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1.
BMJ Open ; 11(2): e040718, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608398

RESUMO

INTRODUCTION: Acute kidney injury (AKI) is one of the most common organ dysfunction in sepsis, and increases the risk of unfavourable outcomes. Renal replacement therapy (RRT) is the predominant treatment for sepsis-associated AKI (SAKI). However, to date, no prospective randomised study has adequately addressed whether initiating RRT earlier will attenuate renal injury and improve the outcome of sepsis. The objective of the trial is to compare the early strategy with delayed strategy on the outcomes in patients with SAKI in the intensive care unit (ICU). METHODS AND ANALYSIS: This is a large-scale, multicentre, randomised controlled trial about SAKI. In total, 460 patients with sepsis and evidence of AKI stage 2 of Kidney Disease Improving Global Outcomes (KDIGO) will be recruited and equally randomised into the early group and the delay group in a ratio of 1:1. In the early group, continuous RRT (CRRT) will be started immediately after randomisation. In the delay group, CRRT will initiated if at least one of the following criteria was met: stage 3 of KDIGO, severe hyperkalaemia, pulmonary oedema, blood urea nitrogen level higher than 112 mg/dL after randomisation. The primary outcome is overall survival in a 90-day follow-up period (90-day all-cause mortality). Other end points include 28-day, 60-day and 1-year mortality, recovery rate of renal function by day 28 and day 90, ICU and hospital length of stay, the numbers of CRRT-free days, mechanical ventilation-free days and vasopressor-free days, the rate of complications potentially related to CRRT, CRRT-related cost, and concentrations of inflammatory mediators in serum. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2017-31-ks-01). Participants will be screened and enrolled from patients in the ICU with SAKI by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION: NCT03175328.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33493666

RESUMO

Ammonia is a major pollutant in aquatic environments and poses a considerable threat to the survival of fish. In this study, we investigated the toxic effects of ammonia on the hematological and biochemical parameters, oxidative stress, and immune responses in Takifugu rubripes. Juvenile T. rubripes (average weight 246.17 ± 3.54 g) were exposed to different concentrations of ammonia (0, 5, 50, 100, and 150 mg/L) for 96 h. The results showed that the hematological parameters (hemoglobin, hematocrit, red blood cell, and white blood cell count) were significantly reduced in response to ammonia exposure. Of the plasma components, such as serum total protein, albumin, glucose, glutamic-oxalacetic transaminase, and glutamic-pyruvic transaminase, were significantly altered in response to ammonia exposure. Additionally, the levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx) were increased after exposure to low concentration ammonia exposure. However, when fish were exposed to a high concentration of ammonia, these parameters showed the opposite trend, suggesting that an increase in antioxidant enzymes during the early stages of ammonia exposure may contribute to the removal of the induced reactive oxygen species (ROS) and protect the cells from oxidative damage. However, as the ammonia concentration and exposure time increased, the overproduction of ROS accelerated the depletion of antioxidant enzymes. Ammonia exposure significantly increased the expression of heat shock proteins (HSP70 and HSP90). Ammonia poisoning elevated gene expressions of TLR-3, TNF-α, IL-6, IL-12, and IL-1ß in the gills, causing an inflammatory response. Our findings provide new insights into the mechanisms involved in ammonia-induced aquatic toxicology in marine fish, which may aid in their captive management.

3.
Ying Yong Sheng Tai Xue Bao ; 32(1): 23-30, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33477209

RESUMO

We examined nutrient release and ecological stoichiometric characteristics of litters under N deposition in an evergreen broadleaved forest in Mopan Mountain in central Yunnan. Nylon net bag method was used for in situ decomposition of leaf litter and twig litter. There were four treatments, including control (CK, 0 g N·m-2·a-1), low nitrogen (LN, 5 g N·m-2·a-1), medium nitrogen (MN, 15 g N·m-2·a-1), and high nitrogen (HN, 30 g N·m-2·a-1). The results showed that after one year of N addition, the contents of C and N in leaf litter, twig litter and soil increased gradually with the increases of N addition rates, with increases of 0.3%-8.2% and 4.9%-69.0%, respectively. C/N gradually decreased with increasing N addition rates, with a decrease of 0.8%-37.8%. There was no significant difference in P content, C/P and N/P of twig litter under different treatments. Treatment duration and N application rate significantly affected the N and P contents and stoichiometric ratios of leaf litter, twig litter and soil. During the 1-year decomposition process, the residual rates of C, N and P in litters were successively in the modes of release, leaching-enriched-released and leaching-enriched. Exogenous N addition significantly inhibited the release process of C, N and P in litter. The contents of C and P in soil were significantly positively correlated with the contents of N and P in litter, while the contents of N in soil were significantly positively correlated with the contents of C and N in litter. There was a significant correlation of stoichiometric characteristics between litter and soils of evergreen broadleaved forest under N deposition. Our results were helpful to understand the response mechanism of litter decomposition process of forest ecosystem to N deposition.


Assuntos
Ecossistema , Nitrogênio , China , Florestas , Nitrogênio/análise , Nutrientes , Folhas de Planta/química , Solo
4.
BMC Bioinformatics ; 21(Suppl 16): 543, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33323106

RESUMO

BACKGROUND: Although biomedical publications and literature are growing rapidly, there still lacks structured knowledge that can be easily processed by computer programs. In order to extract such knowledge from plain text and transform them into structural form, the relation extraction problem becomes an important issue. Datasets play a critical role in the development of relation extraction methods. However, existing relation extraction datasets in biomedical domain are mainly human-annotated, whose scales are usually limited due to their labor-intensive and time-consuming nature. RESULTS: We construct BioRel, a large-scale dataset for biomedical relation extraction problem, by using Unified Medical Language System as knowledge base and Medline as corpus. We first identify mentions of entities in sentences of Medline and link them to Unified Medical Language System with Metamap. Then, we assign each sentence a relation label by using distant supervision. Finally, we adapt the state-of-the-art deep learning and statistical machine learning methods as baseline models and conduct comprehensive experiments on the BioRel dataset. CONCLUSIONS: Based on the extensive experimental results, we have shown that BioRel is a suitable large-scale datasets for biomedical relation extraction, which provides both reasonable baseline performance and many remaining challenges for both deep learning and statistical methods.


Assuntos
Pesquisa Biomédica , Mineração de Dados , Software , Bases de Dados como Assunto , Humanos , Aprendizado de Máquina , Redes Neurais de Computação
5.
Transl Oncol ; 14(1): 100889, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065386

RESUMO

Small cell lung cancer (SCLC), an aggressive and devastating malignancy, is characterized by rapid growth and early metastasis. Although most patients respond to first-line chemotherapy, the majority of patients rapidly relapse and have a relatively poor prognosis. Fortunately, immunotherapy, mainly including antibodies that target the cytotoxic T lymphocyte antigen-4 (CTLA-4), checkpoints programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) to block immune regulatory checkpoints on tumor cells, immune cells, fibroblasts cells and endothelial cells, has achieved the milestone in several solid tumors, such as melanoma and non-small-cell lung carcinomas (NSCLC). In recent years, immunotherapy has made progress in the treatment of patients with SCLC, while its response rate is relatively low to monotherapy. Interestingly, the combination of immunotherapy with other therapy, such as chemotherapy, radiotherapy, and targeted therapy, preliminarily achieve greater therapeutic effects for treating SCLC. Combining different immunotherapy drugs may act synergistically because of the complementary effects of the two immune checkpoint pathways (CTLA-4 and PD-1/PD-L1 pathways). The incorporation of chemoradiotherapy in immunotherapy may augment antitumor immune responses because chemoradiotherapy can enhance tumor cell immunogenicity by rapidly inducing tumor lysis and releasing tumor antigens. In addition, since immunotherapy drugs and the molecular targets drugs act on different targets and cells, the combination of these drugs may achieve greater therapeutic effects in the treatment of SCLC. In this review, we focused on the completed and ongoing trials of the combination therapy for immunotherapy of SCLC to find out the rational combination strategies which may improve the outcomes for SCLC.

6.
Cancer Med ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33058542

RESUMO

Breast cancer (BC) poses one of the major threats to female's health worldwide. Immune infiltration in BC is a key representative of the tumor microenvironment and has been proven highly relevant for prognosis. The role of the FREM1 (FRAS1-Related Extracellular Matrix 1) gene in carcinoma has not studied, moreover, the underlying mechanism remains largely unknown. This study aims to investigate the expression profile and potential action of FREM1 on BC progression. We applied series of bioinformatic methods as well as immunohistochemistry (IHC) and immunofluorescence (IF) to analyze FREM1 expression profile, its relationship with clinicopathological characteristics, impact on clinical outcomes, relevant functions, correlation with immune infiltration in BC. The results demonstrated that FREM1 had a dramatically reduced expression in BC tissues, possessed an inverse correlation with stage, age, and metastasis, and exhibited a higher level in invasive lobular breast carcinoma than in ductal one. Furthermore, decreased FREM1 expression was often associated with estrogen receptor (ER)/progesterone receptor (PR) negative and triple negative breast carcinoma (TNBC) status while human epidermal growth factor 2 (Her-2) positive status, and considerably correlated with a worse overall survival (OS) and recurrence-free survival (RFS). Meanwhile, the univariate/multivariate Cox model revealed that low-FREM1 expression can be an independent prognostic factor for BC. Additionally, FREM1 was mainly involved in the cell metabolism and immune cells infiltration. Moreover, IHC and IF demonstrated a positive correlation of its expression with the immune infiltrating levels of CD4+ , CD8+ T cells, and CD86+ M1 macrophages while a negative correlation with CD68+ pan-macrophages and CD163+ M2 macrophages. These findings suggest that FREM1 can be a potential biomarker for evaluating the immune infiltrating status, and the BC prognosis.

8.
Onco Targets Ther ; 13: 8475-8493, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922036

RESUMO

Background: Gastrin (GAST) is a well-known hormone regulating gastric biofunctions in the secretion of acid and maintaining its structural integrity. Furthermore, the dysregulation of GAST is also involved in the development of various forms of cancer. However, there are some limitations for illustrating the cellular regulation of GAST and its regulatory mechanisms in gastric malignant transformation and the potential epigenetic regulators systematically. Methods: We explored the role of GAST expression in gastric cancer (GC) and normal tissues with the clinical features and investigated the potential relationship between GAST and STAT3/MMP11 pathway by gain or loss of function analyses. Besides, based on our microRNA/mRNA expression profiles, miR-30a-3p was the potential epigenetic regulator and additional experiments were performed to identify the hypothesis. Results: Elevated GAST expression was frequently detected in GC and was associated with worse outcomes (p<0.001). And we firstly demonstrated that GAST was negatively regulated by miR-30a-3p. Moreover, GAST induced GC cell proliferation, migration and invasion mediating STAT3/MMP11 pathway in this study. Conclusion: MiR-30a-3p was the promising suppressor gene through negatively regulating the expression of GAST, and dysregulation of GAST was a prognostic signature associated cell proliferation and metastasis through STAT3/MMP11 pathway in GC.

9.
Cell Immunol ; 356: 104176, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32736174

RESUMO

CSL(CBF1, Su(H) and LAG-1)-dependent Hes-1 signaling plays an important part in regulating Th17 cell differentiation. However, little is known about influence of CSL-independent Deltex-1 signaling on this subset. The current focus is on roles of the Deltex-1 signaling in the Th17 cell differentiation. IL-17-producing CD4+ T cell subpopulation could be induced in vitro by treatment of both IL-6 and TGF-ß. This could be reversed by knockdown of the deltex-1 gene, following the attenuation of retinoic acid-related orphan receptor γt (RORγt) and its DNA-binding activity in nuclei. Subsequently, Th17-associated cytokines generated by the treated cells were also diminished by the inhibition of Deltex-1 signaling, but the production of IL-10 was enhanced. Contrary to the alteration of RORγt, both zinc-finger transcription factor-3 (GATA3) and transcription factor Forkhead box P3 (Foxp3) were augmented at their mRNA and protein levels as well as DNA-binding activities with the emerging phenotypes of the corresponding cellular subpopulation and T-bet (encoded by TBX21) was not changed. These results reveal for the first time that Deltex-1 is indispensible for the IL-6 and TGF-ß treatment-triggered differentiation of Th17 cells, indicating that CSL-independent Deltex-1 signaling favors naïve CD4+ T cells to deviate into Th17 cells via the enhancement of RORγt/IL-17A.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32612577

RESUMO

Purpose: This systematic review and meta-analysis was carried out with the aim of investigating the relationship between Foxp3 polymorphisms (rs3761547, r3761548, and rs3761549) and the risk of Graves' disease (GD). Methods: Four online database including PubMed, EMBASE, ISI Web of Science, and CNKI were searched to identify observational studies that evaluated the association between Foxp3 polymorphisms and risk of GD. The strength of associations was indicated as odds ratio (OR) and corresponding 95% confidence interval (95%CI) under the allelic model. The Newcastle-Ottawa Scale was used to assess the methodological quality. Pre-specified subgroup analysis and sensitivity analysis were performed using RevMan 5.3 software. Publication bias was detected by Egger's and Begg's tests. Results: Eight case control studies involving 3,104 GD patients and 3,599 healthy controls were included. The methodological quality of included studies was considered to be moderate to high. The results of our meta-analysis supported no association of rs3761547 and risk of GD in Asians (OR: 1.07, 95%CI 0.97, 1.19, P = 0.18). Evidence for rs3761547 and GD risk among Caucasians was still limited because only one study reported marginally increased risk of GD with the minor allele of rs3761547 (P = 0.04). The variant allele of both rs3761548 (OR: 1.31, 95%CI 1.04, 1.64; P = 0.02) and rs3761549 (OR: 1.30, 95%CI 1.03, 1.64; P = 0.03) was associated with increased risk of GD among Asians, but neither polymorphism turned out to be related with GD among Caucasians. Conclusion: Rs3761548 and rs3761549 polymorphisms in Foxp3 were associated with risk of GD among Asians, possibly due to suppressed function of regulatory T cells and augmented autoimmune response. Their genetic effect among Caucasians remained to be confirmed by future large-scale and well-designed studies.

11.
Turk J Gastroenterol ; 31(6): 474-481, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32721919

RESUMO

BACKGROUND/AIMS: Intraoperative blood loss more than 400 mL during gastrointestinal surgery is an independent predictor of mortality. Desmopressin acetate (DDAVP) could reduce perioperative blood loss. Few studies have prompted concerning the effects of DDAVP on gastrointestinal surgery. This study was to investigate whether DDAVP can decrease blood loss in patients with massive hemorrhage undergoing gastrointestinal surgery. MATERIALS AND METHODS: A multiple-centers, double-blind clinical trial was conducted, patients who underwent gastrointestinal surgery were recruited from 3 hospitals, randomly assigned to two different groups. Patients in the treatment group received desmopressin 0.3 ug/kg,30 min once a day after surgery, patients in the control group received 50 ml saline for 30 min. The primary outcome was the changes of hemoglobin at 24 hours after the surgery. And the secondary outcomes included coagulation function, urine volume, serum creatinine, and safety. RESULTS: There were 59 patients enrolled between 1 June 2015 and 1 June 2017. At 24hr.after surgery, a decrease in hemoglobin in the DDAVP group was significantly lower than that in the NS group (-5.0±6.9 g/L vs. -10.2±9.3g/L, p=0.03). Sonoclot® showed that the platelet function in the DDAVP group was higher than that in NS group at 24 hr. (2.56 ±0.59 vs. 1.91 ±0.72, p<0.05). There was no difference in urine volume and serum creatinine at 24 hr. between two group. CONCLUSION: DDAVP could reduce post-operation blood loss in patients with massive hemorrhage undergoing surgery by improving the platelet function. We observed no difference in urine volume and serum creatinine in two groups.

12.
Kaohsiung J Med Sci ; 36(10): 786-792, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32492291

RESUMO

Parkinson's disease (PD) is a neurological degenerative disorder that is partially induced by inflammation in the neural system. To explore the roles of disordered microRNAs in the development of PD, we screened 10 miRNAs in the brain samples of 15 postmortem PD patients and 10 postmortem healthy controls by qRT-PCR. The direct targets of miRNAs were predicted by informatics tools and further confirmed by dual luciferase assay and immunoblotting. The function of miRNAs in regulating NF-κB/p65 translocation was examined by immunoblotting, and the overactivation of NF-κB signaling was examined by ELISA. The relationship between dysregulated miRNAs and cytokines was analyzed by correlation analysis. Three miRNAs were found to be reduced in the brains of patients with PD. KPNB1, KPNA3, and KPNA4 were identified as direct targets of miR-218, miR-124, and miR-144. Additionally, KPNA3 was identified as a direct target of miR-124, and KPNA4 was a direct target of both miR-124 and miR-218. The p65 translocation from the cytoplasm to the nucleus was repressed by miR-124, miR-218, and miR-144 in the SH-SY5Y cells. The NF-κB signaling pathway was overactivated after miRNA inhibitor transfection. The upregulation of KPNB1, KPNA3, and KPNA4 in the brain samples of PD patients was confirmed by immunoblotting, and negative correlations were found between dysregulated miRNAs and cytokines. In conclusion, we identified that the downregulation of miR-218, miR-124, and miR-144 in the brain was related to PD via activation of NF-κB signaling, helping to unveil the role played by dysregulated miRNAs in the pathogenesis of PD and provide new potential targets for PD treatment.

13.
Front Psychiatry ; 11: 456, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528327

RESUMO

Objective: Neuroimaging-based brain signatures may be informative in identifying patients with psychosis who will respond to antipsychotics. However, signatures that inform the electroconvulsive therapy (ECT) health care professional about the response likelihood remain unclear in psychosis with radiomics strategy. This study investigated whether brain structure-based signature in the prediction of ECT response in a sample of schizophrenia patients using radiomics approach. Methods: This high-resolution structural magnetic resonance imaging study included 57 patients at baseline. After ECT combined with antipsychotics, 28 and 29 patients were classified as responders and non-responders. Features of gray matter were extracted and compared. The logistic regression model/support vector machine (LRM/SVM) analysis was used to explore the predictive performance. Results: The regularized multivariate LRM accurately discriminated responders from non-responders, with an accuracy of 90.91%. The structural features were further confirmed in the validating data set, resulting in an accuracy of 87.59%. The accuracy of the SVM in the training set was 90.91%, and the accuracy in the validation set was 91.78%. Conclusion: Our results support the possible use of structural brain feature-based radiomics as a potential tool for predicting ECT response in patients with schizophrenia undergoing antipsychotics, paving the way for utilization of markers in psychosis.

14.
BMC Med Imaging ; 20(1): 50, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32408867

RESUMO

BACKGROUND: To investigate the ability of amide proton transfer (APT) weighted magnetic resonance imaging (MRI), arterial spin labeling (ASL), diffusion weighted imaging (DWI) and the combination for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs). METHODS: Twenty-seven patients including nine LGGs and eighteen HGGs underwent conventional, APT, ASL and DWI MRI with a 3.0-T MR scanner. Histogram analyses was performed and quantitative parameters including mean apparent diffusion coefficient (ADC mean), 20th-percentile ADC (ADC 20th), mean APT (APT mean), 90th-percentile APT (APT 90th), relative mean cerebral blood flow (rCBF mean) and relative 90th-percentile CBF (rCBF 90th) were compared between HGGs and LGGs. The diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis of each parameter and their combination. Correlations were analyzed among the MRI parameters and Ki-67. RESULTS: The APT values were significantly higher in the HGGs compared to the LGGs (p <  0.005), whereas ADC values were significantly lower in HGGs than LGGs (P <  0.0001). The ADC 20th and APT mean had higher discrimination abilities compared with other single parameters, with the area under the ROC curve (AUC) of 0.877 and 0.840. Adding ADC parameter, the discrimination ability of APT and rCBF significantly improved. The ADC was negatively correlated with the APT and rCBF value, respectively, while APT value was positively correlated with rCBF value. Significant correlations between ADC values and Ki-67 were also observed. CONCLUSIONS: APT and DWI are valuable in differentiating HGGs from LGGs. The combination of APT, DWI and ASL imaging could improve the ability for discriminating HGGs from LGGs.

15.
J Anal Methods Chem ; 2020: 8548126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32399312

RESUMO

Sedimentary phosphorus (P) forms are important representatives of P sources and their bioavailability as well as the potential of sediments to release P in water. In this study, surface sediments along a transect of the Changjiang Estuary and two transects along the Andong salt marsh in the southwest of Hangzhou Bay were subjected to the elucidation of sedimentary P species using the standards, measurements, and testing (SMT) and sequential extraction (SEDEX) methods. The results showed that the mean sedimentary P forms elucidated by the SMT method were as follows: organic P (OP; ∼11-14 mg/kg; ∼30-45% of total P; TP) > apatite P (∼5-15 mg/kg; ∼21-36% TP) > Fe/Al-P (∼8-14 mg/kg; ∼31-34% TP), with inorganic P (IP) composing 54-70% of TP. The mean sedimentary P forms elucidated by the SEDEX method were as follows: authigenic P (∼54-68 mg/kg; ∼41-46% TP) > extractable P (Ex-P; ∼36-53 mg/kg; ∼28-34%) > Fe-P (∼21-27 mg/kg; ∼13-19%) > OP (∼8.7-13 mg/kg; ∼5-8%) > detrital P (De-P; ∼2 mg/kg; ∼1-2% TP), with IP composed of ∼91-94% TP. These results showed that the SEDEX method elucidated higher concentrations of sedimentary P forms as well as the TP from these coastal sediments although the SMT method had the advantage of being more economic and faster. The results of both the SMT and SEDEX methods showed that the Andong salt marsh and Changjiang Estuary sediments had much bioavailable P. The mean percentages of bioavailable P from the SMT and SEDEX methods were ∼64-74% and 52-56% of TP, respectively, indicating that these sediments were prone to release P to the coastal areas.

16.
Front Chem ; 8: 140, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32257994

RESUMO

Biochar is widely used for the adsorptive removal of Cd from water and soil, but the Cd-enriched biochar produced carries a risk of secondary pollution. In this work, biochar derived from rice straw was used to adsorb Cd from plating wastewater. The Cd-enriched biochar showed a saturated adsorption capacity of about 63.5 mg/g and could be recycled and used in a mesoporous carbon-supported CdS (CdS@C) photocatalyst after pyrolysis carbonization and a hydrothermal reaction. The results demonstrated that the as-prepared CdS@C photocatalyst contained mixed cubic and hexagonal CdS phases, with a considerably lower band gap (2.1 eV) than pure CdS (2.6 eV). CdS@C exhibited an enhanced photocatalytic performance for the degradation of organic dyes under visible light irradiation compared with pure CdS due to its excellent light-harvesting capacity and efficient electron-hole separation. Moreover, the continuous formation of active species (h+, •OH, and O2•-) was responsible for the photodegradation of organic dyes using CdS@C. This work provides new insights for the safe disposal of Cd-enriched wastewater and for improving the economic viability of Cd-contaminated resources by recovering a value-added photocatalyst.

17.
Oncol Lett ; 19(3): 2163-2174, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32194714

RESUMO

ZW10 interacting kinetochore protein (ZWINT) is an essential component for the mitotic spindle checkpoint and has been reported to be upregulated in numerous types of human cancer. Nonetheless, its role in breast cancer (BC) remains unclear. Herein, it was demonstrated that the expression of ZWINT was significantly higher in BC than in normal breast tissues, on the basis of integrated analysis of bioinformatics studies, cancer database analyses and immunohistochemical detection. Elevated ZWINT levels were associated with a number of clinicopathological characteristics in patients with BC. These characteristics include: i) Positive human epidermal growth factor receptor 2 expression; ii) triple-negative BC; iii) younger age; iv) basal-like subtype; and v) greater Scarff-Bloom-Richardson grades. Additionally, prognostic analysis indicated that shorter relapse-free survival, overall survival and metastatic relapse-free survival may be associated with high ZWINT expression. A total of 16 pathways associated with high ZWINT expression, including Myc targets V1/2, DNA repair and mitotic spindle pathways, were identified using Gene Set Enrichment Analysis. In addition, a positive correlation between cyclin-dependent kinase 1 (CDK1) and ZWINT mRNA expression was identified by co-expression analysis. The present study suggested that ZWINT may serve as an effective prognostic biomarker for BC. In addition, ZWINT may be implicated in the CDK1-mediated initiation and progression of BC. However, further research is required to understand the role of ZWINT in BC.

18.
Int J Mol Med ; 45(4): 1112-1120, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31985020

RESUMO

The present study sought to investigate the correlation between adipose cytokines (visfatin, leptin and adiponectin) and markers of multiple myeloma bone disease, and to determine the effects and mechanism of action of adiponectin on the differentiation and maturation of osteoclasts in multiple myeloma (MM). The levels of visfatin, leptin and adiponectin were measured. Their association with the indices of myeloma tumor load and bone disease were analyzed. Reverse transcription­quantitative PCR was used to detect the expression of receptor activator of nuclear factor­κB ligand (RANKL), osteoclast associated Ig­like receptor (OSCAR), tartrate­resistant acid phosphatase (TRAP) and Cathepsin K genes. Flow cytometry was used to detect the expression of adiponectin receptor 1 (AdipoR1) and the phosphorylation of the mechanistic target of rapamycin kinase (mTOR) pathway­associated proteins mTOR and eukaryotic translation initiation factor 4E­binding protein (4EBP1). There were no significant correlations among leptin, visfatin and the indexes of myeloma tumor load and bone disease. Serum adiponectin levels were significantly lower in patients with newly diagnosed multiple myeloma compared with healthy volunteers (12.37±3.13 vs. 13.80±0.95; P<0.05). The number of mature osteoclasts in the adiponectin group was lower compared with in the control group. Adiponectin also inhibited the mRNA expression of the osteoclast­associated factors RANKL, OSCAR, TRAP and Cathepsin K. Comparison between the non­adiponectin group and the adiponectin group revealed that adiponectin increased the expression of AdipoR1 on the surface of osteoclast precursor cells (26.21±4.27% vs. 29.86±6.23%; P<0.05) and reduced the expression of phosphorylated (p­)mTOR (7.89±1.00% vs. 5.91±1.26%; P<0.05) and p­4EBP1 (26.78±5.00% vs. 22.49±4.24%; P<0.05). The p­mTOR and p­4EBP1 levels in the adiponectin + MHY1485 (an mTOR signaling pathway­specific agonist) group were significantly higher compared with those in the adiponectin group. It was revealed that adiponectin may inhibit osteoclast differentiation and maturation via the mTOR pathway. In conclusion, adiponectin inhibits the differentiation and maturation of osteoclasts by increasing the expression of AdipoR1 and reducing the phosphorylation levels of mTOR and 4EBP1 in patients with MM.


Assuntos
Adiponectina/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Mieloma Múltiplo/tratamento farmacológico , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Serina-Treonina Quinases TOR/genética
19.
J Biomater Sci Polym Ed ; 31(3): 376-393, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31724490

RESUMO

Biological modifications of the silk fibroin (silk) material have broad applications in textiles, biomedical materials and other industrial materials. It is economical to incorporate nanoparticles to the biosynthesis of silk fibroin by adding them to silkworm larval diets. This strategy may result in the rapid stable production of modified silk. Glucose-coated silver nanoparticles (AgNPs) were used to improve the AgNPs' biocompatibility, and the AgNPs were efficiently incorporated into silk by feeding. Larvae fed with AgNPs produced silk with significantly improved antibacterial properties and altered silk secondary structures. Both positive and negative effects on the growth and synthesis of silk proteins were observed after different AgNPs doses. Larvae feeding with low concentration of 0.02% and medium 0.20% AgNPs have greater transfer efficiencies of AgNPs to silk compared with feeding high concentration of 2.00% AgNPs. In addition, the elongation and tensile strength of the produced silk fibers were also significantly increased, with greater mammalian cell compatibility. The appropriate AgNPs concentration in the diet of silkworms can promote the synthesis of silk proteins, enhance their mechanical properties, improve their antibacterial property and inhibit the presence of Gram-negative bacteria.

20.
Radiology ; 294(1): 19-28, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746687

RESUMO

Background Deep learning (DL) algorithms are gaining extensive attention for their excellent performance in image recognition tasks. DL models can automatically make a quantitative assessment of complex medical image characteristics and achieve increased accuracy in diagnosis with higher efficiency. Purpose To determine the feasibility of using a DL approach to predict clinically negative axillary lymph node metastasis from US images in patients with primary breast cancer. Materials and Methods A data set of US images in patients with primary breast cancer with clinically negative axillary lymph nodes from Tongji Hospital (974 imaging studies from 2016 to 2018, 756 patients) and an independent test set from Hubei Cancer Hospital (81 imaging studies from 2018 to 2019, 78 patients) were collected. Axillary lymph node status was confirmed with pathologic examination. Three different convolutional neural networks (CNNs) of Inception V3, Inception-ResNet V2, and ResNet-101 architectures were trained on 90% of the Tongji Hospital data set and tested on the remaining 10%, as well as on the independent test set. The performance of the models was compared with that of five radiologists. The models' performance was analyzed in terms of accuracy, sensitivity, specificity, receiver operating characteristic curves, areas under the receiver operating characteristic curve (AUCs), and heat maps. Results The best-performing CNN model, Inception V3, achieved an AUC of 0.89 (95% confidence interval [CI]: 0.83, 0.95) in the prediction of the final clinical diagnosis of axillary lymph node metastasis in the independent test set. The model achieved 85% sensitivity (35 of 41 images; 95% CI: 70%, 94%) and 73% specificity (29 of 40 images; 95% CI: 56%, 85%), and the radiologists achieved 73% sensitivity (30 of 41 images; 95% CI: 57%, 85%; P = .17) and 63% specificity (25 of 40 images; 95% CI: 46%, 77%; P = .34). Conclusion Using US images from patients with primary breast cancer, deep learning models can effectively predict clinically negative axillary lymph node metastasis. Artificial intelligence may provide an early diagnostic strategy for lymph node metastasis in patients with breast cancer with clinically negative lymph nodes. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Bae in this issue.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Metástase Linfática/diagnóstico por imagem , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Pessoa de Meia-Idade , Redes Neurais de Computação , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
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