS: Our findings show that enhancing ASCL1 activity in a neurogenic environment both increases binding at endogenous ASCL1 sites and also results in additional binding to new low affinity sites that favours neuronal differentiation over the proliferating neuroblast programme supported by the endogenous protein. These findings have important implications for controlling processes of neurogenesis in cancer and cellular reprogramming.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Células-Tronco Neurais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Reprogramação Celular/genética , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Neurônios/metabolismo
10.
Front Cell Dev Biol ; 9: 725821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869313

RESUMO

The recent increases in cancer incidences have been linked to lifestyle changes that result in obesity and metabolic syndrome. It is now evident that these trends are associated with the profound changes that occur in the intestinal microbiome, producing altered microbial population signatures that interact, directly or indirectly, with potentially pro-carcinogenic molecular pathways of transcription, proliferation, and inflammation. The effects of the entire gut microbial population on overall health are complex, but individual bacteria are known to play important and definable roles. Recent detailed examinations of a large number of subjects show a tight correlation between habitual diets, fecal microbiome signatures, and markers of metabolic health. Diets that score higher in healthfulness or diversity such as plant-based diets, have altered ratios of specific bacteria, including an increase in short-chain fatty acid producers, which in turn have been linked to improved metabolic markers and lowered cancer risk. Contrarily, numerous studies have implicated less healthy, lower-scoring diets such as the Western diet with reduced intestinal epithelial defenses and promotion of specific bacteria that affect carcinogenic pathways. In this review, we will describe how different dietary patterns affect microbial populations in the gut and illustrate the subsequent impact of bacterial products and metabolites on molecular pathways of cancer development, both locally in the gut and systemically in distant organs.

11.
Ann Vasc Surg ; 76: 488-499, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33823252

RESUMO

BACKGROUND: Visceral artery aneurysms (VAAs) are associated with a very high mortality rate when ruptured and may present as a surgical emergency. Due to their rarity and varying pathophysiology, literature concerning the optimal management of VAAs is limited. This review evaluates the evolving management options for VAAs with a focus on open and endovascular repair. METHODS: A combination of databases including OVID, PubMed and Medline were used to perform a literature search. Search terms employed include 'visceral artery aneurysms', 'angiography', '3D-volumetric rendering', 'management', 'open repair' and 'endovascular repair', amongst others. RESULTS: 3D modelling in conjunction with existing diagnostic techniques, such as computed tomography and angiography, may improve diagnostic sensitivity. The literature surrounding operative management of VAAs highlights the effectiveness of endovascular repair for anatomically suitable aneurysms. Advances in endovascular technologies may expand the type and number of aneurysms amenable to catheter-based treatment approaches. For aneurysms not amenable to endovascular treatment, or those with an emergency indication, open repair remains an appropriate management choice. CONCLUSION: Although rare, VAAs pose a high mortality risk, especially when ruptured. Practical limitations that restrict current operative approaches may be overcome by recent developments including novel neurointerventional techniques that have been applied in VAA management.


Assuntos
Aneurisma/diagnóstico por imagem , Aneurisma/cirurgia , Procedimentos Endovasculares , Procedimentos Cirúrgicos Vasculares , Vísceras/irrigação sanguínea , Aneurisma/mortalidade , Aneurisma/fisiopatologia , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Tomada de Decisão Clínica , Difusão de Inovações , Emergências , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Humanos , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
12.
AEM Educ Train ; 5(2): e10499, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33842812

RESUMO

OBJECTIVES: Emergency medical services (EMS) clinicians are on the front lines of the opioid epidemic and are often the first health care personnel system to contact patients experiencing opioid toxicity. Although national educational guidelines include opioid toxicity, no specific standardized prehospital educational objectives or competencies exist. The goal of this project was to identify objectives for an EMS opioid toxicity curriculum that could be used for EMS training. METHODS: A list of preliminary educational objectives from U.S. EMS training programs was compiled and reviewed by a group of experts. The Delphi method was used to attain consensus on a final list of objectives for an EMS opioid curriculum. RESULTS: A total of 107 opioid-related preliminary objectives were identified and then narrowed down to 81 preliminary objectives after accounting for redundancy. After four successive rounds of evaluating/accepting/rejecting objectives, 18 final objectives were identified and unanimously approved by the expert panel. CONCLUSION: We identified 18 objectives to serve as a framework for an opioid toxicity curriculum for EMS clinicians. These objectives can serve as a basis for creating a standardized didactic training program for EMS training programs nationwide. Further evaluation will be needed to explore the best means for educational program delivery.

13.
Mol Cancer Res ; 18(12): 1759-1766, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046535

RESUMO

Pediatric cancers often resemble trapped developmental intermediate states that fail to engage the normal differentiation program, typified by high-risk neuroblastoma arising from the developing sympathetic nervous system. Neuroblastoma cells resemble arrested neuroblasts trapped by a stable but aberrant epigenetic program controlled by sustained expression of a core transcriptional circuit of developmental regulators in conjunction with elevated MYCN or MYC (MYC). The transcription factor ASCL1 is a key master regulator in neuroblastoma and has oncogenic and tumor-suppressive activities in several other tumor types. Using functional mutational approaches, we find that preventing CDK-dependent phosphorylation of ASCL1 in neuroblastoma cells drives coordinated suppression of the MYC-driven core circuit supporting neuroblast identity and proliferation, while simultaneously activating an enduring gene program driving mitotic exit and neuronal differentiation. IMPLICATIONS: These findings indicate that targeting phosphorylation of ASCL1 may offer a new approach to development of differentiation therapies in neuroblastoma. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/18/12/1759/F1.large.jpg.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Neuroblastoma/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Fosforilação , Processamento de Proteína Pós-Traducional , Regulação para Cima
14.
Xenobiotica ; 50(7): 858-862, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32216504

RESUMO

The current research explored the effect of hepatic and renal dysfunctions on the pharmacokinetics of thymoquinone (TQ) in a rat model.An acute kidney injury was induced using gentamicin and a liver damage was elicited using a single dose of d-galactosamine. For the pharmacokinetic studies, TQ was administered as IV injection or and PO route to rats.The concentrations of TQ and pharmacokinetic parameters were calculated using a non-compartmental analysis. The systemic clearance (Cl) of TQ after IV dosing was slightly reduced in the liver dysfunction group compared to healthy controls (p = 0.0013). Similarly, the estimated volume of distribution at steady state (Vss) was marginally decreased (p = 0.001). However, in rats with acute kidney injury exhibited a larger Vss as opposed to normal renal function (511.28 ± 21.03 ml/kg vs. 442.25 ± 31.43 ml/kg; p = 0.0001). Whereas oral Cl and terminal volume of distribution (Vz) of TQ were reduced by ∼50% in the liver dysfunction group (p = 0.0001). These changes were associated with more systemic exposure as measured by AUC0-∞ in rats with compromised liver functions. The estimated plasma protein binding TQ was 99.84 ± 0.03% in healthy controls, 97.05 ± 0.57% with kidney injury rats, and 95.75 ± 0.64% in liver dysfunctionThe findings of the present study suggest that liver dysfunction could potentially modify the disposition of TQ administered orally, and therefore, a smaller maintenance dose is probably required to avoid accumulation.


Assuntos
Benzoquinonas/farmacocinética , Injúria Renal Aguda , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado/metabolismo , Masculino , Ratos
15.
CNS Neurol Disord Drug Targets ; 18(5): 352-365, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30892166

RESUMO

Luteolin is a naturally occurring, yellow crystalline flavonoid found in numerous dietary supplements we frequently have in our meals. Studies in the last 2 decades have revealed its therapeutic potential to reduce the Alzheimer's disease (AD) symptoms in various in vitro and in vivo models. The anti-Alzheimer's potential of luteolin is attributed to its ability to suppress Aß as well as tau aggregation or promote their disaggregation, down-regulate the expression of COX-2, NOS, MMP-9, TNF-α, interleukins and chemokines, reduce oxidative stress by scavenging ROS, modulate the activities of transcription factors CREB, cJun, Nrf-1, NF-κB, p38, p53, AP-1 and ß-catenine and inhibiting the activities of various protein kinases. In several systems, luteolin has been described as a potent antioxidant and anti-inflammatory agent. In addition, we have also discussed about the bio-availability of the luteolin in the plasma. After being metabolized luteolin persists in plasma as glucuronides and sulphate-conjugates. Human clinical trials indicated no dose limiting toxicity when administered at a dose of 100 mg/day. Improvements in the formulations and drug delivery systems may further enhance the bioavailability and potency of luteolin. The current review describes in detail the data supporting these studies.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Luteolina/farmacocinética , Luteolina/uso terapêutico , Animais , Disponibilidade Biológica , Humanos , Luteolina/farmacologia , Fármacos Neuroprotetores/farmacocinética , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
16.
Int J Mol Sci ; 20(4)2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30791357

RESUMO

Grain quality improvement is a key target for rice breeders, along with yield. It is a multigenic trait that is simultaneously influenced by many factors. Over the past few decades, breeding for semi-dwarf cultivars and hybrids has significantly contributed to the attainment of high yield demands but reduced grain quality, which thus needs the attention of researchers. The availability of rice genome sequences has facilitated gene discovery, targeted mutagenesis, and revealed functional aspects of rice grain quality attributes. Some success has been achieved through the application of molecular markers to understand the genetic mechanisms for better rice grain quality; however, researchers have opted for novel strategies. Genomic alteration employing genome editing technologies (GETs) like clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) for reverse genetics has opened new avenues of research in the life sciences, including for rice grain quality improvement. Currently, CRISPR/Cas9 technology is widely used by researchers for genome editing to achieve the desired biological objectives, because of its simple targeting. Over the past few years many genes that are related to various aspects of rice grain quality have been successfully edited via CRISPR/Cas9 technology. Interestingly, studies on functional genomics at larger scales have become possible because of the availability of GETs. In this review, we discuss the progress made in rice by employing the CRISPR/Cas9 editing system and its eminent applications. We also elaborate possible future avenues of research with this system, and our understanding regarding the biological mechanism of rice grain quality improvement.


Assuntos
Sistemas CRISPR-Cas , Grão Comestível/genética , Grão Comestível/normas , Edição de Genes , Oryza/genética , Qualidade dos Alimentos , Genoma de Planta , Genômica , Mutagênese , Valor Nutritivo , Oryza/metabolismo , Melhoria de Qualidade , Amido/metabolismo
17.
J Diet Suppl ; 16(5): 550-563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29969325

RESUMO

Parkinson's disease (PD) is the second-most common neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress has also been linked with the progression of PD, hence the involvement of a natural plant product could offer neuroprotection. The present study deals with the effect of genistein on the transgenic flies expressing normal human alpha synuclein panneurally. The PD flies were exposed to 10, 20, 30, and 40 µM of genistein (mixed in diet) for 24 days. A significant dose-dependent increase in the life span and delay in the loss of climbing ability were observed in the PD flies exposed to genistein (p < .05). A significant dose-dependent decrease in oxidative stress markers and increase in dopamine content were observed in PD flies exposed to genistein. However, the exposure of genistein did not inhibit the expression of α-synuclein in the brains of PD flies.


Assuntos
Animais Geneticamente Modificados , Drosophila , Genisteína/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Dopamina/análise , Drosophila/genética , Drosophila/metabolismo , Expressão Gênica , Humanos , Locomoção/efeitos dos fármacos , Monoaminoxidase/metabolismo , Neurônios/metabolismo , alfa-Sinucleína/genética
18.
Neurosci Lett ; 692: 90-99, 2019 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-30420334

RESUMO

A transgenic fly line expressing wild type human Aß42 were exposed to luteolin mixed in diet at final concentration of 5, 10, 15 and 20µM. The climbing assay, activity pattern, life span, aversive phototaxis suppression assay (APS) along with the estimation of protein carbonyl content (PCC), glutathione-S-transferase (GSTs) activity, glutathione (GSH) content, lipid peroxidation (LPO), acetylcholinesterase activity (AChE), superoxide dismutase (SOD) activity, catalase (CAT) activity, caspase 3 and 9 activities in the brain of treated as well as untreated AD flies (Positive control) were studied. Histopathology of Drosophila brain sections was done by performing thioflavin-S, Bielschowsky's silver staining and toluidine blue staining. A dose-dependent increase in the life span, delay in the loss of climbing ability as well as activity was observed in AD flies exposed to luteolin compared to unexposed AD flies. A dose-dependent reduction in LPO, PCC, GST, AChE, SOD, CAT, caspase 9 and caspase 3 activity and an increase in the GSH content was also observed. Histopathological examination of fly brains using thioflavin-S and silver staining has revealed a significant dose-dependent reduction in the expression of Aß42 peptides in AD fly groups exposed to 10, 15 and 20µM of luteolin. No gross morphological changes were observed in the brain sections of AD and control flies stained with toluidine blue. Molecular docking results have revealed that luteolin binds to AChE and Aß42 at specific sites that might result in the inhibition of AChE and disaggregation/prevention of Aß42 plaque formation.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Luteolina/administração & dosagem , Fragmentos de Peptídeos/metabolismo , Acetilcolinesterase/metabolismo , Doença de Alzheimer/patologia , Animais , Animais Geneticamente Modificados , Encéfalo/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Drosophila , Humanos , Simulação de Acoplamento Molecular , Agregação Patológica de Proteínas/tratamento farmacológico
19.
JACC Case Rep ; 1(2): 235-237, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34316794

RESUMO

At 22 years following heart transplantation, a patient presented with incessant atrial flutter. During electrophysiologic study, 2 simultaneous atrial arrhythmias were mapped, 1 from the donor and 1 from the recipient's heart. High-density mapping allowed for rapid identification of electrically abnormal areas, which were successfully ablated, thus restoring sinus rhythm. (Level of Difficulty: Advanced.).

20.
Cureus ; 10(7): e2931, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-30310762

RESUMO

The United States (US) is the third most expensive health care system in the world, but despite that, the US ranked last in the top 50 countries of the world when it comes to the performance measures, such as healthcare efficiency, life expectancy, health care costs, and gross domestic product (GDP) percentage. The spending health care cost keeps increasing and most of the healthcare costs go to waste. Due to this reason, it is therefore extremely important to focus on improving the quality and to bring the costs in appropriate control. To avoid this issue, the Choosing Wisely Campaign (CWC) came into being in 2012. The CWC encourages discussions between providers and patients regarding the care based on the evidence base, free from harm, duplicative or redundant tests/procedures that the patient already received, and whether medications, tests, or procedures are really necessary. Although diagnostic tests or procedures are highly valued for decision-making, unnecessary testing creates harmful health services and an economic impact on the healthcare system. The CWC has spread widely throughout the world but has many challenges which are limiting the CWC in further adoption and spread in the US. To overcome challenges in implementing and spreading the CWC, the government, physicians, social media, and mass media play an important role.

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