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1.
FEMS Microbiol Lett ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32196075

RESUMO

All well-established cell size homeostasis paradigms are based on the researches of rod bacteria like B. subtilis and E. coli, suggesting a constant division time (timer model), division size (sizer model) or added size (adder model) before division. However, Lysinibacillus varians, a new species with regular filament-to-rod cell cycle, is inconsistent with existing models. In this study, the cell size parameters of the type strain GY32, were investigated by combing multiple microscopy techniques and single-cell approach. Our results showed that the filaments of strain GY32 were unicellular cells with multiple nucleoids. The division time of GY32 cells was variable and their daughter cells produced by asymmetric binary fission had different birth sizes, which were proportional to their elongation rates, resulting in high heterogeneity among the sister cells. Furthermore, the added size from birth to division was significantly shorter than birth size (P < 0.01) and decreased along generations. The results above revealed that the asymmetric division site and varied cell size parameters resulted in filament-to-rod cell cycle of L. varians, and cell size homeostasis could be a more complex and dynamic process than previously assumed. These findings would be helpful in elucidating the open questions in cell division and cell size heterogeneity.

2.
Cancer Med ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160655

RESUMO

OBJECTIVE: To explore the biological function and molecular mechanism of Sp2 in hepatocellular carcinoma (HCC). METHODS: Tissue microarray immunohistochemistry and western blot were used to study the expression of Sp2 in hepatocellular tissue and adjacent non-neoplastic tissues (ANT). In HCC cell lines, the role of Sp2 was determined by in vitro experiments such as CCK8, clone formation test, Transwell assay, wound-healing assay, and flow cytometry apoptotic analysis, and its possible mechanism was analyzed. RESULTS: Compared with ANT, Sp2 expression in HCC tissues was significantly up-regulated, which was strongly associated with stage of tumor and poor prognosis of patients. TCGA database were further confirmed these results. Besides, functional studies had shown that Sp2 knockdown not only leads to a decrease in cell proliferation and an increase in cell apoptosis but also inhibits the cells' abilities of migration and invasion. Sp2 silencing could inhibit the expression of TRIB3 protein and down-regulate the endoplasmic reticulum stress (ERS) level of HCC. CONCLUSION: Sp2 may play a part in promoting cancer by regulating TRIB3 protein, which may be a factor of prognostic and a potential new therapeutic target for HCC.

3.
Curr Med Sci ; 40(1): 145-154, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32166677

RESUMO

Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy. In this study, polyethylene glycol (PEG)-coated magnetic polymeric liposome (MPL) nanoparticles (NPs) assembled from octadecyl quaternized carboxymethyl chitosan (OQC), PEGylated OQC, cholesterol, and magnetic NPs, and functionalized with epithelial growth factor receptor (EGFR) peptide, were successfully prepared for in-vivo liver targeting. The two-step liver targeting strategy, based on both magnetic force and EGFR peptide conjugation, was evaluated in a subcutaneous hepatocellular carcinoma model of nude mouse. The results showed that EGFR-conjugated MPLs not only accumulated in the liver by magnetic force, but could also diffuse into tumor cells as a result of EGFR targeting. In addition, paclitaxel (PTX) was incorporated into small EGFR-conjugated MPLs (102.0±0.7 nm), resulting in spherical particles with high drug encapsulation efficiency (>90%). The use of the magnetic targeting for enhancing the transport of PTX-loaded EGFR-conjugated MPLs to the tumor site was further confirmed by detecting PTX levels. In conclusion, PTX-loaded EGFR-conjugated MPLs could potentially be used as an effective drug delivery system for targeted liver cancer therapy.

4.
Environ Pollut ; 260: 113984, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32041019

RESUMO

1-nitropyrene (1-NP) is a key component of diesel exhaust-sourced fine particulate matter (PM2.5). Our recent study demonstrated that gestational 1-NP exposure caused placental proliferation inhibition and fetal intrauterine growth restriction (IUGR). This study aimed to investigate the role of genotoxic stress on 1-NP-induced placental proliferation inhibition and fetal IUGR. Human trophoblasts were exposed to 1-NP (10 µM). Growth index was reduced and PCNA was downregulated in 1-NP-exposed placental trophoblasts. More than 90% of 1-NP-exposed trophoblasts were arrested in either G0/G1 or G2/M phases. CDK1 and cyclin B, two G2/M cycle-related proteins, and CDK2, a G0/G1 cycle-related protein, were reduced in 1-NP-exposed trophoblasts. Phosphorylated Rb, a downstream molecule of CDK2, was inhibited in 1-NP-exposed trophoblasts. Moreover, DNA double-strand break was observed and γ-H2AX, another indicator of DNA double-strand break, was upregulated in 1-NP-exposed trophoblasts. Phosphorylated ATM, a key molecule of genotoxic stress, and its downstream molecule Chk2 were elevated. By contrast, Cdc25A, a downstream target of Chk2, was reduced in 1-NP-exposed trophoblasts. Phenyl-N-t-butylnitrone (PBN), a free radical scavenger, inhibited 1-NP-induced genotoxic stress and trophoblast cycle arrest. Animal experiment showed that N-acetylcysteine (NAC), an antioxidant, rescued 1-NP-induced placental proliferation inhibition and fetal IUGR in mice. These results provide evidence that reactive oxygen species (ROS)-mediated cellular genotoxic stress partially contributes to 1-NP-induced placental proliferation inhibition and fetal IUGR.

5.
J Cell Physiol ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957872

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the predominant esophageal cancer type in China. The aberrant activation of glioma-associated oncogene homolog1 (Gli1), a key factor in Hedgehog (Hh) signaling pathway, has been found in esophageal carcinoma. Moreover, Yes-associated protein 1 (YAP1), the major mediator of Hippo signaling pathway, has been linked to esophageal carcinoma progression. However, the precise roles and the underlying mechanism of both Gli1 and YAP1 in ESCC are unclear. Here, we found that Gli1 and YAP1 are overexpressed in ESCC and are associated with poor prognosis. In addition, we confirmed that knockdown of Gli1 or YAP1 suppresses ESCC cell growth, migration, and invasion in ESCC TE1 and EC109 cells. Significantly, Gli1 interacts with YAP1 in ESCC cells. Both Gli1 and YAP1 proteins are closely correlated with each other in human ESCC samples. Mechanistically, Gli1 upregulates YAP1 in a LATS1-independent manner. Conversely, YAP1 induces Gli1 by regulating phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Most importantly, we demonstrated that the interaction between Gli1 and YAP1 promotes ESCC tumor growth in vitro and in vivo. Our findings established a novel signaling mechanism by which the interaction between Gli1 and YAP1 promotes ESCC cell growth. This signaling regulation of the tumorigenesis provides a new therapeutic strategy for highly lethal ESCC.

6.
Mol Biol Evol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913480

RESUMO

The ancestral homeland of Australian dingoes and Pacific dogs is proposed to be in South China. However, the location and timing of their dispersal and relationship to dog domestication is unclear. Here, we sequenced 7,000 to 2,000-year-old complete mitochondrial DNA (mtDNA) genomes of 27 ancient canids (one gray wolf and 26 domestic dogs) from the Yellow River and Yangtze River basins (YYRB). These are the first complete ancient mtDNA of Chinese dogs from the cradle of early Chinese civilization. We found that most ancient dogs (18/26) belong to the haplogroup A1b lineage that is found in high frequency in present-day Australian dingoes and pre-colonial Pacific Island dogs, but low frequency in present-day China. Particularly, a 7,000-year-old dog from the Tianluoshan site in Zhejiang province possesses a haplotype basal to the entire haplogroup A1b lineage. We propose that A1b lineage dogs were once widely distributed in the YYRB area. Following their dispersal to South China, and then into Southeast Asia, New Guinea and remote Oceania, they were largely replaced by dogs belonging to other lineages in the last 2,000 years in present-day China, especially North China.

7.
Cancer Sci ; 111(1): 59-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729097

RESUMO

Low vitamin D status is associated with progression in patients with renal cell carcinoma (RCC). The present study found that vimentin, a mesenchymal marker, was accordingly upregulated, and E-cadherin, an epithelial marker, was downregulated in RCC patients with low vitamin D status. Thus, we investigated the effects of calcitriol or vitamin D3, an active form of vitamin D, on epithelial-mesenchymal transition (EMT) in RCC cells. RCC cells were treated by two models. In model 1, three RCC cell lines, ACHN, 786-O and CAKI-2, were incubated with either LPS (2.0 µg/mL) or transforming growth factor (TGF)-ß1 (10 ng/mL) in the presence or absence of calcitriol (200 nmol/L). In model 2, two RCC cell lines, ACHN and CAKI-2, were incubated with calcitriol (200 nmol/L) only. Calcitriol inhibited migration and invasion not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated RCC cells. Moreover, calcitriol suppressed E-cadherin downregulation and vimentin upregulation not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated ACHN and CAKI-2 cells. Calcitriol attenuated LPS-induced upregulation of MMP-2, MMP-7, MMP-9, MMP-26 and urokinase-type plasminogen activator (u-PA) in ACHN cells. In addition, calcitriol blocked TGF-ß1-induced nuclear translocation of ZEB1, Snail and Twist1 in ACHN and CAKI-2 cells. Mechanistically, calcitriol suppressed EMT through different signaling pathways: (i) calcitriol suppressed Smad2/3 phosphorylation by reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-ß1-stimulated RCC cells; (ii) calcitriol inhibited signal transducer and activator of transcription (STAT)3 activation in LPS-stimulated RCC cells; (iii) calcitriol inhibited ß-catenin/TCF-4 activation by promoting integration of VDR with ß-catenin in TGF-ß1-unstimulated RCC cells. Taken together, calcitriol inhibits migration and invasion of RCC cells partially by suppressing Smad2/3-, STAT3- and ß-catenin-mediated EMT.


Assuntos
Calcitriol/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Adulto , Idoso , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Renais/metabolismo , Masculino , Metaloendopeptidases/metabolismo , Pessoa de Meia-Idade , Fator de Transcrição STAT3/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , beta Catenina/metabolismo
8.
Environ Technol ; 41(8): 1034-1043, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30175689

RESUMO

A sequencing batch biofilm reactor under intermittent micro-aerobic or anaerobic conditions was investigated to remove pyridine at various concentrations from synthetic wastewater. The results showed that over 98% of pyridine (influent concentration ≤200 mg L-1) was degraded under intermittent micro-aerobic condition, while about 21% of pyridine was removed under anaerobic condition. Additionally, at least 60% of nitrogen located in the pyridine ring was transformed to ammonium. At the same time, the sulphate reduction was obviously inhibited under intermittent micro-aerobic conditions. The microscopic observation showed that abundant microorganisms were attached on the surface or inside of porous biocarriers under intermittent micro-aerobic conditions after a short-term period of operation. High-throughput sequencing analysis demonstrated that Azotobacter, Rhodobacteraceae and Tolumonas were the dominant species in the intermittent micro-aerobic system. The kinetic study at steady period showed that pyridine degradation was fitted well with the pseudo-first-order model (R2 > 0.96). The two possible intermediate products were identified and the possible biodegradation pathway of pyridine was proposed under micro-aerobic condition.

9.
Biosens Bioelectron ; 148: 111832, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706173

RESUMO

Fluorescence-activated cell sorting (FACS) has rarely been applied to screening of microorganisms because of poor detection resolution, which is compromised by poor stability, toxicity, or interference from background fluorescence of the fluorescence sensors used. Here, a fluorescence-based rapid high-throughput cell sorting method was first developed using a fluorescence resonance energy transfer (FRET) fluorescent nanoprobe NP-RA, which was constructed by coating a silica nanoparticle with Rhodamine B and methyl-red (an azo dye). Rhodamine B (inner layer) is the FRET donor and methyl-red (outer layer) is the acceptor. This ready-to-use NP-RA is non-fluorescent, but fluoresces once the outer layer is degraded by microorganisms. In our experiment, NP-RA was ultrasensitive to model strain Shewanella decolorationis S12, showing a broad detection range from 8.0 cfu/mL to 8.7 × 108 cfu/mL under confocal laser scanning microscopy, and from 1.1 × 107 to 9.36 × 108 cfu/mL under a fluorometer. In addition, NP-RA bioimaging can clearly identify other azo-respiring cells in the microbial community, including Bosea thiooxidans DSM 9653 and Lysinibacillus pakistanensis NCCP-54. Furthermore, the fluorescent probe NP-RA is compatible with downstream FACS so that azo-respiring cells can be rapidly sorted out directly from an artificial microbial community. To our knowledge, no fluorescent nanoprobe has yet been designed for tracking and sorting azo-respiration functional microorganisms.

10.
Leuk Lymphoma ; : 1-6, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31858854

RESUMO

Hematological toxicity is a common adverse effect of tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML). We retrospectively investigated the incidence of hematological toxicity after TKI administration in 143 CML patients and parameters associated with hematological toxicity. Severe hematological toxicity (grade 3-4) existed in 26 (18.2%) patients. Marrow fibrosis (MF), age, Sokal score, and spleen enlargement were associated with severe hematological toxicity. Further multivariate analysis showed that only MF was an independent predictor. Complete cytogenetic response(CCyR) rates and major molecular response (MMR) rates with grade 3-4 hematological toxicity were 42.3% and 26.9%, respectively, significantly lower than patients with grade 1-2 and without hematological toxicity (p = .032 for CCyR and p = .044 for MMR). Similar results were observed regarding progression-free survival (PFS) and overall survival (OS) (p = .011 for PFS and p = .037 for OS). This study indicated that MF was an independent predictor of severe hematological toxicity of TKIs.

11.
Sci Rep ; 9(1): 16719, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723229

RESUMO

Low vitamin D status is associated with an increased risk of renal cell carcinoma (RCC). This study investigated the association of vitamin D status with serum C-reactive protein (CRP) and adhesion molecules among RCC patients. Fifty newly diagnosed RCC patients and 100 age- and sex-matched controls were recruited. As expected, serum 25(OH)D level was lower in RCC patients than in controls. By contrast, serum levels of CRP, an inflammatory molecule, and ICAM, LAMA4 and EpCAM, three adhesion molecules, were higher in RCC patients than in controls. All RCC patients were divided into two groups: H-VitD (>20 ng/ml) or L-VitD (<20 ng/ml). Interestingly, the levels of serum CRP and all adhesion molecules were higher in RCC patients with L-VitD than those with H-VitD. Nuclear vitamin D receptor (VDR) was downregulated and nuclear factor kappa B (NF-κB) was activated in cancerous tissues. The in vitro experiments found that VitD3 suppressed NF-κB activation and adhesion molecules in RCC cells. Moreover, VitD3 suppressed NF-κB through reinforcing physical interaction between VDR and NF-κB p65 subunit in RCC cells. These results provide a mechanistic explanation for the association among low vitamin D status, local inflammation and increased expression of adhesion molecules among RCC patients.

12.
J Cancer ; 10(25): 6244-6251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772657

RESUMO

Background: To investigate the prognostic significance of the cumulative score based on preoperative fibrinogen and pre-albumin (FP score) in patients with gastric cancer after radical gastrectomy. Methods: Baseline characteristics, preoperative fibrinogen and pre-albumin levels were retrospectively reviewed in patients who underwent radical gastrectomy. The optimal cut-off values for fibrinogen and pre-albumin were defined as 4.0 g/L and 230.0 mg/L, respectively. Patients with elevated fibrinogen (≥ 4.0 g/L) and decreased pre-albumin (< 230.0 mg/L) levels were allocated an FP score of 2, those with only one of these two abnormalities were assigned a score of 1, and those with neither of the two abnormalities were allocated a score of 0. The prognostic value was examined by univariate and multivariate regression analyses. Results: The preoperative FP score was significantly correlated with age, tumor size, fibrinogen level, pre-albumin level and white blood cell count. No significant differences based on sex, tumor location, degree of differentiation, depth of invasion, lymph node status, tumor-node-metastasis (TNM) stage or adjuvant chemotherapy were identified between the groups. In addition, univariate survival analysis revealed that a high preoperative FP score was significantly associated with unfavorable disease-free survival (DFS) [hazard ratio (HR), 1.482; 95% confidence interval (CI), 1.222-1.796; P < 0.001] and overall survival (OS) (HR, 1.623; 95% CI, 1.315-2.002; P < 0.001). Moreover, after adjusting for other factors, a high preoperative FP score remained an independent predictor for impaired DFS (HR, 1.434; 95% CI, 1.177-1.747; P < 0.001) and OS (HR, 1.413; 95% CI, 1.136-1.758; P = 0.002) in multivariate Cox regression analysis. Conclusions: The preoperative FP score significantly predicts long-term survival for gastric cancer patients who have undergone radical gastrectomy.

13.
Cancer Med ; 8(17): 7253-7264, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31612596

RESUMO

PURPOSE: We aimed to explore the value of palliative resection or radiation of primary tumor for metastatic esophageal cancer (EC) patients. METHODS: Surveillance, Epidemiology, and End Results database was used for identifying metastatic EC patients. The patients were divided into resection and nonresection groups. And patients without resection were divided into radiation and nonradiation groups. Propensity score matching (PSM) analyses were adopted to reduce the baseline differences between the groups. Cancer specific survivals (CSSs) and overall survivals (OSs) were compared by Kaplan-Meier (K-M) curves. Multivariable analyses by COX proportion hazards model were performed to identify risk factors for CSS and OS. Predictive nomograms were conducted according to both postoperative factors and preoperative factors. RESULTS: A total of 7982 metastatic EC patients were selected for our analyses. After PSM, 978 patients were included in the survival analyses comparing palliative resection and nonresection. The CSS and OS for patients underwent palliative resection were significantly longer than those without resection (median CSS: 21 months vs 7 months, P < .001; median OS: 20 months vs 7 months, P < .001). In the overall population without resection, 654 patients were matched for radiation and nonradiation groups. And K-M curves showed that patients with radiation had longer CSS and OS than those without radiation (median CSS: 11 months vs 6 months, P < .001; median OS: 10 months vs 6 months, P < .001). Nomograms were generated for prediction of 1-, 2-, and 3-year CSS and OS. All C-indexes implied moderate discrimination and accuracy. And all nomograms had good calibration. CONCLUSION: Palliative resection or radiation of primary tumor could prolong CSS and OS of metastatic EC patients.

14.
Front Microbiol ; 10: 2263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632374

RESUMO

Electronic waste (e-waste) has caused a severe worldwide pollution problem. Despite increasing isolation of degradative microorganisms from e-waste contaminated environments, the mechanisms underlying their adaptive evolution in such habitats remain unclear. Sphingomonads generally have xenobiotic-degrading ability and may play important roles in bioremediation. Sphingobium hydrophobicum C1T, characterized with superior cell surface hydrophobicity, was recently isolated from e-waste contaminated river sediment. To dissect the mechanisms driving its adaptive evolution, we evaluated its stress resistance, sequenced its genome and performed comparative genomic analysis with 19 other Sphingobium strains. Strain C1T can feed on several kinds of e-waste-derived xenobiotics, exhibits a great resistance to heavy metals and possesses a high colonization ability. It harbors abundant genes involved in environmental adaptation, some of which are intrinsic prior to experiencing e-waste contamination. The extensive genomic variations between strain C1T and other Sphingobium strains, numerous C1T-unique genes, massive mobile elements and frequent genome rearrangements reflect a high genome plasticity. Positive selection, gene duplication, and especially horizontal gene transfer drive the adaptive evolution of strain C1T. Moreover, presence of type IV secretion systems may allow strain C1T to be a source of beneficial genes for surrounding microorganisms. This study provides new insights into the adaptive evolution of sphingomonads, and potentially guides bioremediation strategies.

15.
Echocardiography ; 36(9): 1682-1688, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31503352

RESUMO

Eighty-three breast cancer patients who underwent six cycles of EC chemotherapy regimen (epirubicin + cyclophosphamide) without symptoms and signs of heart disease were enrolled in the study. Three-dimensional speckle tracking imaging technique (3D-STI) was used to measure left ventricular global area strain (GAS), overall annular strain (GCS), overall longitudinal strain (GLS), and overall radial strain (GRS). Meanwhile, serum troponin T (Hs-cTnT) was measured. The clinical value of each index on cardiotoxicity after chemotherapy was analyzed using the receiver operating characteristic (ROC) curve. Hs-cTnT increased from the early stage to the end during chemotherapy, but it was still in the normal range. During the mid-chemotherapy and the end-chemotherapy, GAS, GLS, GCS, and E/A significantly reduced, while the changes in LVESV, LVEDV, LVEF, and GRS were not significant after chemotherapy. Pearson correlation analysis showed a significant negative correlation between GAS and anthracycline doses (r = -.772, P < .01); GAS and Hs-cTnT were significantly negatively correlated (P < .05). The area under the curve (AUC) of GAS, GLS, GCS, and GRS are 0.815, 0.683, 0.645, and 0.585, respectively. A GAS of -31.5% was used as the cutoff value for diagnosing left ventricular systolic dysfunction after receiving chemotherapy. The sensitivity of the previous parameters was 81.9%, and the specificity was 80.3%. Interobserver consistency analysis showed that 3D-STI strain parameter measurement has good repeatability. GAS has greater value in predicting early myocardial damage after anthracycline chemotherapy.

16.
Int J Biol Sci ; 15(9): 1905-1920, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523192

RESUMO

The mechanisms of resistance to the targeted drug sorafenib in the treatment of hepatocellular carcinoma (HCC) are poorly understood. The purpose of this study was to investigate the mechanism of sorafenib resistance and to elucidate the role of melatonin in overcoming sorafenib resistance. We first observed that sorafenib induced endoplasmic reticulum (ER) stress and activated autophagy in HCC, and the inhibition of ER stress and autophagy by specific inhibitors (PBA, TUDC and 3-MA) increased sorafenib-induced apoptosis, indicating that cells resist apoptosis by inducing ER stress and autophagy in the presence of sorafenib. Furthermore, specimens from patients with HCC revealed a close relationship between ER stress and autophagy, as demonstrated by the high correlation between expression of the autophagy-associated protein Beclin1 and expression of unfolded protein response (UPR) pathway proteins, especially PKR-like ER stress kinase (PERK); moreover, patients with combined expression of PERK and Beclin1 had more advanced disease (higher clinical stage) and a shorter overall survival time. ER stress inhibitors significantly blocked sorafenib-induced autophagy, selective knockdown of PERK and activating transcription factor 4 (ATF4) expression reduced sorafenib-induced autophagy activity compared with knockdown of the other two UPR pathways, and silencing ATF4 inhibited the expression of Beclin1. These results suggest that autophagy is downstream of ER stress and that the PERK-ATF4-Beclin1 pathway plays a role in ER stress-related autophagy. Interestingly, a low concentration of melatonin increased the sensitivity of HCC to sorafenib by inhibiting autophagy through the PERK-ATF4-Beclin1 pathway. Taken together, our findings suggest that cotreatment with sorafenib and melatonin is a potential therapy for HCC. Furthermore, ER stress-related autophagy plays key roles in apoptosis resistance. Therefore, targeting the PERK-ATF4-Beclin1 pathway may prove instrumental in HCC therapy.

17.
BMC Cancer ; 19(1): 852, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462229

RESUMO

BACKGROUND: Recently, evidence has emerged that palliative gastrectomy in patients with stage IV gastric cancer may offer some survival benefits. However, the decision whether to perform primary tumor surgery remains challenging for surgeons, and investigations into models that are predictive of prognosis are scarce. Current study aimed to develop and validate prognostic nomograms for patients with metastatic gastric adenocarcinoma treated with palliative gastrectomy. METHODS: The development dataset comprised 1186 patients from the Surveillance, Epidemiology, and End Results Program who were diagnosed with metastatic gastric adenocarcinoma in 2004-2011, while the validation dataset included 407 patients diagnosed in 2012-2015. Variables were incorporated into a Cox proportional hazards model to identify independent risk factors for survival. Both pre- and postoperative nomograms for predicting 1- or 2-year survival probabilities were constructed using the development dataset. The concordance index (c-index) and calibration curves were plotted to determine the accuracy of the nomogram models. Finally, the cut-off value of the calculated total scores based on preoperative nomograms was set and validated by comparing survival with contemporary cases without primary tumor surgery. RESULTS: Age, tumor size, location, grade, T stage, N stage, metastatic site, scope of gastrectomy, number of examined lymph node(s), chemotherapy and radiotherapy were risk factors of survival and were included as variables in the postoperative nomogram; the c-indices of the development and validation datasets were 0.701 (95% confidence interval [CI]: 0.693-0.710) and 0.699 (95% CI: 0.682-0.716), respectively. The preoperative nomogram incorporated age, tumor size, location, grade, depth of invasion, regional lymph node(s) status, and metastatic site. The c-indices for the internal (bootstrap) and external validation sets were 0.629 (95% CI: 0.620-0.639) and 0.607 (95% CI: 0.588-0.626), respectively. Based on the preoperative nomogram, patients with preoperative total score > 28 showed no survival benefit with gastrectomy compared to no primary tumor surgery. CONCLUSIONS: Our survival nomograms for patients with metastatic gastric adenocarcinoma undergoing palliative gastrectomy can assist surgeons in treatment decision-making and prognostication.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia/métodos , Nomogramas , Neoplasias Gástricas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Cuidados Paliativos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento
18.
Chemosphere ; 237: 124520, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31404739

RESUMO

The quality of the bio-treated coking wastewater (BTCW) is difficult to meet increasingly stringent coking wastewater discharge standards and future wastewater recycling needs. In this study, the pre-treatment process of BTCW was installed including the two up-flow fixed-bed bioreactors (UFBRs) which were separately filled with alkali-pretreated or no alkali-pretreated corncobs used as solid carbon sources as well as biofilm carriers. Results showed that this pre-treatment process could significantly improve the biodegradability of BTCW and increase the C/N ratio. Thus, over 90% of residual nitrate in BTCW were removed stably. Furthermore, GC-MS analysis confirmed that the typical refractory organic matters decreased significantly after UFBRs pre-treatment. High-throughput sequencing analysis using 16S rRNA demonstrated that dominant denitrifiers, fermentative bacteria and refractory-organic-pollutants-degrading bacteria co-existed inside the UFBRs system. Compared with no alkali-pretreated corncobs, alkali-pretreated corncobs provided more porous structure and much stable release of carbon to guarantee the growth and the quantity of the functional bacteria such as denitrifiers. This study indicated that the UFBRs filled with alkali-pretreated corncobs could be utilized as an effective alternative for the enhanced treatment of the BTCW.


Assuntos
Biodegradação Ambiental , Coque/análise , Nitratos/análise , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/análise , Biofilmes , Reatores Biológicos , Carbono , Poluentes Ambientais , Nitratos/metabolismo , RNA Ribossômico 16S , Reciclagem , Poluentes Químicos da Água/metabolismo , Zea mays
19.
BMC Cancer ; 19(1): 650, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266459

RESUMO

BACKGROUND: DNA aneuploidy has attracted growing interest in clinical practice. Nevertheless, its prognostic value in gastric cancer patients remains controversial. This meta-analysis aims to explore the impact of DNA ploidy status on the survival of gastric cancer patients. METHODS: We used PubMed and Web of Science databases to retrieve relevant articles. The correlation between DNA aneuploidy and the clinicopathological features of gastric cancer, such as stage, depth of invasion (T), lymph node metastasis (N), distant metastasis (M), differentiation (G), tumor types (Lauren classification) and overall survival (OS) were evaluated. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were collected carefully from each article OS was presented with HRs. The relationships between DNA aneuploidy and each characteristic were analyzed using risk ratios (RR) and a 95% confidence interval (CI). Significance was established using P < 0.05. Funnel plot was conducted to detect the publication bias. RESULTS: After careful selection, 25 studies involving 3449 cases were eligible for further analyses. Patients with DNA aneuploidy were considered at risk of more advanced stages (stage III-IV vs. stages I-II, RR = 1.23; 95% CI, 1.07 to 1.42; P = 0.003), lymph node metastasis (N+ vs. N-: RR = 1.43; 95% CI, 1.12 to 1.82, P = 0.004), and intestinal tumor type (intestinal vs. diffuse: RR = 1.45; 95% CI, 1.02 to 2.06; P = 0.04). And an adverse relation was observed between DNA aneuploidy and tumor differentiation. While no association was found between DNA aneuploidy and distant metastasis (P = 0.42) nor depth of tumor invasion (P = 0.86). Regarding overall survival, aneuploid tumors were associated with worse survival in all patients (P < 0.00001). CONCLUSIONS: We found that DNA aneuploidy was an important predictor for gastric cancer patients, and should be used as a potential biomarker for further classification in gastric cancer.


Assuntos
Aneuploidia , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Intervalos de Confiança , DNA de Neoplasias , Humanos , Metástase Linfática , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/patologia
20.
Steroids ; 150: 108445, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295461

RESUMO

Low vitamin D status has been associated with increased risks of renal cell carcinoma (RCC). This study aimed to analyze the link between low vitamin D status and interleukin (IL)-6/STAT3 hyper-activation in clear cell RCC (ccRCC) patients. Forty-three newly diagnosed ccRCC patients and 86 age- and sex-matched controls were recruited. The association between low vitamin D status and IL-6/STAT3 hyper-activation was analyzed. Proliferation makersand STAT3 signal were evaluated. As expected, serum IL-6 level was higher in ccRCC patients than in controls. Moreover, serum IL-6 level was reversely correlated with serum 25(OH)D in ccRCC patients but not in controls. In addition, STAT3 signaling was hyper-activated in cancerous tissue. CcRCC patients were divided into three groups according to serum 25(OH)D level: vitamin D sufficiency (VitD-S, ≥30 ng/ml), vitamin D insufficiency (VitD-I, ≥20 and <30 ng/ml) or vitamin D deficiency (VitD-D, <20 ng/ml). Serum IL-6 was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. Cancerous pSTAT3 level was higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The number of pSTAT3+ nuclei in cancerous tissue was more in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The expressions of cancerous PCNA, cyclin D1 and Ki-67, three markers of proliferation, were higher in ccRCC patients with VitD-D than those with VitD-S/VitD-I. The in vitro experiments showed that active vitamin D3 inhibited LPS-induced STAT3 phosphorylation in ACHN cells. Our results provide evidence that low vitamin D status is correlated with hyper-activation of cancerous IL-6/STAT3 and proliferation in ccRCC patients.

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