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1.
Cancer Epidemiol ; 73: 101966, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34146915

RESUMO

BACKGROUND: Observational studies have examined the association between fatty acid intake and breast cancer (BC), and the association might vary depending on menopausal status, but the results remain controversial. The objective of this study was to investigate the associations between fatty acid intake and BC. METHODS: The National Health and Nutrition Examination Survey (NHANES) 1999-2016 was used in the study, and stratified analysis by menopausal status was performed. Logistic regression models were used to evaluate the associations between BC and intake of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs), adjusting for covariates. Three two-sample Mendelian randomization (MR) methods-inverse variance weighted (IVW), weighted median, and Mendelian randomization-Egger (MR-Egger) regression-were applied to further verify the associations between intake of fatty acids and BC. RESULTS: Higher intake of MUFAs was associated with lower risk of BC in premenopausal women: ORs (95 %CI): 0.325 (0.110, 0.964). IVW showed that increased intake of MUFAs was associated with a reduced risk of BC: 0.997 (0.995, 1.000), p = 0.024. No associations between BC and SFAs, MUFAs or PUFAs were found in postmenopausal women or in the overall population. CONCLUSIONS: Increasing intake of MUFAs might reduce the risk of BC in premenopausal women. The protective effect of MUFAs on BC was also supported by MR study.

2.
J Affect Disord ; 292: 30-35, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34091380

RESUMO

OBJECTIVE: Depression is one of the leading causes of disability burden and frequently co-occurs with multiple chronic diseases, but limited research has yet evaluated the correlation between multimorbidity and depression status by sex and age. METHODS: 29303 adults from 2005-2016 National Health and Nutrition Examination Survey were involved in the study. The validated Patient Health Questionnaire (PHQ-9) was used to assess depression status. The linear trend of the prevalence of multimorbidity was tested by logistic regressions, which was visualized by the weighted network. Gamma coefficient (γ) was used to evaluate the correlation between multimorbidity and depression status. RESULTS: The prevalence of multimorbidity in participants with no depression, mild depression, moderate depression and severe depression was 52.1%, 63.0%, 68.4% and 76.1%, respectively (p for trend < 0.001). In network analysis, the absolute network density increased with the levels of depression status (from 4.54 to 15.04). Positive correlation was identified between multimorbidity and depression status (γ=0.21, p<0.001), and the correlation was different by sex and age, where it was stronger in women than men (females: γ=0.23, males: γ=0.16), and stronger in the young and the middle-age (young: γ=0.30, middle-age: γ=0.29, old: γ=0.22). LIMITATIONS: This is a cross-sectional study and thus we cannot draw firm conclusions on causal correlations. CONCLUSIONS: Positive correlation between multimorbidity and depression status was identified, where the number of multimorbidity increased with the levels of depression status, especially in females, the young and the middle-age.

3.
Adv Clin Exp Med ; 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34118139

RESUMO

BACKGROUND: Gallbladder cancer (GBC) is one of the common malignant tumors of the biliary tract. There is no report that miR-197 is involved in GBC. OBJECTIVES: The relationship between miR-197 expression and survival time of GBC patients was analyzed. Furthermore, the role and mechanism of miR-197 in GBC was explored. MATERIAL AND METHODS: A total of 39 GBC patients (21 males, 18 females; average age 56.1 ±8.5 years) were included from December 2013 to November 2014. All patients were admitted to our hospital for surgical treatment (excluding patients with preoperative chemotherapy). The expression of miR-197 in GBC tissues was examined, and the relationship between miR-197 and patient survival time was analyzed. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect cell proliferation. Flow cytometry and TUNEL staining were used to detect apoptosis. Expressions of proteins related with proliferation and apoptosis were detected. The target of miR-197 was predicted through bioinformatics website and verified using the dual luciferase reporter gene assay. The target gene was interfered to so that the effect of miR-197 on the regulation of GBC cell proliferation and apoptosis could be observed. RESULTS: MiR-197 was highly expressed in GBC tissues, and the expression was closely related to the poor prognosis of GBC. Downregulation of miR-197 inhibited the proliferation and promoted the apoptosis of GBC cells; it also decreased the expressions of proliferation-related proteins p-ERK1/2 and p-AKT, and increased that of apoptosis pathway-related proteins Bax/Bcl-2 and c-caspase-3. The upregulation of miR-197 induced an opposite trend. MiR-197 directly regulated IGFBP3. CONCLUSIONS: Our study proved that the expression of miR-197 is closely related to the poor prognosis of GBC. The miR-197-IGFBP3 axis regulates the proliferation and apoptosis of GBC cells. Downregulation of miR-197 inhibited the proliferation and promoted the apoptosis of GBC cells, indicating potential therapeutic effects.

4.
J Sci Food Agric ; 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33982308

RESUMO

BACKGROUND: Rice α-globulin has been reported to have serum cholesterol-lowering activity in rats. However, it is still unclear whether α-globulin exerts this effect when taken as one of the dietary components. In the present study, we investigated the effect of two cultivars of rice, low glutelin content (LGC)-1 and LGC-Jun, on reducing serum cholesterol in exogenously hypercholesterolemic (ExHC) rats. LGC-1 is enriched in α-globulin (10.6 mg g-1 rice flour, which is an approximately 1.5 times higher α-globulin content than in Koshihikari a predominant rice cultivar in Japan), whereas LGC-Jun is a globulin-negative cultivar. METHODS: ExHC rats, the model strain of diet-induced hypercholesterolemia, were fed 50% LGC-1 or LGC-Jun and 0.5% cholesterol-containing diets for 2 weeks, followed by measurement of cholesterol metabolism parameters in serum and tissues. RESULTS: Serum cholesterol and non-high-density lipoprotein cholesterol levels were significantly lower in the LGC-1 group compared to the LGC-Jun group. Cholesterol intestinal absorption markers, hepatic and serum levels of campesterol and ß-sitosterol, and lymphatic cholesterol transport were not different between the two groups. Levels of 7α-hydroxycholesterol, an intermediate of bile acid synthesis, showed a downward trend in the livers of rats that were fed LGC-1 (P = 0.098). There was a significant decrease in the hepatic mRNA expression of Cyp7a1 (a synthetic enzyme for 7α-hydroxycholesterol) in the LGC-1 group compared to the LGC-Jun group. CONCLUSION: Dietary LGC-1 significantly decreased serum cholesterol levels in ExHC rats. The possible mechanism for the cholesterol-lowering activity of LGC-1 is partial inhibition of bile acid and cholesterol synthesis in the liver. © 2021 Society of Chemical Industry.

5.
Int J Biol Macromol ; 181: 390-397, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33794237

RESUMO

This study focused on exploring the effects of damaged starch on glutinous rice flour properties and sweet dumpling qualities. Glutinous rice flours with different damaged starch contents (2-8%) and the same particle size were prepared through sifting and blending of semidry-milled and dry-milled rice flour. The increase of damaged starch content led to an increase in elastic modulus (G'), viscous modulus (G″) and agglomeration of starch granules, and a decrease in peak viscosity, breakdown value and enthalpy change (ΔH). Among all the samples, the rice flour batters with damaged starch content 3% and 4% were more stable and structured, and rice flours with damaged starch content 2% and 3% showed better pasting properties. As for the sweet dumpling qualities, compact structure, weak water mobility, less water loss, slight cracking and desirable cooking and texture properties were observed in the sweet dumplings made from rice flour with damaged starch content of less than 5%. All the results demonstrated that glutinous rice flour with damaged starch content of less than 5% had good flour properties and was suitable for the production of sweet dumplings.

6.
Brain Res ; 1765: 147502, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33901488

RESUMO

In dynamic video target detection tasks, distractors may suddenly appear due to the dynamicity of the visual scene and the uncertainty of the visual information, strongly influencing participants' attention and target detection performance. Moreover, the neural mechanism that accounts for dynamic distractor processing remains unknown, which makes it difficult to compensate for in EEG-based video target detection. Here, cortical activities with high spatiotemporal resolution were reconstructed using the source localization method. The time-varying networks among important brain regions in different cognitive phases, including information integration, decision-making, and execution, were identified to investigate the neural mechanism of dynamic distractor processing. The experimental results indicated that dynamic distractors could induce a P3-like component. In addition, there was obvious asymmetry between the two hemispheres during video target detection. Specifically, the brain responses induced by dynamic distractors were weak and more concentrated in the left hemisphere during the information integration phase; left superior frontal gyrus activity related to preparation for the presence of distractors was critical, while the attention network and primary visual network, especially in the left visual pathway, were more active for dynamic targets during the decision-making phase. These findings provide guidance for designing an effective EEG-based model for dynamic video target detection.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33882010

RESUMO

Researchers seek help from machine learning methods to alleviate the enormous burden of reading radiological images for clinicians under the COVID- 19 pandemic. However, clinicians often feel reluctant to trust AI-based models because of its black-box characteristic and lack of proper explainability. This paper proposes an explainable attention transfer classification model based on the knowledge distillation network structure to automatically differentiate COVID-19, community acquired pneumonia (CAP) from healthy lungs with radiographic imaging. The proposed network structure can be divided into teacher network and student network based on the attention transfer direction. Firstly, the teacher network extracts global features and concentrates on the infection regions to generate attention maps. We propose a deformable attention module (DAM) to strengthen infection regions response and suppress noise in irrelevant regions with expanded reception field. Moreover, combining essential information in original input, attention knowledge transfers from teacher network to student network via an image fusion module. Trained with teacher network jointly, the student branch with weighted dense connectivity can focus on irregularly shaped lesion regions to learn discriminative features and improve network performance. Comprehensive experiments have been conducted on public chest X-ray and CT imaging datasets. The proposed architecture achieves state-of-art performance and improves the AI-based model's explainable ability by attention map, severity assessment, and prediction confidence.

8.
Thorac Cancer ; 12(7): 1106-1114, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33565277

RESUMO

BACKGROUND: ALK rearrangement is a very rare subset of squamous cell carcinoma (SCC) and one of the clinical features in patients is lack of data. Here, we report eight patients diagnosed with SCC of the lung harboring ALK rearrangement. METHODS: We collected primary NSCLC samples at the Beijing Chest Hospital between January 2012 and December 2018 for Ventana (D5F3) immunohistochemical detection. Among the 148 patients was diagnosed ALK-rearranged non small cell lung cancer (NSCLC), only eight cases was SCC. We collected patients information from electronic patent records (EPRs). RESULTS: The eight cases of SCC were diagnosed by immunohistochemistry (IHC). Two were given crizotinib as second-line therapy. One patient had stable disease (SD) and progression-free survival (PFS) of six months. The other patient had progressive disease (PD) but PFS was only one month. The side effects were tolerable. This report identified 31 cases of ALK rearrangement in SCC patients from a literature search (including the eight patients in this study). These fusion genes are often seen in a younger age group (mean age: 55.6 years) and non-smokers (18/31, 58.1%). A total of 20 cases received an ALK inhibitor as first- or second-line treatment which included 11 with a partial response (PR), four with SD, and five with PD. The DCR and ORR was 75.0% (15/20) and 55.0% (11/20), respectively. The median duration time of therapy was 6.4 ± 4.4 months. CONCLUSIONS: Patients with ALK-rearranged SCC obtained clinical benefit from ALK-inhibitor therapy, especially those who were non-smokers and whose tumors had been identified by IHC+/FISH+.

9.
Neuroscience ; 461: 44-56, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33607228

RESUMO

Emotion plays an important role in people's lives. However, the neural mechanism of affective perception is still unclear. In this study, steady-state visual evoked potentials (SSVEPs) were used to explore information processing speed and interactions among cortical structures involved in affective perception. Pleasant, unpleasant, and neutral pictures selected from the International Affective Picture System were presented either in intact or phase-scrambled form at a fixed frequency, where the induced SSVEPs could be used as a frequency marker of brain activity with high temporal resolution and signal-to-noise ratio. Source estimation methods were used to reconstruct the cortical signals. The information processing of affective images was studied by phase and causal connection analysis in the cortical space to investigate the information processing speed of the local brain region and the dynamic interactions across brain regions. Experimental results showed that affective and semantic perception was accompanied by the acceleration of information processing speed in the ventral pathway. Unpleasant emotions had the fastest information processing speed in the ventral stream compared with pleasant and neutral emotions, including the middle occipital gyrus and the middle temporal gyrus, with a right hemisphere bias. In addition, unpleasant emotions were stronger than pleasant emotions in long-term causal connections in the bilateral middle temporal gyrus, and the direction was from the right hemisphere to the left hemisphere. These results provide unique insights into the cortical activities for affective perception and support the view that unpleasant emotions have priority in information perception in the middle temporal gyrus compared with pleasant and neutral emotions, with a right hemisphere bias.


Assuntos
Eletroencefalografia , Potenciais Evocados Visuais , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Emoções , Humanos , Percepção , Estimulação Luminosa , Percepção Visual
10.
Sci Rep ; 11(1): 3254, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547343

RESUMO

Most current Alzheimer's disease (AD) and mild cognitive disorders (MCI) studies use single data modality to make predictions such as AD stages. The fusion of multiple data modalities can provide a holistic view of AD staging analysis. Thus, we use deep learning (DL) to integrally analyze imaging (magnetic resonance imaging (MRI)), genetic (single nucleotide polymorphisms (SNPs)), and clinical test data to classify patients into AD, MCI, and controls (CN). We use stacked denoising auto-encoders to extract features from clinical and genetic data, and use 3D-convolutional neural networks (CNNs) for imaging data. We also develop a novel data interpretation method to identify top-performing features learned by the deep-models with clustering and perturbation analysis. Using Alzheimer's disease neuroimaging initiative (ADNI) dataset, we demonstrate that deep models outperform shallow models, including support vector machines, decision trees, random forests, and k-nearest neighbors. In addition, we demonstrate that integrating multi-modality data outperforms single modality models in terms of accuracy, precision, recall, and meanF1 scores. Our models have identified hippocampus, amygdala brain areas, and the Rey Auditory Verbal Learning Test (RAVLT) as top distinguished features, which are consistent with the known AD literature.

11.
Radiother Oncol ; 157: 255-262, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33600871

RESUMO

PURPOSE: To describe the utilization pattern of head and neck (HN) surveillance imaging and explore the optimal strategy for radiologic "residual" lymph node (LN) surveillance following definitive (chemo)radiotherapy (RT/CRT) in human papillomavirus (HPV)+ oropharyngeal carcinoma (OPC). METHODS: All HPV+ OPC patients who completed RT/CRT from 2012 to 2015 were included. Schedule and rationale for post-treatment HN-CT/MRI were recorded. Imaging findings and oncologic outcomes were evaluated. RESULTS: A total of 1036 scans in 412 patients were reviewed: 414 scans for first post-treatment response assessment and 622 scans for the following reasons: follow-up of radiologic "residual" LN(s) (293 scans/175 patients); local symptoms (227/146); other (17/16); unknown (85/66). Rate of scans with "unstated" reason varied significantly among clinicians (3-28%, p < 0.001) and none of them yielded any positive imaging findings. First post-treatment scans identified 192 (47%) patients with radiologic "residual" LNs. Neck dissection (ND) was performed in 28 patients: 16 immediately (6/16 positive), 10 after one follow-up scan (2/10 positive), and 2 after 2nd follow-up scan (1/2 positive). Thirty patients had >2 consecutive follow-up scans at 2-3-month intervals, and none showed subsequent imaging progression or regional failure. CONCLUSIONS: Pattern of HN imaging utilization for surveillance varied significantly among clinicians. Imaging surveillance reduces the need for ND. However, routine HN-CT/MR surveillance without clinical symptoms/signs does not demonstrate proven value in identifying locoregional failure or toxicity. Radiologic "residual" LNs without adverse features are common. If two subsequent follow-up scans demonstrate stable/regressing radiologic "residual" LNs, clinical surveillance without further imaging appears to be safe in this population.


Assuntos
Carcinoma , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/terapia , Estudos Retrospectivos
12.
Oral Oncol ; 114: 105167, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33508706

RESUMO

BACKGROUND/OBJECTIVES: We evaluate the performance between the TNM-8 versus TNM-7 cN-classification and explore the relative prognostic contribution of radiologic extranodal extension (rENE) for HPV-negative oropharyngeal cancer (HPV-OPC). MATERIALS/METHODS: All HPV- OPC treated with IMRT between 2005 and 2016 were included. cENE was defined as unambiguous "fixation" of a neck mass or "skin involvement" on clinical examination. rENE was recorded by re-reviewing pre-treatment CT/MR. Disease-free survival (DFS) stratified by cENE or rENE were compared. Multivariable analyses (MVA) calculated the adjusted hazard ratio (aHR) for the separate cENE and rENE attributes and their combination. A refined cN-category incorporating both cENE and rENE parameters was proposed. The performance of the revision was compared to TNM-8 and TNM-7. RESULTS: Of 361 HPV- OPC, 97 were cN0 and 264 were cN+ with 48 cENE+ and 72 rENE+ respectively. Median follow-up was 5.4 years. The 3-year DFS was lower in cENE+ vs cENE-negative (cENE-) (23% vs 45%; aHR = 1.68, p = 0.008) and rENE+ vs rENE-negative (rENE-) patients (29% vs 45%; aHR = 1.44, p = 0.037). The cENE+/rENE+ subset had the worse DFS vs cENE-/rENE+ or cENE-/rENE- (24%/37%/46%, p = 0.005). We propose a refined cN-category wherein any cENE-/rENE+ case is reclassified one N-stratum higher while any cENE+ case remains cN3b. The stage schema with the refined N-categorization outperformed TNM-8, and both outperformed TNM-7. CONCLUSIONS: cENE and rENE are both prognostic but the cENE+/rENE+ subset has the worst outcome. The TNM-8 cN-categories improves outcome prediction compared to the TNM-7. Incorporation of rENE into TNM-8 cN-categories may further augment performance.

13.
J Xray Sci Technol ; 29(1): 91-109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33459686

RESUMO

The excessive radiation doses in the application of computed tomography (CT) technology pose a threat to the health of patients. However, applying a low radiation dose in CT can result in severe artifacts and noise in the captured images, thus affecting the diagnosis. Therefore, in this study, we investigate a dual residual convolution neural network (DRCNN) for low-dose CT (LDCT) imaging, whereby the CT images are reconstructed directly from the sinogram by integrating analytical domain transformations, thus reducing the loss of projection information. With this new framework, feature extraction is performed simultaneously on both the sinogram-domain sub-net and the image-domain sub-net, which utilize the residual shortcut networks and play a complementary role in suppressing the projection noise and reducing image error. This new DRCNN approach helps not only decrease the sinogram noise but also preserve significant structural information. The experimental results of simulated and real projection data demonstrate that our DRCNN achieve superior performance over other state-of-art methods in terms of visual inspection and quantitative metrics. For example, comparing with RED-CNN and DP-ResNet, the value of PSNR using our DRCNN is improved by nearly 3 dB and 1 dB, respectively.

14.
Pediatr Emerg Care ; 37(2): 123-125, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33512891

RESUMO

OBJECTIVES: To determine if boys with acute testicular torsion, a surgical emergency requiring prompt diagnosis and treatment to optimize salvage of the testicle, delayed presentation to a medical facility and experienced an extended duration of symptoms (DoS), and secondarily, a higher rate of orchiectomy, during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Single-center, descriptive retrospective chart review of boys presenting with acute testicular torsion from March 15, to May 4, 2020 ("during COVID-19" or group 2), as well as for the same time window in the 5-year period from 2015 to 2019 ("pre-COVID-19" or group 1). RESULTS: A total of 78 boys met inclusion criteria, group 1 (n = 57) and group 2 (n = 21). The mean age was 12.86 ± 2.63 (group 1) and 12.86 ± 2.13 (group 2). Mean DoS before presentation at a medical facility was 23.2 ± 35.0 hours in group 1 compared with 21.3 ± 29.7 hours in group 2 (P < 0.37). When DoS was broken down into acute (<24 hours) versus delayed (≥24 hours), 41 (71.9%) of 57 boys in group 1 and 16 (76.2%) of 21 boys in group 2 presented within less than 24 hours of symptom onset (P < 0.78). There was no difference in rate of orchiectomy between group 1 and group 2 (44.7% vs 25%, P < 0.17), respectively. CONCLUSIONS: Boys with acute testicular torsion in our catchment area did not delay presentation to a medical facility from March 15, to May 4, 2020, and did not subsequently undergo a higher rate of orchiectomy.


Assuntos
COVID-19/epidemiologia , Torção do Cordão Espermático/cirurgia , Adolescente , Criança , Serviço Hospitalar de Emergência , Humanos , Masculino , Orquiectomia/estatística & dados numéricos , Estudos Retrospectivos , SARS-CoV-2 , Torção do Cordão Espermático/diagnóstico , Torção do Cordão Espermático/epidemiologia , Testículo/cirurgia , Fatores de Tempo , Tempo para o Tratamento
15.
Thorac Cancer ; 12(3): 364-371, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33325119

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer which is the most frequently diagnosed malignancy in China. Colon cancer associated transcript 1 (CCAT1) acts as an oncogene in enhancing tumor progression. However, the effects of CCAT1 in NSCLC remain unclear. The purpose of this study was to explore the role of CCAT1 in NSCLC. METHODS: Wound healing and transwell assays were performed to measure cell migration. RT-qPCR was employed to calculate the mRNA level of CCAT1 and miR-490. RESULTS: High expression of CCAT1 was observed in NSCLC tissues and cells, with low expression of miR-490. CCAT1 promoted the proliferation and metastasis of H1299 and A549 cells, while miR-490 had the opposite effect. CCAT1 could specifically bind to miR-490 and regulate its expression. MiR-490 partially reversed the inhibitory effect of CCAT1 on cell proliferation and metastasis. CONCLUSIONS: The CCAT1/miR-490 molecular axis has been shown to be important for the treatment of NSCLC.

16.
Bioengineered ; 11(1): 1334-1349, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33200654

RESUMO

Regulatory mechanisms of microRNAs (miRNAs) in the development of intestinal sepsis are unclear. This study investigated the role of rno-miR-146b-5p in sepsis-induced intestinal injury. A rat sepsis model was created using the cecal ligation and puncture method. The expression profiles of miRNA and mRNA in sepsis rats were examined using miRNA and mRNA sequencing; rno-miR-146b was selected for further investigation. The mimics and inhibitors of rno-miR-146b-5p were transfected into IEC-6 cells and then with or without lipopolysaccharide (LPS) treatment, and the expressions of Kruppel-like factor 4 (Klf4) and Cyclin D2 (Ccnd2) were assessed by quantitative real-time transcriptase-polymerase chain reaction (qRT-PCR) and western blotting. Next, cell counting kit-8 assay was used to detect cell viability, and scratch wound healing assay was used to assess cell migration. In sepsis rat model, crypt cell proliferation was inhibited and crypt cell apoptosis was increased. Compared with the sham control, results of miRNA and mRNA sequencing showed that there were 17 miRNAs and 1617 mRNAs that were upregulated and 123 miRNAs and 1917 mRNAs that were downregulated in the sepsis model group. The network diagrams and qRT-PCR validation indicated that rno-miR-146b-5p may inhibit the expression of Klf4. By adjusting the expression of rno-miR-146b-5p in IEC-6 cells with or without LPS treatment, we found that increased expression of rno-miR-146b-5p inhibited cell proliferation and migration and inhibited the expression of Ccnd2. rno-miR-146b-5p may play a vital role in the development of sepsis intestinal injury through targeting Klf4 expression and affecting promoter activity of Ccnd2.

17.
Biomed Pharmacother ; 133: 110965, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33166766

RESUMO

Exploring key genes associated with non-small cell lung carcinoma (NSCLC) may lead to targeted therapies for NSCLC patients. The protein kinase MAP4K3 has been established as an important modulator of cell growth and autophagy in mammals. Herein, we investigated the somatic mutations and the expression pattern of MAP4K3 detected in NSCLC patients based on the TCGA database. Abnormal MAP4K3 expression and its somatic mutations are associated with the carcinogenesis and thereby becoming an attractive therapeutic target. Baicalein, a natural product, was determined to be the first-reported MAP4K3 binding ligand with its KD values of 6.47 µM measured by microscale thermophoresis. Subsequent in silico docking and mutation studies demonstrated that baicalein directly binds to MAP4K3, presumably to the substrate-binding pocket of this kinase domain, causing inactivity of MAP4K3. We further showed that baicalein could induce degradation of MAP4K3 through decreasing its stability and promoting the ubiquitin proteasome pathway. Degradation of MAP4K3 could cause dissociation of the transcription factor EB and 14-3-3 complex, enhance rapid transport of TFEB to the nucleus and trigger TFEB-dependent autophagy, resulting in lung cancer cells proliferation arrest. Knockdown of MAP4K3 expression by siRNA was sufficient to mimic baicalein-induced autophagy. Ectopic expression of the MAP4K3 protein resulted in significant resistance to baicalein-induced autophagy. Baicalein exhibited good tumor growth inhibition in a nude mouse model for human H1299 xenografts, which might be tightly related to its binding to MAP4K3 and degradation of MAP4K3. Our data provide novel mechanistic insights of baicalein/ MAP4K3/ mTORC1/ TFEB axis in regulating baicalein-induced autophagy in NSCLC, suggesting potential therapies for treatment of NSCLC.

18.
Phytochemistry ; 181: 112573, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33142148

RESUMO

Terpenes form a class of highly diverse natural products. The diversity of terpenes is created by terpene synthases. During the reaction, carbocation intermediates form and their rearrangement could lead to the formation of various products. Terpene synthases determine the final product profile by controlling the conformation of the intermediate or stabilizing the carbocation. Pinene synthase is a monoterpene synthase catalyzing the cyclization of geranyl pyrophosphate (GPP) to form pinene. Our study suggests that by mutating the aromatic residue F482 to Ala, Val, Ile and Thr, the enzyme can be converted to sabinene synthase, with more than 90% of its total terpene products becoming sabinene, which indicates the aromaticity of this residue is essential for stabilizing the pinyl carbocation. We also identified a mutation S491A that could cause an about 29% increase in the overall activity of the enzyme without altering its produce selectivity. Molecular dynamic simulation indicates this mutation could decrease the flexibility of the enzyme when it forms a complex with the pinyl carbocation. Our study suggests the active pocket of pinene synthase has a certain level of plasticity, making it relatively easy to change the product selectivity or overall activity. This property could have an important implication in the evolution of terpene synthases and thereby terpene diversity, as by changing a few residues an enzyme could synthesize a completely different terpene product in a significant amount, which allows selection to take place.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33132032

RESUMO

INTRODUCTION: Our previous study showed that high-fat diet inhibited the increase in nitric oxide and endothelial nitric oxide synthase expression in the aortic endothelium of rats exposed to hypoxia, and hypoxia plus a high-fat diet led to earlier and more severe vascular endothelial dysfunction (VED) than hypoxia alone. The purpose of the present study was to investigate the effects of L-arginine on high-fat diet-induced VED of rats in hypoxia. METHODS: Forty male Sprague-Dawley rats were randomly divided into 4 groups and treated with hypoxia (H group), hypoxia plus high-fat diet (H+HFD group), hypoxia plus L-arginine (H+L-Arg group), and hypoxia plus high-fat diet and L-arginine (H+HFD+L-Arg group) for 1 wk. Hypoxia was simulated in a hypobaric chamber with an altitude of 5000 m. Aortic morphology and endothelium-dependent vasorelaxation were used to assess VED. RESULTS: High-fat diet impaired vascular remodeling and reduced endothelium-dependent vasodilator response to acetylcholine in rats exposed to hypoxia, secondary to dysregulation of the nitric oxide pathway. L-arginine supplementation significantly increased plasma nitrates and nitrites and endothelial nitric oxide synthase mRNA levels and improved ultrastructural changes in aortic endothelium and endothelium-dependent vasodilator response. CONCLUSIONS: L-arginine prevents aortic ultrastructural changes and reverses VED induced by high-fat diet in rats exposed to hypoxia, which may have implications for VED induced by high-fat diet in high altitude dwellers.

20.
Laryngoscope ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002201

RESUMO

OBJECTIVES: To assess the prognostic value of pre-/post-radiotherapy (pre-/post-RT) radiologic lymph node (LN) features in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal carcinoma (OPC) patients treated with definitive (chemo-)RT. METHODS: Clinical node-positive OPCs treated from 2011 to 2015 were reviewed. Nodal features were reviewed by a radiologist on pre-/post-RT computed tomography (CTs). Univariable analysis calculated hazard ratio (HR) for regional failure (RF), distant metastasis (DM), and deaths. Multivariable analysis estimated adjusted HR (aHR) of significant nodal features identified in univariable analysis adjusting for confounders. RESULTS: Pre-RT CT was undertaken in 344 HPV-positive and 94 HPV-negative OPC patients, of whom 242 (70%) HPV-positive and 67 (71%) HPV-negative also had a post-RT CT. Median follow-up was 4.9 years. Pre-RT LN calcification (pre-RT_LN-cal) increased the risk of RF in HPV-negative (aHR: 5.3, P = .007) but not HPV-positive patients (P = .110). Pre-RT radiologic extranodal extension (pre-RT_rENE+) increased the risk of DM and death in both HPV-negative (DM: aHR 6.6, P < .001; death: aHR 2.1, both P = .019) and HPV-positive patients (DM: aHR 4.9; death: aHR 3.0, both P < .001). Increased risk of RF occured with < 20% post-RT LN size reduction in both HPV-negative (HR 6.0, P = .002) and HPV-positive cases (HR 3.0, P = .049). Post-RT_LN-cal did not affect RF, DM, or death regardless of tumor HPV status (all P > .05). CONCLUSION: Pre-RT_LN-cal is associated with higher RF risk in HPV-negative but not in HPV-positive patients. Pre-RT_rENE increases risk of DM and death regardless of tumor HPV status. Minimal post-RT LN size reduction (< 20%) increases risk of RF in both diseases. Post-RT_LN-cal + has no apparent influence on outcomes in either disease. LEVEL OF EVIDENCE: 4 (a single institution case-control series) Laryngoscope, 2020.

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