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1.
Front Comput Neurosci ; 18: 1391025, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38634017

RESUMO

According to experts in neurology, brain tumours pose a serious risk to human health. The clinical identification and treatment of brain tumours rely heavily on accurate segmentation. The varied sizes, forms, and locations of brain tumours make accurate automated segmentation a formidable obstacle in the field of neuroscience. U-Net, with its computational intelligence and concise design, has lately been the go-to model for fixing medical picture segmentation issues. Problems with restricted local receptive fields, lost spatial information, and inadequate contextual information are still plaguing artificial intelligence. A convolutional neural network (CNN) and a Mel-spectrogram are the basis of this cough recognition technique. First, we combine the voice in a variety of intricate settings and improve the audio data. After that, we preprocess the data to make sure its length is consistent and create a Mel-spectrogram out of it. A novel model for brain tumor segmentation (BTS), Intelligence Cascade U-Net (ICU-Net), is proposed to address these issues. It is built on dynamic convolution and uses a non-local attention mechanism. In order to reconstruct more detailed spatial information on brain tumours, the principal design is a two-stage cascade of 3DU-Net. The paper's objective is to identify the best learnable parameters that will maximize the likelihood of the data. After the network's ability to gather long-distance dependencies for AI, Expectation-Maximization is applied to the cascade network's lateral connections, enabling it to leverage contextual data more effectively. Lastly, to enhance the network's ability to capture local characteristics, dynamic convolutions with local adaptive capabilities are used in place of the cascade network's standard convolutions. We compared our results to those of other typical methods and ran extensive testing utilising the publicly available BraTS 2019/2020 datasets. The suggested method performs well on tasks involving BTS, according to the experimental data. The Dice scores for tumor core (TC), complete tumor, and enhanced tumor segmentation BraTS 2019/2020 validation sets are 0.897/0.903, 0.826/0.828, and 0.781/0.786, respectively, indicating high performance in BTS.

2.
J Neurosci Methods ; 406: 110128, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38554787

RESUMO

BACKGROUND: In recent times, the expeditious expansion of Brain-Computer Interface (BCI) technology in neuroscience, which relies on electroencephalogram (EEG) signals associated with motor imagery, has yielded outcomes that rival conventional approaches, notably due to the triumph of deep learning. Nevertheless, the task of developing and training a comprehensive network to extract the underlying characteristics of motor imagining EEG data continues to pose challenges. NEW METHOD: This paper presents a multi-scale spatiotemporal self-attention (SA) network model that relies on an attention mechanism. This model aims to classify motor imagination EEG signals into four classes (left hand, right hand, foot, tongue/rest) by considering the temporal and spatial properties of EEG. It is employed to autonomously allocate greater weights to channels linked to motor activity and lesser weights to channels not related to movement, thus choosing the most suitable channels. Neuron utilises parallel multi-scale Temporal Convolutional Network (TCN) layers to extract feature information in the temporal domain at various scales, effectively eliminating temporal domain noise. RESULTS: The suggested model achieves accuracies of 79.26%, 85.90%, and 96.96% on the BCI competition datasets IV-2a, IV-2b, and HGD, respectively. COMPARISON WITH EXISTING METHODS: In terms of single-subject classification accuracy, this strategy demonstrates superior performance compared to existing methods. CONCLUSION: The results indicate that the proposed strategy exhibits favourable performance, resilience, and transfer learning capabilities.


Assuntos
Interfaces Cérebro-Computador , Eletroencefalografia , Imaginação , Humanos , Eletroencefalografia/métodos , Imaginação/fisiologia , Atenção/fisiologia , Redes Neurais de Computação , Atividade Motora/fisiologia , Encéfalo/fisiologia , Movimento/fisiologia , Processamento de Sinais Assistido por Computador
3.
Diabetes Metab Syndr ; 16(9): 102591, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35995030

RESUMO

BACKGROUND AND AIM: The insulin resistance-mediated abnormal gluconeogenesis when exceeds a given threshold culminates in type 2 diabetes mellitus (T2DM). This induces severe cellular oxidative stress that may eventually facilitate typical neoplastic transformations. This narrative review aims to portray some of the plausible key mechanistic links bridging T2DM and specific cancers. METHODS: A thorough literature search was conducted in the PubMedCentral database to retrieve information from various reputed biomedical reports/articles published from the year 2000. The information regarding the key biochemical signaling pathways mediating the carcinogenic transformation, especially in T2DM patients, was extensively excavated to systematically compile and present a narrative review. RESULTS: T2DM-associated insulin resistance is known to negatively influence certain crucial genetic and metabolic components (such as insulin/IGFs, PI-3K/Akt, AMPK, and AGEs/RAGE) that may eventually lead to neoplastic transformation. In particular, the risk of developing cancers like pancreatic, colorectal, breast, liver, endometrial, and bladder seems to be more significant in T2DM patients. CONCLUSION: Despite the fact that several studies have suggested a possible correlation between T2DM and cancer mortality, a more detailed research at both pre-clinical and clinical levels is still required so as to fully understand the intricate relationship and make a precise conclusion.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Neoplasias , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Insulina/metabolismo , Fosfatidilinositol 3-Quinases , Neoplasias/etiologia
4.
Life Sci ; 271: 119182, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33577851

RESUMO

Glitazones are synthetic derivatives of thiazolidinedione, and are designated as oral anti-diabetic agents, primarily acting on peroxisome proliferator-activated receptor-gamma (PPAR-γ) receptors and driving some crucial metabolic pathways linked to glucose and lipid metabolism at transcriptional level. Despite presenting adverse effects, including weight gain, fluid retention, prostate hyperplasia, hyperinsulinemia, and myocardial infarction, they are still preferred in clinical settings due to their utmost efficacy and selectivity. However, these complications kept glitazones restrained for long-term usage. The present review briefly highlights some important synthetic derivatives of thiazolidine2,4-dione and emphasizes the influence of various structural manipulations on their bio-efficacy.


Assuntos
Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Tiazolidinedionas/química , Tiazolidinedionas/metabolismo , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucose/antagonistas & inibidores , Glucose/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Resistência à Insulina/fisiologia , PPAR gama/metabolismo , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Tiazolidinedionas/uso terapêutico
6.
Nutr Metab (Lond) ; 14: 72, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29176994

RESUMO

Background: Black pepper or Piper nigrum is a well-known spice, rich in a variety of bioactive compounds, and widely used in many cuisines across the world. In the Indian traditional systems of medicine, it is used to treat gastric and respiratory ailments. The purpose of this investigation is to study the antihyperlipidemic and antiobesity effects of piperonal in high-fat diet (HFD)-induced obese rats. Methods: Piperonal, an active constituent of Piper nigrum seeds, was isolated and confirmed by HPLC, 1H and 13C NMR spectroscopy. Male SD rats were fed on HFD for 22 weeks; Piperonal was supplemented from the 16th week as mentioned in the experimental design. Changes in body weight and body composition were measured by TOBEC, bone mineral composition and density were measured by DXA, and adipose tissue distribution was measured by 7 T-MRI. Plasma levels of glucose, insulin, insulin resistance and lipid profiles of plasma, liver and kidney, adipocyte hormones and liver antioxidants were evaluated using standard kit methods. Expression levels of adipogenic and lipogenic genes, such as PPAR-γ, FAS, Fab-4, UCP-2, SREBP-1c, ACC, HMG-COA and TNF-α were measured by RT-PCR. Histopathological examination of adipose and liver tissues was also carried out in experimental rats. Results: HFD substantially induced body weight, fat%, adipocyte size, circulatory and tissue lipid profiles. It elevated the plasma levels of insulin, insulin resistance and leptin but decreased the levels of adiponectin, BMC and BMD. Increased expression of PPAR-γ, FAS, Fab-4, UCP-2, SREBP-1c, ACC, and TNF-α was noticed in HFD-fed rats. However, supplementation of piperonal (20, 30 and 40 mg/kg b.wt) for 42 days considerably and dose-dependently attenuated the HFD-induced alterations, with the maximum therapeutic activity being noticed at 40 mg/kg b.wt. Conclusions: Piperonal significantly attenuated HFD-induced body weight and biochemical changes through modulation of key lipid metabolizing and obesogenic genes. Our findings demonstrate the efficacy of piperonal as a potent antiobesity agent, provide scientific evidence for its traditional use and suggest the possible mechanism of action.

7.
Org Biomol Chem ; 11(29): 4778-91, 2013 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-23778751

RESUMO

Novel quinazolinone based α-glucosidase inhibitors have been developed. For this purpose a virtual screening model has been generated and validated utilizing acarbose as a α-glucosidase inhibitor. Homology modeling, docking, and virtual screening were successfully employed to discover a set of structurally diverse compounds active against α-glucosidase. A search of a 3D database containing 22,500 small molecules using the structure based virtual model yielded ten possible candidates. All ten candidates were N-3-pyridyl-2-cyclopropyl quinazolinone-4-one derivatives, varying at the 6 position. This position was modified by Suzuki-Miyaura cross coupling with aryl, heteroaryl, and alkyl boronic acids. A catalyst screen was performed, and using the best optimal conditions, a series of twenty five compounds was synthesized. Notably, the C-C cross coupling reactions of the 6-bromo-2-cyclopropyl-3-(pyridyl-3-ylmethyl)quinazolin-4(3H)-one precursor have been accomplished at room temperature. A comparison of the relative reactivities of 6-bromo and 6-chloro-2,3-disubstituted quinazolinones with phenyl boronic acid was conducted. An investigation of pre-catalyst loading for the reaction of the 6-bromo-2-cyclopropyl-3-(pyridyl-3-ylmethyl)quinazolin-4(3H)-one substrate was also carried out. Finally, we submitted our compounds to biological assays against α-glucosidase inhibitors. Of these, three hits (compounds 4a, 4t and 4r) were potentially active as α-glucosidase inhibitors and showed activity with IC50 values <20 µM. Based on structural novelty and desirable drug-like properties, 4a was selected for structure-activity relationship study, and thirteen analogs were synthesized. Nine out of thirteen analogs acted as α-glucosidase inhibitors with IC50 values <10 µM. These lead compounds have desirable physicochemical properties and are excellent candidates for further optimization.


Assuntos
Inibidores Enzimáticos/farmacologia , Inibidores de Glicosídeo Hidrolases , Quinazolinonas/farmacologia , Temperatura , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estrutura Molecular , Quinazolinonas/síntese química , Quinazolinonas/química , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo
8.
Bioorg Med Chem ; 14(8): 2545-51, 2006 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-16337386

RESUMO

A series of four naturally occurring homoisoflavonoids and eight analogs have been synthesized starting from an appropriately substituted phenol through chroman-4-one, in four steps. The products were assigned as E-isomers based on NMR spectroscopic data. The E-isomers were converted into Z-isomers by photoisomerization. The E- and Z-isomers showed distinct chemical shifts and the differences between (E) and (Z)-homoisoflavonoids in the proton NMR spectra afford a useful method for ascertaining the stereochemistry. The antioxidant activity of homoisoflavonoids was determined by superoxide (NBT) and DPPH free radical scavenging methods. The analog 7-hydroxy-3-[(3,4,5-trihydroxyphenyl)methylene]chroman-4-one displayed excellent activity followed by sappanone A in both the methods and were several times potent than the commercial antioxidants like BHA, BHT, etc. These compounds were evaluated in vitro for their inhibitory activities against 5-lipoxygenase (5-LOX) enzyme. The analog 7-hydroxy-3-[(N,N-dimethylaminophenyl)methylene]chroman-4-one was found to possess potent inhibitory activity and was comparable to that of the standard, nordihydroguiaretic acid. These results suggest that these homoisoflavonoids, with their potent antioxidant and 5-LOX inhibitory activities, may have useful applications as antioxidants and lead compounds for asthma and inflammatory diseases.


Assuntos
Antioxidantes/síntese química , Antioxidantes/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Flavonoides/síntese química , Flavonoides/farmacologia , Antioxidantes/química , Inibidores Enzimáticos/química , Flavonoides/química , Inibidores de Lipoxigenase , Espectroscopia de Ressonância Magnética , Estereoisomerismo
9.
Chem Pharm Bull (Tokyo) ; 51(12): 1374-6, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14646312

RESUMO

Phytochemical investigation of the whole plant of Andrographis viscosula has led to the isolation of three new 2'-oxygenated flavonoids, (2R)-5-hydroxy-7,2',3'-trimethoxyflavanone (1), 7,2',5'-trimethoxyflavone (2), 5,7,2',3'-tetramethoxyflavone (3), and eight known flavones, 5,7,2'-trimethoxyflavone (4), 5,7,2',4',5'-pentamethoxyflavone (5), echioidinin (6), 5,2',6'-trihydroxy-7-methoxyflavone (7), 5-hydroxy-7,2'-dimethoxyflavone (8), echioidin (9), echioidinin 5-O-glucoside (10), and 5,2',6'-trihydroxy-7-methoxyflavone 2'-O-glucoside (11). The structures of 1-11 were elucidated by physical and spectral methods, including extensive 2D NMR studies. The presence of 2'-oxygenated flavonoids is apparently restricted to Andrographis species in Acanthaceae. Therefore, 2'-oxygenated flavonoids are regarded as chemotaxonomic markers of Andrographis genus in the Acanthaceae family.


Assuntos
Andrographis , Flavonoides/química , Flavonoides/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Estruturas Vegetais
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