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1.
Artigo em Inglês | MEDLINE | ID: mdl-38564359

RESUMO

Medical multi-modal pre-training has revealed promise in computer-aided diagnosis by leveraging large-scale unlabeled datasets. However, existing methods based on masked autoencoders mainly rely on data-level reconstruction tasks, but lack high-level semantic information. Furthermore, two significant heterogeneity challenges hinder the transfer of pre-trained knowledge to downstream tasks, i.e., the distribution heterogeneity between pre-training data and downstream data, and the modality heterogeneity within downstream data. To address these challenges, we propose a Unified Medical Multi-modal Diagnostic (UMD) framework with tailored pre-training and downstream tuning strategies. Specifically, to enhance the representation abilities of vision and language encoders, we propose the Multi-level Reconstruction Pre-training (MR-Pretrain) strategy, including a feature-level and data-level reconstruction, which guides models to capture the semantic information from masked inputs of different modalities. Moreover, to tackle two kinds of heterogeneities during the downstream tuning, we present the heterogeneity-combat downstream tuning strategy, which consists of a Task-oriented Distribution Calibration (TD-Calib) and a Gradient-guided Modality Coordination (GM-Coord). In particular, TD-Calib fine-tunes the pre-trained model regarding the distribution of downstream datasets, and GM-Coord adjusts the gradient weights according to the dynamic optimization status of different modalities. Extensive experiments on five public medical datasets demonstrate the effectiveness of our UMD framework, which remarkably outperforms existing approaches on three kinds of downstream tasks.

2.
IEEE Trans Med Imaging ; 42(8): 2200-2210, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37027665

RESUMO

Semi-supervised learning (SSL) has demonstrated remarkable advances on medical image classification, by harvesting beneficial knowledge from abundant unlabeled samples. The pseudo labeling dominates current SSL approaches, however, it suffers from intrinsic biases within the process. In this paper, we retrospect the pseudo labeling and identify three hierarchical biases: perception bias, selection bias and confirmation bias, at feature extraction, pseudo label selection and momentum optimization stages, respectively. In this regard, we propose a HierArchical BIas miTigation (HABIT) framework to amend these biases, which consists of three customized modules including Mutual Reconciliation Network (MRNet), Recalibrated Feature Compensation (RFC) and Consistency-aware Momentum Heredity (CMH). Firstly, in the feature extraction, MRNet is devised to jointly utilize convolution and permutator-based paths with a mutual information transfer module to exchanges features and reconcile spatial perception bias for better representations. To address pseudo label selection bias, RFC adaptively recalibrates the strong and weak augmented distributions to be a rational discrepancy and augments features for minority categories to achieve the balanced training. Finally, in the momentum optimization stage, in order to reduce the confirmation bias, CMH models the consistency among different sample augmentations into network updating process to improve the dependability of the model. Extensive experiments on three semi-supervised medical image classification datasets demonstrate that HABIT mitigates three biases and achieves state-of-the-art performance. Our codes are available at https://github.com/CityU-AIM-Group/HABIT.


Assuntos
Aprendizado de Máquina Supervisionado , Viés , Movimento (Física)
3.
Virol J ; 20(1): 79, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37101205

RESUMO

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen, characterized by its genetic and antigenic variation. The PRRSV vaccine is widely used, however, the unsatisfied heterologic protection and the risk of reverse virulence raise the requirement to find some new anti-PRRSV strategies for disease control. Tylvalosin tartrate is used to inhibit PRRSV in the field non-specifically, however, the mechanism is still less known. METHODS: The antiviral effects of Tylvalosin tartrates from three producers were evaluated in a cell inoculation model. Their safety and efficacy concentrations, and effecting stage during PRRSV infection were analyzed. And, the Tylvalosin tartrates regulated genes and pathways which are potentially related to the anti-viral effect were further explored by using transcriptomics analysis. Last, the transcription level of six anti-virus-related DEGs was selected to confirm by qPCR, and the expression level of HMOX1, a reported anti-PRRSV gene, was proved by western blot. RESULTS: The safety concentrations of Tylvalosin tartrates from three different producers were 40 µg/mL (Tyl A, Tyl B, and Tyl C) in MARC-145 cells and 20 µg/mL (Tyl A) or 40 µg/mL (Tyl B and Tyl C) in primary pulmonary alveolar macrophages (PAMs) respectively. Tylvalosin tartrate can inhibit PRRSV proliferation in a dose-dependent manner, causing more than 90% proliferation reduction at 40 µg/mL. But it shows no virucidal effect, and only achieves the antiviral effect via long-term action on the cells during the PRRSV proliferation. Furthermore, GO terms and KEGG pathway analysis was carried out based on the RNA sequencing and transcriptomic data. It was found that the Tylvalosin tartrates can regulate the signal transduction, proteolysis, and oxidation-reduction process, as well as some pathways such as protein digestion and absorption, PI3K-Akt signaling, FoxO signaling, and Ferroptosis pathways, which might relate to PRRSV proliferation or host innate immune response, but further studies still need to confirm it. Among them, six antivirus-related genes HMOX1, ATF3, FTH1, FTL, NR4A1, and CDKN1A were identified to be regulated by Tylvalosin tartrate, and the increased expression level of HMOX1 was further confirmed by western blot. CONCLUSIONS: Tylvalosin tartrate can inhibit PRRSV proliferation in vitro in a dose-dependent manner. The identified DEGs and pathways in transcriptomic data will provide valuable clues for further exploring the host cell restriction factors or anti-PRRSV target.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Suínos , Animais , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Antivirais/farmacologia , Antivirais/metabolismo , Tartaratos/metabolismo , Tartaratos/farmacologia , Transcriptoma , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Macrófagos Alveolares , Replicação Viral
5.
IEEE Trans Med Imaging ; 41(10): 2953-2964, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35576425

RESUMO

Multi-modal Magnetic Resonance Imaging (MRI) can provide complementary information for automatic brain tumor segmentation, which is crucial for diagnosis and prognosis. While missing modality data is common in clinical practice and it can result in the collapse of most previous methods relying on complete modality data. Current state-of-the-art approaches cope with the situations of missing modalities by fusing multi-modal images and features to learn shared representations of tumor regions, which often ignore explicitly capturing the correlations among modalities and tumor regions. Inspired by the fact that modality information plays distinct roles to segment different tumor regions, we aim to explicitly exploit the correlations among various modality-specific information and tumor-specific knowledge for segmentation. To this end, we propose a Dual Disentanglement Network (D2-Net) for brain tumor segmentation with missing modalities, which consists of a modality disentanglement stage (MD-Stage) and a tumor-region disentanglement stage (TD-Stage). In the MD-Stage, a spatial-frequency joint modality contrastive learning scheme is designed to directly decouple the modality-specific information from MRI data. To decompose tumor-specific representations and extract discriminative holistic features, we propose an affinity-guided dense tumor-region knowledge distillation mechanism in the TD-Stage through aligning the features of a disentangled binary teacher network with a holistic student network. By explicitly discovering relations among modalities and tumor regions, our model can learn sufficient information for segmentation even if some modalities are missing. Extensive experiments on the public BraTS-2018 database demonstrate the superiority of our framework over state-of-the-art methods in missing modalities situations. Codes are available at https://github.com/CityU-AIM-Group/D2Net.


Assuntos
Neoplasias Encefálicas , Neoplasias Encefálicas/diagnóstico por imagem , Bases de Dados Factuais , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos
6.
PLoS One ; 16(11): e0260001, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34807927

RESUMO

OBJECTIVE: To compare the reliability of different methods for measuring fat content of pancreas by MR modified Dixon(mDixon) Sequence and accurately evaluate pancreatic fat in as simple a way as possible. METHODS: This is a retrospective study, 64 patients were included in this study who underwent abdominal MR scan that contained the mDixon sequence from June 2019 to May 2020(Included 7 patients with type 2 diabetes and 4 patients with impaired glucose tolerance (IGT), they were admitted to hospital through the obesity clinic set up by endocrine department, all of them were initially diagnosed and untreated). All of the 64 patients were scanned in 3.0T MR (Philips Ingenia II) due to their condition, 10-34 slice pancreas images were obtained, which were different from each other. Three different methods of measurement were employed by two observers using Philips Intellispace Portal software: (1) All images (whole-pancreas) measurement, the whole-pancreatic fat fraction (wPFF) was calculated by software. (2) Interval slices measurement, that is half-pancreatic slices fat fraction (hPFF) measured in the same way, fat fraction obtained by the interlayer assay was calculated. (3) As usual, the fat content of pancreatic head, body and tail fat was measured respectively, and in order to improve credibility, we also measured head、 body and tail in every layer, and its average value was taken. The elapsed time of the above different measurement methods was recorded. Intra-group correlation coefficient (ICC) was used to analyze the consistency of the measured data within and between observers. T-tests and Friedman tests were applied to compare the difference of measured values among groups. RESULTS: No matter in normal person or diabetic or IGT, hPFF has shown good stability (ICChPFF = 0.988), and there was no significant difference compared with wPFF. But the average fat percentage composition of head, body and tail were significantly different from wPFF and hPFF (P < 0.01). At the same time, compared with normal person, pancreatic fat content in IGT and diabetic patients showed progressive significance(P<0.05). CONCLUSION: The distribution of pancreatic fat is not uniform, the method of measuring half pancreas by interlayer data collection can reflect the fat content of the entire pancreas, this suggests that measuring 50% of the pancreas is sufficient, this method effectively saves time and effort without affecting the results, which may have a better clinical application prospect.


Assuntos
Adiposidade/fisiologia , Distribuição da Gordura Corporal/métodos , Processamento de Imagem Assistida por Computador/métodos , Pâncreas/metabolismo , Tecido Adiposo/metabolismo , Adulto , Feminino , Intolerância à Glucose/diagnóstico por imagem , Intolerância à Glucose/metabolismo , Hospitais , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Pancreatopatias/diagnóstico por imagem , Reprodutibilidade dos Testes , Projetos de Pesquisa , Estudos Retrospectivos
7.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209701

RESUMO

The present study aims to reveal the mechanism by which miR-430s regulate steroidogenesis in larval rice field eel Monopterus albus. To this end, M. albus embryos were respectively microinjected with miRNA-overexpressing mimics (agomir430a, agomir430b, and agomir430c) or miRNA-knockdown inhibitors (antagomir430a, antagomir430b, and antagomir430c). Transcriptome profiling of the larvae indicated that a total of more than 149 differentially expressed genes (DEGs) were identified among the eight treatments. Specifically, DEGs related to steroidogenesis, the GnRH signaling pathway, the erbB signaling pathway, the Wnt signaling pathway, and other pathways were characterized in the transcriptome. We found that steroidogenesis-related genes (hydroxysteroid 17-beta dehydrogenase 3 (17ß-hsdb3), hydroxysteroid 17-beta dehydrogenase 7 (17ß-hsdb7), hydroxysteroid 17-beta dehydrogenase 12 (17ß-hsdb12), and cytochrome P450 family 19 subfamily a (cyp19a1b)) were significantly downregulated in miR-430 knockdown groups. The differential expressions of miR-430 in three gonads indicated different roles of three miR-430 (a, b, and c) isoforms in regulating steroidogenesis and sex differentiation. Mutation of the miR-430 sites reversed the downregulation of cytochrome P450 family 17 (cyp17), cyp19a1b, and forkhead box L2 (foxl2) reporter activities by miR-430, indicating that miR-430 directly interacted with cyp17, cyp19a1b, and foxl2 genes to inhibit their expressions. Combining these findings, we concluded that miR-430 regulated the steroidogenesis and the biosynthesis of steroid hormones by targeting cyp19a1b in larval M. albus. Our results provide a novel insight into steroidogenesis at the early stage of fish at the molecular level.


Assuntos
Vias Biossintéticas/genética , Peixes/genética , Peixes/metabolismo , Regulação da Expressão Gênica , MicroRNAs/genética , Esteroides/biossíntese , Regiões 3' não Traduzidas , Animais , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Família Multigênica , Transcriptoma
8.
Front Oncol ; 10: 538779, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194600

RESUMO

BACKGROUND: Asparaginase-associated pancreatitis (AAP) is one of the most common complications occurring in patients with asparaginase-treated acute lymphoblastic leukemia (ALL). Peg-asparaginase (peg-asp), a chemically recombined asparaginase with lower hyposensitivity and better patient tolerance, is now approved as the first line asparaginase formulation in ALL chemotherapy regimens. Due to the differences in pharmacokinetic characteristics and administration procedure between l-asp and peg-asp, this study aimed to investigate the clinical manifestations of peg-asp-associated pancreatitis. METHOD: Patients with peg-asp-associated pancreatitis diagnosed within a 5-year period (July 2014 to July 2019) were identified and retrospectively studied. The clinical manifestations, laboratory findings, and imaging results of patients with AAP were analyzed. AAP patients were further classified into mild/moderate and severe groups based on criteria used in previous studies. Clinical outcomes were compared between groups. RESULTS: A total of 38 patients were enrolled in this study. The underlying disease included ALL (n=35) and lymphoma (n=3). The majority of patients developed AAP during the first phase, called remission induction (n=26, 68.4%), after a median of 2 peg-asp doses (range: 1-11). The DVLP regimen (n=23) is the most common peg-asp regimen used in AAP patients. Abdominal pain occurred after a median of 14.5 days (range: 1-50) from the last peg-asp administration, accompanied by abdominal distension (n=14), nausea (n=17), vomiting (n=21), and fever (n=19). Serum amylase elevation was reported in all AAP patients, of whom 65.8% (n=25) exhibited an elevation in the level of this enzyme three times the upper normal level, fulfilling the Atlanta criteria. The level of serum lipase (median days of elevation=23 days, range: 4-75) was significantly elevated compared with that of serum amylase (median days of elevation=9 days, range: 2-71) and persisted at a markedly high level after the level of serum amylase returned to normal. Common local complications included abdominal ascites (n=10) and peripancreatic fluid collection (n=8). Approximately 42.1% (n=16) of patients with severe AAP experienced systemic complications (septic shock or hypovolemic shock) or severe local complications (pseudocyst), among whom 5 failed to recover. Approximately 84.8% (n=28/33) of the remaining patients resumed chemotherapy; among them, peg-asp formulation in 30.3% (n=10/33) of these patients was adjusted, while asparaginase treatment in 39.4% (n=13/33) was permanently discontinued. Five patients experienced an AAP relapse in later stages of asparaginase treatment. Comparison between mild/moderate and severe AAP patients showed a statistically significant difference in the number of pediatric intensive care unit stays (p=0.047), survival rate (p=0.009), AAP prognosis (p=0.047), and impacts on chemotherapy (p=0.024), revealing a better clinical outcome in mild/moderate AAP patients. CONCLUSION: Early recognition and management of AAP is essential in reversing the severity of AAP. The existing AAP criteria had a low strength in determining the severity of pediatric AAP. A well-defined AAP definition could help distinguish patients with high anticipated risk for redeveloping AAP and ALL relapse, in order to prevent unnecessary withdrawal of asparaginase. Our study could serve as a basis for conducting future large cohort studies and for establishing an accurate definition of pediatric AAP.

9.
Front Pharmacol ; 10: 242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941037

RESUMO

Agomelatine (AGO) is a new type of antidepressant with demonstrated antidepressant effects and a unique modulating circadian rhythm action. However, AGO has hepatotoxicity, which limits its clinical application. In order to develop new drugs that cause less liver injury than AGO, a series of derivatives were synthesized; compound GW117 was screened from derivatives due to its high receptor affinity. This study will investigate its sub-acute oral toxicity profile in rats in a sex-dependent manner. GW117 and AGO was administrated by gavage (200, 400, or 800 mg/kg/day) for 28 days. Hematological, biochemical tests, organ weights, histopathological examinations were carried out, the results showed that AGO and GW117 had adverse effects on platelet, liver and kidney, and had sex-differences in some indicators. Hematological tests showed that AGO and GW117 reduced the platelet count in male animals but had no effect in females. AGO increased plasma alanine aminotransferase (ALT) and total bilirubin in male animals, and GW117 had no effect on these two indicators. For females, AGO moderately elevated ALT, alkaline phosphatase (ALP), and total bilirubin, while GW117 only elevated ALP slightly. Two drugs could increase liver weight and coefficient, and cause liver pathological injury, including hepatic sinusoidal dilatation, hepatocyte fatty deposition and dotted cell necrosis in two genders. AGO caused mild to moderate hepatocyte and hepatobiliary injury in both genders, while only a mild hepatobiliary injury was caused by GW117 in females. Renal function tests showed that both drugs can increase blood urea nitrogen levels in males, while AGO, but not GW117, can slightly increase blood creatinine and urea nitrogen in females. The kidney weight and coefficient could be significantly increased by two drugs in males, and by AGO medium and GW117 high and low doses in females. The kidney pathological damage was mainly characterized by tubule dilatation, a thinning of the renal cortex. Kidney damage caused by GW117 was less than that of AGO, and there was no sex-difference. In summary, GW117 can cause mild liver and kidney damage in both genders, as well as mild platelets reduction in males, while degree of damage is less severe than AGO. Therefore, as an excellent derivative, GW117 deserves further development as an antidepressant.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(2): 439-444, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30998151

RESUMO

OBJECTIVE: To explore whether tumor suppressor gene Foxo1 and PTEN play a critical role in the tumorigenesis of mouse natural killer-cell lymphoma. METHODS: NKp46-iCre mice were crossed with mice carrying floxed Foxo1 alleles (Foxo1fl/fl) as well as floxed PTEN alleles (PTENfl/fl) to generate mice in which Foxo1 and PTEN in NK cells were knock-out, referred as Foxo1△NKPTEN△NK. The growth and development of the mice and tumor formation were observed. The flow cytometry was used to detect the percentages of NK cells in main lymphatic organs. B16F10 metanoma model of tumor metastasis was utilized to investigate NK cell-mediated tumor surveillance in vivo after NK cells special deletion of Foxol and PTEN. RESULTS: The mouse model with NK cell-special Foxo1 and PTEN double knockout was established. Compared with control group (Foxo1fl/flPTENfl/fl mice), Foxo1△NKPTEN△NK mice were born alive and appeared to be healthy over a period of 46 weeks. No spontaneous tumor formation was observed at this stage. There were no significant differences in NK cell percentages of gated lymphocytes from various organs including blood, bone marrow, peripheral lymph node and spleen between Foxo1△NKPTEN△NK mice and Foxo1fl/flPTENfl/fl mice [PB: 4.76%±0.46% vs 4.17%±0.64% (P>0.05, n=8); BM: 1.13%±0.23% vs 1.31%±0.10% (P>0.05, n=8) ; LN: 0.50%±0.10% vs 0.85%±0.20% (P>0.05, n=8); SP: 4.41%±0.65% vs 3.50%±0.24% (P>0.05, n=8)]. B16F10 melanoma metastasis model of tumor was established, No differences in median survival time were observed in the 2 types of mice (P>0.05, n=13). CONCLUSION: The simultaneous deletion of the Foxo1 and PTEN genes may not plays significant role in the tumorigenesis of mouse natural killer-cell lymphoma and NK cell-mediated tumor surveillance in vivo.


Assuntos
Genes Supressores de Tumor , Linfoma , Animais , Transformação Celular Neoplásica , Proteína Forkhead Box O1 , Células Matadoras Naturais , Camundongos , Camundongos Knockout
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(5): 1390-1396, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29070113

RESUMO

OBJECTIVE: To investigate the clinical characteristics, treatment and prognostic factors of patients with extranodal NK/T cell lymphoma. METHODS: The clinical data of patients with extranodal NK/T cell lymphoma admitted in the Hospital Affiliated to the Academy of Military Medical Science from June 2006 to June 2016 were retrospectively analyzed. The clinical features, therapeutic efficacy and prognosis-related factors were clarified. RESULTS: A total of 84 patients with extranodal NK/T cell lymphoma with complete clinical data were collected, with a median follow-up of 21 months (1-123 months), the overall survival (OS) and progression free survival (PFS) were 58.9% and 52.1% years, respectively. Univariate analysis showed that anemia, the copy number of EBV-DNA, LDH level, IPI score, ECOG score, Ann Arbor staging, complete remission after the initial therapy were statistically significant for both OS and PFS of the patients, and chemotherapy regimens were only statistically significant for PFS. Multivariate analysis showed that complete remission after the initial therapy, LDH level and ECOG score were statistically significant for both OS and PFS in patients with NK/T cell lymphoma. CONCLUSION: LDH level, ECOG score and complete remission after the initial therapy are independent prognostic factors for patients with extranodal NK/T cell lymphoma.


Assuntos
Linfoma Extranodal de Células T-NK/patologia , Intervalo Livre de Doença , Humanos , Linfoma Extranodal de Células T-NK/terapia , Prognóstico , Indução de Remissão , Estudos Retrospectivos
12.
Fish Physiol Biochem ; 43(4): 1081-1093, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28315160

RESUMO

Microcystin-LR (MCLR), one of the most popular microcystins (MCs) found in many field water bodies around the world, poses great health risks to animals and humans. In the present study, healthy common carp (initial weight 24.8 ± 2.3 g) were randomly assigned to five groups. Group I was fed on normal diet as control. Group II was maintained on normal diet and received MCLR intraperitoneal injection (150 µg kg-1 BW). Common carp in groups III, IV, and V were daily pretreated with L-carnitine (LC) at doses of 0.5, 1.0, and 2.0 g kg-1 of the diet for 4 weeks prior to MCLR intraperitoneal injection. The results showed that MCLR alone led to a significant downregulation in immune response, including serum complement C3, lysozyme, and bactericidal activity. However, oxidative stress response: catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and lipid peroxidation (LPO) levels were significantly increased. Similarly, gene expressions of inflammatory IL-1ß, TNF-α, IFN I, and heat shock proteins (HSP70 and HSP90) were also upregulated after challenged with MCLR. However, LC pretreated group caused a significant elevation in immune response (C3, lysozyme, and bactericidal activity) and gene expressions of inflammatory IL-1ß, TNF-α, IFN I, and heat shock proteins (HSP70 and HSP90) after MCLR stress. Antioxidant activities (CAT, SOD, GSH, GPx, and LPO) were returned to background levels at 96 h after MCLR challenge. Strikingly, LC supplementation at 2.0 g kg-1 has been considered the optimum for common carp since it exhibited enhancement of immune response and antioxidant activity over the level 0.5 and 1.0 g kg-1, and even better than that of control level. It was concluded that LC as a functional feed additive significantly inhibited the progression of MCLR-induced immunotoxicity and oxidative stress in common carp.


Assuntos
Ração Animal/análise , Carnitina/farmacologia , Carpas/fisiologia , Microcistinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Antioxidantes/metabolismo , Dieta/veterinária , Enzimas/metabolismo , Toxinas Marinhas
13.
Fish Shellfish Immunol ; 51: 365-372, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26945938

RESUMO

The present study was conducted to evaluate the effects of different L-alanyl-l-glutamine (Ala-Gln) feeding strategies on the growth performance, metabolism and crowding stress resistance related parameters in juvenile Jian carp (Cyprinus carpio var. Jian) under crowded condition (80 g/L). Juvenile Jian carp (initial weight 26.1 ± 0.6 g) were distributed into five groups which fed with graded concentrations (0% or 1.0%) of Ala-Gln for eight weeks. Control group (I, 0/0) fed with control diet (0% Ala-Gln) throughout the feeding trial. The other four groups employed different control and experimental diet feeding strategies ranging from two weeks control diet fed and two weeks experimental diet (1% Ala-Gln) fed (II, 0/2) to eight weeks experimental diet fed (V, 4/4). Results revealed that Mean weight gain (MEG) under all different feeding strategies of Ala-Gln were significantly higher than that of the control group (p < 0.05), and MEG of group II (201.90%) was even higher than that of group IV (184.70%). Liver glycogen and blood total protein of groups II, III and V were significantly higher than that in groups I and IV (p < 0.05). The highest level of serum thyroxine (10.07 ng/ml), insulin-like growth factor-I (52.40 ng/ml) and insulin (9.73 µ IU/mL) were observed in group V. However, diet supplemented with Ala-Gln did not affect the levels of serum glucose, cortisol and catecholamine in fish. The mRNA expression of GR1a, GR1b and GR2 were also significantly changed in Ala-Gln supplementation groups compared with control group (p < 0.05). After fish intraperitoneally injected with virulent Aeromonas hydrophila, the fish survival rates were significantly increased in all Ala-Gln supplementation groups compared with control group (p < 0.05). Results from the present experiment showed the importance of dietary supplementation of Ala-Gln in benefaction of the growth performance, metabolism and crowding stress resistance in Jian carp breeding. The optimal feeding strategy was alternatively fed with control diet and then experimental diet at an interval of two weeks for juvenile Jian carp under crowded condition.


Assuntos
Carpas/fisiologia , Dieta , Dipeptídeos/farmacologia , Animais , Aquicultura/métodos , Glicemia/análise , Catecolaminas/sangue , Aglomeração , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Glicogênio/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hidrocortisona/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/genética , Estresse Fisiológico
14.
Drug Deliv ; 23(6): 1955-61, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25816053

RESUMO

CONTEXT: Transporting drugs through the lymphatic system has attracted increasing attention. Lipid-based formulations have been proved to be an effective way to improve systemic bioavailability of highly lipophilic drugs by increasing intestinal lymphatic transport. OBJECTIVE: The formulation of polymer micelle was developed for probucol to improve its intestinal lymphatic transport. MATERIALS AND METHODS: Methoxy-polyethylenelglycol-distearyl phosphatidyl-ethanolamine (mPEG-DSPE) polymer was chosen to develop the micelles for probucol. The physicochemical properties were characterized. Caco-2 cell model, unconscious and conscious lymph duct cannulated rat models were established for in vitro and in vivo evaluation of lymphatic transport. RESULTS: In vitro evaluation in the Caco-2 cell model showed that the micellar formulation could significantly increase the uptake and transport of probucol. The study in unconscious and conscious lymph duct cannulated rat models further verified the significant enhancement of lymphatic transport of probucol by mPEG-DSPE micelles. DISCUSSION AND CONCLUSION: These results suggested that mPEG-DSPE micellar formulation could provide a useful alternative approach for improving the lymphatic transport of hydrophobic compounds.


Assuntos
Células CACO-2/química , Sistema Linfático/química , Sistema Linfático/efeitos dos fármacos , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Probucol/administração & dosagem , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2/metabolismo , Portadores de Fármacos , Humanos , Absorção Intestinal , Micelas , Fosfatidiletanolaminas/farmacocinética , Polietilenoglicóis/farmacocinética , Probucol/química , Probucol/farmacocinética , Ratos
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(3): 598-602, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22739163

RESUMO

This study was designed to compare the curative effect, prognosis and safety of different preconditioning regimens for patients who received autologous hematopoietic stem cell transplantation (AHSCT) for malignant lymphoma (ML). The clinical data of 100 ML patients (Sep 1992 to Aug 2010 in 307 Hospital) were retrospectively analyzed, and were divided into two groups by different preconditioning regimens: the high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group. The overall survival (OS) rate, progress free survival (PFS) rate and adverse effect were analyzed. The results showed that until Feb 2011, the median follow-up was 33.5 months. All patients were engrafted and their hematopoiesis was reconstituted. The median time of WBC recovery up to > 1.0×1.0(9)/L in high-dose chemotherapy preconditioning group and high-dose chemotherapy/radiotherapy preconditioning group were (6.0 ± 0.4) d and (8.2 ± 0.4) d, platelet up to > 20.0×1.0(9)/L in two groups were (7.1 ± 0.8) d and (11.4 ± 2.5) d (P < 0.05). The 3-year OS rate of the two groups were 67.3% and 68.9%. 5-year OS rates of two groups were 62.8% and 60.6%, 10-year OS rates of two groups were 57.6% and 56.2% respectively; 3-year PFS of two group were 63.6% and 63.2%, 5-year of two group were 59.4% and 58.3%, 10-year of two group were 50.8% and 55.3% respectively (P > 0.05). Meanwhile, the incidence of fever, infection, bleeding, secondary cancer between two groups was not significant different (P > 0.05). It is concluded that the hematopoietic reconstitution of high-dose chemotherapy/radiotherapy preconditioning group is later than that of high-dose chemotherapy preconditioning group. However, there is no significant difference in curative effect and prognosis between the two groups.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Criança , Terapia Combinada , Feminino , Humanos , Linfoma/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Autólogo , Adulto Jovem
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