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1.
Nucl Med Commun ; 44(7): 653-662, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37038954

RESUMO

AIM OF WORK: To determine the predictive value of initial [ 18 F]FDG PET/computed tomography (CT) volumetric and radiomics-derived analyses in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Forty-six adult patients had pathologically proven HNSCC and underwent pretherapy [ 18 F]FDG PET/CT were enrolled. Semi-quantitative PET-derived volumetric [(maximum standardized uptake value (SUVmax) and mean SUV (SUVmean), total lesion glycolysis (TLG) and metabolic tumor volume (MTV)] and radiomics analyses using LIFEx 6.73.3 software were performed. RESULTS: In the current study group, the receiver operating characteristic curve marked a cutoff point of 21.105 for primary MTV with area under the curve (AUC) of 0.727, sensitivity of 62.5%, and specificity of 86.8% ( P value 0.041) to distinguish responders from non-responders, while no statistically significant primary SUVmean or max or primary TLG cut off points could be determined. It also marked the cutoff point for survival prediction of 10.845 for primary MTV with AUC 0.728, sensitivity of 80%, and specificity of 77.8% ( P value 0.026). A test of the synergistic performance of PET-derived volumetric and textural features significant parameters was conducted in an attempt to develop the most accurate and stable prediction model. Therefore, multivariate logistic regression analysis was performed to detect independent predictors of mortality. With a high specificity of 97.1% and an overall accuracy of 89.1%, the combination of primary tumor MTV and the textural feature gray-level co-occurrence matrix correlation provided the most accurate prediction of mortality ( P value < 0.001). CONCLUSION: Textural feature indices are a noninvasive method for capturing intra-tumoral heterogeneity. In our study, a PET-derived prediction model was successfully generated with high specificity and accuracy.


Assuntos
Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço , Adulto , Humanos , Fluordesoxiglucose F18/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Tomografia Computadorizada por Raios X , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Carga Tumoral , Estudos Retrospectivos , Compostos Radiofarmacêuticos
2.
Am J Physiol Gastrointest Liver Physiol ; 321(5): G461-G476, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34431405

RESUMO

Multiple theories have been proposed describing the pathogenic mechanisms of Helicobacter pylori (H. pylori)-associated gastric motility disorders. We assessed ex vivo pyloric activity in H. pylori-infected rats, and tried to explore the associated ghrelin hormone alteration and pyloric fibrogenesis. In addition, miR-1 was assessed in pyloric tissue samples, being recently accused of having a role in smooth muscle dysfunction. Ninety adult male Wistar albino rats were assigned into nine groups: 1) control group, 2) sterile broth (vehicle group), 3) amoxicillin control, 4) omeperazole control, 5) clarithromycin control, 6) triple therapy control, 7) H. pylori- group, 8) H. pylori-clarithromycin group, and 9) H. pylori-triple therapy group. Urease enzyme activity was applied as an indicator of H. pylori infection. Ex vivo pyloric contractility was evaluated. Serum ghrelin was assessed, and histological tissue evaluation was performed. Besides, pyloric muscle miR-1 expression was measured. The immunological epithelial to mesenchymal transition (EMT) markers; transforming growth factor ß (TGFß), α-smooth muscle actin (α-SMA), and E-cadherin-3 were also evaluated. By H. pylori infection, a significant (P < 0.001) reduced pyloric contractility index was recorded. The miR-1 expression was decreased (P < 0.001) in the H. pylori-infected group, associated with reduced serum ghrelin, elevated TGFß, and α-SMA levels and reduced E-cadherin levels. Decreased miR-1 and disturbed molecular pattern were improved by treatment. In conclusion, H. pylori infection was associated with reduced miR-1, epithelial to mesenchymal transition, and pyloric hypomotility. The miR-1 may be a target for further studies to assess its possible involvement in H. pylori-associated pyloric dysfunction, which might help in the management of human H. pylori manifestations and complications.NEW & NOTEWORTHY This work is investigating functional, histopathological, and molecular changes underlying Helicobacter pylori hypomotility and is correlating these with miR-1, whose disturbance is supposed to be involved in smooth muscle dysfunction and cell proliferation according to literature. Epithelial to mesenchymal transition and reduced ghrelin hormone may contribute to H. pylori infection-associated hypomotility. H. pylori infection was associated with reduced pyloric miR-1 expression. Targeting miR-1 could be valuable in the clinical management of pyloric hypofunction.


Assuntos
Transição Epitelial-Mesenquimal , Motilidade Gastrointestinal , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Músculo Liso/microbiologia , Piloro/microbiologia , Gastropatias/microbiologia , Actinas/metabolismo , Animais , Antibacterianos/farmacologia , Caderinas/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Grelina/sangue , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/fisiopatologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Músculo Liso/fisiopatologia , Inibidores da Bomba de Prótons/farmacologia , Piloro/efeitos dos fármacos , Piloro/metabolismo , Piloro/fisiopatologia , Ratos Wistar , Gastropatias/tratamento farmacológico , Gastropatias/metabolismo , Gastropatias/fisiopatologia , Fator de Crescimento Transformador beta/metabolismo
3.
J Psychopharmacol ; 33(5): 615-631, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30896354

RESUMO

BACKGROUND: The neuropathology of depression is quite complex. Thus, treatment failures are frequent with current antidepressants, raising the need for more effective ones. AIMS: This study aimed to investigate the influence of silymarin on depressive-like behavior induced by chronic unpredictable mild stress (CUMS) and explore the underlying mechanisms. METHODS: Silymarin was formulated as nanostructured lipid carriers (a lipid-based type of nanoparticle with the advantages of physical stability, good release profile, and targeted delivery). Mice were subjected to CUMS paradigm during 14 days. During this period, mice received silymarin (200 mg/kg, p.o.) per se or in its nanoparticle form or fluoxetine (10 mg/kg, p.o.). On the 15th day behavioral and biochemical parameters were analyzed. RESULTS: Oral administration of silymarin (200 mg/kg), particularly in its nanoparticulate form, exerted an antidepressant-like effect, comparable with fluoxetine in mice, as demonstrated in the behavioral despair tests. Silymarin also reversed prefrontal cortical and hippocampal CUMS-induced oxidative stress and neuroinflammation. Furthermore, silymarin augmented neurotransmitter levels, enhanced neurogenesis and inhibited nod-like receptor protein 3 inflammasome activation. Silymarin nanoparticles were superior to silymarin in certain parameters probably due to significantly higher brain silybinin (the major active component of silymarin) concentration by 12.46 fold in the group administered silymarin nanoparticles compared with the mice which were administered silymarin per se. CONCLUSIONS: The antidepressant-like effect of silymarin can be attributed to its antioxidant and anti-inflammatory effects as well as increased neurogenesis in the prefrontal cortex and hippocampus, which delineates silymarin, especially in nanoparticle form, as a promising strategy for treatment of depression.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Inflamassomos/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Nanopartículas/administração & dosagem , Neurogênese/efeitos dos fármacos , Silimarina/farmacocinética , Estresse Psicológico/complicações , Animais , Antidepressivos/administração & dosagem , Depressão/etiologia , Fluoxetina/farmacologia , Hipocampo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Silimarina/administração & dosagem
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