Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.110
Filtrar
1.
Microb Cell Fact ; 20(1): 6, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413404

RESUMO

BACKGROUND: The majority of microbial fermentations are currently performed in the batch or fed-batch manner with the high process complexity and huge water consumption. The continuous microbial production can contribute to the green sustainable development of the fermentation industry. The co-culture systems of photo-autotrophic and heterotrophic species can play important roles in establishing the continuous fermentation mode for the bio-based chemicals production. RESULTS: In the present paper, the co-culture system of Synechococcus elongates-Escherichia coli was established and put into operation stably for isoprene production. Compared with the axenic culture, the fermentation period of time was extended from 100 to 400 h in the co-culture and the isoprene production was increased to eightfold. For in depth understanding this novel system, the differential omics profiles were analyzed. The responses of BL21(DE3) to S. elongatus PCC 7942 were triggered by the oxidative pressure through the Fenton reaction and all these changes were linked with one another at different spatial and temporal scales. The oxidative stress mitigation pathways might contribute to the long-lasting fermentation process. The performance of this co-culture system can be further improved according to the fundamental rules discovered by the omics analysis. CONCLUSIONS: The isoprene-producing co-culture system of S. elongates-E. coli was established and then analyzed by the omics methods. This study on the co-culture system of the model S. elongates-E. coli is of significance to reveal the common interactions between photo-autotrophic and heterotrophic species without natural symbiotic relation, which could provide the scientific basis for rational design of microbial community.

2.
Theranostics ; 11(6): 2670-2690, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456566

RESUMO

Glucocorticoids are widely used in the treatment of nephritis, however, its dose-dependent side effects, such as the increased risk of infection and metabolic disturbances, hamper its clinical use. This study reports a visualized podocyte-targeting and focused ultrasound responsive glucocorticoid nano-delivery system (named as Dex/PFP@LIPs-BMS-α), which specific delivers dexamethasone (Dex) to podocyte targets and reduces systemic side effects. Methods: The glucocorticoid nano-delivery system was synthesized by a lipid thin film and a simple facile acoustic-emulsification method. This glucocorticoid nano-delivery system used BMS-470539 (BMS-α), a synthetic compound, as a "navigator" to specifically identify and target the melanocortin-1 receptor (MC-1R) on podocytes. The loaded perfluoropentane (PFP) realizes the directed "explosion effect" through ultrasound-targeted microbubble destruction (UTMD) technology under the coordination of low intensity focused ultrasound (LIFU) to completely release Dex. Results: Both in vitro and in vivo experiments have demonstrated that Dex/PFP@LIPs-BMs-α accurately gathered to podocyte targets and improved podocyte morphology. Moreover, in vivo, proteinuria and serum creatinine levels were significantly reduced in the group treated with Dex/PFP@LIPs-BMS-α, and no severe side effects were detected. Furthermore, Dex/PFP@LIPs-BMS-α, with capabilities of ultrasound, photoacoustic and fluorescence imaging, provided individualized visual guidance and the monitoring of treatment. Conclusion: This study provides a promising strategy of Dex/PFP@LIPs-BMS-α as effective and safe against immune-associated nephropathy.

3.
Eur J Clin Nutr ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462462

RESUMO

BACKGROUND: Malnutrition is prevalent that can impair multiple clinical outcomes in oncology populations. This study aimed to develop and utilize a tool to optimize the early identification of malnutrition in patients with cancer. METHODS: We performed an observational cohort study including 3998 patients with cancer at two teaching hospitals in China. Hierarchical clustering was performed to classify the patients into well-nourished or malnourished clusters based on 17 features reflecting the phenotypic and etiologic dimensions of malnutrition. Associations between the identified clusters and patient characteristics were analyzed. A nomogram for predicting the malnutrition probability was constructed and independent validation was performed to explore its clinical significance. RESULTS: The cluster analysis identified a well-nourished cluster (n = 2736, 68.4%) and a malnourished cluster (n = 1262, 31.6%) in the study population, which showed significant agreement with the Patient-Generated Subjective Global Assessment and the Global Leadership Initiative on Malnutrition criteria (both P < 0.001). The malnourished cluster was negatively associated with the nutritional status, physical status, quality of life, short-term outcomes and was an independent risk factor for survival (HR = 1.38, 95%CI = 1.22-1.55, P < 0.001). Sex, gastrointestinal symptoms, weight loss percentages (within and beyond 6 months), calf circumference, and body mass index were incorporated to develop the nomogram, which showed high performance to predict malnutrition (AUC = 0.972, 95%CI = 0.960-0.983). The decision curve analysis and independent external validation further demonstrated the effectiveness and clinical usefulness of the tool. CONCLUSIONS: Nutritional features-based clustering analysis is a feasible approach to define malnutrition. The derived nomogram shows effectiveness for the early identification of malnutrition in patients with cancer.

4.
JAMA ; 325(3): 234-243, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33464335

RESUMO

Importance: For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. Objective: To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke. Design, Setting, and Participants: Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020). Interventions: A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. Main Outcomes and Measures: The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was -10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. Results: The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, -5.1% to ∞)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, -0.8%; 95% CI, -7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, -0.5%; 95% CI, -10.3% to 9.2%). Conclusions and Relevance: Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IOR-17013568.

5.
Rapid Commun Mass Spectrom ; : e9042, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33395499

RESUMO

RATIONALE: The matrix effect is tricky in GC/MS analyses. Although several methods have been proposed to solve this problem, the results were unsatisfactory. Even fewer studies have assessed the performance of corrective methods. Hence, our study focused on assessing several common corrective methods, and then proposed a new strategy to correct for the matrix effect in GC/MS analyses. METHODS: In GC/MS analyses, the internal standard method (ISM) was employed to overcome the matrix effect during the detection of pyruvic acid (PA) in a healthy adult female's serum samples. The accuracy of ISM was evaluated by comparing it with the standard addition method (SAM). To employ the ISM-SAM strategy, correction factors (CFs) were established by combining the ISM and the SAM based on different groups. The CFs were used to normalize data onto the results of subsequent analyses. RESULTS: When using the ISM to detect pyruvic acid levels, a serious bias is observed, thereby affecting the conclusions reached. In contrast, more reliable data can be obtained after normalizing results by undertaking the ISM-SAM strategy. The feasibility of this strategy was verified by comparing it with the results of the SAM alone. The ISM-SAM strategy was successfully applied to quantify the PA levels in healthy people and nephrotic syndrome patients. CONCLUSIONS: Our results indicated that a false outcome was presented when only the ISM was used to adjust the data, and important information would be missed if the correction strategy was not carried out. Therefore, ISM-SAM, as an available correction method, should be adapted to improve the reliability of research results.

7.
Genet Test Mol Biomarkers ; 25(1): 1-11, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33470887

RESUMO

Objective: The aim of this study was to use bioinformatic analyses to identify key genes and pathways driving gastric cancer (GC). Materials and Methods: The gene expression profiles, from human gastric tissue samples were downloaded from the Gene Expression Omnibus (GSE)29272 dataset. These data revealed 284 differentially expressed genes (DEGs) that included a group upregulated in cancer tissues (n = 142) and another group that were downregulated in cancer tissues. (n = 142). These DEGs were identified using the GEO2R. We used multiple online analysis tools, including, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction networks, gene expression profiling interactive analysis (GEPIA), and the cBio Cancer Genomics Portal (cBioportal) database. Next, we identified the most significant DEGs using the Kaplan-Meier plotter (KM-plotter) database. Multiple bioinformatic platforms were used to identify candidate prognostic marker genes. We then analyzed freshly frozen GC tissues for the expression of these marker genes to validate the informatic findings. Results: We identified three DEGs related to overall survival from our analyses of the GEO data. Next, we analyzed these three DEGs in GEPIA and the cBioportal database and found that the biglycan (BGN) gene was related to invasion and metastases of GCs. This finding of differential gene expression was confirmed in a separate laboratory analysis of normal and GC tissues. In this analysis we found that high levels of BGN expression were correlated with GC clinicopathological characteristics, including microvascular tumor thrombus (p = 0.018), lymph node metastases (p = 0.013), and vessel invasion (p = 0.004). Conclusions: BGN expression levels appear to be an independent prognostic factor for predicting the survival times of GC patients.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33415743

RESUMO

BACKGROUND: The newly-proposed Global Leadership Initiative on Malnutrition (GLIM) framework is promising to gain global acceptance for diagnosing malnutrition. However, the role of machine learning in facilitating its application in clinical practice remains largely unknown. METHODS: We performed a multicenter, observational cohort study including 3998 patients with cancer. Baseline malnutrition was defined using the GLIM criteria, and the study population was randomly divided into a derivation group (n = 2998) and a validation group (n = 1000). A Classification and Regression Trees (CART) algorithm was used to develop a decision tree for classifying the severity of malnutrition in the derivation group. The model performance was evaluated in the validation group. RESULTS: The GLIM criteria diagnosed 588 patients (14.7%) with moderate malnutrition and 532 patients (13.3%) with severe malnutrition among the study population. The CART cross-validation identified five key predictors for the decision tree construction, including age, weight loss within six months, body mass index, calf circumference and the nutritional risk screening 2002 (NRS2002) score. The decision tree showed high performance, with an area under curve (AUC) of 0.964 (Kappa = 0.898, P<0.001, Accuracy = 0.955) in the validation group. Subgroup analysis showed that the model had apparently good performance in different cancers. Among the five predictors constituting the tree, age contributed the least to the classification power. CONCLUSION: Using the machine learning, we visualized and validated a decision tool based on the GLIM criteria that can be conveniently used to accelerate the pre-treatment identification of malnutrition in patients with cancer. This article is protected by copyright. All rights reserved.

9.
Oncogene ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420361

RESUMO

Myeloma cells produce excessive levels of dickkopf-1 (DKK1), which mediates the inhibition of Wnt signaling in osteoblasts, leading to multiple myeloma (MM) bone disease. Nevertheless, the precise mechanisms underlying DKK1 overexpression in myeloma remain incompletely understood. Herein, we provide evidence that hypoxia promotes DKK1 expression in myeloma cells. Under hypoxic conditions, p38 kinase phosphorylated cAMP-responsive element-binding protein (CREB) and drove its nuclear import to activate DKK1 transcription. In addition, high levels of DKK1 were associated with the presence of focal bone lesions in patients with t(4;14) MM, overexpressing the histone methyltransferase MMSET, which was identified as a downstream target gene of hypoxia-inducible factor (HIF)-1α. Furthermore, we found that CREB could recruit MMSET, leading to the stabilization of HIF-1α protein and the increased dimethylation of histone H3 at lysine 36 on the DKK1 promoter. Knockdown of CREB in myeloma cells alleviated the suppression of osteoblastogenesis by myeloma-secreted DKK1 in vitro. Combined treatment with a CREB inhibitor and the hypoxia-activated prodrug TH-302 (evofosfamide) significantly reduced MM-induced bone destruction in vivo. Taken together, our findings reveal that hypoxia and a cytogenetic abnormality regulate DKK1 expression in myeloma cells, and provide an additional rationale for the development of therapeutic strategies that interrupt DKK1 to cure MM.

10.
Health Aff (Millwood) ; 40(1): 165-169, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33400577

RESUMO

Physician consolidation into health systems increased in nearly all metropolitan statistical areas (MSAs) from 2016 to 2018. Of the 382 US MSAs, 113 had more than half of their physicians in health systems in 2018. Consolidation of physicians was most notable in the Midwest and Northeast and in small-to-midsize MSAs.

11.
J Leukoc Biol ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404078

RESUMO

Excessive monocyte activation with the development of excessive or uncontrolled release of proinflammatory cytokines often results in host tissue injury and even death in patients with pneumonia caused by the 2019 novel coronavirus. However, the changes of cytokine profiles of coronavirus disease 2019 (COVID-19) patients, as well as the underlying mechanisms that are involved, remain unknown. Using a cytokine array containing 174 inflammation-related cytokines, we found significantly altered cytokine profiles in severe COVID-19 patients compared with those in mild patients or healthy controls, and identified leptin, CXCL-10, IL-6, IL-10, IL-12, and TNF-α as the top differentially expressed cytokines. Notably, leptin showed high consistency with CXCL-10 and TNF-α in predicting disease severity, and correlated with body mass index, decreased lymphocyte counts, and disease progression. Further analysis demonstrated that monocytes in severe patients with higher leptin levels were inclined toward M1 polarization. Mechanistic studies revealed that leptin synergistically up-regulated expression levels of inflammatory cytokines and surface markers with IL-6 in monocytes through STAT3 and NF-κB signaling pathways. Collectively, our results suggest that overweight COVID-19 patients were prone to have higher leptin levels, which further activated monocytes, resulting in amplified or dysregulated immune responses. Taken together, our findings argue that leptin correlates severity of COVID-19 and may indicate a possible mechanism by which overweight patients have a greater tendency to develop severe conditions.

12.
Prenat Diagn ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411373

RESUMO

OBJECTIVES: To study the feasibility of using unbalanced embryos as a reference in distinguishing euploid carrier and non-carrier embryos by SNP array-based preimplantation genetic testing (PGT) for reciprocal translocations. METHODS: After comprehensive chromosome screening (CCS), euploid embryos were identified as normal or carriers using a family member as a reference. Next, unbalanced embryos were used as a reference, and the results were compared with the previous ones. Karyotypes of transferred embryos were validated by prenatal diagnosis. RESULTS: Of 995 embryos from 110 couples, 288 were found to be euploid. Using a family member as a reference, 142 and 144 embryos were tested to be euploid non-carrier and carrier respectively, and the remaining 2 embryos were undetermined. When unbalanced embryos were selected as references, all the results were consistent with the previous ones. A total of 107 embryos were transferred, resulting in 66 clinical pregnancies. Karyotypes of prenatal diagnosis were all in accordance with the results of tested embryos. CONCLUSIONS: SNP array-based haplotyping is a rapid and effective way to distinguish between euploid carrier and non-carrier embryos. In case no family member is available as a reference, unbalanced embryos can be used for identification of euploid carrier and non-carrier embryos. This article is protected by copyright. All rights reserved.

13.
Phys Chem Chem Phys ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33458726

RESUMO

In this work, combining first-principles calculations with kinetic Monte Carlo (KMC) simulations, we constructed an irregular carbon bridge on the graphene surface and explored the process of H migration from the Pt catalyst to carbon bridge, and further migration to the graphene surface. The calculated reaction diagrams show that the hydrogen atoms can easily migrate from the Pt cluster to the carbon bridge with a low barrier of 0.22-0.86 eV, and KMC simulations indicate that the migration reactions can take place at intermediate temperatures (91.9-329.5 K). Our research clarified the role of the carbon bridge: (1) the close combination of Pt clusters and carbon bridges reduces H2 adsorption enthalpy, which facilitates the spillover of H atoms from the Pt cluster to the carbon bridges and (2) the unsaturated carbon atoms on the carbon bridges have radical character and tend to bind radical H atoms. The subsequent study shows that the F atoms decorated on graphene can greatly reduce the migration barrier of H atoms from the carbon bridge to graphene. With F atoms decorated, the carbon atoms are in an electron-deficient state, which have a strong ability to bind the hydrogen atoms, and it promotes the migration of H atoms to the graphene surface. The migration barrier and reaction temperature are reduced to 0.72 eV and 279 K, respectively.

15.
CNS Neurosci Ther ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459523

RESUMO

AIMS: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic-related neurodegeneration. The aim of the present study was to investigate whether 5-PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to autophagy. METHODS: 5-PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a range of inflammatory factors. RESULTS: Although there was no significant improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL decreased significantly following the administration of 5-PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5-PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms of apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5-PAHSA. CONCLUSION: We found that 5-PAHSA can enhance autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice.

16.
Theranostics ; 11(4): 1795-1813, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33408782

RESUMO

Background: Ovarian cancer is a fatal malignant gynecological tumor. Ovarian cancer stem cells (OCSCs) contribute to resistance to chemotherapy. The polycomb group protein enhancer of zeste homolog 2 (EZH2) plays a key role in maintaining CSCs. Here, we aimed to investigate the specific mechanism by which EZH2 regulates CSCs to result in chemoresistance and poor prognosis of ovarian cancer. Methods: We used a nude mouse model to obtain a cell line enriched for OCSCs, named SK-3rd cells. The CRISPR and Cas9 endonuclease system was used to establish an EZH2-knockout SK-3rd ovarian cancer cell line. High-throughput PCR array and bioinformatics methods were used to screen the EZH2 target involved in CSC stemness. A luciferase reporter assay and chromatin immunoprecipitation assay were performed to identify activation of CHK1 by EZH2. We evaluated associations between EZH2/CHK1 expression and the chemoresistance and prognosis of ovarian cancer patients. Results: EZH2 plays a critical role in maintaining ovarian CSC stemness and chemo-resistance. CHK1 is an EZH2 target involved in CSC stemness. Knockdown of EZH2 in ovarian CSCs decreased CHK1 expression, while CHK1 overexpression was sufficient to reverse the inhibitory effect on spheroid formation and chemoresistance caused by repression of EZH2. In addition, EZH2 was also shown to play a unique role in activating rather than repressing CHK1 signaling through binding to the CHK1 promoter in epithelial ovarian cancer cells. Finally, in clinical samples, ovarian cancer patients with high levels of EZH2 and CHK1 not only were more resistant to platinum but also had a poorer prognosis. Conclusions: Our data revealed a previously unidentified functional and mechanistic link between EZH2 levels, CHK1 signaling activation, and ovarian CSCs and provided strong evidence that EZH2 promotes ovarian cancer chemoresistance and recurrence.

17.
Int Immunopharmacol ; 90: 107052, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310296

RESUMO

Numerous studies have focused on the treatment of melanoma, but the current therapies for melanoma have limited therapeutic effects. To find a more effective therapy for melanoma, we combined artificially designed CpG ODN (cytosine-phosphate-guanine oligodeoxynucleotides) and siRNAs (small-interfering ribonucleic acids) targeting PD-1 (programmed cell death protein 1), which were delivered by attenuated Salmonella to treat melanoma in mice, and explored the underlying antitumor mechanisms. We found that mice receiving the combination therapy had the smallest tumor size and the longest survival time. The possible mechanisms underlying this phenomenon include pathways mediated by cyclin D1, p-STAT3 (phosphorylated signal transducers and activators of transcription protein 3), MMP2 (matrix metallopeptidase 2) and cleaved caspase 3, since after treatment, the expression of cyclin D1, p-STAT3, and MMP2 decreased but that of cleaved caspase 3 increased; additional mechanisms include increases in the recruitment of immune cells to tumor sites and in the number of immune cells in mouse spleens and the upregulation of TNF-α (tumor necrosis factor) and IL-6 (interleukin 6). We demonstrated that the combination therapy composed of CpG ODN and PD-1-siRNA delivered by attenuated Salmonella exhibited a strong ability to inhibit melanoma and improve the antitumor immune responses of tumor-bearing mice.

18.
Br J Cancer ; 124(1): 270-280, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33239678

RESUMO

BACKGROUND: Emerging evidence suggests the involvement of caudal-related homoeobox transcription factor 2 (CDX2) in tumorigenesis of various cancers. Although CDX2 functions in cancer invasion and metastasis, fewer studies focus on the role of CDX2 during the induction of epithelial-mesenchymal transition (EMT) in colorectal cancer (CRC). METHODS: Immunohistochemical analysis of CDX2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of CDX2 in the invasion and metastasis of CRC. RESULTS: CDX2 was downregulated in CRC tissues and reduced CDX2 correlated with poor prognosis. Knockdown of CDX2 promoted colon cancer cell invasion in vitro and facilitated liver metastasis in vivo with inducing EMT phenotypes. Further investigation indicated that CDX2 retarded Akt and GSK-3ß phosphorylation, and thereby diminished Snail expression, ß-catenin stabilisation and nuclear translocation. The depletion of ß-catenin neutralised the regulation of Slug and ZEB1 by CDX2 knockdown. Mechanistically, CDX2 antagonised PI3K/Akt activity in CRC by modulating PTEN expression. CDX2 directly bound to the promoter of PTEN and transactivated its expression. CONCLUSIONS: Our study first uncovered that CDX2 inhibits EMT and metastasis of CRC by regulation of Snail expression and ß-catenin stabilisation via transactivation of PTEN expression.

19.
Phytomedicine ; 81: 153367, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33260064

RESUMO

BACKGROUND: Treatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy. METHODS: From January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients). RESULTS: A total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups. CONCLUSIONS: Our findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.


Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Combinação de Medicamentos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Lopinavir/efeitos adversos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Ritonavir/efeitos adversos , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
J Proteome Res ; 20(1): 972-981, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33231461

RESUMO

Antibiotic-resistant bacteria are a serious threat to human and animal health. Metabolite-enabled eradication of drug-resistant pathogens is an attractive strategy, and metabolite adjuvants, such as fumarate, are used for restoring the bactericidal ability of antibiotics. However, we show that metabolites in the TCA cycle increase the viability of Edwardsiella tarda against chloramphenicol (CAP), based on the survival assay of differential metabolites identified by LC-MS/MS. Furthermore, NADPH promotes CAP resistance in the CAP-resistant strain, while oxidants restore the bactericidal ability. Finally, we show that the intracellular redox state determines the sensitivity to CAP, and the total antioxidative capacity is decreased significantly in the antibiotic-resistant strain. Considering that the metabolites promote CAP resistance, metabolite adjuvants should be applied very cautiously. Overall, our research expands on the knowledge that the redox state is related to the bactericidal ability of CAP.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA