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1.
Oncogene ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32372060

RESUMO

Hepatocellular carcinoma (HCC) metastasis is largely responsible for HCC-associated recurrence and mortality. We aimed to identify metastasis-related long non-coding RNAs (lncRNAs) to understand the molecular mechanism of HCC metastasis. We first identified that miR-1258 was downregulated in HCC tissues both in The Cancer Genome Atlas (TCGA) and Sun Yat-sen University Cancer Center (SYSUCC) dataset. MiR-1258 expression negatively correlated with recurrence-free survival and overall survival of HCC patients. MiR-1258 overexpression inhibited migration and invasion of HCC cells both in vitro and in vivo, whereas miR-1258 downregulation promoted cell metastasis. Luciferase assays verified direct binding of miR-1258 to Smad2 and Smad3, thereby attenuating TGF-ß/Smad signaling. We further established that lncRNA LINC01278 was a negative regulator of miR-1258. In vivo and in vitro assays demonstrated that LINC01278-mediated HCC metastasis was dependent on miR-1258 expression. Furthermore, miR-1258 downregulation in turn increased LINC01278 expression. We also observed that TCF-4 could bind to the LINC01278 promoter site. In addition, LINC01278 downregulation decreased migration and invasion of HCC cells induced by ß-catenin and TGF-ß1 both in vitro and in vivo. We uncovered a novel mechanism for ß-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 feedback loop activation in HCC metastasis, and the study indicated that LINC01278 could serve as a therapeutic target for HCC metastasis.

2.
Shock ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32433208

RESUMO

Macrophages play a key role in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that glycolysis plays an important role in regulating macrophage polarization through metabolic reprogramming. Bone marrow mesenchymal stem cells (BMSCs) can alleviate sepsis-induced lung injury and possess potent immunomodulatory and immunosuppressive properties via secreting exosomes. However, it is unknown whether BMSCs-derived exosomes exert their therapeutic effect against sepsis-induced lung injury by inhibiting glycolysis in macrophages. Therefore, the present study aimed to evaluate the anti-inflammatory effects of exosomes released from BMSCs on acute lung injury induced by lipopolysaccharide (LPS) in mice and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs inhibited M1 polarization and promoted M2 polarization in MH-S cells (a murine alveolar macrophage cell line) by releasing exosomes. Further experiments showed that exosomes secreted by BMSCs modulated LPS-treated MH-S cells polarization by inhibiting cellular glycolysis. Moreover, our results showed that BMSCs-derived exosomes down-regulated the expression of several essential proteins of glycolysis via inhibition of HIF-1α. Finally, a model of LPS-induced ARDS in mice was established, we found that BMSCs-derived exosomes ameliorated the LPS-induced inflammation and lung pathological damage. Meanwhile, we found that intratracheal delivery of BMSCs-derived exosomes effectively down-regulated LPS-induced glycolysis in mice lung tissue. These findings reveal new mechanisms of BMSCs-derived exosomes in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of LPS-induced ARDS.

3.
Med Sci Monit ; 26: e922012, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32433460

RESUMO

BACKGROUND The purpose of this work was to unearth the effects and underlying mechanism of long non-coding RNA (lncRNA) MALAT1 in ovarian cancer cell stemness. MATERIAL AND METHODS Western blot, quantitative polymerase chain reaction (qPCR) and sphere forming analysis were performed to evaluate the stem-like traits of cells and MALAT1-induced effects on ovarian cancer cell stemness. Cell viability was performed to evaluate MALAT1 role in the chemoresistance of ovarian cancer cells. RNA immunoprecipitation (RIP) and luciferase reporter analysis were constructed to investigate the underlying mechanisms. RESULTS Here, qPCR assay showed that MALAT1 level was remarkably higher in non-adherent spheres formed by adherent ovarian cancer cells, as well as cisplatin-resistant ovarian cancer cells. Additionally, MALAT1 knockdown reduced ovarian cancer cell stemness, characterized as the decrease of sphere forming ability, expression of stemness regulatory masters, and attenuation of cisplatin resistance. Moreover, MALAT1 interacted with yes-associated protein (YAP), inhibited its nuclear-cytoplasm translocation, promoted YAP protein stability and expression and thus increased its activity. Notably, rescuing expression of YAP attenuated the inhibition of MALAT1 knockdown on ovarian cancer cell stemness. CONCLUSIONS In conclusion, these results demonstrate a MALAT1/YAP axis responsible for ovarian cancer cell stemness.

4.
Balkan Med J ; 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32267139

RESUMO

Background: Brain metastasis is a major cause for cancer death in patients with lung cancer. Sirtuin 1 (SIRT1) and hsa-miR-217 has been identified to mediate the development of non-small cell lung cancer (NSCLC). Aims: We performed this study to investigate the roles of hsa-miR-217, its target SIRT1, as well as P53/KAI1 axis in the brain metastasis from NSCLC. Study design: This is a cell culture study. Methods: Human pulmonary adenocarcinoma brain metastasis cell line PC-14/B were incubated and treated with constructed lentiviral plasmids expressing miR-217 and/or SIRT1. BEAS-2B cell line was used as a control. The targeted regulation of miR-217 to SIRT1 was examined using dual luciferase reporter assay. Cell proliferation, migration, invasion and the expression of relate proteins were detected to examine the effect of miR-217/SIRT1 expression on metastasis. Results: PC-14/B cells expressed higher SIRT1 and lower p53 and KAI1 compared with BEAS-2B control cells (P<0.05). SIRT1 was a direct target of miR-217. MiR-217 expression suppressed PC-14/B cell invasion (P=0.004), migration (P=0.001) and proliferation (P<0.05), whereas SIRT1 overexpression reversed all processes. SIRT1 expression inhibited P53, KAI1/CD82, matrix metalloproteinase (MMP)-9 and ß-catenin but upregulated E-cadherin protein. MiR-217 overexpression induced reverse changes. Conclusions: Hsa-miR-217 and its target SIRT1 acted as metastasis suppressor and promoter gene in NSCLC, respectively. The hsa-miR-217/SIRT1/P53/KAI1 metastasis regulatory pathway showed novel and crucial roles in brain metastasis from NSCLC. This axis might be a potential target for the treatment of brain metastasis of lung cancer.

5.
Clin Cancer Res ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32234760

RESUMO

PURPOSE: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. EXPERIMENTAL DESIGN: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). RESULTS: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. CONCLUSIONS: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

6.
Virology ; 545: 1-9, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32174453

RESUMO

The emergence of resistant mutants to the wildly used neuraminidase inhibitors (NAIs) makes the development of novel drugs necessary. Favipiravir (T-705) is one of the RNA-dependent RNA polymerase (RdRp) inhibitors developed in recent years. To examine the efficacy of T-705 against influenza B virus infections in vivo, C57BL/6 mice infected with wild-type or oseltamivir-resistant influenza B/Memphis/20/96 viruses were treated with T-705. Starting 2 h post inoculation (hpi), T-705 was orally administered to mice BID at dosages of 50, 150, or 300 mg/kg/day for 5 days. Oseltamivir was used as control. Here, we showed that T-705 protected mice from lethal infection in a dose-dependent manner. T-705 administration also significantly reduced viral loads and suppressed pulmonary pathology. In addition, phenotypic assays demonstrated that no T-705-resistant viruses emerged after T-705 treatment. In conclusion, T-705 can be effective to protect mice from lethal infection with both wild-type and oseltamivir-resistant influenza B viruses.

7.
Oral Oncol ; 104: 104583, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32008912

RESUMO

We reported a rare case of submandibular oral cutaneous fistula (OCF) in a 27-year-old female. A submandibular gland flap (SMGF) was prepared after fistula resection to fill the dead space under the mouth floor. Based on this case report and a literature review, we discussed the pathogenesis and treatment of OCF, and compared the differences between the SMGF and other types of flaps.

8.
Onco Targets Ther ; 13: 1613-1624, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110057

RESUMO

Background: Circular RNAs (circRNAs) play important regulatory roles in cancer development. However, the mechanisms by which circRNAs regulate gene expression in gastric cancer (GC) remain unclear. Methods: Human GC samples and their matched normal adjacent tissues were obtained from 30 patients to assess the expression of circHIPK3 and its relationship with GC proliferation and migration. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circHIPK3 in GC proliferation and migration, and its underlying molecular mechanisms. Results: Using a circRNA microarray we found a circRNA termed circHIPK3 that performed a significant regulatory role in GC. circHIPK3 was further confirmed to be upregulated in all GC tissues and cells tested. Furthermore, circHIPK3 levels were associated with Tumor & Lymph Node & Metastasis(TNM) stage (P = 0.032). The area under the receiver operating characteristic curve (ROC) was 0.743 (95% confidence interval 0.615-0.872; P = 0.001). CCK-8, colony formation, Transwell and EdU assays were performed to evaluate the effects of circHIPK3 on cell proliferation and migration in GC. Moreover, circHIPK3 was identified as a sponge of miR-107, and as such it regulated brain-derived neurotrophic factor (BDNF), which plays a pivotal role in the development of GC. Conclusion: circHIPK3 represents a novel potential biomarker and therapeutic target of GC.

9.
Leukemia ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080345

RESUMO

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

10.
Plants (Basel) ; 9(2)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085442

RESUMO

In Arabidopsis thaliana, LONG-CHAIN ACYL-COA SYNTHETASEs (LACSs) catalyze the synthesis of long-chain acyl-CoAs and function in diverse biological processes. We have recently revealed that LACS2 is primarily involved in the production of polyunsaturated linolenoyl-CoA, essential for the activation of ethylene response transcription factors-mediated hypoxia signaling. Here, we further reported the dual role of LACS2 in the regulation of submergence tolerance by modulating cuticle permeability in Arabidopsis cells. LACS2-overexpressors (LACS2-OEs) showed improved tolerance to submergence, with higher accumulation of cuticular wax and cutin in their rosettes. In contrast, knockout of LACS2 in the lacs2-3 mutant resulted in hypersensitivity to submergence with reduced wax crystals and thinner cutin layer. By analyses of plant surface permeability, we observed that the hypoxic sensitivities in the LACS2-OEs and lacs2-3 mutant were physiologically correlated with chlorophyll leaching, water loss rates, ionic leakage, and gas exchange. Thus, our findings suggest the role of LACS2 in plant response to submergence by modulating cuticle permeability in plant cells.

11.
Mol Plant ; 13(3): 515-531, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32087368

RESUMO

Light is arguably one of the most important environmental factors that determines virtually all aspects of plant growth and development, but the molecular link between light signaling and the autophagy pathway has not been elucidated in plants. In this study, we demonstrate that autophagy is activated during light-to-dark conversion though transcriptional upregulation of autophagy-related genes (ATGs). We showed that depletion of the ELONGATED HYPOCOTYL 5 (HY5), a key component of light signaling, leads to enhanced autophagy activity and resistance to extended darkness and nitrogen starvation treatments, contributing to higher expression of ATGs. HY5 interacts with and recruits HISTONE DEACETYLASE 9 (HDA9) to ATG5 and ATG8e loci to repress their expression by deacetylation of the Lys9 and Lys27 of histone 3. Furthermore, we found that both darkness and nitrogen depletion induce the degradation of HY5 via 26S proteasome and the concomitant disassociation of HDA9 from ATG5 and ATG8e loci, leading to their depression and thereby activated autophagy. Genetic analysis further confirmed that HY5 and HDA9 act synergistically and function upstream of the autophagy pathway. Collectively, our study unveils a previously unknown transcriptional and epigenetic network that regulates autophagy in response to light-to-dark conversion and nitrogen starvation in plants.

12.
Med Sci Monit ; 26: e921389, 2020 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-32088727

RESUMO

BACKGROUND RNA binding protein RNPC1 has a tumor-suppressive role in various tumors, nevertheless, the role of RNPC1 in human endometrial cancer (EC) are never been reported. MATERIAL AND METHODS Western blot, quantitative polymerase chain reaction and sphere forming analysis were performed to evaluate the stem-like traits of cells and RNPC1-induced effects on EC cell stemness. RNA immunoprecipitation (RIP) was constructed to investigate the underlying mechanisms. RESULTS The spheres formed by EC cells, named EC spheres, exhibited a remarkably higher stemness than the parental cells, which is characterized as the increase of sphere forming ability, ALDH1 activity, stemness marker expression and migration ability. Notably, RNPC1 expression was decreased in poorly differentiated EC cells than that in EC cells with moderately differentiated. Additionally, RNPC1 expression was significantly decreased in EC spheres and RNPC1 overexpression attenuated the stemness of EC spheres. Moreover, RNPC1 overexpression decreased the migration ability of EC spheres. Mechanistic studies showed that RNPC1 overexpression activated the Hippo pathway through directly binding to MST1/2. Inhibition of MST1/2 rescued RNPC1-mediated effects on EC sphere stemness. CONCLUSIONS Therefore, our results indicate a novel RNPC1/MST1/2 signaling responsible for EC cell stemness.

13.
Diabetes Ther ; 11(3): 701-710, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32020552

RESUMO

INTRODUCTION: The aim of this study was to compare the efficacy of vildagliptin as add-on therapy to short-term continuous subcutaneous insulin infusion (CSII) with CSII monotherapy in hospitalized patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 200 hospitalized patients with inadequately controlled T2DM were randomized into groups, with one group receiving CSII monotherapy (CSII group, n =100) and the other group receiving CSII plus vildagliptin as add-on (CSII + Vig group, n = 100). Of these, 191 completed the 7-day trial (CSII group, n = 99; CSII + Vig group, n = 92) and included in the analysis. The glycemic control and variability of the patients were measured using all-day capillary blood glucose (BG) monitoring. Weight and fasting C-peptide levels were evaluated before and after the interventions. RESULTS: Mean BG concentrations during the whole treatment period were lower and the time to reach target BG was reduced in the CSII + Vig group compared with the CSII group (9.89 ± 3.37 vs. 9.46 ± 3.23 mmol/L, P < 0.01; 129 ± 4 vs. 94 ± 5 h, P < 0.01, respectively). Similarly, the indicators of glycemic variability, namely the standard deviation of BG and the largest amplitude of glycemic excursion, were significantly decreased in the CSII + Vig group compared with the CSII group (2.68 ± 1.05 vs. 2.39 ± 1.00 mmol/L, P < 0.01; 7.19 ± 2.86 vs. 6.23 ± 2.73 mmol/L, P < 0.01, respectively). CONCLUSIONS: Short-term CSII with vildagliptin as add-on therapy may be an optimized treatment for hospitalized patients with T2DM compared with short-term CSII monotherapy.

14.
Sci Rep ; 10(1): 1549, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005877

RESUMO

The growth trajectory of Chinese preschoolers still remains unclear. Our objective was to determine whether there was an association between adverse pregnancy outcomes and overweight offspring. We analyzed population-based retrospective cohort data from the Medical Birth Registry of Xiamen, which comprised 33,157 children examined from 1 to 6 years of age. Longitudinal analyses were used to evaluate the growth trajectories of offspring body mass index (BMI). Multivariate logistic regression was used to assess the effects of two adverse pregnancy outcomes, gestational diabetes mellitus (GDM) and being large-for-gestational age (LGA), on childhood overweight. Offspring of mothers with GDM and LGA has a higher annual BMI z-score from 1 to 6 years of age (all P < 0.05). But, a higher annual BMI z-score was only observed in children aged 1-5 years in models 1-3. Overall BMI z-score of offspring aged 1-6 who were born to mothers with GDM and LGA were also higher in models 1-3 (all P < 0.05). Additionally, offspring of mothers with GDM and LGA had a higher risk for overweight in model 1, from 1 to 6 years of age (odds ratio (OR), 1.814; 95% confidence interval (CI), 1.657-1.985; P < 0.0001). However, this association was attenuated after adjusting for maternal pre-pregnancy BMI (OR, 1.270; 95% CI, 0.961-1.679; P = 0.0930). Offspring of mothers with GDM and LGA had a higher BMI z-score and increased risk for overweight. Indeed, intrauterine exposure to maternal GDM and LGA could bias offspring to overweight, whereas maternal pre-pregnancy BMI may play a key role in offspring overweight for children born to mothers with GDM and LGA.

15.
Cell Death Dis ; 11(1): 35, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959742

RESUMO

Vascular smooth muscle cell (SMC) from arterial stenotic-occlusive diseases is featured with deficiency in mitochondrial respiration and loss of cell contractility. However, the regulatory mechanism of mitochondrial genes and mitochondrial energy metabolism in SMC remains elusive. Here, we described that DNA methyltransferase 1 (DNMT1) translocated to the mitochondria and catalyzed D-loop methylation of mitochondrial DNA in vascular SMCs in response to platelet-derived growth factor-BB (PDGF-BB). Mitochondrial-specific expression of DNMT1 repressed mitochondrial gene expression, caused functional damage, and reduced SMC contractility. Hypermethylation of mitochondrial D-loop regions were detected in the intima-media layer of mouse carotid arteries subjected to either cessation of blood flow or mechanical endothelial injury, and also in vessel specimens from patients with carotid occlusive diseases. Likewise, the ligated mouse arteries exhibited an enhanced mitochondrial binding of DNMT1, repressed mitochondrial gene expression, defects in mitochondrial respiration, and impaired contractility. The impaired contractility of a ligated vessel could be restored by ex vivo transplantation of DNMT1-deleted mitochondria. In summary, we discovered the function of DNMT1-mediated mitochondrial D-loop methylation in the regulation of mitochondrial gene transcription. Methylation of mitochondrial D-loop in vascular SMCs contributes to impaired mitochondrial function and loss of contractile phenotype in vascular occlusive disease.

16.
J Am Soc Mass Spectrom ; 31(2): 267-276, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31922736

RESUMO

Amyloid fibril formation is a hallmark in a range of human diseases. Analysis of the molecular details of amyloid aggregation, however, is limited by the difficulties in solubilizing, separating, and identifying the aggregated biomolecules. Additional labeling or protein modification is required in many current analytical techniques in order to provide molecular details of amyloid protein aggregation, but these modifications may result in protein structure disruption. Herein, ultrahigh resolution mass spectrometry (MS) with electron capture dissociation tandem MS (ECD MS/MS) has been applied to monitor the formation of early oligomers of human islet amyloid polypeptide (hIAPP), which aggregate rapidly in the pancreas of type II diabetes (T2D) patients. ECD MS/MS results show the aggregation region of the early oligomers is at the Ser-28/Ser-29 residue of a hIAPP unit and at the Asn-35 residue of another hIAPP unit near the C-terminus in the gas phase. These data contribute to the understanding of the binding site between hIAPP units which may help for specific target region therapeutic development in the future. Furthermore, MS has also been applied to quantify the amount of soluble amyloid protein remaining in the incubated solutions, which can be used to estimate the aggregation rate of amyloid protein during incubation (28 days). These data are further correlated with the results obtained using fluorescence spectroscopy and transmission electron microscopy (TEM) to generate a general overview of amyloid protein aggregation. The methods demonstrated in this article not only explore the aggregation site of hIAPP down to an amino acid residue level, but are also applicable to many amyloid protein aggregation studies.

17.
Ecotoxicol Environ Saf ; 191: 110223, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31991395

RESUMO

Differences of cytotoxicity associated with exposure to different extracts of atmospheric particulate matters (PMs) are still not well characterized by in vitro toxicoproteomics. In this study, in vitro cytotoxicity assays and toxicoproteomic analyses were carried out to investigate toxic effects of PM collected using polytetrafluoroethylene (PTFE) filters extracted with acetone for PM2.1 and water for PM2.1 and PM10 on A549 human lung epithelial cells. The cytotoxicity assays based on cell viability, cell apoptosis and reactive oxygen species generation indicated that PM2.1 extracted with acetone had the highest toxicity. iTRAQ labeling and LC-MS/MS analyses indicated that the number of differentially expressed proteins in A549 cells affected by PM2.1 extracted with acetone was noticeably higher than that of the other two groups. Hierarchical cluster analyses showed that the influences of the extracts of PM2.1 and PM10 using water on the proteome of A549 cells were similar, whereas significantly different from the effect of PM2.1 extracted with acetone. Pathways analyses indicated that PM2.1 extracted with acetone influenced the expression of proteins involved in 14 pathways including glycolysis/gluconeogenesis, pentose phosphate pathway, proteasome, etc. PM2.1 extracted with water affected the expression of proteins involved in 3 pathways including non-homologous end-joining, ribosome and endocytosis. However, PM10 extracted with water affected the expression of proteins involved in only spliceosome pathway. The extracts of PM using different extractants to detach PM from PTFE filters influenced the cytotoxic effects of PM and the proteome of A549 cells. Therefore, extractants should be assessed carefully before the investigations on cytotoxicity to improve the compatibility of experimental results among research teams.


Assuntos
Poluentes Atmosféricos/toxicidade , Material Particulado/toxicidade , Células A549 , Acetona , Apoptose , Atmosfera/química , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/toxicidade , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Politetrafluoretileno , Proteoma/metabolismo , Proteômica/métodos , Água
18.
Neurogastroenterol Motil ; 32(2): e13741, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31613423

RESUMO

BACKGROUND: Low-grade inflammation occurs in some patients with irritable bowel syndrome (IBS). However, the exact inflammatory markers of IBS and the relationship of these markers with IBS subtypes and symptoms are poorly defined. Peroxiredoxin 1 (PRDX1) plays an important role in inflammatory responses, including intestinal inflammation. We investigated whether PRDX1 is associated with the diagnosis, subtypes, and symptom severity of IBS. METHODS: A total of 177 IBS patients and 174 sex- and age-matched healthy controls (HCs) were recruited. The PRDX1 levels in the sera and colonic mucosa of the participants were detected by enzyme-linked immunosorbent assays and immunohistochemistry. The severity of IBS symptoms was assessed using the IBS Severity Scoring System (SSS) questionnaire. RESULTS: The PRDX1 levels in the sera (F = 71.81, P < .001) and colonic mucosa (F = 5.359, P < .001) of postinfectious (PI-IBS) and diarrhea-predominant IBS (IBS-D) groups were significantly higher than those of the other three IBS subtypes and HC group. The PRDX1 level in the serum and colonic mucosa of IBS-D (serum, P < .01, mucosa, P < .001) and PI-IBS (serum, P < .05, mucosa, P < .001) groups with the most severe symptoms was significantly higher than that in the groups with mild and moderate symptoms. Correlation analysis revealed that in patients with IBS-D (P < .001) and PI-IBS (P < .05), the levels of PRDX1 and TNF-α in sera had a significant positive correlation with IBS-SSS. CONCLUSION: Elevated PRDX1 in the serum and colon mucosa may be closely related to the progression of IBS (especially IBS-D and PI-IBS) and the expression of gastrointestinal symptoms.

19.
Anal Chem ; 92(1): 699-706, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31789017

RESUMO

Pulmonary fibrosis (PF) is a fatal disease with increasing prevalence. Nonradioactive and noninvasive diagnosis of PF at an early stage can improve the prognosis but represents a daunting challenge. Up-regulation of nitric oxide (NO) is a typical microenvironmental feature of PF. Here, we report a small-molecule probe, PNO1, that can fluorogenically sense this microenvironmental feature for PF diagnosis. We demonstrate that PNO1 fluorescence is 6-fold higher in PF-diseased mice lungs than in normal-control groups. In addition to this in vivo result, PNO1 can also be applied in vitro to detect PF-diseased cells and ex vivo to detect PF-diseased tissues from clinical patients. These results highlight PNO1 as a complement to the traditional immunostaining-based methods for PF detection to facilitate quick screening for anti-PF drug candidates.

20.
Cancer Biomark ; 27(2): 139-145, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30689557

RESUMO

BACKGROUND: Circular RNAs (circRNA) play key regulatory roles in cancer progression. Human circRNA microarray was performed to screen for abnormally expressed circRNA in gastric cancer tissues. In this study, we found circRNA102958 was up-regulated in gastric cancer tissues and cell lines. METHODS: The hsa_circRNA_102958 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in gastric tissue and cell. Then, the association between the expression level of hsa_circRNA_102958 and the clinicopathological features of patients with gastric cancer was further analyzed. Finally, a network of hsa_circRNA_102958-miRNA-mRNA interactions was predicated. RESULTS: In this study, we analyzed 30 patients and found that hsa_circRNA_102958 was significantly overexpressed in gastric cancer tissues compared with paired adjacent normal tissues. Clinicopathological features showed that hsa_circRNA_102958 level in GC tissues was positively associated with TNM stage (p= 0.032). The area under the ROC curve was 0.74. Finally, a total of 5 miRNAs were predicted to have an interaction with hsa_circRNA_102958. CONCLUSIONS: hsa_circRNA_102958 may be a potential novel and stable biomarker for the diagnosis of gastric carcinoma.

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