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1.
World Allergy Organ J ; 17(4): 100897, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38655570

RESUMEN

Background: A low-clean living environment (LCLE) can increase gut microbial diversity and prevent allergic diseases, whereas gut microbial dysbiosis is closely related to the pathogenesis of asthma. Our previous studies suggested that soil in the LCLE is a key factor in shaping intestinal microbiota. We aimed to explore whether sterilized soil intake as a prebiotic while being incubated with microbes in the air can attenuate mouse asthma inflammation by modifying gut microbiota. Methods: 16S rRNA gene sequencing was used to analyze the gut microbial composition, in combination with immune parameters measured in the lung and serum samples. Results: 16S rRNA gene sequencing results showed significant differences in the fecal microbiota composition between the test and control mice, with a higher abundance of Allobaculum, Alistipes, and Lachnospiraceae_UCG-001, which produce short-chain fatty acids and are beneficial for health in the test mice. Soil intake significantly downregulated the concentrations of IL-4 and IL-9 in serum and increased the expression of IFN-γ, which regulated the Th1/Th2 balance in the lung by polarizing the immune system toward Th1, alleviating ovalbumin-induced asthma inflammation. The effect of sensitization on gut microbiota was greater than that of air microbes and age together but weaker than that of soil. Conclusions: Soil intake effectively reduced the expression of inflammatory cytokines in asthmatic mice, possibly by promoting the growth of multiple beneficial bacteria. The results indicated that the development of soil-based prebiotic products might be used for allergic asthma management, and our study provides further evidence for the hygiene hypothesis.

2.
Brain Behav Immun ; 115: 179-190, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37848098

RESUMEN

The decline in gut microbial diversity in modern humans is closely associated with the rising prevalence of various diseases. It is imperative to investigate the underlying causes of gut microbial loss and restoring methods. Although the impact of non-perinatal antibiotic use on gut microbiota has been recognized, its intergenerational effects remain unexplored. Our previous research has highlighted soil in the farm environment as a key factor for gut microbiome health by restoring gut microbial diversity and balance. In this study, we investigated the intergenerational consequences of antibiotic exposure and the therapeutic potential of sterile soil. We treated C57BL/6 mice with vancomycin and streptomycin for 2 weeks continuously, followed by a 4-8 week withdrawal period before breeding. The process was repeated across 3 generations. Half of the mice in each generation received an oral sterile soil intervention. We assessed gut microbial diversity, anxiety behavior, microglial reactivity, and gut barrier integrity across generations. Antibiotic exposure led to a decrease in gut microbial diversity over generations, along with aggravated anxiety behavior, microgliosis, and altered intestinal tight junction protein expression. Oral sterile soil intervention restored gut microbial diversity in adult mice across generations, concomitantly rescuing abnormalities in behavior, microgliosis, and intestinal barrier integrity. In conclusion, this study simulated an important process of the progressive loss of gut microbiota diversity in modern humans and demonstrated the potential of sterile soil to reverse this process. This study provides a theoretical and experimental basis for research and interventions targeting multiple modern chronic diseases related to intestinal microorganisms.


Asunto(s)
Antibacterianos , Microbioma Gastrointestinal , Humanos , Animales , Ratones , Antibacterianos/farmacología , Suelo , Ratones Endogámicos C57BL
3.
Comput Struct Biotechnol J ; 21: 4432-4445, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37731598

RESUMEN

Highly transcribed noncoding elements (HTNEs) are critical noncoding elements with high levels of transcriptional capacity in particular cohorts involved in multiple cellular biological processes. Investigation of HTNEs with persistent aberrant expression in abnormal tissues could be of benefit in exploring their roles in disease occurrence and progression. Breast cancer is a highly heterogeneous disease for which early screening and prognosis are exceedingly crucial. In this study, we developed a HTNE identification framework to systematically investigate HTNE landscapes in breast cancer patients and identified over ten thousand HTNEs. The robustness and rationality of our framework were demonstrated via public datasets. We revealed that HTNEs had significant chromatin characteristics of enhancers and long noncoding RNAs (lncRNAs) and were significantly enriched with RNA-binding proteins as well as targeted by miRNAs. Further, HTNE-associated genes were significantly overexpressed and exhibited strong correlations with breast cancer. Ultimately, we explored the subtype-specific transcriptional processes associated with HTNEs and uncovered the HTNE signatures that could classify breast cancer subtypes based on the properties of hormone receptors. Our results highlight that the identified HTNEs as well as their associated genes play crucial roles in breast cancer progression and correlate with subtype-specific transcriptional processes of breast cancer.

4.
J Med Chem ; 66(18): 12678-12696, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37725577

RESUMEN

Eukaryotic translation initiation factors (eIFs) are highly expressed in cancer cells, especially eIF4E, the central regulatory node driving cancer cell growth and a potential target for anticancer drugs. eIF4E-targeting strategies primarily focus on inhibiting eIF4E synthesis, interfering with eIF4E/eIF4G interactions, and targeting eIF4E phosphorylation and peptide inhibitors. Although some small-molecule inhibitors are in clinical trials, no eIF4E inhibitors are available for clinical use. We provide an overview of the regulatory mechanisms of eIF4E and summarize the progress in developing and discovering eIF4E inhibitor strategies. We propose that interference with eIF4E/eIF4G interactions will provide a new perspective for the design of eIF4E inhibitors and may be a preferred strategy.

5.
Adv Sci (Weinh) ; 10(28): e2301852, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37552043

RESUMEN

Despite the development of advanced technologies for interventional coronary reperfusion after myocardial infarction, a substantial number of patients experience high mortality due to myocardial ischemia-reperfusion (MI/R) injury. An in-depth understanding of the mechanisms underlying MI/R injury can provide crucial strategies for mitigating myocardial damage and improving patient survival. Here, it is discovered that the 4-hydroxy-2-nonenal (4-HNE) accumulates during MI/R, accompanied by high rates of myocardial ferroptosis. The loss-of-function of aldehyde dehydrogenase 2 (ALDH2), which dissipates 4-HNE, aggravates myocardial ferroptosis, whereas the activation of ALDH2 mitigates ferroptosis. Mechanistically, 4-HNE targets glutathione peroxidase 4 (GPX4) for K48-linked polyubiquitin-related degradation, which 4-HNE-GPX4 axis commits to myocyte ferroptosis and forms a positive feedback circuit. 4-HNE blocks the interaction between GPX4 and ovarian tumor (OTU) deubiquitinase 5 (OTUD5) by directly carbonylating their cysteine residues at C93 of GPX4 and C247 of OTUD5, identifying OTUD5 as the novel deubiquitinase for GPX4. Consequently, the elevation of OTUD5 deubiquitinates and stabilizes GPX4 to reverse 4-HNE-induced ferroptosis and alleviate MI/R injury. The data unravel the mechanism of 4-HNE in GPX4-dependent ferroptosis and identify OTUD5 as a novel therapeutic target for the treatment of MI/R injury.

6.
Cancers (Basel) ; 15(8)2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37190266

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide, and the pronounced intra- and inter-tumor heterogeneity restricts clinical benefits. Dissecting molecular heterogeneity in HCC is commonly explored by endoscopic biopsy or surgical forceps, but invasive tissue sampling and possible complications limit the broadeer adoption. The radiomics framework is a promising non-invasive strategy for tumor heterogeneity decoding, and the linkage between radiomics and immuno-oncological characteristics is worth further in-depth study. In this study, we extracted multi-view imaging features from contrast-enhanced CT (CE-CT) scans of HCC patients, followed by developing a fused imaging feature subtyping (FIFS) model to identify two distinct radiomics subtypes. We observed two subtypes of patients with distinct texture-dominated radiomics profiles and prognostic outcomes, and the radiomics subtype identified by FIFS model was an independent prognostic factor. The heterogeneity was mainly attributed to inflammatory pathway activity and the tumor immune microenvironment. The predominant radiogenomics association was identified between texture-related features and immune-related pathways by integrating network analysis, and was validated in two independent cohorts. Collectively, this work described the close connections between multi-view radiomics features and immuno-oncological characteristics in HCC, and our integrative radiogenomics analysis strategy may provide clues to non-invasive inflammation-based risk stratification.

7.
Folia Microbiol (Praha) ; 68(1): 115-120, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35976485

RESUMEN

A Gram stain-positive, rod-shaped, motile, aerobic and terminal endospore formation bacterium, designated YIM B00362T, was isolated from saline soil samples collected from a salt lake in Xinjiang Province, north-west China. Phylogenetic analysis based on the 16S rRNA gene sequences and whole genomes indicated that the isolate belongs to the genus Paenibacillus. However, the highest sequence similarity between strain YIM B00362T and the relatives was only 94.4%. Moreover, the DNA-DNA relatedness and ANI values between the novel isolate and the relative type strain, Paenibacillus antri SYSU K30003T was 13.6% and 70.3%, respectively. The major cellular fatty acids were anteiso-C15:0, C16:0 and the major quinone was MK-7. The isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylglyceride, and two unidentified polar lipids. The genomic DNA G + C content was 50.9 mol%. The major whole-cell sugars contained glucose and galactose. On the basis of physiological, phenotypic, and chemotaxonomic data, strain YIM B00362T represents a novel species of genus Paenibacillus, for which the name Paenibacillus alkalitolerans sp. nov. is proposed. The type strain is YIM B00362T (= KCTC 43272 T = CGMCC 1.18801 T = NBRC 114667 T).


Asunto(s)
Paenibacillus , Lagos , Filogenia , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Ácidos Grasos/análisis , China , Análisis de Secuencia de ADN , Fosfolípidos/química
8.
Front Oncol ; 12: 943326, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35965527

RESUMEN

Background: To investigate reliable associations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) features and gene expression characteristics in breast cancer (BC) and to develop and validate classifiers for predicting PAM50 subtypes and prognosis from DCE-MRI non-invasively. Methods: Two radiogenomics cohorts with paired DCE-MRI and RNA-sequencing (RNA-seq) data were collected from local and public databases and divided into discovery (n = 174) and validation cohorts (n = 72). Six external datasets (n = 1,443) were used for prognostic validation. Spatial-temporal features of DCE-MRI were extracted, normalized properly, and associated with gene expression to identify the imaging features that can indicate subtypes and prognosis. Results: Expression of genes including RBP4, MYBL2, and LINC00993 correlated significantly with DCE-MRI features (q-value < 0.05). Importantly, genes in the cell cycle pathway exhibited a significant association with imaging features (p-value < 0.001). With eight imaging-associated genes (CHEK1, TTK, CDC45, BUB1B, PLK1, E2F1, CDC20, and CDC25A), we developed a radiogenomics prognostic signature that can distinguish BC outcomes in multiple datasets well. High expression of the signature indicated a poor prognosis (p-values < 0.01). Based on DCE-MRI features, we established classifiers to predict BC clinical receptors, PAM50 subtypes, and prognostic gene sets. The imaging-based machine learning classifiers performed well in the independent dataset (areas under the receiver operating characteristic curve (AUCs) of 0.8361, 0.809, 0.7742, and 0.7277 for estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2)-enriched, basal-like, and obtained radiogenomics signature). Furthermore, we developed a prognostic model directly using DCE-MRI features (p-value < 0.0001). Conclusions: Our results identified the DCE-MRI features that are robust and associated with the gene expression in BC and displayed the possibility of using the features to predict clinical receptors and PAM50 subtypes and to indicate BC prognosis.

9.
Chin J Nat Med ; 20(8): 627-632, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36031234

RESUMEN

Six new (1-6) and seven known depsidones (7-13) were isolated from the culture of an ant (Monomorium chinensis)-derived fungus Spiromastix sp. MY-1. Their structures were elucidated by extensive spectroscopic analysis including high resolution MS, 1D and 2D NMR data. The new bromide depsidones were obtained through supplementing potassium bromide in the fermentation medium of Spiromastix sp. MY-1. All isolated compounds showed various bioactivities against the tested phytopathogenic bacteria. Particularly, new bromide compound 4, named spiromastixone S, exhibited the strongest activity against Xanthomonas oryzae pv. oryzae with a MIC value of 5.2 µmol·-1.


Asunto(s)
Hormigas , Bromuros , Animales , Antibacterianos , Depsidos , Hongos , Lactonas , Pruebas de Sensibilidad Microbiana , Estructura Molecular
10.
Environ Microbiol ; 24(9): 3898-3911, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35315566

RESUMEN

Traditional farm environments induce protection from allergic diseases. In this study, farm environmental factors were classified into three categories, environmental microbes, soil, and organic matter. To explore the impact of soil and environmental microorganisms on gut microbiota and immune function, mice were fed sterilized soil and inhaling microbes, soil microbes, or non-sterilized soil. Metagenomic sequencing results showed the intake of sterile soil, that is, inhaling a small amount of soil microbes in the air increased gut microbial diversity and the abundance of type III secretion system (T3SS) genes, and decreased serum immune IgE levels induced by 2-4-dinitrofluorobenzene (DNFB). The intake of soil microbes increased the abundance of genes involved in the metabolism of short-chain fatty acids and amino acid biosynthesis. Meanwhile, the intake of soil increased gut microbial diversity, the abundance of T3SS genes and related infectious elements, and genes associated with the metabolism of short-chain fatty acids and amino acid biosynthesis, and decreased serum IgE levels. Therefore, soil may be useful as a potential 'prebiotic' promoting the reproduction and growth of some intestinal microorganisms that harbour bacterial secretion system genes, especially those of T3SS, whose abundance was positively and significantly correlated with innate immune function of mice.


Asunto(s)
Microbioma Gastrointestinal , Aminoácidos , Animales , Dinitrofluorobenceno , Ácidos Grasos Volátiles , Microbioma Gastrointestinal/genética , Inmunoglobulina E , Ratones , Suelo/química , Sistemas de Secreción Tipo III
11.
Front Oncol ; 12: 810526, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35311093

RESUMEN

Lung adenocarcinoma (LUAD) is the most diagnosed subtype of lung cancer; ferroptosis is widely involved in the pathological cell death associated with various cancers, including lung cancer. However, the comprehensive relationship between ferroptosis and LUAD is little known in molecular levels until now. In the present study, 513 LUAD patients could be aggregated into three clusters by consensus clustering based on RNA sequencing data of 291 ferroptosis-related genes (FRGs) in The Cancer Genome Atlas (TCGA) database; cluster2 had significant survival advantage compared to the other two clusters. A novel prognostic model of 8 differential FRGs was constructed to effectively divide LUAD patients into high- or low-risk group according to the risk scores by the Cox and LASSO regression analyses. The overall survival of LUAD patients in the high-risk group was significantly worse in the TCGA and GEO cohorts. Moreover, patients with radiation therapy or high clinical stage had obviously higher risk scores. We validated the differential mRNA and protein expression of four FRGs in paired tumor and normal samples from our clinical cohort. Our study constructed a novel FRG signature to predict the prognosis of LUAD patients, which might provide a new prognostic tool and potential therapeutic targets for LUAD.

12.
Bioorg Med Chem ; 59: 116676, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35220163

RESUMEN

We report herein the design, synthesis, and structure-activity relationship studies of pleuromutilin derivatives containing urea/thiourea functionalities. The antibacterial activities of these new pleuromutilin derivatives were evaluated in vitro against Gram-positive pathogens (GPPs) (Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium) and Mycoplasma pneumoniae by the broth dilution method. Most of the targeted compounds exhibit good potency in inhibiting the growth of pathogens including Methicillin-susceptible S. aureus (MSSA, ATCC29213, MIC: 0.0625-16 µg/mL), Methicillin-resistant S. aureus (MRSA, ATCC43300, MIC: 0.125-16 µg/mL) and M. pneumoniae (ATCC15531 MIC: 0.125-1 µg/mL, ATCC29342 MIC: 0.0625-0.25 µg/mL and drug resistant strain MIC: 0.5-2 µg/mL). In particular, the compounds 6m and 6n containing phenyl-urea group showed excellent activity with the MIC value less than 0.0625 µg/mL against S. aureus ATCC29213. The compound 6h exhibited better activity than tiamulin against Methicillin-resistant S. aureus ATCC43300.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Staphylococcus aureus , Antibacterianos/farmacología , Diterpenos , Pruebas de Sensibilidad Microbiana , Compuestos Policíclicos , Urea , Pleuromutilinas
13.
Anticancer Agents Med Chem ; 22(13): 2468-2476, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35189801

RESUMEN

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) plays a key role in DNA damage repair. A novel compound (E)-N'-(2,3-dibromo-4,5-dihydroxyphenyl)-N-(phenylcarbamothioyl)formimidamide (DDPF-20) with excellent PARP inhibitory activity was synthesized. OBJECTIVE: In this study, we aimed to clarify the mechanism of the novel PARP inhibitor DDPF-20 against lung cancer by inducing DNA damage and inhibiting angiogenesis. METHODS: The cytotoxic effect of DDPF-20 on the A549 cell line was determined with an MTT assay. Cell cycle and apoptosis were determined by a flow cytometer. Moreover, the γH2AX foci were detected by immunofluorescence. Capillary-like tube formation assay and chick chorioallantoic membrane (CAM) assay were used to detect the angiogenesis inhibitory effect of DDPF-20. The expressions of related proteins were detected by western blot. The anticancer activity of DDPF-20 in vivo was also detected. RESULTS: With an IC50 value of 52.42 ± 15.13 nM, DDPF-20 inhibited the proliferation, induced G2/M cycle arrest, and induced apoptosis of human lung cancer A549 cells. Further research showed that DDPF-20 induced DNA doublestrand breaks (DSBs). Interestingly, DDPF-20 inhibited the tube formation of HUVEC cells, as well as inhibited the neovascularization of CAM, proving the angiogenesis inhibitory ability of DDPF-20. Mechanism studies proved that DDPF-20 inhibited the PI3K/Akt/VEGF signaling pathway. In an in vivo study, DDPF-20 inhibited tumor growth of an A549 xenograft. Analysis of the molecular mechanism underlying this effect revealed that the PI3K/Akt/VEGF pathway was involved in DDPF-20-induced cell death and inhibited angiogenesis in vivo. CONCLUSION: This study suggested that the novel PARP inhibitor DDPF-20 may have therapeutic potential in treating lung cancer.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Antineoplásicos/farmacología , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Daño del ADN , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
14.
IEEE J Biomed Health Inform ; 26(11): 5289-5297, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-33735087

RESUMEN

Computer-aided early diagnosis of Alzheimer's disease (AD) and its prodromal form mild cognitive impairment (MCI) based on structure Magnetic Resonance Imaging (sMRI) has provided a cost-effective and objective way for early prevention and treatment of disease progression, leading to improved patient care. In this work, we have proposed a novel computer-aided approach for early diagnosis of AD by introducing an explainable 3D Residual Attention Deep Neural Network (3D ResAttNet) for end-to-end learning from sMRI scans. Different from the existing approaches, the novelty of our approach is three-fold: 1) A Residual Self-Attention Deep Neural Network has been proposed to capture local, global and spatial information of MR images to improve diagnostic performance; 2) An explainable method using Gradient-based Localization Class Activation mapping (Grad-CAM) has been introduced to improve the interpretability of the proposed method; 3) This work has provided a full end-to-end learning solution for automated disease diagnosis. Our proposed 3D ResAttNet method has been evaluated on a large cohort of subjects from real datasets for two changeling classification tasks (i.e. Alzheimer's disease (AD) vs. Normal cohort (NC) and progressive MCI (pMCI) vs. stable MCI (sMCI)). The experimental results show that the proposed approach has a competitive advantage over the state-of-the-art models in terms of accuracy performance and generalizability. The explainable mechanism in our approach is able to identify and highlight the contribution of the important brain parts (e.g., hippocampus, lateral ventricle and most parts of the cortex) for transparent decisions.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Redes Neurales de la Computación , Disfunción Cognitiva/diagnóstico por imagen , Progresión de la Enfermedad , Atrofia , Atención
15.
Chem Biol Interact ; 352: 109773, 2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-34902296

RESUMEN

eIF4E plays an important role in regulating tumor growth and angiogenesis, and eIF4E is highly expressed in a variety of lung cancer cell lines. siRNA eIF4E can significantly inhibit the proliferation of lung cancer cells, indicating that inhibition of eIF4E may become a novel anti-tumor target. In the previous study, we synthesized a series of small molecule compounds with the potential to inhibit eIF4E. Among them, the compound EGPI-1 significantly inhibited the proliferation of a variety of lung cancer cells such as A549, NCI-H460, NCI-H1650 and 95D without inhibiting the proliferation of HUVEC cells. Further studies found that EGPI-1 interfered with the eIF4E/eIF4G interaction and inhibited the phosphorylation of eIF4E in NCI-H460 cells. The results of flow cytometry showed that EGPI-1 induced apoptosis and G0/G1 cycle arrest in NCI-H460 cell. Interestingly, we also found that EGPI-1 induced autophagy and DNA damage in NCI-H460 cells. The mechanism results showed that EGPI-1 inhibited the Ras/MNK/ERK/eIF4E signaling pathway. Moreover, EGPI-1 inhibited tube formation of HUVECs, as well as inhibited the neovascularization of CAM, proving the anti-angiogenesis activity of EGPI-1. The NCI-H460 xenograft studies showed that EGPI-1 inhibited tumor growth and angiogenesis in vivo by regulating Ras/MNK/ERK/eIF4E pathway. Our studies proved that eIF4E was a novel target for regulating tumor growth, and the eIF4E/eIF4G interaction inhibitor EGPI-1 was promising to develop into a novel anti-lung cancer drug.


Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Compuestos de Bencilideno/farmacología , Factor 4E Eucariótico de Iniciación/antagonistas & inhibidores , Factor 4G Eucariótico de Iniciación/antagonistas & inhibidores , Hidrazinas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Tiazoles/farmacología , Células A549 , Inhibidores de la Angiogénesis/química , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Compuestos de Bencilideno/química , Compuestos de Bencilideno/uso terapéutico , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Embrión de Pollo , Factor 4E Eucariótico de Iniciación/genética , Factor 4E Eucariótico de Iniciación/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Hidrazinas/química , Hidrazinas/uso terapéutico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica/prevención & control , Transducción de Señal/efectos de los fármacos , Tiazoles/química , Tiazoles/uso terapéutico , Regulación hacia Arriba , Ensayos Antitumor por Modelo de Xenoinjerto
16.
J Virol Methods ; 301: 114408, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34896455

RESUMEN

Immunization is the most effective way to respond to an influenza epidemic. To produce Vero cell-derived influenza vaccines, a more efficient, stable and economical purification process is required. In this study, we purified the H7N9 influenza virus grown in Vero cells that were cultured in a serum-free medium by using a combination of anion exchange chromatography (AEC) and ligand-activated core chromatography (LCC), which avoids the virus capture step. After purification, 99.95 % host cell DNA (hcDNA) (final concentration: 28.69 pg/dose) and 98.87 % host cell protein (HCP) (final concentration: 28.28 ng/dose) were removed. The albumin content was 11.36 ng/dose. All these remnants met the current Chinese Pharmacopoeia and WHO requirements. The final virus recovery rate was 58.74 %, with the concentration of hemagglutinin recorded at 132.12 µg/mL. The flow-through chromatography purification process represents an alternative to the existing processes for cell-derived influenza viruses and might be suitable for the purification of other viruses as well.


Asunto(s)
Subtipo H7N9 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Animales , Chlorocebus aethiops , Cromatografía/métodos , Glicoproteínas Hemaglutininas del Virus de la Influenza , Humanos , Subtipo H7N9 del Virus de la Influenza A/genética , Gripe Humana/prevención & control , Células Vero
17.
World J Clin Cases ; 9(26): 7870-7875, 2021 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-34621840

RESUMEN

BACKGROUND: Mediastinal mature teratoma is the most common histological type of primary extragonadal germ cell tumor. In this report, we describe a rare case of giant mature teratoma located primarily in the anterior mediastinum and causing partial atelectasis of the upper and middle lobes of the right lung, as well as extrinsic compression of the right atrium. CASE SUMMARY: A 31-year-old male with a giant mediastinal mature teratoma presented with progressive exertional dyspnea and chest pain for 1 mo. Computed tomography of the chest indicated the diagnosis of anterior mediastinal teratoma. The patient underwent right uniportal anterior approach video-assisted thoracoscopic surgery (VATS). En bloc resection of the giant teratoma, wedge resection of the upper and middle lobes of the right lung, resection of the thymus and partial excision of the pericardium were successfully performed. The pathological diagnosis revealed a mature cystic teratoma with foreign-body reaction that was closely related to the right lung, atrium dextrum, superior vena cava and ascending aorta. An atrophic thymic tissue was also discovered at the external teratoma surface. The patient was discharged on postoperative day 7. CONCLUSION: This is the first report of the use of uniportal VATS for complete resection of a teratoma in combination with wedge resection of the right upper and middle lung lobes and partial resection of the pericardium.

18.
Curr Microbiol ; 78(8): 3307-3312, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34181048

RESUMEN

A bacterial strain, Gram staining negative, aerobic, long rod, motile bacterium with flagellum, designated strain YIM 98829T, was isolated from the Aiding Lake in Xinjiang province, North-West China. The isolate produced oval subterminal endospores in swollen sporangia. The predominant menaquinone was MK-7. The cell wall peptidoglycan contained ornithine, serine, aspartic acid, glutamic acid, and alanine, while diaminopimelic acid could not be detected. The major whole-cell sugars contained xylose, glucose, galactose, and mannose. Diphosphatidylglycerol, phosphatidylglycerol, one unknown phospholipid, and two unidentified aminophospholipids were part of the polar lipid profile. Iso-C15:0 and anteiso-C15:0 were the major fatty acids. The DNA G + C content of the type strain was 38.0 mol%. Phylogenetic analysis indicated that the isolate belongs to the genus Alkalibacillus. However, it differed from its closest relatives, A. haloalkaliphilus DSM 5271T (97.04%), A. filiformis 4AGT (96.99%), and A. silvisoli BM2T (96.95%) in some physiological characteristics. DNA-DNA hybridization result indicated low levels of relatedness between strain YIM 98829T and A. haloalkaliphilus JCM 12303T (16.9%). On the basis of physiological, phenotypic, and chemotaxonomic data, strain YIM 98829T represents a novel species of genus Alkalibacillus, for which the name Alkalibacillus aidingensis sp. nov. is proposed. The type strain is YIM 98829T (= NBRC 114103T = CGMCC 1.17260T = DSM 112470T).


Asunto(s)
Ácidos Grasos , Lagos , Técnicas de Tipificación Bacteriana , China , ADN Bacteriano/genética , Ácidos Grasos/análisis , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
19.
Langmuir ; 37(21): 6540-6548, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34013722

RESUMEN

Regarding methods of process and use of carbon nanotubes (CNTs), solvents are generally employed to disperse or dissolve CNTs as a pretreatment or intermediate process step. This naturally imposes an essential issue on how CNTs and solvents interact with each other, which seems trivial, comparatively inconsequential, and might often be overlooked from the perspective of engineering scenarios. However, as a matter of fact, it is indeed a fascinating and significant topic. In this article, to investigate the interfacial properties of multiwalled CNTs (MWCNTs) exposed to widely utilized solvents, we applied sum frequency generation vibrational spectroscopy (SFG-VS) to probe solvent-wetted MWCNTs and proved that polar solvents can substantially alter the interfacial optical property of MWCNTs. First, the interfacial optical phonon vibrational modes were detected when MWCNTs were wetted by polar solvents, i.e., water and dimethylformamide (DMF), while such modes were inactive when the solvents were nonpolar, i.e., decalin and air. Second, the interfacial optical phonon vibration frequency displayed distinct dependence on surface defects of MWCNTs. Combining theoretical analysis with experimental verification, a valid conjecture with respect to surface phonon vibration activity for MWCNTs was proposed. This phenomenon of polar solvent-induced SFG activity may have the potential to find applications in optical detection and environmental sensing in the near future.

20.
IEEE Trans Med Imaging ; 40(9): 2354-2366, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33939609

RESUMEN

Structural magnetic resonance imaging (sMRI) is widely used for the brain neurological disease diagnosis, which could reflect the variations of brain. However, due to the local brain atrophy, only a few regions in sMRI scans have obvious structural changes, which are highly correlative with pathological features. Hence, the key challenge of sMRI-based brain disease diagnosis is to enhance the identification of discriminative features. To address this issue, we propose a dual attention multi-instance deep learning network (DA-MIDL) for the early diagnosis of Alzheimer's disease (AD) and its prodromal stage mild cognitive impairment (MCI). Specifically, DA-MIDL consists of three primary components: 1) the Patch-Nets with spatial attention blocks for extracting discriminative features within each sMRI patch whilst enhancing the features of abnormally changed micro-structures in the cerebrum, 2) an attention multi-instance learning (MIL) pooling operation for balancing the relative contribution of each patch and yield a global different weighted representation for the whole brain structure, and 3) an attention-aware global classifier for further learning the integral features and making the AD-related classification decisions. Our proposed DA-MIDL model is evaluated on the baseline sMRI scans of 1689 subjects from two independent datasets (i.e., ADNI and AIBL). The experimental results show that our DA-MIDL model can identify discriminative pathological locations and achieve better classification performance in terms of accuracy and generalizability, compared with several state-of-the-art methods.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Aprendizaje Profundo , Enfermedad de Alzheimer/diagnóstico por imagen , Atención , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética
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