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1.
Plant Physiol ; 192(2): 1517-1531, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-36852887

RESUMO

Meristem maintenance, achieved through the highly conserved CLAVATA-WUSCHEL (CLV-WUS) regulatory circuit, is fundamental in balancing stem cell proliferation with cellular differentiation. Disruptions to meristem homeostasis can alter meristem size, leading to enlarged organs. Cotton (Gossypium spp.), the world's most important fiber crop, shows inherent variation in fruit size, presenting opportunities to explore the networks regulating meristem homeostasis and to impact fruit size and crop value. We identified and characterized the cotton orthologs of genes functioning in the CLV-WUS circuit. Using virus-based gene manipulation in cotton, we altered the expression of each gene to perturb meristem regulation and increase fruit size. Targeted alteration of individual components of the CLV-WUS circuit modestly fasciated flowers and fruits. Unexpectedly, controlled expression of meristem regulator SELF-PRUNING (SP) increased the impacts of altered CLV-WUS expression on flower and fruit fasciation. Meristem transcriptomics showed SP and genes of the CLV-WUS circuit are expressed independently from each other, suggesting these gene products are not acting in the same path. Virus-induced silencing of GhSP facilitated the delivery of other signals to the meristem to alter organ specification. SP has a role in cotton meristem homeostasis, and changes in GhSP expression increased access of virus-derived signals to the meristem.


Assuntos
Proteínas de Arabidopsis , Meristema , Meristema/metabolismo , Proteínas de Arabidopsis/metabolismo , Flores/genética , Flores/metabolismo , Frutas/genética , Frutas/metabolismo , Homeostase , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio/genética
2.
Eur J Pediatr ; 183(3): 1183-1193, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38078969

RESUMO

Non-invasive cardiac imaging like echocardiogram, cardiac magnetic resonance imaging (CMR), and computed tomography angiography (CTA) play a key role in the diagnosis, aid in management and follow-up of congenital heart disease patients. Normative data for intracardiac and extracardiac vascular structures in children are currently available for echocardiogram, CMR, and non-gated CTA. We sought to establish systolic and diastolic normative data for main and branch pulmonary arteries in children using electrocardiogram (ECG)-gated CTA. Diameters and cross-sectional areas of the main and branch pulmonary arteries were measured in systole and diastole based on the aortic valve position (open versus closed) in 100 subjects who had ECG-gated cardiac CTA at our center between January 2015 through December 2020 and met our inclusion criteria. The allometric exponent (AE) for each parameter was derived, and the parameter/body surface area (BSAAE) was established using the previously described methods. A total of 100 children aged 0-18 years were analyzed; mean age was 5.3 years (SD, 6.1 years). Z-score curves were plotted in relation to the BSA for the mean, maximum, and minimum diameters and cross-sectional area of the main and branch pulmonary arteries for systole and diastole.   Conclusion: We report systolic and diastolic mean, maximum, and minimum diameters and cross-sectional areas along with Z-scores and normative curves for the main and branch pulmonary arteries in children derived using ECG-gated cardiac CTA. We believe our results can help identify abnormally sized main and branch pulmonary arteries. What is Known: • Normative data for intracardiac and extracardiac vascular structures in the pediatric population are available for echocardiography, cardiac MRI and non-ECG gated CTA. • Z-scores with standard deviations are commonly used in children, but SDs are not constant across body sizes due to heteroscedasticity. What is New: • Allometric exponent was derived for each parameter and the parameter/body surface area (BSA) was established. • This is the first ECG-gated CTA study to provide normative en face systolic, diastolic diameters and cross-sectional areas along with Z-scores and normative curves for the main and branch pulmonary arteries in children.


Assuntos
Angiografia por Tomografia Computadorizada , Artéria Pulmonar , Criança , Humanos , Pré-Escolar , Artéria Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Ecocardiografia , Eletrocardiografia
3.
Dig Dis Sci ; 68(2): 497-513, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35984611

RESUMO

BACKGROUND: Hyperfibrinolysis and coagulation dysfunction may occur in cirrhotic patients with acute variceal bleed (AVB) despite successful endotherapy. AIMS: To prospectively study the association of endogenous heparinoids and coagulation dysfunction with variceal rebleeding and outcome in cirrhosis. METHODS: Consecutive patients were assessed with conventional coagulation tests, SONOCLOT™ [(global(gb) and heparinase(h) treated] and factors VII, VIII, XIII, X, tissue plasminogen activator, and plasminogen activator inhibitor ELISA assays in a university hospital. Heparin-like-effect (HLE) was defined as ≥ 20% difference in paired gb/h-SONOCLOT™ traces for activated clotting time (ACT). RESULTS: Of 143 patients screened, 90 (46.4 ± 11.7 years, males 82.2%, ethanol-related 58.8%) were recruited, who bled from esophageal varices (81,90.0%), gastric varices (6,6.6%), or esophageal varices with portal hypertensive gastropathy (3,3.3%). Twenty (21.7%) had early rebleeding, mainly post-variceal ligation ulcer related (70%). Patients who rebled had low Factor XIII [1.6 (1.2-2.1) vs 2.4 ng/ml (2.0-2.8) P = 0.035] and Factor VII (94.1 ± 46.9 vs. 124.0 ± 50.4, P = 0.023). On receiver operating curve analysis, the gbACT > 252 s (sensitivity 86.8%, specificity 76.9%, P < 0.001), hACT > 215 s (sensitivity 71.1%, specificity 70.3%, P < 0.001), and HLE > 50% (sensitivity 69.5%, specificity 70.3%, P = 0.006) predicted rebleeding. Baseline Factor VIII (HR 1.26; 95% CI 1.17-1.34, P < 0.001), low factor VII (HR 0.89; 95% CI 0.76-0.98, P = 0.035), and lysis (HR 1.25, 95% CI 1.17-1.33, P < 0.001) predicted mortality. Endogenous heparinoids at baseline predicted sepsis (HR 1.8; 95% CI 1.4-6.5; P = 0.022), rebleeding events (HR 1.2; 95% CI 1.1-6.3; P = 0.030), and mortality (HR 1.1; 95% CI 1.0-4.6; P = 0.030). CONCLUSIONS: Hyperfibrinolysis, Factor VII/XIII deficiency, and HLE are associated with rebleeding after AVB. Trial Registration NCT04111120 available from https://clinicaltrials.gov/ct2/show/NCT04111120 .


Assuntos
Varizes Esofágicas e Gástricas , Heparinoides , Masculino , Humanos , Varizes Esofágicas e Gástricas/etiologia , Fator VII , Ativador de Plasminogênio Tecidual , Hemorragia Gastrointestinal/etiologia , Heparina , Fibrinólise , Cirrose Hepática/complicações , Ligadura/efeitos adversos
4.
Drug Chem Toxicol ; : 1-10, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594462

RESUMO

7-Methylxanthine (7-MX, CAS No. 552-62-5, purity 99.46%) is the first orally administered drug candidate, which showed anti-myopic activity in different pre-clinical studies. In the present study, we investigated the in-vivo genotoxic and mutagenic toxicity of 7-MX in Wistar rats using comet/single-cell gel electrophoresis, chromosomal aberration and micronucleus assays after oral administration. For the single-dose study (72 h), two doses of 7-MX 300 and 2000 mg/kg body weight were selected. For a repeated dose 28 d study, three doses (250, 500, and 1000 mg/kg) of 7-MX were selected. The doses were administered via oral gavage in the suspension form. Blood and major vital organs such as bone marrow, lung and liver were used to perform comet/single cell gel electrophoresis, chromosomal aberration, and micronucleus assays. The in-vitro Ames test was performed on TA98 and TA100 strains. In the chromosomal aberration study, a non-significant increase in deformities such as stickiness, ring chromosome, and endoreduplication was observed in bone marrow cells of 7-MX treated groups. These chromosomal alterations were observed upon treatment with doses of 2000 mg/kg single dose for 72 h and 1000 mg/kg repeated dose for 28 d. At a dose of 500 mg/kg, DNA damage in terms of tail length, tail moment, % tail DNA and the olive tail moment was also found to be non-significant in 7-MX treated groups. The Ames test showed the non-mutagenic nature of 7-MX in both strains of TA98 and TA100 of Salmonella typhimurium with or without metabolic activation. Thus, the present work is interesting in view of the non- genotoxicity and non-mutagenicity of repeated doses of 7-MX.

5.
J Viral Hepat ; 29(5): 395-406, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35266624

RESUMO

Chronic hepatitis C virus (HCV) infection is associated with neuropsychiatric changes. Also, patients with cirrhosis may develop overt or minimal hepatic encephalopathy. Sustained virological response (SVR) with direct-acting antiviral agents (DAAs) may improve the neuropsychiatric manifestations and quality of life (QoL). Consecutive patients (with and without cirrhosis, all genders and aged 18-65 years) with hepatitis C were assessed at enrolment and at 12 weeks after therapy completion for mood (Beck's Depression Inventory [BDI]), anxiety (generalized anxiety disorder [GAD-7]), QoL (SF-36 ver.2) and computer-based tests for number connection (NCT), visual memory, Stroop test and reaction times. We recruited 385 viraemic chronic HCV patients (76.1% male, 21.0% cirrhotic, mean age 39.4 ± 14.2 years, 59.3% genotype 3, mean HCV RNA load 5.8 log). Overall SVR-12 rates were 90.6%, with cure rates 87.6% and 91.4% in patients with and without cirrhosis, respectively. Patients who achieved SVR-12 had mean percentage reduction in BDI (11.3%, p = .000), GAD (8.6%, p = .001) and Stroop test (58.4%, p = .001), with improved NCT (1.7%, p = .001), visual memory (13.7%, p = .001) and digit span (23.8%, p = .002). On multivariate logistic regression, adherence (OR, 17.5 [95% CI 2.80-110.50], p = .000), high ALT (OR 1.02 [95% CI 1.00-1.05]), and BDI score (OR 1.73 [95% CI 1.42-3.26] p = .039) predicted cure. SVR-12 was associated with improved visual memory ≥5.5 (AUC-0.708; sensitivity 62.5%, specificity 63%, p = .000) and % correct Stroop test responses >26.6% (AUC-0.918, sensitivity 94.4% specificity 80.4%, p = .000). In conclusion, given the cumulative evidence of the safety of DAAs and efficacy of improving cognitive and neuropsychological and quality-of-life outcomes irrespective of age and gender, as shown in our study, future recommendations should focus on integrated universal HCV care to enable HCV elimination.


Assuntos
Hepatite C Crônica , Hepatite C , Adulto , Antivirais/uso terapêutico , Ansiedade , Transtornos de Ansiedade/induzido quimicamente , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/tratamento farmacológico , Estudos de Coortes , Depressão , Feminino , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resposta Viral Sustentada , Resultado do Tratamento
6.
Biofouling ; 38(5): 455-481, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35673761

RESUMO

Enzymes, also known as biocatalysts, display vital properties like high substrate specificity, an eco-friendly nature, low energy inputs, and cost-effectiveness. Among their numerous known applications, enzymes that can target biofilms or their components are increasingly being investigated for their anti-biofouling action, particularly in healthcare, food manufacturing units and environmental applications. Enzymes can target biofilms at different levels like during the attachment of microorganisms, formation of exopolymeric substances (EPS), and their disruption thereafter. In this regard, a consortium of carbohydrases that can target heterogeneous polysaccharides present in the EPS matrix may provide an effective alternative to conventional chemical anti-biofouling methods. Further, for complete annihilation of biofilms, enzymes can be used alone or in conjunction with other antimicrobial agents. Enzymes hold the promise to replace the conventional methods with greener, more economical, and more efficient alternatives. The present article explores the potential and future perspectives of using carbohydrases as effective anti-biofilm agents.


Assuntos
Bactérias , Biofilmes , Incrustação Biológica , Glicosídeo Hidrolases , Química Verde , Anti-Infecciosos , Bactérias/enzimologia , Incrustação Biológica/prevenção & controle , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Glicosídeo Hidrolases/isolamento & purificação , Glicosídeo Hidrolases/metabolismo , Química Verde/métodos
8.
J Ultrasound Med ; 36(1): 109-120, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27925675

RESUMO

OBJECTIVES: Functional appliances are used for treatment of lower-jaw deficiencies in growing individuals; however, their effectiveness is debatable. Low-intensity pulsed ultrasound (US) is a noninvasive method, which has been shown to stimulate cartilage and bone formation with 20 minutes of application. This study was designed to test the hypothesis that increasing low-intensity pulsed US application from 20 to 40 min/d will enhance mandibular condylar growth in growing rats, especially when combined with a functional appliance. METHODS: Fifty-four Sprague Dawley rats were divided into 6 groups (n = 9): control, low-intensity pulsed US for 20 minutes, low-intensity pulsed US for 40 minutes, the functional appliance, the functional appliance plus low-intensity pulsed US for 20 minutes, and the functional appliance plus low-intensity pulsed US for 40 minutes. Low-intensity pulsed US was applied for 28 days. All rats were then euthanized, and their mandibles were dissected for morphometric, histomorphometric, and micro-computed tomographic analyses. RESULTS: Among all study groups, the 20-minute US group showed significant increases in most of the measured variables (P < .05) except for condylar process length (P = .18), whereas the functional appliance-plus-40-min US group showed the least favorable results. The 20-minute US group showed increases in proliferative and hypertrophic cell counts and widths and enhanced microarchitecture of trabecular bone compared with the 40-minute US group. The functional appliance-plus-20-minute US group showed better results compared with the functional appliance-alone and functional appliance-plus-40-minute US groups. CONCLUSIONS: A daily application of low-intensity pulsed US for 20 minutes in growing rats affects mandibular growth, either alone or in combination with a functional appliance. Further study with a longer observation period is required to study the long-term effects and stability of newly formed bone.


Assuntos
Côndilo Mandibular/diagnóstico por imagem , Aparelhos Ortodônticos Funcionais , Osteogênese/fisiologia , Ondas Ultrassônicas , Animais , Modelos Animais , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Tomografia Computadorizada por Raios X
9.
J Ultrasound Med ; 35(2): 349-58, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26782167

RESUMO

OBJECTIVES: The objectives of this systematic review with a meta-analysis were to critically analyze the available scientific literature regarding the effects of low-intensity pulsed ultrasound (US) on stimulating bone regeneration and bone maturation during distraction osteogenesis in humans and to determine whether the stimulatory effect of low-intensity pulsed US can effectively reduce the associated treatment time. METHODS: Studies were considered for inclusion if they were randomized clinical trials that examined the effect of low-intensity pulsed US on distraction osteogenesis compared to conventional distraction osteogenesis. The primary outcome was reduced treatment time. Study selection, risk of bias assessment, and data extraction were performed in duplicate. A random-effects meta-analysis model was used when more than 3 trials were eligible for a quantitative analysis and considering the expected differences in interventions and measurement tools. RESULTS: Five randomized clinical trials, with a moderate to high risk of bias, met the eligibility criteria. Four trials examining tibial distraction osteogenesis in 118 patients were combined in a meta-analysis. A statistically significant difference for reduced treatment time between distraction osteogenesis with low-intensity pulsed US and standard distraction osteogenesis was evident (mean difference, -15.236 d/cm; random-effects 95% confidence interval, -19.902 to -10.569 d/cm; P < .0001). As for the mandible, only 1 clinical trial was available, which showed no significant effect of low-intensity pulsed US therapy on distraction osteogenesis. CONCLUSIONS: Current available evidence suggests that low-intensity pulsed US therapy may provide a reduction in the overall treatment time for tibial distraction osteogenesis. However, this conclusion should be considered with caution, given the moderate to high risk of bias in the included randomized clinical trials.


Assuntos
Regeneração Óssea/efeitos da radiação , Osteogênese por Distração , Ondas Ultrassônicas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Int J Cardiovasc Imaging ; 40(1): 139-147, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37861812

RESUMO

PURPOSE: Cardiac Magnetic resonance (CMR) derived left ventricular longitudinal and circumferential strain is known to be abnormal in myocarditis. CMR strain is a useful additional tool that can identify subclinical myocardial involvement and may help with longitudinal follow-up. Right ventricular strain derived by CMR in children has not been studied. We sought to evaluate CMR derived biventricular strain in children with acute myocarditis. METHODS: Children with acute myocarditis who underwent CMR between 2016-2022 at our center were reviewed, this group included subjects with COVID-19 myocarditis. Children with no evidence of myocarditis served as controls Those with congenital heart disease and technically limited images for CMR strain analysis were excluded from final analysis. Biventricular longitudinal, circumferential, and radial peak systolic strains were derived using circle cvi42®. Data between cases and controls were compared using an independent sample t-test. One-way ANOVA with post hoc analysis was used to compare COVID-19, non-COVID myocarditis and controls. RESULTS: 38 myocarditis and 14 controls met inclusion criteria (mean age 14.4 ± 3 years). All CMR derived peak strain values except for RV longitudinal strain were abnormal in myocarditis group. One-way ANOVA revealed that there was a statistically significant difference with abnormal RV and LV strain in COVID-19 myocarditis when compared to non-COVID-19 myocarditis and controls. CONCLUSION: CMR derived right and left ventricular peak systolic strain using traditionally acquired cine images were abnormal in children with acute myocarditis. All strain measurements were significantly abnormal in children with COVID-19 even when compared to non-COVID myocarditis.


Assuntos
COVID-19 , Miocardite , Criança , Humanos , Adolescente , Função Ventricular Esquerda , Estudos Retrospectivos , Imagem Cinética por Ressonância Magnética/métodos , Valor Preditivo dos Testes , Imageamento por Ressonância Magnética , COVID-19/complicações
11.
Curr Med Imaging ; 20: 1-13, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38389343

RESUMO

BACKGROUND: Modern medical imaging modalities used by clinicians have many applications in the diagnosis of complicated diseases. These imaging technologies reveal the internal anatomy and physiology of the body. The fundamental idea behind medical image fusion is to increase the image's global and local contrast, enhance the visual impact, and change its format so that it is better suited for computer processing or human viewing while preventing noise magnification and accomplishing excellent real-time performance. OBJECTIVE: The top goal is to combine data from various modal images (CT/MRI and MR-T1/MR-T2) into a solitary image that, to the greatest degree possible, retains the key characteristics (prominent features) of the source images. METHODS: The clinical accuracy of medical issues is compromised because innumerable classical fusion methods struggle to conserve all the prominent features of the original images. Furthermore, complex implementation, high computation time, and more memory requirements are key problems of transform domain methods. With the purpose of solving these problems, this research suggests a fusion framework for multimodal medical images that makes use of a multi-scale edge-preserving filter and visual saliency detection. The source images are decomposed using a two-scale edge-preserving filter into base and detail layers. Base layers are combined using the addition fusion rule, while detail layers are fused using weight maps constructed using the maximum symmetric surround saliency detection algorithm. RESULTS: The resultant image constructed by the presumed method has improved objective evaluation metrics than other classical methods, as well as unhindered edge contour, more global contrast, and no ringing effect or artifacts. CONCLUSION: The methodology offers a dominant and symbiotic arsenal of clinical symptomatic, therapeutic, and biomedical research competencies that have the prospective to considerably strengthen medical practice and biological understanding.


Assuntos
Algoritmos , Imageamento por Ressonância Magnética , Humanos , Estudos Prospectivos
12.
Curr Med Imaging ; 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38284702

RESUMO

BACKGROUND: A clinical medical image provides vital information about a person's health and bodily condition. Typically, doctors monitor and examine several types of medical images individually to gather supplementary information for illness diagnosis and treatment. As it is arduous to analyze and diagnose from a single image, multi-modality images have been shown to enhance the precision of diagnosis and evaluation of medical conditions. OBJECTIVE: Several conventional image fusion techniques strengthen the consistency of the information by combining varied image observations; nevertheless, the drawback of these techniques in retaining all crucial elements of the original images can have a negative impact on the accuracy of clinical diagnoses. This research develops an improved image fusion technique based on fine-grained saliency and an anisotropic diffusion filter to preserve structural and detailed information of the individual image. METHOD: In contrast to prior efforts, the saliency method is not executed using a pyramidal decomposition, but rather an integral image on the original scale is used to obtain features of superior quality. Furthermore, an anisotropic diffusion filter is utilized for the decomposition of the original source images into a base layer and a detail layer. The proposed algorithm's performance is then contrasted to those of cutting-edge image fusion algorithms. RESULTS: The proposed approach cannot only cope with the fusion of medical images well, both subjectively and objectively, according to the results obtained, but also has high computational efficiency. CONCLUSION: Furthermore, it provides a roadmap for the direction of future research.

13.
Nutrients ; 16(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38337731

RESUMO

BACKGROUND: In the context of global shifts in food systems, this paper explores the unique dietary practices of the Santal tribe, an indigenous group in eastern India, to understand the health, nutrition, and sustainability aspects of their traditional food systems. This study evaluates the nutritional content of the Santal diet in comparison to the EAT-Lancet Commission's 2019 dietary guidelines for healthy and sustainable diets. METHODS: The University of East Anglia, in collaboration with the NNEdPro Global Institute for Food, Nutrition and Health in Cambridge, PRADAN; colleagues in India and local Santal youth, conducted nutritional analyses of traditional Santal recipes. Two menu templates, Kanhu Thali and Jhano Thali, were selected for comparative analysis based on their representation of diverse dietary practices within the Santal community. Nutritional data, including energy as well as the distribution of macronutrients and micronutrients, were compiled and compared with the EAT-Lancet guidelines. RESULTS: The Santal menu templates (nutritionally complete meals) demonstrated alignment with EAT-Lancet recommendations in aspects such as whole grains, starchy vegetables, vegetables, plant-based protein sources, unsaturated fats, and limited added sugars. However, notable deviations included the absence of animal-based protein sources and dairy. The Santal diet showed high protein intake, largely from plant-based sources, and emphasised the importance of whole grains. Seasonal variations in nutritional content were observed between the two templates. CONCLUSIONS: While the Santal diet aligns with some aspects of global dietary guidelines, there are notable deviations that underscore the complexity of aligning traditional diets with universal recommendations. The findings emphasise the need for culturally sensitive dietary recommendations that respect traditional diets while promoting sustainability. Research needs to support tailored global guidelines enshrining core principles of nutritional adequacy which are inter-culturally operable in order to accommodate cultural diversity, local practices, and seasonal variations, crucial for fostering sustainable and healthy eating habits in diverse sociodemographic contexts.


Assuntos
Dieta Saudável , Dieta , Estado Nutricional , Política Nutricional , Verduras
14.
bioRxiv ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38645223

RESUMO

Lineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage plasticity remain poorly understood. Here, we describe a versatile in vivo platform to identify and interrogate the molecular determinants of neuroendocrine lineage transformation at different stages of prostate cancer progression. Adenocarcinomas reliably develop following orthotopic transplantation of primary mouse prostate organoids acutely engineered with human-relevant driver alterations (e.g., Rb1-/-; Trp53-/-; cMyc+ or Pten-/-; Trp53-/-; cMyc+), but only those with Rb1 deletion progress to ASCL1+ neuroendocrine prostate cancer (NEPC), a highly aggressive, androgen receptor signaling inhibitor (ARSI)-resistant tumor. Importantly, we show this lineage transition requires a native in vivo microenvironment not replicated by conventional organoid culture. By integrating multiplexed immunofluorescence, spatial transcriptomics and PrismSpot to identify cell type-specific spatial gene modules, we reveal that ASCL1+ cells arise from KRT8+ luminal epithelial cells that progressively acquire transcriptional heterogeneity, producing large ASCL1+;KRT8- NEPC clusters. Ascl1 loss in established NEPC results in transient tumor regression followed by recurrence; however, Ascl1 deletion prior to transplantation completely abrogates lineage plasticity, yielding adenocarcinomas with elevated AR expression and marked sensitivity to castration. The dynamic feature of this model reveals the importance of timing of therapies focused on lineage plasticity and offers a platform for identification of additional lineage plasticity drivers.

15.
Semin Thromb Hemost ; 39(6): 663-73, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23934752

RESUMO

Compared with coagulation factor defects, little attention is given to defects of platelet function as causes of rare bleeding disorders. Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant bleeding disorder and is unique among platelet disorders because it is characterized by platelet hyperresponsiveness rather than decreased function. The disease is caused by gain-of-function mutations in the platelet GP1BA gene, which codes for the platelet von Willebrand factor (VWF) receptor, GPIbα. Only five mutations (four missense and one deletion) have so far been reported. Affected patients suffer from mild to moderate mucocutaneous bleeding, low VWF activity compared with antigen, decreased high-molecular-weight VWF multimers, variable degree of thrombocytopenia and typically platelet aggregation in response to low concentrations of ristocetin. All reported PT-VWD missense mutations occur within the R-loop of GPIbα and it was speculated that the introduction of short branched chain mutations such as Val in PT-VWD stabilized the extended ß-hairpin. Examination of this theory by surveying all the available GPIbα structures showed that a distinct conformation predominates for the R-loop when GPIbα is not bound to VWF-A1 and this provides the framework of a new hypothesis for the molecular basis of PT-VWD. Worldwide efforts to improve diagnosis of PT-VWD continue, and international systematic studies are required to further our understanding of the phenotype and the influence of the hyperresponsive GPIbα beyond hemostasis.


Assuntos
Plaquetas/metabolismo , Glicoproteínas de Membrana/genética , Mutação , Doenças de von Willebrand/genética , Plaquetas/fisiologia , Hemorragia/genética , Hemorragia/fisiopatologia , Hemostasia/genética , Hemostasia/fisiologia , Humanos , Glicoproteínas de Membrana/metabolismo , Agregação Plaquetária/genética , Agregação Plaquetária/fisiologia , Complexo Glicoproteico GPIb-IX de Plaquetas , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/fisiopatologia , Fator de von Willebrand/metabolismo
16.
Hip Pelvis ; 35(1): 1-5, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36937215

RESUMO

Piriformis syndrome is a common differential diagnosis related to sciatica. The following review provides a concise synopsis of the diagnosis, management, history, and alternatives to diagnosis of piriformis syndrome. A search of the literature for research articles related to piriformis syndrome and associated differential diagnosis of sciatica was conducted. A thorough review of the included articles found that the condition known as piriformis syndrome is over-diagnosed and that potential anatomic and biomechanical variations originating in the pelvic region might be related to the complaint of sciatica. The criteria for diagnosis are based on findings from both physical examination and radio imaging. Piriformis syndrome resembles a variety of clinical conditions; therefore, conduct of future studies should include development of a validated method for evaluation as well as clinical criteria for diagnosis of piriformis syndrome.

17.
BMJ Open ; 13(9): e071658, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37699639

RESUMO

OBJECTIVES: The primary objective of our study was to evaluate the effectiveness of renal cell carcinoma (RCC) screening in renal transplant (RT) recipients. DESIGN: Single-centre retrospective study. SETTING AND PARTICIPANTS: 1998 RT recipients who underwent RT at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC) between 1 January 1999 and 31 December 2019 were included and we identified 16 patients (0.8%) with RCC. An additional four patients with RCC who underwent RT elsewhere but received follow-up at MHH TMC were also included. Subject races included white (20%), black (50%), Hispanic (20%) and Asian (10%). OUTCOME MEASURES: The RCC stage at diagnosis and outcomes were compared between patients who were screening versus those who were not. RESULTS: We identified a total of 20 patients with post-RT RCC, 75% of whom were men. The median age at diagnosis was 56 years. RCC histologies included clear cell (75%), papillary (20%) and chromophobe (5%). Patients with post-RT RCC who had screening (n=12) underwent ultrasound or CT annually or every 2 years, whereas eight patients had no screening. All 12 patients who had screening had early-stage disease at diagnosis (stage I (n=11) or stage II (n=1)) and were cured by nephrectomy (n=10) or cryotherapy (n=2). In patients who had no screening, three (37.5%) had stage IV RCC at diagnosis and all of whom died of metastatic disease. There was a statistically significant difference in RCC-specific survival in patients who were screened (p=0.01) compared with those who were not screened. CONCLUSION: All RT recipients who had RCC diagnosed based on screening had early-stage disease and there were no RCC-related deaths. Screening is an effective intervention in RT recipients to reduce RCC-related mortality.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Transplante de Rim , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Carcinoma de Células Renais/diagnóstico , Estudos Retrospectivos , Rim , Neoplasias Renais/diagnóstico
18.
Biomed Pharmacother ; 167: 115512, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37725878

RESUMO

Sesamol is a lignan of sesame seeds and a natural phenolic molecule that has emerged as a useful medical agent. Sesamol is a non-toxic phytoconstituent, which exerts certain valuable effects in the management of cancer, diabetes, cardiovascular diseases, neurodegenerative diseases (NDs), etc. Sesamol is known to depict its neuroprotective role by various mechanisms, such as metabolic regulators, action on oxidative stress, neuroinflammation, etc. However, its poor oral bioavailability, rapid excretion (as conjugates), and susceptibility to gastric irritation/toxicity (particularly in rats' forestomach) may restrict its effectiveness. To overcome the associated limitations, novel drug delivery system-based formulations of sesamol are emerging and being researched extensively. These can conjugate with sesamol and enhance the bioavailability and solubility of free sesamol, along with delivery at the target site. In this review, we have summarized various research works highlighting the role of sesamol on various NDs, including Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Parkinson's disease. Moreover, the formulation strategies and neuroprotective role of sesamol-based nano-formulations have also been discussed.

19.
Biol Chem ; 393(7): 595-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22944663

RESUMO

Thymosin ß4 (Tß4) is a small, low-molecular-weight peptide ubiquitously expressed in all cells and extracellular fluids. It is a major actin sequestering protein present in the cells. In addition to this, Tß4 has also been shown to be involved in endothelial cell migration, angiogenesis, corneal wound healing, and stem cell differentiation. It is also released by platelets after activation. The amount of Tß4 increases at sites of injury and thus suggests an important role of this biopeptide in wound healing. Herein, we provide an overview of the role of Tß4 in thrombosis and platelet aggregation.


Assuntos
Plaquetas/fisiologia , Timosina/química , Timosina/metabolismo , Animais , Plaquetas/citologia , Humanos , Agregação Plaquetária , Transporte Proteico , Trombose
20.
Front Genet ; 13: 1061168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36704344

RESUMO

Flowering is a complex developmental process, with physiological and morphological phases influenced by a variety of external and internal factors. Interestingly, many mango cultivars tend to bear fruit biennially because of irregular flowering, and this has a negative impact on mango flowering and the subsequent yield, resulting in significant economic losses. In this article, transcriptome analysis was carried out on four tissues of mango cv. Dashehari (bearing tree leaf, shoot apex, inflorescence, and non-bearing tree leaf). De novo transcriptome assembly of RNA-seq reads of Dashehari using the Trinity pipeline generated 67,915 transcripts, with 25,776 genes identified. 85 flowering genes, represented by 179 transcripts, were differentially expressed in bearing vs. non-bearing leaf tissues. Gene set enrichment analysis of flowering genes identified significant upregulation of flowering related genes in inflorescence tissues compared to bearing leaf tissues. The flowering genes FT, CO, GI, ELF 4, FLD, FCA, AP1, LHY, and SCO1 were upregulated in the bearing leaf tissues. Pathway analysis of DEGs showed significant upregulation of phenylpropanoid and sucrose and starch pathways in non-bearing leaf tissue compared with bearing leaf tissue. The comparative transcriptome analysis performed in this study significantly increases the understanding of the molecular mechanisms driving the flowering process as well as alternative bearing in mango.

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