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1.
Biomed Pharmacother ; 125: 109995, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32187954

RESUMO

BACKGROUND: We previously observed that amphiregulin (Areg), a ligand of epithelial growth factor receptor (EGFR), was highly expressed in lipopolysaccharide (LPS)-induced acute lung injury (ALI) lung tissues mainly by the classically activated (M1) alveolar macrophages (AMs). Areg also plays a protective role in LPS-induced injury in lung tissues and alveolar epithelial cells (AECs). However, whether Areg is co-expressed with tumor necrosis factor (TNF)-α in ALI lung tissues, and can directly inhibit TNF-α-induced AEC injury remains unclear. METHODS: We first detected the kinetic expressions of Areg and TNF-α in LPS-stimulated lung tissues and M1 AMs and then identified the role of exogenous recombinant Areg (rmAreg) in the injured lung tissues. The effect of Areg on TNF-α-induced apoptosis in MLE-12 cells, a kind of AECs, was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The activation of the EGFR-AKT pathway and caspase-3, -8, and -9 were detected by Western blotting. The EGFR knockdown by small interfering RNA was used to assess the role of EGFR in Areg functions. RESULTS: Areg production occurred in close parallel with TNF-α expression in M1 AMs and ALI lung tissues, and rmAreg attenuated LPS-induced ALI in mice. TNF-α stimulation induced significant apoptosis in MLE-12 cells, but this apoptosis was inhibited under rmAreg treatment. Moreover, rmAreg enhanced the activation of EGFR and AKT, and reduced the expressions of cleaved caspase-3, -8, and -9 in ALI lung tissues and TNF-α-challenged MLE-12 cells. However, the EGFR knockdown significantly inhibited the Areg-induced improvement in apoptosis, enhancement of EGFR and AKT activation, and reduction of cleaved caspase-3, -8, and -9 expressions. CONCLUSIONS: Areg and TNF-α were synchronously produced by ALI lung tissues and M1 AMs, and Areg directly inhibited the TNF-induced apoptosis and transduction of caspase death signals in AECs via the EGFR pathway.

2.
Aging (Albany NY) ; 12(3): 2347-2372, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32023222

RESUMO

The present study focused on the expression patterns, prognostic values and potential mechanism of the PDI family in gliomas. Most PDI family members' mRNA expressions were observed significantly different between gliomas classified by clinical features. Construction of the PDI signature, cluster and risk score models of glioma was done using GSVA, consensus clustering analysis, and LASSO Cox regression analysis respectively. High values of PDI signature/ risk score and cluster 1 in gliomas were associated with malignant clinicopathological characteristics and poor prognosis. Analysis of the distinctive genomic alterations in gliomas revealed that many cases having high PDI signature and risk score were associated with genomic aberrations of driver oncogenes. GSVA analysis showed that PDI family was involved in many signaling pathways in ERAD, apoptosis, and MHC class I among many more. Prognostic nomogram revealed that the risk score was a good prognosis indicator for gliomas. The qRT-PCR and immunohistochemistry confirmed that P4HB, PDIA4 and PDIA5 were overexpressed in gliomas. In summary, this research highlighted the clinical importance of PDI family in tumorigenesis and progression in gliomas.

3.
Sci Total Environ ; 715: 136954, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32041052

RESUMO

With the increased interest in allocating more carbon (C) belowground for C sequestration, total belowground C flux (TBCF) and its dynamics have become an important research topic. However, it remains uncertain whether TBCF responds nonlinearly to increased nitrogen (N) availability and how its main components (root and ectomycorrhizal (ECM) fungi) contribute to TBCF. We established a four-year N addition experiment with control, low-N, medium-N, and high-N fertilization treatments in a N-limited temperate forest in northern China. We measured TBCF and its three main components including root respiration, ECM fungal respiration, and root production. The involved edaphic and plant factors were also measured. TBCF showed a nonlinear response to the increasing amounts of N addition, accelerated by 10.37% in low-N addition and restrained by 10.29% in high-N addition. Contrasting patterns of the contributions of root respiration and ECM fungal respiration to TBCF implies different strategies of investment in roots and ECM fungi under the different N-availability statuses. The ratio of production and respiration in roots under N addition was nearly 1:2, which indicated that when soil N availability increases, roots prefer to lose C by overflow respiration rather than fix C in new biomass. The low-N addition increased TBCF by directly increasing root respiration and indirectly increasing coarse root biomass. The medium-N addition positively affected TBCF by increasing root respiration but this positive effect was cancelled out by the significantly negative effect of the increased soil total N concentration. The decrease in soil pH was the most effective pathway to decrease TBCF in high-N addition. Because of a large-scale reforestation program for C sink management in recent years, our findings of the nonlinear response of TBCF to different N fertilization treatments could provide insight for predicting belowground C sequestration potential and its response to atmospheric N deposition.

4.
J Colloid Interface Sci ; 561: 793-800, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31791697

RESUMO

The photo-Fenton activity of ZnFe2O4 was enhanced by the ZnFe2O4/α-Fe2O3 (ZFO/FO) heterostructure synthesized via a one-step hydrothermal method. The degradation efficiency was further improved by loading Pt nanoparticles on the surface of the heterostructure. The degradation efficiencies of MB for ZnFe2O4, ZFO/FO, and ZFO/FO/Pt were 57.82%, 83.71%, and 99.96%, respectively. This can be ascribed to Pt working as an "electron bridge" to transfer the photo-generated electrons from the α-Fe2O3 to solution, thus improving the photo-Fenton efficiency. A noteworthy feature of this study is the successful strategy to fabricate heterostructures photo-Fenton for solving environmental problems at the alkaline condition of pH 9.

5.
J Colloid Interface Sci ; 561: 257-264, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31830737

RESUMO

Magnesium oxide (MgO) nanosheets and hydrogen peroxide (H2O2) are respectively employed as a photocatalyst and an oxidant to enhance the photocatalytic efficiency for photo-degradation of methylene blue (MB). During the photocatalytic process, highly-oxidizing magnesium dioxide (MgO2) is generated by reacting with H2O2 on the edge of MgO nanosheets, which is verified by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HR-TEM). The synergistic catalysis of H2O2, MgO2 (highly-oxidizing) and MgO (photocatalysis) has significantly improved the photocatalytic efficiency. The photocatalytic efficiency of MgO nanosheets with H2O2 under visible-light irradiation reaches 98.1%, which is 3.2 times greater than that without H2O2 under visible light (30.5%). Moreover, the photocatalytic efficiency is comparable with that of traditional photocatalysts, such as titanium dioxide (TiO2), graphitic carbon nitride (g-C3N4), etc. This study indicates that the synergistic effect of the homologous oxide catalyst (MgO) effectively improves photo-degradation efficiency via in-situ generating a highly-oxidizing metal peroxide (MgO2) during the photocatalytic process.

6.
Ophthalmic Res ; : 1-11, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31614358

RESUMO

BACKGROUND: The purpose of this study is to determine the mutation frequencies of key driver genes in uveal melanoma (UM) in Chinese patients and to detect associations between metastasis and the mutation of these genes. METHOD: A total of 85 patients with UM were enrolled in this study, including 18 patients with metastasis and 67 without metastasis. Sanger sequencing covering the mutational hotspot regions of the G protein subunit alpha Q (GNAQ), GNA11, splicing factor 3B subunit 1 (SF3B1), X-linked eukaryotic translation initiation factor 1A (EIF1AX), phospholipase C beta 4 (PLCB4) and cysteinyl leukotriene receptor 2 (CYSLTR2) genes was used to analyse the mutations in Chinese patients. RESULTS: The frequencies of GNAQ and GNA11 mutations in UM were 45% (38/85) and 35% (30/85) respectively. The frequencies of SF3B1 and EIF1AX mutations were 37% (31/85) and 9% (8/85) respectively. Only 2 mutations were detected in exon 4 of GNAQ, and no mutations were detected in exon 4 of GNA11. A novel mutation, c.627G>T (Q209H) in GNA11 was found. The detected mutations affecting SF3B1 were c.1873C>T (R625C), c.1874G>A (R625H) and c.1874G>T (R625L). The association between the mutations in SF3B1 and low risk of metastasis was statistically significant (OR 0.17, 95% CI 0.035-0.819). The mutations affecting EIF1AX were -23G>A (5'-UTR), c.5C>G (P2R), c.23G>A (G8Q), c.25G>C (G9A) and c.38_39GC>CT (R13P). No mutations were found in the PLCB4 and CYSLTR2 genes. Unfortunately, information on BRCA1-associated protein 1 could not be obtained. CONCLUSIONS: These data indicate that mutations in the PLCB4 and CYSLTR2 genes are rare in Chinese UM patients. The mutations in GNAQ, GNA11 and EIF1AX were not associated with metastasis, whereas SF3B1 mutations were correlated with low risk of metastasis and demonstrated a protective effect in UM patients in China.

7.
Chin Med Sci J ; 34(3): 184-193, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601301

RESUMO

Objective Our previous study has revealed that iASPP is elevated in human head and neck squamous cell carcinoma (HNSCC) and iASPP overexpression signifcantly correlates with tumor malignant progression and poor survival of HNSCC. This study investigated the function of iASPP playing in proliferation and invasion of HNSCC in vitro. Methods HNSCC cell line Tu686 transfected with Lentiviral vector-mediated iASPP-specific shRNA and control shRNA were named the shRNA-iASPP group and shRNA-NC group, respectively. The non-infected Tu686 cells were named the CON group. CCK-8 assay, flow cytometry, transwell invasion assay were performed to detect the effects of iASPP inhibition in vitro. Results Our results demonstrated that the proliferation of shRNA-iASPP cells at the time of 72 h (F=32.459, P=0.000), 96 h (F=51.407, P=0.000), 120 h (F=35.125, P=0.000) post-transfection, was significantly lower than that of shRNA-NC cells and CON cells. The apoptosis ratio of shRNA-iASPP cells was 9.42% ± 0.39% (F=299.490, P=0.000), which was significantly higher than that of CON cells (2.80% ± 0.42%) and shRNA-NC cells (3.18% ± 0.28%). The percentage of shRNA-iASPP cells in G0/G1 phase was 74.65% ± 1.09% (F=388.901, P=0.000), which was strikingly increased, compared with that of CON cells (55.19% ± 1.02%) and shRNA-NC cells (54.62% ± 0.88%). The number of invading cells was 56 ± 4 in the shRNA-iASPP group (F=84.965, P=0.000), which decreased significantly, compared with the CON group (111 ± 3) and the shRNA-NC group (105 ± 8). The survival rate of shRNA-iASPP cells administrated with paclitaxel was highly decreased, compared with CON cells and shRNA-NC cells (F=634.841, P=0.000). Conclusion These results suggest iASPP may play an important role in progression and aggressive behavior of HNSCC and may be an efficient chemotherapeutic target for the treatment of HNSCC.


Assuntos
Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Proteínas de Neoplasias/biossíntese , Paclitaxel/farmacologia , Proteínas Repressoras/biossíntese , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linhagem Celular Tumoral , Humanos , Invasividade Neoplásica , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
8.
Int J Mol Sci ; 20(19)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554168

RESUMO

Salt stress is one of the key abiotic stresses that causes great loss of yield and serious decrease in quality in maize (Zea mays L.). Therefore, it is very important to reveal the molecular mechanism of salt tolerance in maize. To acknowledge the molecular mechanisms underlying maize salt tolerance, two maize inbred lines, including salt-tolerant 8723 and salt-sensitive P138, were used in this study. Comparative proteomics of seedling roots from two maize inbred lines under 180 mM salt stress for 10 days were performed by the isobaric tags for relative and absolute quantitation (iTRAQ) approach. A total of 1056 differentially expressed proteins (DEPs) were identified. In total, 626 DEPs were identified in line 8723 under salt stress, among them, 378 up-regulated and 248 down-regulated. There were 473 DEPs identified in P138, of which 212 were up-regulated and 261 were down-regulated. Venn diagram analysis showed that 17 DEPs were up-regulated and 12 DEPs were down-regulated in the two inbred lines. In addition, 8 DEPs were up-regulated in line 8723 but down-regulated in P138, 6 DEPs were down-regulated in line 8723 but up-regulated in P138. In salt-stressed 8723, the DEPs were primarily associated with phenylpropanoid biosynthesis, starch and sucrose metabolism, and the mitogen-activated protein kinase (MAPK) signaling pathway. Intriguingly, the DEPs were only associated with the nitrogen metabolism pathway in P138. Compared to P138, the root response to salt stress in 8723 could maintain stronger water retention capacity, osmotic regulation ability, synergistic effects of antioxidant enzymes, energy supply capacity, signal transduction, ammonia detoxification ability, lipid metabolism, and nucleic acid synthesis. Based on the proteome sequencing information, changes of 8 DEPs abundance were related to the corresponding mRNA levels by quantitative real-time PCR (qRT-PCR). Our results from this study may elucidate some details of salt tolerance mechanisms and salt tolerance breeding of maize.


Assuntos
Proteínas de Plantas/metabolismo , Proteoma , Proteômica , Tolerância ao Sal , Estresse Fisiológico , Zea mays/fisiologia , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Endogamia , Fenótipo , Melhoramento Vegetal , Proteínas de Plantas/genética , Proteômica/métodos , Tolerância ao Sal/genética , Plântula/genética , Plântula/metabolismo , Estresse Fisiológico/genética
9.
J Transl Med ; 17(1): 220, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291961

RESUMO

BACKGROUND: The influence of DNMT3A R882 mutations on adult acute myeloid leukemia (AML) prognosis is still controversial presently. The influence of R882 allele ratio on drug response and prognosis of AML is unknown yet. Besides, it is obscure whether anthracyclines are involved in chemoresistance resulted from R882 mutations. METHODS: DNMT3A R882 mutations in 870 adult AML patients receiving standard induction therapy were detected by pyrosequencing. Associations of the mutants with responses to induction therapy and disease prognosis were analyzed. RESULTS: DNMT3A R882 mutations were detected in 74 (8.51%) patients and allele ratio of the mutations ranged from 6 to 50% in the cohort. After the first and second courses of induction therapy including aclarubicin, complete remission rates were significantly lower in carriers of the DNMT3A R882 mutants as compared with R882 wildtype patients (P = 0.022 and P = 0.038, respectively). Compared with R882 wild-type patients, those with the R882 mutations showed significantly shorter overall survival (OS) and disease-free survival (DFS) (P = 1.92 × 10-4 and P = 0.004, respectively). Patients with higher allele ratio of R882 mutations showed a significantly shorter OS as compared with the lower allele ratio group (P = 0.035). CONCLUSION: Our results indicate that the impact of DNMT3A R882 mutations on AML prognosis was determined by the mutant-allele ratio and higher allele ratio could predict a worse prognosis, which might improve AML risk stratification. In addition, DNMT3A R882 mutations were associated with an inferior response to induction therapy with aclarubicin in Chinese AML patients.

10.
J Exp Clin Cancer Res ; 38(1): 298, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291988

RESUMO

BACKGROUND: Gliomas are the most common primary tumors in central nervous system. Despite advances in diagnosis and therapy, the prognosis of glioma remains gloomy. Autophagy is a cellular catabolic process that degrades proteins and damaged organelles, which is implicated in tumorigenesis and tumor progression. Autophagy related 4C cysteine peptidase (ATG4C) is an autophagy regulator responsible for cleaving of pro-LC3 and delipidation of LC3 II. This study was designed to investigate the role of ATG4C in glioma progression and temozolomide (TMZ) chemosensitivity. METHODS: The association between ATG4C mRNA expression and prognosis of gliomas patients was analyzed using the TCGA datasets. The role of ATG4C in proliferation, apoptosis, autophagy, and TMZ chemosensitivity were investigated by silencing ATG4C in vivo. Ectopic xenograft nude mice model was established to investigate the effects of ATG4C on glioma growth in vivo. RESULTS: The median overall survival (OS) time of patients with higher ATG4C expression was significantly reduced (HR: 1.48, p = 9.91 × 10- 7). ATG4C mRNA expression was evidently increased with the rising of glioma grade (p = 2.97 × 10- 8). Knockdown ATG4C suppressed glioma cells proliferation by inducing cell cycle arrest at G1 phase. ATG4C depletion suppressed autophagy and triggered apoptosis through ROS accumulation. Depletion of ATG4C suppressed TMZ-activated autophagy and promoted sensitivity of glioma cells to TMZ. Additionally, ATG4C knockdown suppressed the growth of glioma remarkably in nude mice. CONCLUSION: ATG4C is a potential prognostic predictor for glioma patient. Targeting ATG4C may provide promising therapy strategies for gliomas treatment.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Cisteína Endopeptidases/genética , Resistencia a Medicamentos Antineoplásicos/genética , Glioma/genética , Glioma/patologia , Adulto , Idoso , Animais , Biomarcadores Tumorais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glioma/metabolismo , Glioma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
JBJS Case Connect ; 9(3): e0302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31343998

RESUMO

CASE: Recurrent carpal tunnel syndrome is a challenging problem. Nerve wraps have been introduced as a barrier to prevent scar traction neuritis for use during revision carpal tunnel surgery. We present 3 cases of inflammatory responses to bovine collagen and porcine subintestinal mucosal nerve wraps in patients undergoing revision carpal tunnel surgery. No patient had evidence of infection, and pathology revealed acute and chronic inflammation. All 3 patients responded favorably following wrap removal. CONCLUSIONS: We recommend caution with the routine use of nerve wraps in the setting of revision carpal tunnel surgery.

12.
Int J Mol Sci ; 20(11)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181633

RESUMO

The growth and development of maize roots are closely related to drought tolerance. In order to clarify the molecular mechanisms of drought tolerance between different maize (Zea mays L.) varieties at the protein level, the isobaric tags for relative and absolute quantitation (iTRAQ) quantitative proteomics were used for the comparative analysis of protein expression in the seedling roots of the drought-tolerant Chang 7-2 and drought-sensitive TS141 maize varieties under 20% polyethylene glycol 6000 (PEG 6000)-simulated drought stress. We identified a total of 7723 differentially expressed proteins (DEPs), 1243 were significantly differentially expressed in Chang 7-2 following drought stress, 572 of which were up-regulated and 671 were down-regulated; 419 DEPs were identified in TS141, 172 of which were up-regulated and 247 were down-regulated. In Chang 7-2, the DEPs were associated with ribosome pathway, glycolysis/gluconeogenesis pathway, and amino sugar and nucleotide sugar metabolism. In TS141, the DEPs were associated with metabolic pathway, phenylpropanoid biosynthesis pathway, and starch and sucrose metabolism. Compared with TS141, the higher drought tolerance of Chang 7-2 root system was attributed to a stronger water retention capacity; the synergistic effect of antioxidant enzymes; the strengthen cell wall; the osmotic stabilization of plasma membrane proteins; the effectiveness of recycling amino acid; and an improvement in the degree of lignification. The common mechanisms of the drought stress response between the two varieties included: The promotion of enzymes in the glycolysis/gluconeogenesis pathway; cross-protection against the toxicity of aldehydes and ammonia; maintenance of the cell membrane stability. Based on the proteome sequencing information, the coding region sequences of eight DEP-related genes were analyzed at the mRNA level by quantitative real-time PCR (qRT-PCR). The findings of this study can inform the future breeding of drought-tolerant maize varieties.


Assuntos
Secas , Pressão Osmótica , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Zea mays/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Proteoma/genética , Zea mays/metabolismo
13.
J BUON ; 24(1): 310-314, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941986

RESUMO

PURPOSE: To investigate the growth inhibitory effect of Sorghumol on the circulating renal cancers cells and to investigate the underlying mechanisms including its effects on apoptosis, cell cycle phase distribution and m-TOR/PI3K/AKT signalling pathway. METHODS: The antiproliferative effects were assessed by WST-1 and colony formation assay. Apoptosis was detected by the Hoechst and AO/EB staining using fluorescence microscopy. Cell cycle analysis was carried out by flow cytometry. Protein expression was checked by western blotting. RESULTS: The results revealed that Sorghumol inhibited the growth of the renal cancer cell (RCC) line A498 and circulating RCCs. However, more profound effects were observed on the RCC cells. The anticancer effects were found to be due to induction of apoptosis. Moreover, Sorghumol could also caused G2/M cell cycle arrest of the RCC cells. Besides, examination of the effect of Sorghumol on m-TOR/PI3K/AKT revealed that Sorghumol inhibited the expression of p-mTOR, p-PI3K and p-AKT in a concentration-dependent manner. CONCLUSION: Taken together, we conclude that Sorghumol inhibited the proliferation of circulating RCCs and may therefore prove to be an important lead molecule for the treatment of renal cancer.


Assuntos
Neoplasias Renais/tratamento farmacológico , Células Neoplásicas Circulantes/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias Renais/enzimologia , Neoplasias Renais/patologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores
14.
Oncol Lett ; 17(1): 1094-1100, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30655870

RESUMO

Prostate cancer is the most common form of cancer in men, with increased incidence rates observed in older individuals. Prostate cancer is primarily driven via activation of the androgen receptor (AR), the principal transcriptional factor governing prostate cancer cellular programming and its associated metabolism. One of the downstream targets of AR is hepatocyte nuclear factor-1ß (HNF1B), an important oncogenic transcription factor in prostate cancer. In the present study, the regulatory role of HNF1B in enoyl-CoA-(Δ) isomerase 2 (ECI2) expression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model was investigated. Using this model, tumor progression and associated pathological alterations at 12, 18 and 24 weeks were analyzed. Histological sectioning revealed pathological alterations over time, including thickening of glandular epithelial cells (12 weeks), increases in cellular proliferation (18 weeks), and extensive thickening and hardening of the tissue layer (24 weeks). Expression levels of HNF1B and ECI2 proteins were validated by immunohistochemistry and western blotting at different stages of prostate cancer development. HNF1B and ECI2 exhibited minimal differences in protein expression at 12 weeks in TRAMP+ mice. However, by 18 weeks, TRAMP+ mice exhibited multi-fold increases in HNF1B expression levels, along with downregulation of ECI2. These effects were reversed at 24 weeks, indicating an important time-dependent regulation of gene expression. Taken together, these results demonstrated that upon tumor progression, the initial tumor-protective effect of HNF1B is lost along with downregulated expression of HNF1B and increased expression of ECI2.

15.
Environ Pollut ; 243(Pt A): 75-86, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30172126

RESUMO

China has been experiencing a rapid increase in nitrogen (N) deposition due to intensified anthropogenic N emissions since the late 1970s. By synthesizing experimental and observational data taken from literature, we reviewed the responses of China's forests to increasing N deposition over time, with a focus on soil biogeochemical properties and acidification, plant nutrient stoichiometry, understory biodiversity, forest growth, and carbon (C) sequestration. Nitrogen deposition generally increased soil N availability and soil N leaching and decreased soil pH in China's forests. Consequently, microbial biomass C and microbial biomass N were both decreased, especially in subtropical forests. Nitrogen deposition increased the leaf N concentration and phosphorus resorption efficiency, which might induce nutrient imbalances in the forest ecosystems. Although experimental N addition might not affect plant species richness in the overstorey, it did significantly alter species composition of understory plants. Increased N stimulated tree growth in temperate forests, but this effect was weak in subtropical and tropical forests. Soil respiration in temperate forests was non-linearly responsive to N additions, with an increase at dosages of <60 kg N ha-1 yr-1 and a decrease at dosages of >60 kg N ha-1 yr-1. However, it was consistently decreased by increased N inputs in subtropical and tropical forests. In light of future trends in the composition (e.g., reduced N vs. oxidized N) and the loads of N deposition in China, further research on the effects of N deposition on forest ecosystems will have critical implications for the management strategies of China's forests.


Assuntos
Ecossistema , Florestas , Nitrogênio/metabolismo , Desenvolvimento Vegetal , Solo/química , Árvores/metabolismo , Carbono/análise , China , Microbiota/efeitos dos fármacos , Nitrogênio/análise , Nitrogênio/farmacologia , Fósforo/análise , Desenvolvimento Vegetal/efeitos dos fármacos , Microbiologia do Solo , Árvores/química , Árvores/efeitos dos fármacos
16.
Eur J Pharmacol ; 833: 201-209, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29864410

RESUMO

Patients with somatic mutations of epigenetic regulators are characterized by aberrant chromatin modification patterns. Recent mechanistic studies pairing chemical tool compounds and deep-sequencing technology have greatly broadened our understanding of epigenetic regulation in glioma progression and underpinned alternative treatment of epigenetic inhibitors. However, the effect of most inhibitors is condition-dependent, and the overall results of clinical trials still have not been applied to patients. There is an intense need to develop more potent and specific compounds as well as identify the population who may achieve clinical benefits. Besides, combination therapy with conventional therapeutics is another alternative strategy. In this review, we summarize well-characterized chemical probes in glioma research and clinical translation. We also discuss the target population and combination of therapy regimens of various agents. In a holistic sense, we try to provide guidance for selecting targeted chemical probes and pave the way for personalized rational therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias Encefálicas/tratamento farmacológico , Epigênese Genética/efeitos dos fármacos , Glioma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Ensaios Clínicos como Assunto , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Epigênese Genética/genética , Glioma/genética , Histonas/genética , Histonas/metabolismo , Humanos
17.
Sci Total Environ ; 642: 646-655, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29909332

RESUMO

Nutrient availability is one of the key regulator of the global forest carbon balance. The use of fossil fuels and fertilizers has increased the amount of biologically reactive nitrogen (N) in recent decades and N fertilization also changes the availability of other nutrients such as phosphorous (P) and potassium (K). The increased soil nutrient availability is known to stimulate forest growth, but we currently lack comprehensive understanding of the response of soil respiration and its three components (roots, microbes, and ectomycorrhizal (ECM) fungi) to the increased soil N, P and K availability. We conducted a 4-year field fertilization experiment with N, P and K addition in an N-limited temperate forest and separated ECM fungi respiration (Rm), root respiration (Rr) and heterotrophic microbial respiration (Rh) from total soil respiration. Our results showed that Rr increased with N and P addition while Rh and Rm did not respond to nutrient addition. Rm, Rr and Rh varied substantially from year to year, but their responses to nutrient addition did not fluctuate in different years. Our results indicate that in N-limited forest ecosystems, Rh and Rm may not respond substantially to future changes in nutrient addition and that inter-annual variation in climate may be the determinant of soil CO2 efflux in response to global changes.

18.
Cell Physiol Biochem ; 47(1): 428-439, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29794476

RESUMO

BACKGROUND/AIMS: In the current study, we performed an integrated analysis of genome-wide methylation and gene expression data to find novel prognostic genes for lower-grade gliomas (LGGs). METHODS: First, TCGA methylation data were used to identify prognostic genes associated with promoter methylation. Second, candidate genes that were stably regulated by promoter methylation were explored. Third, Cox proportional hazards regression analysis was used to generate a prognostic signature, and the signature genes were used to construct a survival risk score system. RESULTS: Three genes (EMP3, GSX2 and EMILIN3) were selected as signature genes. These three signature genes were used to construct a survival risk score system. The high-risk group exhibited significantly worse overall survival (OS) and relapse-free survival (RFS) as compared to the low-risk group in the TCGA dataset. The association of the three-gene prognostic signature with patient' survival was then validated using the CGGA dataset. Moreover, Kaplan-Meier plots showed that the three-gene prognostic signature risk remarkably stratified grade II and grade III patients in terms of both OS and RFS in the TCGA cohort. There was also a significant difference between the low- and high-risk groups in IDH wild-type glioma patients, indicating that the three-gene signature may be able to help in predicting prognosis for patients with IDH wild-type gliomas. CONCLUSION: We identified and validated a three-gene (EMP3, GSX2 and EMILIN3) prognostic signature in LGGs by integrating multidimensional genomic data from the TCGA and CGGA datasets, which may help in fine-tuning the current histology-based tumors classification system and providing better stratification for future clinical trials.


Assuntos
Antígenos de Superfície/genética , Neoplasias do Sistema Nervoso Central/genética , Metilação de DNA , Glioma/genética , Proteínas de Homeodomínio/genética , Glicoproteínas de Membrana/genética , Adulto , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Glioma/diagnóstico , Glioma/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Regiões Promotoras Genéticas , Transcriptoma
19.
Oncotarget ; 8(52): 90338-90350, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-29163833

RESUMO

Purpose: To assess the effectiveness and safety of botulinum toxin A (BTX-A) at different dosages for overactive bladder (OAB). Materials and Methods: The MEDLINE, EMBASE, and Cochrane Controlled Trials Register databases were searched through November 3, 2016 to identify relevant randomized controlled trials (RCTs). Results: Eleven studies were identified in this meta-analysis. Compared with placebo, the urinary incontinence (UI) episodes per week as the primary outcomes, urodynamic parameters including maximum cystometric capacity (MCC), and maximum detrusor pressure (MDP) for neurogenic detrusor overactivity (NDO) at 6 weeks, and for idiopathic detrusor overactivity (IDO) at 36 weeks were evaluated. These and other outcomes for effectiveness of BTX-A at different dosages in two observation periods indicate that a dose greater than 50 U is significantly more effective for certain symptoms of OAB compared with placebo. However, there were no significant differences between some dosages. Compared with placebo, the outcomes of total adverse events for NDO and for IDO show that doses of 300 U and 200 U for NDO are associated with more complications. Conclusions: In consideration that the treatments of BTX-A were with minimal, local, and manageable adverse effects, this meta-analysis demonstrates that BTX-A 200 U is recommended for management of NDO for short-term treatment for there was no significant difference from the larger dose of 300U. The short-term efficacies of BTX-A for IDO remain to be investigated.

20.
Gene ; 637: 145-151, 2017 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-28942034

RESUMO

Patients with chronic heart failure (CHF) are often accompanied with varying degrees of renal diseases. The purpose of this study was to identify rs37369 polymorphism of AGXT2 specific to the renal function of CHF patients. A total of 1012 southern Chinese participants, including 487 CHF patients without history of renal diseases and 525 healthy volunteers, were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes of AGXT2 rs37369 polymorphism. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected to indicate the renal function of the participants. BUN level was significantly higher in CHF patients without history of renal diseases compared with healthy volunteers (p=0.000). And the similar result was also obtained for SCr (p=0.000). Besides, our results indicated that the level of BUN correlated significantly with SCr in both the CHF patients without renal diseases (r=0.4533, p<0.0001) and volunteers (r=0.2489, p<0.0001). Furthermore, we found that the AGXT2 rs37369 polymorphism could significantly affect the level of BUN in CHF patients without history of renal diseases (p=0.036, AA+AG vs GG). Patients with rs37369 GG genotype showed a significantly reduced level of BUN compared to those with the AA genotype (p=0.024), and the significant difference was still observed in the smokers of CHF patients without renal diseases (p=0.023). In conclusion, we found that CHF might induce the impairment of kidney and cause deterioration of renal function. AGXT2 rs37369 polymorphism might affect the renal function of CHF patients free from renal diseases, especially in patients with cigarette smoking.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Nefropatias/patologia , Polimorfismo Genético , Transaminases/genética , Nitrogênio da Ureia Sanguínea , Estudos de Casos e Controles , China/epidemiologia , Doença Crônica , Feminino , Humanos , Incidência , Nefropatias/epidemiologia , Nefropatias/genética , Masculino , Pessoa de Meia-Idade
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