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1.
BMC Cancer ; 21(1): 1196, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758762

RESUMO

Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

2.
PeerJ ; 9: e12197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616632

RESUMO

Dysregulation and prognostic roles of Karyopherin α2 (KPNA2) were reported in many malignancies including hepatocellular carcinoma (HCC). A multi-omics analysis of KPNA2 is needed to gain a deeper understanding of its multilevel molecular characteristics and provide novel clues for HCC diagnosis, prognosis, and target therapy. Herein multi-omic alterations of KPNA2 were analyzed at genetic, epigenetic, transcript, and protein levels with evaluation of their relevance with clinicopathological features of HCC by integrative analyses. The significant correlations of KPNA2 expression with its gene copy number variation (CNV) and methylation status were shown through Spearman correlation analyses. With Cox regression, Kaplan-Meier survival, and receiver operating characteristic (ROC) analyses, based on the factors of KPNA2 CNV, methylation, expression, and tumor stage, risk models for HCC overall survival (OS) and disease-free survival (DFS) were constructed which could discriminate the 1-year, 3-year, and 5-year OS/DFS status effectively. With Microenvironment Cell Populations-counter (MCP-counter), the immune infiltrations of HCC samples were evaluated and their associations with KPNA2 were shown. KPNA2 expression in liver was found to be influenced by low fat diet and presented significant correlations with fatty acid metabolism and fatty acid synthase activity in HCC. KPNA2 was detected lowered in HCC patient's plasma by enzyme linked immunosorbent assay (ELISA), consistent with its translocation to nuclei of HCC cells. In conclusion, KPNA2 multilevel dysregulation in HCC and its correlations with immune infiltration and the fatty acid metabolism pathway indicated its multiple roles in HCC. The clinicopathological significance of KPNA2 was highlighted through the in-depth analyses at multilevels.

3.
Regen Biomater ; 8(6): rbab051, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34603743

RESUMO

The ideal scaffold material of angiogenesis should have mechanical strength and provide appropriate physiological microporous structures to mimic the extracellular matrix environment. In this study, we constructed an integrated three-dimensional scaffold material using porous tantalum (pTa), gelatin nanoparticles (GNPs) hydrogel, and seeded with bone marrow mesenchymal stem cells (BMSCs)-derived endothelial cells (ECs) for vascular tissue engineering. The characteristics and biocompatibility of pTa and GNPs hydrogel were evaluated by mechanical testing, scanning electron microscopy, cell counting kit, and live-cell assay. The BMSCs-derived ECs were identified by flow cytometry and angiogenesis assay. BMSCs-derived ECs were seeded on the pTa-GNPs hydrogel scaffold and implanted subcutaneously in nude mice. Four weeks after the operation, the scaffold material was evaluated by histomorphology. The superior biocompatible ability of pTa-GNPs hydrogel scaffold was observed. Our in vivo results suggested that 28 days after implantation, the formation of the stable capillary-like network in scaffold material could be promoted significantly. The novel, integrated pTa-GNPs hydrogel scaffold is biocompatible with the host, and exhibits biomechanical and angiogenic properties. Moreover, combined with BMSCs-derived ECs, it could construct vascular engineered tissue in vivo. This study may provide a basis for applying pTa in bone regeneration and autologous BMSCs in tissue-engineered vascular grafts.

4.
Plant Biotechnol J ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34679252

RESUMO

N6 -methyladenosine (m6 A) reader protein plays an important role in trichome morphology, developmental timing and morphogenesis in Arabidopsis. However, the function of m6 A readers in plant-microbe interaction remains unclear. Here, a Malus YTH-domain family protein MhYTP2 was initially characterized as an m6 A reader. MhYTP2 overexpression increased mRNA m6 A modification level and translation efficiency. The m6 A in the exon regions appeared to destabilize the mRNAs, whereas m6 A in the untranslated regions positively correlated with the associated mRNA abundance. MhYTP2 overexpression enhanced apple powdery mildew resistance, possibly by rapidly degrading the bound mRNAs of MdMLO19 and MdMLO19-X1 and improving the translation efficiency of the antioxidant genes. To conclude, the results shed light on the apple m6 A profile, the effect of MhYTP2 on m6 A profile, and the m6 A roles in MdMLO19 and MdMLO19-X1 mRNAs stability and glutamate dehydrogenase 1-like MdGDH1L mRNA translation efficiency.

5.
Adv Clin Chem ; 103: 1-45, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34229848

RESUMO

Lung cancer (LC) accounts for the majority of cancer-related deaths worldwide. Although screening the high-risk population by low-dose CT (LDCT) has reduced mortality, the cost and high false positivity rate has prevented its general diagnostic use. As such, better and more specific minimally invasive biomarkers are needed in general and for early LC detection, specifically. Autoantibodies produced by humoral immune response to tumor-associated antigens (TAA) are emerging as a promising noninvasive biomarker for LC. Given the low sensitivity of any one single autoantibody, a panel approach could provide a more robust and promising strategy to detect early stage LC. In this review, we summarize the background of TAA autoantibodies (TAAb) and the techniques currently used for identifying TAA, as well as recent findings of LC specific antigens and TAAb. This review provides guidance toward the development of accurate and reliable TAAb as immunodiagnostic biomarkers in the early detection of LC.


Assuntos
Anticorpos Antineoplásicos/sangue , Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Humanos , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/metabolismo
6.
Comput Math Methods Med ; 2021: 9987067, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257703

RESUMO

Lung cancer has a high mortality rate. Promoting early diagnosis and screening of lung cancer is the most effective way to enhance the survival rate of lung cancer patients. Through computer technology, a comprehensive evaluation of genetic testing results and basic clinical information of lung cancer patients could effectively diagnose early lung cancer and indicate cancer risks. This study retrospectively collected 70 pairs of lung cancer tissue samples and normal human tissue samples. The methylation frequencies of 6 genes (FHIT, p16, MGMT, RASSF1A, APC, DAPK) in lung cancer patients, the basic clinical information, and tumor marker levels of these patients were analyzed. Then, the python package "sklearn" was employed to build a support vector machine (SVM) classifier which performed 10-fold cross-validation to construct diagnostic models that could identify lung cancer risk of suspected cases. Receiver operation characteristic (ROC) curves were drawn, and the performance of the combined diagnostic model based on several factors (clinical information, tumor marker level, and methylation frequency of 6 genes in blood) was shown to be better than that of models with only one pathological feature. The AUC value of the combined model was 0.963, and the sensitivity, specificity, and accuracy were 0.900, 0.971, and 0.936, respectively. The above results revealed that the diagnostic model based on these features was highly reliable, which could screen and diagnose suspected early lung cancer patients, contributing to increasing diagnosis rate and survival rate of lung cancer patients.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Metilação de DNA/genética , Diagnóstico por Computador/métodos , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Máquina de Vetores de Suporte , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Biologia Computacional , Diagnóstico por Computador/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
7.
Medicine (Baltimore) ; 100(6): e24700, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578606

RESUMO

RATIONALE: Double primary lung cancer (DPLC) is a relatively rare type of lung cancers. According to whether the diagnosis interval between lesions is more than 6 months, it can be divided into synchronous DPLC (sDPLC) and metachronous DPLC (mDPLC). Here, we describe a case of sDPLC in which one of the components is a rare colloid adenocarcinoma (CA). PATIENT CONCERNS: A 69-year-old male was admitted to the hospital due to chest distress and shortness of breath for 1 year, getting worse in the last 15 days. DIAGNOSIS: Both HE staining and IHC supported the diagnosis of CA in the right lower lobe and moderately differentiated squamous cell carcinoma in the right upper lobe. INTERVENTIONS: The patient was treated with 3 cycles of adjuvant chemotherapy with pemetrexed and lobaplatin after the right upper lobectomy, wedge resection of the right lower lobe and lymph node dissection under video-assisted thoracoscope. OUTCOMES: Our plan was to follow him up with general physical examination, chest-abdomen CT and serum tumor markers every 6 months for 2 years. The patient was still alive until the last follow-up in November 2020. LESSONS: CA of the lung is a rare primary lung adenocarcinoma. The diagnosis should be based on the patient's clinical characteristics, imaging examination and pathological characteristics, and also need to be differentiated from other mucinous adenocarcinomas. Interestingly, our patient developed not only a CA in the right lower lobe, but also a moderately differentiated squamous cell carcinoma in the right upper lobe.


Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas/patologia , Adenocarcinoma/terapia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/terapia , Assistência ao Convalescente/métodos , Idoso , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Quimioterapia Adjuvante/métodos , Diagnóstico Diferencial , Dispneia/diagnóstico , Dispneia/etiologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Excisão de Linfonodo/métodos , Masculino , Estadiamento de Neoplasias/métodos , Neoplasias Primárias Múltiplas/terapia , Cirurgia Torácica Vídeoassistida/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
8.
Chemosphere ; 267: 129197, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33338710

RESUMO

Biogas slurry retention is a critical problem that cannot be solved by using the reuse method. Therefore, a new approach was taken to compensate for the shortcomings in the reuse method. In this study, after ammonia stripping, the ammonia nitrogen concentration in the stripped biogas slurry (SBS) still cannot reach the effluent standard (80 mg/L), so a variety of processes were needed to treat the SBS. Polyaluminum chloride (PAC) and rice husk biochar (B) were used to pretreat SBS. The effect of different pre-treatments on the COD value, ammonia nitrogen concentration, turbidity, total phosphorus (TP), and other indicators was investigated. After different pre-treatments by PAC and biochar, the pretreated SBS was filtered by a ceramic membrane, and the indicators of SBS were removed in the next step. After adding PAC and biochar together, ammonia nitrogen concentration was decreased to 68.09 mg/L, with a removal rate of 63%. The total phosphorus (TP) was also decreased, and its removal rate reached 92.5%. When the SBS was pretreated with PAC and biochar and then filtered through a ceramic membrane under different operating pressures, the removal rates of COD, total nitrogen (TN), turbidity, and suspended solids (SS) reached 81%, 88%, 96%, and 99% respectively. Moreover, by increasing the pressure from 0.1 to 0.3 MPa, the membrane flux was improved from 45 to 100.6 L/m2·h. This study proves that the combined pre-treatments of PAC and biochar can comprehensively remove various indicators from SBS while ensuring membrane flux during the membrane filtration process.


Assuntos
Biocombustíveis , Fósforo , Adsorção , Hidróxido de Alumínio , Cerâmica , Carvão Vegetal , Nitrogênio/análise
9.
Bioact Mater ; 6(6): 1765-1776, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33313453

RESUMO

Regeneration of long-bone segmental defects remains a challenge for orthopedic surgery. Current treatment options often require several revision procedures to maintain acceptable alignment and achieve osseous healing. A novel hollow tubular system utilizing magnesium-strontium (Mg-Sr) alloy with autogenous morselized bone filled inside to repair segmental defects was developed. To improve the corrosion and biocompatible properties, two coatings, Ca-P and Sr-P coatings, were prepared on surface of the implants. Feasibility of applying these coated implants was systematically evaluated in vitro and in vivo, and simultaneously to have a better understanding on the relationship of degradation and bone regeneration on the healing process. According to the in vitro corrosion study by electrochemical measurements, greater corrosion resistance was obtained for Ca-P coated sample, and attributed to the double-layer protective structure. The cytotoxicity and alkaline phosphatase (ALP) assays demonstrated enhanced bioactivity for Sr-P coated group because of the long-lasting release of beneficial Sr2+. At 12 weeks post-implantation with Mg-Sr alloy porous device, the segmental defects were effectively repaired with respect to both integrity and continuity. In addition, compared with the Ca-P coated implant, the Sr-P coated implant was more proficient at promoting bone formation and mineralization. In summary, the Sr-P coated implants have bioactive properties and exceptional durability, and promote bone healing that is close to the natural rate, implying their potential application for the regeneration of segmental defects.

10.
Stem Cell Res Ther ; 11(1): 480, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176873

RESUMO

BACKGROUND: Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH. METHODS: To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes. RESULTS: The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1. CONCLUSIONS: This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Osteonecrose , Animais , Células Endoteliais , Cabeça do Fêmur , MicroRNAs/genética , Osteonecrose/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Coelhos
11.
Front Genet ; 11: 593273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193737

RESUMO

Karyopherin α2 (KPNA2) was reported to be overexpressed and have unfavorable prognostic effects in many malignancies including hepatocellular carcinoma (HCC). Although its contributions to inflammatory response were reported in many studies, its specific associations with immune infiltrations and immune pathways during cancer progression were unclear. Here, we aimed to identify new markers for HCC diagnosis and prognosis through KPNA2-associated immune analyses. RNA-seq expression data of HCC datasets were downloaded from The Cancer Genome Atlas and International Cancer Genome Consortium. The gene expressions were counts per million normalized. The infiltrations of 24 kinds of immune cells in the samples were evaluated with ImmuCellAI (Immune Cell Abundance Identifier). The Spearman correlations of the immune infiltrations with KPNA2 expression were investigated, and the specific positive correlation of B-cell infiltration with KPNA2 expression in HCC tumors was identified. Fifteen genes in KEGG (Kyoto Encyclopedia of Genes and Genomes) B-cell receptor signaling pathway presented significant correlations with KPNA2 expression in HCC. Among them, GRB2 and NRAS were indicated to be independent unfavorable prognostic factors for HCC overall survival. Clinical Proteomic Tumor Analysis Consortium HCC dataset was investigated to validate the results at protein level. The upregulation and unfavorable prognostic effects of KPNA2 and GRB2 were confirmed, whereas, unlike its mRNA form, NRAS protein was presented to be downregulated and have favorable prognostic effects. Through receiver operating characteristic curve analysis, the diagnostic potential of the three proteins was shown. The RNA-binding proteins (RBPs) of KPNA2, NRAS, and GRB2, downloaded via The Encyclopedia of RNA Interactomes, were investigated for their clinical significance in HCC at protein level. An eight-RBP signature with independent prognostic value and dysregulations in HCC was identified. All the RBPs were significantly correlated with MKI67 expression and at least one of KPNA2, GRB2, and NRAS at protein level in HCC, indicating their roles in HCC progression and the regulation of the three proteins. We concluded that KPNA2, GRB2, NRAS, and their RBPs might have coordinating roles in HCC immunoregulation and progression. They might be new markers for HCC diagnosis and prognosis predication and new targets for HCC immunotherapy.

12.
Int J Mol Sci ; 21(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867065

RESUMO

Ethylene plays an important role in stress adaptation and fruit ripening. Acireductone dioxygenase (ARD) is pivotal for ethylene biosynthesis. However, the response of ARD to fruit ripening or cold stress is still unclear. In this study, we identified three members of Malus ARD family, and expression profile analysis revealed that the transcript level of MdARD4 was induced during apple fruit ripening and after apple plants were being treated with cold stress. To investigate its function in cold tolerance and fruit ripening, MdARD4 was ectopically expressed in Solanum lycopersicum cultivar 'Micro-Tom', which has been considered as an excellent model plant for the study of fruit ripening. At the cellular level, the MdARD protein expressed throughout Nicotiana benthamiana epidermal cells. Overexpression of MdARD4 in tomato demonstrated that MdARD4 regulates the ethylene and carotenoid signaling pathway, increases ethylene and carotenoid concentrations, and accelerates fruit ripening. Furthermore, MdARD4 increased the antioxidative ability and cold hardiness in tomato. To conclude, MdARD4 may potentially be used in apple breeding to accelerate fruit ripening and increase cold hardiness.


Assuntos
Dioxigenases/genética , Dioxigenases/metabolismo , Lycopersicon esculentum/crescimento & desenvolvimento , Malus/genética , Carotenoides/metabolismo , Resposta ao Choque Frio , Etilenos/biossíntese , Evolução Molecular , Frutas/genética , Frutas/crescimento & desenvolvimento , Lycopersicon esculentum/genética , Filogenia , Melhoramento Vegetal , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/crescimento & desenvolvimento
13.
Tree Physiol ; 40(11): 1509-1519, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-32816019

RESUMO

Soil alkalization affects apple production in northwest China. Autophagy is a highly conserved degradative protein pathway in eukaryotes. Autophagy in plants can be activated by various abiotic factors. We previously identified the positive role of the autophagy-related gene MdATG18a in drought, nitrogen deficiency and resistance to Diplocarpon mali infection in apple. However, it is still unclear whether ATG18a is related to alkaline stress. In this study, we used hydroponic culture to simulate alkaline stress and found that the overexpression of MdATG18a significantly improved the tolerance of apple to alkaline stress. The overexpression of MdATG18a increased biomass, photosynthetic rate and antioxidant capacity of transgenic plants compared with wild-type plants under alkaline stress. The overexpression of MdATG18a promoted γ-aminobutyric acid (GABA) shunt via an increase in glutamate (GABA precursor) and GABA contents and upregulation of GABA shunt-related genes. In addition, the overexpression of MdATG18a significantly upregulated the expression of other core ATG genes and increased the formation of autophagosomes under alkaline stress. In conclusion, these results suggest that the overexpression of MdATG18a in apple enhances alkaline tolerance and the GABA shunt, which may be owing to the increase in autophagic activity.


Assuntos
Malus , Ascomicetos , Autofagia , China , Regulação da Expressão Gênica de Plantas , Malus/genética , Malus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico , Ácido gama-Aminobutírico
14.
J Biomed Mater Res B Appl Biomater ; 108(7): 2925-2936, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32662233

RESUMO

Zn alloys are emerging as promising degradable biomedical materials due to their tailorable mechanical properties and moderate biodegradable rate, compared with conventional biodegradable metallic materials. Ag, as an effective antibacterial and reinforcing element, was incorporated into Zn-0.05Mg alloys. In the present work, the effects of the Ag addition on mechanical, cytotoxic, hemolytic, pyrogenic, histological behaviors of the animal were investigated. The compressive yielding strength is enhanced from 198 MPa for Zn-0.05Mg alloy up to 224 and 234 MPa for Zn-0.05Mg-0.5Ag and Zn-0.05Mg-1Ag alloys, respectively. When the compressive strain was 65%, the strength of the Zn-0.05Mg-1.0Ag alloy reached 833 MPa, which was much higher than that of 721 MPa for Zn-0.05Mg alloy. The relative growth rate (RGR) for the extracts of Zn-0.05Mg-1Ag alloy with the concentrations of 10, 50, and 100% after 5 days incubation reaches 98.5, 95.2, and 94.2%, which are higher than those in extracts of Zn-0.05Mg-0.5Ag alloy (98.2, 93.9, 92.1%). The hemolysis rate of the Zn-0.05Mg alloys with 0.5 and 1 wt% Ag is 2.46 and 2.28%, respectively. The variations of body weight and temperature, postinjection symptoms, pathological morphologies of the visceral organs demonstrate that the alloys are nontoxic according to the toxicity rating standards. Zn-0.05wt%Mg-(0.5, 1 wt%) Ag alloys are experimentally safe materials and promising for the future application as biodegradable medical devices.

15.
J Cancer ; 11(11): 3124-3143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231717

RESUMO

Background: Peroxiredoxins (PRDXs) were reported to be associated with inflammation response in previous studies. In colon adenocarcinoma (COAD), however, their correlations and clinical significance were unclear. Methods: The RNA-seq data of 452 COAD patients with clinical information was downloaded from The Cancer Genome Atlas (TCGA) and transcripts per million (TPM) normalized. Comparisons of relative expressions of PRDXs between COAD tumor and normal controls were applied. PRDXs dy-regulations in COAD were validated via Oncomine, Human Protein Atlas (HPA) and Gene Expression Omnibus (GEO) repository. Through Tumor Immune Estimation Resource (TIMER), the immune estimation of TCGA-COAD patients was downloaded and the dy-regulated PRDXs were analyzed for their correlations with immune infiltrations in COAD. The TCGA-COAD patients were divided into younger group (age≤65 years) and older group (age>65 years) to investigate the prognostic roles of age, TNM stage, dy-regulated PRDXs and the immune infiltrations in different age groups through Kaplan-Meier survival and Cox regression analyses. Results: Three of the PRDX members showed their expressional differences both at protein and mRNA level. PRDX2 was consistently up-regulated while PRDX6 down-regulated in COAD. PRDX1 was overexpressed (mRNA) while nuclear absent (protein) in the tumor tissues. PRDX1 overexpression and PRDX6 under-expression were also shown in the stem-like colonospheres from colon cancer cells. Via TIMER, PRDX1, PRDX2, and PRDX6 were found to be negatively correlated with the immune infiltrations in COAD. Both in the younger and older patients, TNM stage had prognostic effects on their overall survival (OS) and recurrence-free survival (RFS). CD4+ T cell had independent unfavorable effects on OS of the younger patients while age had similar effects on RFS of the older ones. CD8+ T cell was independently prognostic for RFS in the two groups. Conclusions: Late diagnosis indicated poor prognosis in COAD and dy-regulated PRDXs w might be new markers for its early diagnosis. Age was prognostic and should be considered in the treatments of the older patients. Dy-regulated PRDXs were negatively correlated with immune infiltration levels. CD4+ T cell and CD8+ T cell infiltrations were prognostic in COAD and their potential as immune targets needed further investigation.

16.
Front Genet ; 11: 273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32265992

RESUMO

To explore the potential functions and clinical significances of peroxisomes during lung cancer development and progression, we investigated the expressional profiles of peroxisome pathway genes and their correlations with clinical features in non-small cell lung cancer (NSCLC). The RNA-seq data of NSCLC including lung squamous carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients with their clinical information were downloaded from The Cancer Genome Atlas (TCGA). Gene expression comparisons between tumor and normal samples were performed with edgeR package in R software and the results of the 83 peroxisome pathway genes were extracted. Through Venn diagram analysis, 38 common differentially expressed peroxisome pathway genes (C-DEPGs) in NSCLC were identified. Principal components analysis (PCA) was performed and the 38 C-DEPGs could discriminate NSCLC tumors from the non-tumor controls well. Through Kaplan-Meier survival and Cox regression analyses, 11 of the C-DEPGs were shown to have prognostic effects on NSCLC overall survival (OS) and were considered as key C-DEPGs (K-DEPGs). Through Oncomine, Human Protein Atlas (HPA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), three K-DEPGs (HSD17B4, ACAA1, and PXMP4) were confirmed to be down-regulated in NSCLC at both mRNA and protein level. Their dy-regulation mechanisms were revealed through their correlations with their copy number variations and methylation status. Their potential functions in NSCLC were explored through their NSCLC-specific co-expression network analysis, their correlations with immune infiltrations, immunomodulator gene expressions, MKI67 expression and their associations with anti-cancer drug sensitivity. Our findings suggested that HSD17B4, ACAA1, and PXMP4 might be new markers for NSCLC diagnosis and prognosis and might provide new clues for NSCLC treatment.

17.
Colloids Surf B Biointerfaces ; 190: 110911, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32146277

RESUMO

Enhanced corrosion resistance and accelerated new bone formation are desired to make Mg and its alloys to be ideal candidate for bone biomaterial. For this purpose, a CDHA/MgF2 bi-layer coating was prepared on high purity Mg by a combination of fluoride treatment and hydrothermal treatment. The coating exhibited a nanoscale surface topography. Enhanced adhesion strength and corrosion resistance was obtained for the CDHA/MgF2 bi-layer coating. In vitro cell experiment showed that the adhesion, proliferation and differentiation of MG63 cells were significantly improved on Mg with CDHA/MgF2 coating compared to that on Mg with HA coating and MgF2 coating. In conclusion, this study provides a promising surface modification method for Mg metal with enhanced corrosion resistance and superior osteogenic bioactivity.


Assuntos
Cálcio/química , Materiais Revestidos Biocompatíveis/química , Durapatita/química , Fluoretos/química , Compostos de Magnésio/química , Magnésio/metabolismo , Nanopartículas/química , Adesão Celular , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Humanos , Magnésio/química , Teste de Materiais , Tamanho da Partícula , Propriedades de Superfície
18.
Biomaterials ; 238: 119829, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32058868

RESUMO

Magnesium (Mg)-based metals can be used as next-generation fracture internal fixation devices due to their specific properties. We used vascularized bone grafting fixed by degradable pure Mg screws and obtained satisfactory results in the treatment of osteonecrosis of the femoral head. However, the mechanical properties of these screws make them weaker than those made of traditional metals. In particular, one of the main challenges of using screws made of Mg-based metals is their application in fixation at important weight-bearing sites in the human body. Femoral neck fracture is a common clinical injury. In this injury, the large bearing stress at the junction requires a fixation device with extremely high mechanical strength. Surgery and appropriate internal fixation can accelerate the healing of femoral neck fractures. Traditional internal fixation devices have some disadvantages after surgery, including stress shielding effects and the need for secondary surgery to remove screws. On the basis of previous work, we developed high-strength pure Mg screws for femoral neck fractures. In this study, we describe the first use of high-purity Mg to prepare large-size weight-bearing screws for the fixation of femoral neck fractures in goats. We then performed a 48 weeks follow-up study using in vivo transformation experiments. The results show that these biodegradable high-purity Mg weight-bearing screws had sufficient mechanical strength and a degradation rate compatible with bone repair. Furthermore, good bone formation was achieved during the degradation process and reconstruction of the bone tissue and blood supply of the femoral head and femoral neck. This study provides a basis for future research on the clinical transformation of biodegradable high-purity Mg weight-bearing screws.


Assuntos
Fraturas do Colo Femoral , Parafusos Ósseos , Fraturas do Colo Femoral/cirurgia , Seguimentos , Fixação Interna de Fraturas , Consolidação da Fratura , Humanos , Magnésio , Suporte de Carga
19.
Plants (Basel) ; 8(12)2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31817831

RESUMO

Arid and semiarid apple producing areas suffer from severe alkalinity of soil, which strongly affects the yield and quality of apples. Dopamine (DA) is involved in metabolic activities in response to abiotic stress in plants. To detect the effects of exogenous DA application on the adaption of apple (Malus hupehensis) seedlings to alkali stress and as a protection from oxidative stress, 0.1 mM DA was identified as the most suitable concentration by hydroponic culture. Further experimentation showed that the growth and photosynthesis of apple seedlings were significantly inhibited under alkali stress, and more reactive oxygen species accumulated, compared with control. However, exogenous DA application suppressed the loss of the plant height, root length, chlorophyll levels, and photosynthetic capacity of apple seedlings that were caused by alkali stress. In the leaves of alkali stressed seedlings, the catalase, superoxide dismutase, and peroxidase activities were lower and hydrogen peroxide and malondialdehyde levels were higher than in the untreated plants. The presence of DA significantly alleviated such effects of alkali stress. In addition, exogenous DA application increased the antioxidant capacity of apple seedlings under alkali stress by increasing the level of chlorogenic acid. These results are significant for improving the alkali tolerance of apple in apple-producing areas with alkalized soil.

20.
Materials (Basel) ; 12(21)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683851

RESUMO

Foamed concrete materials based on sulpoaluminate cement were prepared by the chemical foaming method. The effects of water-cement ratio, foaming agent, and foaming stabilizer on the mechanical and thermal properties of foamed concrete were studied. Meanwhile, a portion of cement was replaced with foamed phenolic particles to further optimize the performance of foamed concrete; the results show that when the water-cement ratio was 0.53, the foaming agent content was 5%, the foam stabilizer was 1%, and the substitution of phenolic particles was 20%, the performance indexes of foamed concrete were the best. Methods, describing briefly the main methods or treatments applied: dry density was 278.4 kg/m3, water absorption was 19.9%, compressive strength was 3.01 MPa, and thermal conductivity was 0.072 W/(m·K). By the pore structure analysis of the foamed concrete suing Micro-CT, it was found that when the replacement amount of phenolic particles was 20%, the pore size of foamed concrete was relatively uniform, the minimum D90 was 225 µm respectively. The combination of organic and inorganic matrix and optimized pore structure improved the performance of foamed concrete.

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