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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 348-325, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812398

RESUMO

OBJECTIVE: To detect the relationship between leukocytes derived microparticle (CD45+ MP) and minimal residual disease (MRD) and prognosis of acute myeloid leukemia (AML). METHODS: The expression of CD45+ MP, CD44+ MP and CD24+ MP in peripheral blood of 47 AML patients at the time after induction chemotherapy were detected by using flow cytometry, and the relationship between MP, MRD and prognosis were analyzed. RESULTS: The percentages of CD45+ MP, CD44+ MP and CD24+ MP in MRD positive group were significantly higher than those in MRD negative group. In MRD positive group, there were positive correlation between CD45+ MP, CD44+ MP, CD24+ MP and MRD level. The AUC of CD45+ MP, CD44+ MP, CD24+ MP in predicting positive MRD was 0.949, 0.782, and 0.817, respectively. The EFS and OS in HCD45+ MP, HCD44+ MP and HCD24+ MP groups were significantly shorter than low level group. CONCLUSION: High level of CD45+ MP, CD44+ MP, CD24+ MP can be used to predict high level MRD and poor prognosis.


Assuntos
Leucemia Mieloide Aguda , Citometria de Fluxo , Humanos , Leucócitos , Neoplasia Residual , Prognóstico
2.
Sci Rep ; 11(1): 8054, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850164

RESUMO

Cromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder formulation, is being tested in a pivotal clinical trial in combination with low dose ibuprofen to treat early Alzheimer's Disease (AD) subjects. To better understand the mechanistic effect cromolyn has in slowing down or halting the neuroinflammatory response associated with AD progression, we tested the effect of cromolyn to dampen the inflammatory response in the human HMC3 microglia cell line. The direct effect of cromolyn on HMC3 microglia is on cytokines and chemokines production following their activation by the inflammatory cytokine TNF-α. Cromolyn and a new fluorinated analog dramatically reduced the secretion of a wide spectrum of inflammatory mediators, which included cytokines such as IL-1ß, IL-6, IL-8 and IFN-γ, and chemokines such as CXCL10, CCL2, CCL3 and CCL4. These results bolster our understanding of how our cromolyn platform modulates toxic microglia behavior as a dynamic future treatment option for neurodegenerative disorders.

3.
Cancers (Basel) ; 13(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802841

RESUMO

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, ranking third in cancer deaths worldwide. Over the last decade, several studies have emphasized the development of tyrosine kinase inhibitors (TKIs) to target the aberrant pathways in HCC. However, the outcomes are far from satisfactory due to the increasing resistance and adverse effects. The family of fibroblast growth factor (FGF) and its receptors (FGFR) are involved in various biological processes, including embryogenesis, morphogenesis, wound repair, and cell growth. The aberrant FGF/FGFR signaling is also observed in multiple cancers, including HCC. Anti-FGF/FGFR provides delightful benefits for cancer patients, especially those with FGF signaling alteration. More and more multi-kinase inhibitors targeting FGF signaling, pan-FGFR inhibitors, and selective FGFR inhibitors are now under preclinical and clinical investigation. This review summarizes the aberrant FGF/FGFR signaling in HCC initiating, development and treatment status, and provide new insights into the treatment of HCC.

4.
Front Endocrinol (Lausanne) ; 12: 620566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33776917

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global public health challenge. Most patients do not experience severe complications, but approximately 25% of patients progress to acute respiratory distress syndrome (ARDS), and the mortality rate is approximately 5-7%. Clinical findings have determined several risk factors for severe complications and mortality in COVID-19 patients, such as advanced age, smoking, obesity, and chronic diseases. Obesity is a common and serious health problem worldwide that initiates a cascade of disorders, including hypertension, cardiovascular disease (CVD), diabetes mellitus, and chronic kidney disease (CKD). The presence of these disorders is linked to a more severe course of COVID-19. Given the "epidemic" of obesity worldwide and the importance of obesity in the progression of COVID-19, we investigated the mechanisms through which obesity increases the susceptibility to and severity of COVID-19 to support the selection of more appropriate therapies for individuals with obesity.


Assuntos
/epidemiologia , Obesidade/epidemiologia , /complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Progressão da Doença , Humanos , Obesidade/complicações , Obesidade/patologia , Obesidade/terapia , Pandemias , Fatores de Risco , Índice de Gravidade de Doença
5.
Nanoscale ; 13(7): 4249-4261, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33595022

RESUMO

Conventional prostate cancer treatment strategies, including chemotherapy and radiotherapy, cannot effectively eradicate prostate cancer, especially castration resistance prostate cancer. Herein, we developed a novel nanotherapy platform that consists of synergic photothermal and photodynamic therapy via the unique properties of photothermal conversion by gold nanorods and free radicals generation by encapsulated initiators (AIPH). Mesoporous silica was employed as a coating material, and the bombesin peptide was conjugated onto the mesoporous silica coating layer as the targeting moiety to prostate cancer via its overexpressed gastrin-releasing peptide receptors. An in vitro study with the castration resistance prostate cancer cell exhibited a significant photothermal therapeutic effect as well as enhanced thermodynamic therapy via generating free radicals. P-p38 and p-JNK proteins, as key proteins involved in the cells' stress responses, were found to be upregulated by the synergetic treatment. The in vivo study demonstrated that a significant eradication of prostate tumour could be achieved by the nanoparticle therapeutic platform with a good biocompatibility profile. This work pioneers a novel approach for high-efficient castration resistance prostate cancer treatment by combining photothermal, thermodynamic, and site-specific drug delivery directed by an integrated nanoparticle system.

6.
J Exp Clin Cancer Res ; 40(1): 50, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522955

RESUMO

BACKGROUND: Forkhead box C1 (FOXC1), as a member of the FOX family, is important for promote HCC invasion and metastasis. FOX family protein lays a pivotal role in metabolism. ROS is involved in tumor progression and is associated with the expression of lots of transcription factors. We next explored the mechanism underlying FOXC1 modulating the metabolism and ROS hemostasis in HCC. METHODS: We used amino acids arrays to verify which metabolism is involved in FOXC1-induced HCC. The kits were used to detect the ROS levels in HCC cells with over-expression or down-expression of FOXC1. After identified the downstream target genes and candidate pathway which regulated by FOXC1 during HCC progression in vitro and in vivo, we used western blot, immunohistochemistry, bisulfite genomic sequencing, methylation-specific PCR, chromatin immunoprecipitation analysis and luciferase reporter assays to explore the relationship of FOXC1 and downstream genes. Moreover, the correlation between FOXC1 and target genes and the correlation between target genes and the recurrence and overall survival were analyzed in two independent human HCC cohorts. RESULTS: Here, we reported that FOXC1 could inhibit the cysteine metabolism and increase reactive oxygen species (ROS) levels by regulating cysteine metabolism-related genes, cystathionine γ-lyase (CTH). Overexpression of CTH significantly suppressed FOXC1-induced HCC proliferation, invasion and metastasis, while the reduction in cell proliferation, invasion and metastasis caused by the inhibition of FOXC1 could be reversed by knockdown of CTH. Meanwhile, FOXC1 upregulated de novo DNA methylase 3B (DNMT3B) expression to induce DNA hypermethylation of CTH promoter, which resulted in low expression of CTH in HCC cells. Moreover, low levels of ROS induced by N-acetylcysteine (NAC) which is an antioxidant inhibited the cell proliferation, migration, and invasion abilities mediated by FOXC1 overexpression, whereas high levels of ROS induced by L-Buthionine-sulfoximine (BSO) rescued the suppression results mediated by FOXC1 knockdown. Our study demonstrated that the overexpression of FOXC1 that was induced by the ROS dependent on the extracellular regulated protein kinases 1 and 2 (ERK1/2)- phospho-ETS Transcription Factor 1 (p-ELK1) pathway. In human HCC tissues, FOXC1 expression was positively correlated with oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), p-ELK1 and DNMT3B expression, but negatively correlated with CTH expression. HCC patients with positive co-expression of 8-OHdG/FOXC1 or p-ELK1/FOXC1 or FOXC1/DNMT3B had the worst prognosis, whereas HCC patients who had positive FOXC1 and negative CTH expression exhibited the worst prognosis. CONCLUSION: In a word, we clarify that the positive feedback loop of ROS-FOXC1-cysteine metabolism-ROS is important for promoting liver cancer proliferation and metastasis, and this pathway may provide a prospective clinical treatment approach for HCC.

7.
Sensors (Basel) ; 21(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578754

RESUMO

Brain-computer interfaces (BCIs) provide humans a new communication channel by encoding and decoding brain activities. Steady-state visual evoked potential (SSVEP)-based BCI stands out among many BCI paradigms because of its non-invasiveness, little user training, and high information transfer rate (ITR). However, the use of conductive gel and bulky hardware in the traditional Electroencephalogram (EEG) method hinder the application of SSVEP-based BCIs. Besides, continuous visual stimulation in long time use will lead to visual fatigue and pose a new challenge to the practical application. This study provides an open dataset, which is collected based on a wearable SSVEP-based BCI system, and comprehensively compares the SSVEP data obtained by wet and dry electrodes. The dataset consists of 8-channel EEG data from 102 healthy subjects performing a 12-target SSVEP-based BCI task. For each subject, 10 consecutive blocks were recorded using wet and dry electrodes, respectively. The dataset can be used to investigate the performance of wet and dry electrodes in SSVEP-based BCIs. Besides, the dataset provides sufficient data for developing new target identification algorithms to improve the performance of wearable SSVEP-based BCIs.


Assuntos
Interfaces Cérebro-Computador , Potenciais Evocados Visuais , Dispositivos Eletrônicos Vestíveis , Algoritmos , Eletroencefalografia , Humanos , Estimulação Luminosa
8.
Oncogene ; 40(11): 2035-2050, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33603166

RESUMO

Use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with reduced risk of colorectal cancer (CRC). However, the mechanism by which NSAIDs suppress colorectal tumorigenesis remains unclear. We previously showed that NSAIDs selectively kill emerging tumor cells via death receptor (DR) signaling and a synthetic lethal interaction mediated by the proapoptotic Bcl-2 family protein BID. In this study, we found NSAIDs induce endoplasmic reticulum (ER) stress to activate DR signaling and BID in tumor suppression. Importantly, our results unveiled an ER stress- and BID-dependent immunogenic effect of NSAIDs, which may be critical for tumor suppression. NSAID treatment induced hallmarks of immunogenic cell death (ICD) in CRC cells and colonic epithelial cells upon loss of APC tumor suppressor, and elevated tumor-infiltrating lymphocytes (TILs) in the polyps of APCMin/+ mice. ER stress inhibition or BID deletion abrogated the antitumor and immunogenic effects of NSAIDs. Furthermore, increased ER stress and TILs were detected in human advanced adenomas from NSAID-treated patients. Together, our results suggest that NSAIDs induce ER stress- and BID-mediated ICD to restore immunosurveillance and suppress colorectal tumor formation.

9.
Theranostics ; 11(6): 2612-2633, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456563

RESUMO

Background: Metastasis is the major reason for the high mortality of colorectal cancer (CRC). However, the molecular mechanism underlying CRC metastasis remains unclear. Here, we report a novel role of homeobox B5 (HOXB5), a member of the HOX family, in promoting CRC metastasis. Method: The expression of HOXB5 and its target genes were examined by immunohistochemistry in human CRC. Chromatin immunoprecipitation and luciferase reporter assays were performed to measure the transcriptional regulation of target genes by HOXB5. The metastatic capacities of CRC cells were evaluated by in vivo lung and liver metastatic models. Results: The elevated expression of HOXB5 was positively correlated with distant metastasis, higher AJCC stage, and poor prognosis in CRC patients. HOXB5 expression was an independent and significant risk factor for the recurrence and survival in CRC patients. Overexpression of HOXB5 promoted CRC metastasis by transactivating metastatic related genes, C-X-C motif chemokine receptor 4 (CXCR4) and integrin subunit beta 3 (ITGB3). C-X-C motif chemokine ligand 12 (CXCL12), which is the ligand of CXCR4, upregulated HOXB5 expression through the extracellular regulated protein kinase (ERK)/ETS proto-oncogene 1, transcription factor (ETS1) pathway. The knockdown of HOXB5 decreased CXCL12-enhanced CRC metastasis. Furthermore, AMD3100, a specific CXCR4 inhibitor, significantly suppressed HOXB5-mediated CRC metastasis. HOXB5 expression was positively correlated with CXCR4 and ITGB3 expression in human CRC tissues, and patients with positive co-expression of HOXB5/CXCR4, or HOXB5/ITGB3 exhibited the worst prognosis. Conclusion: Our study implicates HOXB5 as a prognostic biomarker in CRC, and defines a CXCL12-HOXB5-CXCR4 positive feedback loop that plays an important role in promoting CRC metastasis.

10.
Cell Mol Gastroenterol Hepatol ; 11(5): 1369-1385, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33482392

RESUMO

BACKGROUND AND AIMS: TRIM21 is a ubiquitin E3 ligase that is implicated in numerous biological processes including immune response, cell metabolism, redox homeostasis, and cancer development. We recently reported that TRIM21 can negatively regulate the p62-Keap1-Nrf2 antioxidant pathway by ubiquitylating p62 and prevents its oligomerization and protein sequestration function. As redox homeostasis plays a pivotal role in many cancers including liver cancer, we sought to determine the role of TRIM21 in hepatocarcinogenesis. METHODS: We examined the correlation between TRIM21 expression and the disease using publicly available data sets and 49 cases of HCC clinical samples. We used TRIM21 genetic knockout mice to determine how TRIM21 ablation impact HCC induced by the carcinogen DEN plus phenobarbital (PB). We explored the mechanism that loss of TRIM21 protects cells from DEN-induced oxidative damage and cell death. RESULTS: There is a positive correlation between TRIM21 expression and HCC. Consistently, TRIM21-knockout mice are resistant to DEN-induced hepatocarcinogenesis. This is accompanied by decreased cell death and tissue damage upon DEN treatment, hence reduced hepatic tissue repair response and compensatory proliferation. Cells deficient in TRIM21 display enhanced p62 sequestration of Keap1 and are protected from DEN-induced ROS induction and cell death. Reconstitution of wild-type but not the E3 ligase-dead and the p62 binding-deficient mutant TRIM21 impedes the protection from DEN-induced oxidative damage and cell death in TRIM21-deficient cells. CONCLUSIONS: Increased TRIM21 expression is associated with human HCC. Genetic ablation of TRIM21 leads to protection against oxidative hepatic damage and decreased hepatocarcinogenesis, suggesting TRIM21 as a preventive and therapeutic target.

11.
J Cell Mol Med ; 25(3): 1712-1724, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33471953

RESUMO

This study explored the therapeutic effect of bone marrow mesenchymal stem cell-derived exosomes on the treatment of obesity-induced fracture healing. Quantitative real-time PCR was used to detect the expression of lncRNA H19, miR-467 and Hoxa10 and combined with WB detection to detect osteogenic markers (RUNX2, OPN, OCN). Determine whether exosomes have entered BMSCs by immunofluorescence staining. Alkaline phosphatase (ALP) and alizarin red staining (ARS) staining were used to detect ALP activity and calcium deposition. We found that high-fat treatment can inhibit the secretion of BMSCs-derived exosomes and affect the expression of H19 carried by them. In vivo and in vitro experiments show that high-fat or obesity factors can inhibit the expression of osteogenic markers and reduce the staining activity of ALP and ARS. The treatment of exosomes from normal sources can reverse the phenomenon of osteogenic differentiation and abnormal fracture healing. Further bioinformatics analysis found that miR-467 as a regulatory molecule of lncRNA H19 and Hoxa10, and we verified the targeting relationship of the three through dual luciferase report experiments. Further, we found similar phenomena in ALP and ARS staining. Bone marrow mesenchymal stem cell-derived exosomes improve fracture healing caused by obesity.

12.
Ecotoxicol Environ Saf ; 209: 111732, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33373928

RESUMO

Fluoride, widely presented in drinking water and tea, may be detrimental or beneficial to the human health, depending on its dosages ingested. However, the relationship of different dosages of fluoride and gut microbiota is still unclear. In this work, the fermentation model using fecal samples provided by four volunteers was used to evaluate the effects of different dosages of fluoride (1, 2, 10 and 15 mg/L) on the gut microbiota in vitro. The result showed low dosages of fluoride (1 and 2 mg/L) had limited effect on the structure and functional Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of gut microbiota. Furthermore, the low dosage of fluoride could promote the growth of beneficial gut microbiota, including Faecalibacterium and Lactobacillus. Whereas, the high dosage of fluoride (10 and 15 mg/L) significantly changed the composition and functional KEGG pathway of gut microbiota. Moreover, the high dosage of fluoride could also reduce the beneficial gut microbiota, including Faecalibacterium and Phascolarctobacterium, and increase the harmful bacterium including Proteobacteria and Enterobacteriaceae. Both low and high dosages of fluoride showed limited effect on the productions of short-chain fatty acids (SCFAs). Thus, the beneficial or detrimental fluoride to gut microbiota depends on its dosages. The fluoride is expected to serve as a food additive in suitable dosage to improve human health through modulation of the gut microbiota. Moreover, more attention should be paid to toxicity of fluoride with high dosage to gut microbiota.


Assuntos
Fluoretos/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Bactérias/metabolismo , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/química , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fermentação , Fluoretos/análise , Humanos , Lactobacillus/metabolismo
13.
J Int Med Res ; 48(12): 300060520959502, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33275460

RESUMO

OBJECTIVE: We evaluated the effects of atorvastatin and ticagrelor combination therapy on renal function and the levels of suppression of tumorigenicity 2 (ST2) and interleukin 33 (IL-33) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Eighty-four STEMI patients who underwent emergency percutaneous coronary intervention at our hospital from January 2015 to March 2018 were retrospectively analyzed and divided into a control group (n = 44) and an observation group (n = 40). The control group was treated with atorvastatin as routine STEMI treatment, whereas the observation group was concurrently administered ticagrelor. RESULTS: After treatment, significantly better outcomes were observed in the control group than in the observation group in terms of clinical indices, including chest pain relief, enzyme levels, duration of reperfusion-associated arrhythmia, and depression of the ST segment. Both groups exhibited improvements in cardiac ultrasound indices, whereas the observation group showed lower left ventricular end-diastolic and end-systolic diameters and higher left ventricular ejection fractions than the control group. CONCLUSIONS: Atorvastatin and ticagrelor combination therapy is clinically effective and safe for STEMI patients as it reduces the degree of myocardial infarction, protects the heart and renal functions, improves inflammation, and reduces adverse cardiac event incidences.

14.
Cereb Cortex ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33279971

RESUMO

The present study recorded event-related potentials (ERPs) in a visual object-recognition task under the attentional blink paradigm to explore the temporal dynamics of the cross-modal boost on attentional blink and whether this auditory benefit would be modulated by semantic congruency between T2 and the simultaneous sound. Behaviorally, the present study showed that not only a semantically congruent but also a semantically incongruent sound improved T2 discrimination during the attentional blink interval, whereas the enhancement was larger for the congruent sound. The ERP results revealed that the behavioral improvements induced by both the semantically congruent and incongruent sounds were closely associated with an early cross-modal interaction on the occipital N195 (192-228 ms). In contrast, the lower T2 accuracy for the incongruent than congruent condition was accompanied by a larger late occurring cento-parietal N440 (424-448 ms). These findings suggest that the cross-modal boost on attentional blink is hierarchical: the task-irrelevant but simultaneous sound, irrespective of its semantic relevance, firstly enables T2 to escape the attentional blink via cross-modally strengthening the early stage of visual object-recognition processing, whereas the semantic conflict of the sound begins to interfere with visual awareness only at a later stage when the representation of visual object is extracted.

15.
Mol Nutr Food Res ; : e2000864, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33258303

RESUMO

SCOPE: Large-Leaf yellow tea (YT) exhibited interesting beneficial metabolic effects in previous studies. Here, we elucidated the actions of YT on thermogenesis, energy metabolism and adipocyte metabolic conversion. METHODS AND RESULTS: Five-week-old male C57BL/6 mice were fed low-fat diet, high-fat diet (HFD) and HFD supplemented with 0.5% or 2.5% YT. After treatment for 10 or 14 weeks, YT enhanced energy expenditure, VO2 and VCO2 . YT strongly boosted thermogenic program in brown adipose tissue (BAT) and subcutaneous adipose tissue (SAT), while only weakly in epididymal adipose tissue (EAT). These were accompanied by higher body temperature, increased mitochondrial copy numbers (ATP5A+ ), and upregulation of thermogenic genes (Ucp1, Pgc1α, etc) and proteins. The classic brown adipocyte markers (Eva1, Zic1) were induced only in BAT, while beige adipocyte markers (Tbx1, Tmem26) were boosted only in SAT. Furthermore, subcutaneous-originated preadipocytes were induced by YT in vitro to differentiate to brown-like UCP1+ -adipocytes - a browning effect. CONCLUSION: Dietary YT induces adaptive thermogenesis through increasing mitochondrial biogenesis in EAT, inducing beigeing in SAT and enhancing browning in the BAT. This article is protected by copyright. All rights reserved.

16.
Food Res Int ; 137: 109409, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233096

RESUMO

This study investigated the effects of L-theanine supplementation on the colonic mucosa injury in C57BL/6J male mice treated with dextran sulfate sodium (DSS)-induced colitis. Treatment with L-theanine significantly decreased the disease activity index and ameliorated the inflammation-associated pathological damage in colon length, as well as the histopathological features of DSS-induced colitis. L-Theanine administration also inhibited DSS-induced changes in the colonic tissue that included myeloperoxidase by 4.5-fold and malondialdehyde by 2.3-fold in comparison to the DSS group. In addition, GSH was increased by 85% and lipopolysaccharides level was decreased by 55% in comparison to the DSS group. Proinflammatory cytokines expression, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, at the both protein and mRNA levels were also decreased significantly. Notably, the increase in serum content of lipopolysaccharides and colonic expressions of inducible nitric oxide synthase, cyclooxygenase-2, toll like receptor (TLR)-2, TLR-4, TLR-6, and TLR-9 induced by DSS were also significantly inhibited by L-theanine administration. In addition, L-theanine also attenuated the reduction of serum contents of diamine oxidase and the production of short-chain fatty acids in the colonic tissue, and gene expression of mucosal barrier zonula occludens-1 and claudin-1 in DSS-induced colitis. Furthermore, 16S rRNA phylogenetic sequencing revealed a shift in microbial community composition induced by DSS, but no significant difference was observed following L-theanine supplementation. Overall, our findings demonstrated that L-theanine inhibits intestinal inflammation and protects against intestinal barrier disruption in mice with DSS-induced colitis. Further clinical trials should be considered to assess the effects of L-theanine supplementation on oxidative and inflammatory responses in humans.

17.
Ann Transl Med ; 8(18): 1159, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33241008

RESUMO

Background: To accurately predict the survival rate of patients with hepatocellular carcinoma (HCC) undergoing thermal ablation using nomograms taking early recurrence into account as a risk factor. Methods: A total of 591 patients receiving percutaneous thermal ablation were included in this study. The overall survival (OS) and recurrence-free survival (RFS) rate was analyzed. Two prognostic nomograms with or without taking early recurrence into account as a risk factor were constructed using the independent predictors assessed by the multivariate Cox proportional hazard model. The performance of the nomograms, in terms of discrimination and calibration, was evaluated. Results: The cumulative RFS and OS rates at 1-, 3- and 5-year are 82.2%, 52.5%and 38.4%, 96.6%, 83.6% and 65.5%, respectively. Multivariate analysis without considering the early recurrence shows that tumor number, α-fetoprotein (AFP) level, liver function, and GGT level are associated with OS. The early recurrence, tumor number, AFP level, and liver function are considered associated with the OS when considering early recurrence. Two different nomograms were developed from the above two results. Internal validation with 1,000 bootstrapped sample sets of the two nomograms shows the concordance indexes of 0.69 (95% CI: 0.624-0.748) for the baseline nomogram and 0.81 (95% CI: 0.754-0.857) for the early recurrence-based nomogram, with the latter significantly better in discriminating performance (Z statistics =92.19, P<0.0001). Conclusions: The survival rate of patients with HCC undergoing radical thermal ablation can be reliably predicted by the nomogram presented in this study, which was developed by taking early recurrence into account.

18.
Cell ; 183(5): 1219-1233.e18, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33242418

RESUMO

Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined with varying levels of success. Here, we describe a paradigm to control cancer growth that is based on both direct tumor killing and the triggering of protective immunity. Genetic ablation of serine protease inhibitor SerpinB9 (Sb9) results in the death of tumor cells in a granzyme B (GrB)-dependent manner. Sb9-deficient mice exhibited protective T cell-based host immunity to tumors in association with a decline in GrB-expressing immunosuppressive cells within the tumor microenvironment (TME). Maximal protection against tumor development was observed when the tumor and host were deficient in Sb9. The therapeutic utility of Sb9 inhibition was demonstrated by the control of tumor growth, resulting in increased survival times in mice. Our studies describe a molecular target that permits a combination of tumor ablation, interference within the TME, and immunotherapy in one potential modality.

19.
Front Neurosci ; 14: 579469, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192265

RESUMO

Brain-computer interfaces (BCIs) based on rapid serial visual presentation (RSVP) have been widely used to categorize target and non-target images. However, it is still a challenge to detect single-trial event related potentials (ERPs) from electroencephalography (EEG) signals. Besides, the variability of EEG signal over time may cause difficulties of calibration in long-term system use. Recently, collaborative BCIs have been proposed to improve the overall BCI performance by fusing brain activities acquired from multiple subjects. For both individual and collaborative BCIs, feature extraction and classification algorithms that can be transferred across sessions can significantly facilitate system calibration. Although open datasets are highly efficient for developing algorithms, currently there is still a lack of datasets for a collaborative RSVP-based BCI. This paper presents a cross-session EEG dataset of a collaborative RSVP-based BCI system from 14 subjects, who were divided into seven groups. In collaborative BCI experiments, two subjects did the same target image detection tasks synchronously. All subjects participated in the same experiment twice with an average interval of ∼23 days. The results in data evaluation indicate that adequate signal processing algorithms can greatly enhance the cross-session BCI performance in both individual and collaborative conditions. Besides, compared with individual BCIs, the collaborative methods that fuse information from multiple subjects obtain significantly improved BCI performance. This dataset can be used for developing more efficient algorithms to enhance performance and practicality of a collaborative RSVP-based BCI system.

20.
Front Oncol ; 10: 540239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194601

RESUMO

This study aimed to explore the special efforts required to achieve proficiency in performing thermal ablation of liver cancers, including tumors in difficult locations, and clarify the effects of handing-down teaching on the corresponding process. Major complications of patients receiving percutaneous thermal ablation of liver cancer were analyzed. Polynomial fitting was used to describe the connection between major complication rates and special experience. Learning curve of major complications was plotted both for the whole group and for each operator, respectively. Tumors in difficult locations were further studied. A total of 4,363 thermal ablation sessions were included in this study. 143 of 4,363 patients had major complications, corresponding to an incidence rate of 3.27%. 806 thermal ablation sessions were performed for tumors in difficult locations. The major complication rate of these sessions is 6.33%. According to the trend of the learning curve of the 4363 patients, the experience of the whole group can be classified into five stages, that is, the high-risk, relatively stable, unstable, proficient and stable periods. A learning curve for an individual operator can be classified into the high-risk, proficient and stable periods. The major complication rates for the chronologically first, second and third operator of the group are 3.23, 3.35, and 3.31%, respectively. The special experience needed to bypass the first stage corresponds to 410, 510, and 440 sessions, the second stage, 1850, 850, and 870 sessions, by the three operators, respectively. The major complication rates for the tumors in difficult locations for the first, second and third operator were 7.04, 5.53, and 5.98%, respectively. For the tumors in difficult locations, the special experience needed to bypass the first stage corresponds to 150, 130, and 140 sessions, the second stage, 290, 175, and 185 sessions, by the three operators, respectively. In conclusion, the learning process of an operator percutaneous thermal ablation for liver cancer can be classified into three stages. The major complication rate for tumors in difficult locations were higher than that for all tumors. Handing-down teaching can make an operator arrive at the third stage earlier but not the second stage.

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