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1.
Mol Med Rep ; 22(5): 3629-3634, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000201

RESUMO

Phosphoinositide 3-kinase catalytic subunit δ isoform (P110δ) is mainly expressed in white blood cells. It is involved in T and B lymphocyte differentiation, maturation and the neutrophil chemotaxis process. Apolipoprotein E (ApoE) is an arginine­rich alkaline protein, which is present in plasma chylomicron, low­density lipoprotein and very low­density lipoprotein. The present study aimed to determine the effects of P110δ deletion on myocarditis in ApoE­/­ mice. A mouse model of ApoE and P110δ double deletion was initially constructed; hematoxylin and eosin (H&E) staining was performed to detect the histological alterations in the mouse myocardium. Systolic and diastolic alterations, and alterations in the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were examined by electrocardiogram. Blood cell of ApoE and P110δ double mice was used to detect changes in white blood cells and monocytes. Western blotting was used to detect the expression levels of apoptosis­associated proteins, whereas flow cytometry was used to detect the percentage of apoptosis. Morphological alterations in myocardial cells were observed under a microscope. The results of polymerase chain reaction demonstrated that double deletion mice were successfully constructed. H&E staining revealed that cells in the ApoE­/­ mice were spindle­shaped; however, the nuclei were smaller in the double deletion mice. There was no change in cardiac contraction in normal mice; however, in double deletion mice, the systolic and diastolic contractions were markedly reduced. LVFS and LVEF were decreased compared with in the control group. Blood cell analysis indicated that the content of white blood cells and monocytes in the experimental group was significantly higher than that in the control group. Western blotting demonstrated that the expression levels of apoptotic proteins in double deletion mice were significantly higher compared with in the control group. Flow cytometry revealed that the apoptotic ratio was increased in double deletion mice compared with in the control group (42 vs. 21%). These findings suggested that deletion of P110δ may induce monocyte peritoneal infiltration and increase apoptosis, thus promoting the development of myocarditis.

2.
Sci Rep ; 10(1): 16655, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024135

RESUMO

Long noncoding RNAs play important roles in various biological processes. However, not much is known about their roles in inflammatory response. Mast cells, involved in innate and adaptive immunity, are one of the major effector cells in allergic inflammatory reactions and contribute to the pathogenesis of disorders, including asthma. In the present study, we aimed to verify and elucidate the function and possible role of a novel lncRNA, called lncRNA-AK149641, in the mechanism of lipopolysaccharide (LPS)-induced inflammatory response in P815 mast cells. The results showed that downregulating lncRNA-AK149641 decreased secretion of tumor necrosis factor-α into the supernatants of LPS-stimulated mast cells. Mechanistically, the activity of nuclear factor-kappa B (NF-κB) decreased after downregulating lncRNA-AK149641, as shown by western blot and electrophoretic mobility shift assays. Moreover, RNA binding protein immunoprecipitation (RIP) verified that lncRNA-AK149641 was able to bind to NF-κB in the nucleus. In conclusion, we demonstrated that lncRNA-AK149641 regulated LPS-induced inflammatory response in mast cells through the NF-κB signaling pathway.

3.
JAMA Netw Open ; 3(10): e2014622, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017027

RESUMO

Importance: Breast cancer (BC), a common malignant tumor, ranks first among cancers in terms of morbidity and mortality among female patients. Currently, identifying effective prognostic models has a significant association with the prediction of the overall survival of patients with BC and guidance of clinicians in early diagnosis and treatment. Objectives: To identify a potential DNA repair-related prognostic signature through a comprehensive evaluation and to further improve the accuracy of prediction of the overall survival of patients with BC. Design, Setting, and Participants: In this prognostic study, conducted from October 9, 2019, to February 3, 2020, the gene expression profiles and clinical data of patients with BC were collected from The Cancer Genome Atlas database. This study consisted of a training set from The Cancer Genome Atlas database and 2 validation cohorts from the Gene Expression Omnibus, which included 1096 patients with BC. A prognostic signature based on 8 DNA repair-related genes (DRGs) was developed to predict overall survival among female patients with BC. Main Outcomes and Measures: Primary screening prognostic biomarkers were analyzed using univariate Cox proportional hazards regression analysis and the least absolute shrinkage and selection operator Cox proportional hazards regression. A risk model was completely established through multivariate Cox proportional hazards regression analysis. Finally, a prognostic nomogram, combining the DRG signature and clinical characteristics of patients, was constructed. To examine the potential mechanisms of the DRGs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Results: In this prognostic study based on samples from 1096 women with BC (mean [SD] age, 59.6 [13.1] years), 8 DRGs (MDC1, RPA3, MED17, DDB2, SFPQ, XRCC4, CYP19A1, and PARP3) were identified as prognostic biomarkers. The time-dependent receiver operating characteristic curve analysis suggested that the 8-gene signature had a good predictive accuracy. In the training cohort, the areas under the curve were 0.708 for 3-year survival and 0.704 for 5-year survival. In the validation cohort, the areas under the curve were 0.717 for 3-year survival and 0.772 for 5-year survival in the GSE9893 data set and 0.691 for 3-year survival and 0.718 for 5-year survival in the GSE42568 data set. This DRG signature mainly involved some regulation pathways of vascular endothelial cell proliferation. Conclusions and Relevance: In this study, a prognostic signature using 8 DRGs was developed that successfully predicted overall survival among female patients with BC. This risk model provides new clinical evidence for the diagnostic accuracy and targeted treatment of BC.

4.
Ophthalmic Epidemiol ; : 1-6, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021141

RESUMO

PURPOSE: To report the changes in incidence and risk factors of retinopathy of prematurity (ROP) in extremely low birth weight (ELBW) infants over a 15-year period in South China. METHODS: The medical records of ELBW infants were retrospectively reviewed through established database of Shenzhen Screening for ROP Cooperative Group. The incidence and severity of ROP were compared among three successive 5-year periods (P1: 2004-2008, P2: 2009-2013, P3: 2014-2018). Gestational age, birth weight, plurality, mode of delivery and gender were analyzed as risk factors for ROP in ELBW infants. RESULTS: Among the 1099 included ELBW infants, 557 (50.7%) had ROP, and 328 (29.9%) had severe ROP. The highest incidence of ROP (87.5%) and severe ROP (82.5%) were seen in P1. From P2 to P3, the incidence of ROP and severe ROP increased from 45.9% to 50.3% for ROP (P < .05) and from 26.4% to 28.3% for severe ROP (P < .05), respectively. Multivariate logistic regression analysis found only gestational age has a significant effect on the incidence of ROP and severe ROP. CONCLUSIONS: From 2004 to 2018, the incidence of ROP and severe ROP in ELBW infants in South China was 50.7% and 29.9%, respectively. Controlling for the other risk factors, only gestational age was statistically associated with ROP in ELBW infants.

5.
Histol Histopathol ; : 18266, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006132

RESUMO

BACKGROUND: Sevoflurane is widely used as an inhalational anesthetic in clinical practice. However, sevoflurane can cause cytotoxicity and induce learning capacity decline in patients. A previous publication indicated that miR-204-5p might have a close relationship with sevoflurane-induced neurotoxicity. When exposed to sevoflurane, the expression of miR-204-5p in neonatal hippocampus of rats was significantly increased. Hence, we aimed to investigate the role of miR-204-5p in sevoflurane-induced neurotoxicity using a mouse hippocampal neuronal cell line (HT22). METHODS: The levels of miR-204-5p in HT22 cells were detected by RT-qPCR. In addition, the effects of miR-204-5p on cell viability, apoptosis and proliferation were evaluated by CCK-8, flow cytometric, and immunofluorescence assay, respectively. Western blotting was used to detect expressions of Bax, Bcl-2, active caspase 3, BDNF, TrkB, p-TrkB, Akt and p-Akt in HT22 cells. ELISA assay was used to examine the levels of total superoxide dismutase (SOD), reduced glutathione (GSH), malondialdehyde (MDA) and reactive oxygen species (ROS) in cells. Meanwhile, the dual luciferase reporter system assay was employed to explore the interaction of miR-204-5p and BDNF in cells. RESULTS: The level of miR-204-5p was increased in sevoflurane-treated HT22 cells. Moreover, downregulation of miR-204-5p inhibited sevoflurane-induced apoptosis and promoted cell proliferation by upregulating the proteins of Bcl-2 and downregulating the expressions of Bax and active caspase-3 in HT22 cells. In addition, inhibition of miR-204-5p alleviated sevoflurane-induced oxidative injuries in HT22 cells via decline of ROS and MDA and upregulation of SOD and GSH. Furthermore, bioinformatics and dual luciferase assay demonstrated that miR-204-5p can inhibit the TrkB/Akt pathway by targeting BDNF. CONCLUSION: Our findings indicated that downregulation of miR-204-5p can decrease oxidative status in HT22 cells and alleviate sevoflurane-induced cytotoxicity through stimulating the BDNF/TrkB/Akt pathway. Therefore, miR-204-5p might be a potential biomarker and therapeutic target for the treatment of sevoflurane-induced neurotoxicity.

6.
Oncol Rep ; 44(5): 2080-2092, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000261

RESUMO

Emerging studies have demonstrated that long non­coding RNAs (lncRNAs) play essential roles in tumorigenesis. However, the role and function of lncRNAs in hypopharyngeal squamous cell carcinoma (HSCC) have not been completely elucidated. The present study explored the function of a novel lncRNA, RP11­156L14.1, in HSCC. RP11­156L14.1 was revealed to be highly expressed in HSCC tissues and cell lines. Knockdown of RP11­156L14.1 inhibited proliferation, migration, and invasion in HSCC cells. Furthermore, RP11­156L14.1 regulated epithelial­mesenchymal transition (EMT) by controlling EMT­related protein expression. Mechanistically, RP11­156L14.1 exerted its function as a competing endogenous RNA (ceRNA) and directly interacted with miR­548ao­3p. The present study also demonstrated that miR­548ao­3p regulated signal sequence receptor subunit 1 (SSR1) expression by targeting SSR1 3'­UTR. Moreover, the xenograft HSCC tumor model revealed that knockdown of RP11­156L14.1 markedly suppressed HSCC tumor growth in vivo. In summary, these findings indicated that the lncRNA RP11­156L14.1 functions as an oncogene in HSCC by competing with miR­548ao­3p in regulating SSR1 expression. The RP11­156L14.1/miR­548ao­3p/SSR1 axis could be utilized as a potential novel biomarker and therapeutic target for HSCC.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1611-1617, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067962

RESUMO

OBJECTIVE: To investigate the influence of rFLC and dFLC on clinical prognosis and best cutoff value in patients with newly diagnosed multiple myelome(MM). METHODS: Clinical data of 240 patients with newly diagnosed MM treated in Western Theater General Hospital of People's Liberation Army from January 2010 to June 2016 were collected and retroanalyzed. All patients were divided into different groups according to the interquartile spacing levels of rFLC and dFLC, the median OS and PFS of patients in different groups were compared. The influencing factors of prognosis in newly diagnosed MM patients were analyzed by univariate and multivariate methods, the influence of different cutoff values of rFLC and dFLC on clinical prognosis were evaluated. RESULTS: The median progression-free survival time of female patients with M-protein IgA type and I stage for ISS stage were significantly longer than those of male, other M-protein types and other ISS stage(P<0.05). The median OS of patients without hypercalcemia was significantly higher than that of patients with hypercalcemia(P<0.05). The median progression-free survival(PFS) time of patients with dFLC <110.95 mg/L was significantly longer than that of patients with dFLC=110.95-2 781.44 mg/L and >2 781.44 mg/L(P<0.05). The median overall survival time of patients with dFLC <110.95 mg/L and >2 781.44 mg/L was significantly longer than that of patients with dFLC=110.95-2 781.44 mg/L(P<0.05). The median overall survival time of patients with rFLC <14.71 mg/L was significantly longer than that of patients with rFLC >14.71-367.96 mg/L and >367.96 mg/L(P<0.05). Univariate analysis of Cox regression model indicated that dFLC at all levels showed higher influence on the OS and PFS of patients as compared with rFLC(P<0.05). Multivariate analysis of Cox regression model showed that rFLC and dFLC expression level were the independent prognostic factors of patients(P<0.05). The most significant influence value on clinical prognosis of patients were observed when rFLC level ≤14.71 or dFLC level ≤110.95 mg/L(P<0.05). The median OS of patients with rFLC level ≤14.71 was significantly higher than that of other groups(P<0.05). There was significant difference in median PFS between patients with rFLC ≤14.71 and ≥367.96 mg/L(P<0.05). The median OS and PFS of patients with dFLC ≤110.95 mg/L were significantly longer than those in other two groups(P<0.05). CONCLUSION: The levels of rFLC and dFLC closely relate to clinical prognosis of patients with new diagnosed MM; the risk of recurrence or death is lowest in patients with rFLC level ≤14.71 mg/L or dFLC level ≤110.95 mg/L, which can be used as the ideal cutoff value for prognosis evaluation.

8.
Lancet Infect Dis ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069281

RESUMO

BACKGROUND: The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. We aimed to assess the safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate, BBIBP-CorV, in humans. METHODS: We did a randomised, double-blind, placebo-controlled, phase 1/2 trial at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province, China. In phase 1, healthy people aged 18-80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2 at the time of screening, were separated into two age groups (18-59 years and ≥60 years) and randomly assigned to receive vaccine or placebo in a two-dose schedule of 2 µg, 4 µg, or 8 µg on days 0 and 28. In phase 2, healthy adults (aged 18-59 years) were randomly assigned (1:1:1:1) to receive vaccine or placebo on a single-dose schedule of 8 µg on day 0 or on a two-dose schedule of 4 µg on days 0 and 14, 0 and 21, or 0 and 28. Participants within each cohort were randomly assigned by stratified block randomisation (block size eight) and allocated (3:1) to receive vaccine or placebo. Group allocation was concealed from participants, investigators, and outcome assessors. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity, assessed as the neutralising antibody responses against infectious SARS-CoV-2. This study is registered with www.chictr.org.cn, ChiCTR2000032459. FINDINGS: In phase 1, 192 participants were enrolled (mean age 53·7 years [SD 15·6]) and were randomly assigned to receive vaccine (2 µg [n=24], 4 µg [n=24], or 8 µg [n=24] for both age groups [18-59 years and ≥60 years]) or placebo (n=24). At least one adverse reaction was reported within the first 7 days of inoculation in 42 (29%) of 144 vaccine recipients. The most common systematic adverse reaction was fever (18-59 years, one [4%] in the 2 µg group, one [4%] in the 4 µg group, and two [8%] in the 8 µg group; ≥60 years, one [4%] in the 8 µg group). All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination. Neutralising antibody geometric mean titres were higher at day 42 in the group aged 18-59 years (87·7 [95% CI 64·9-118·6], 2 µg group; 211·2 [158·9-280·6], 4 µg group; and 228·7 [186·1-281·1], 8 µg group) and the group aged 60 years and older (80·7 [65·4-99·6], 2 µg group; 131·5 [108·2-159·7], 4 µg group; and 170·87 [133·0-219·5], 8 µg group) compared with the placebo group (2·0 [2·0-2·0]). In phase 2, 448 participants were enrolled (mean age 41·7 years [SD 9·9]) and were randomly assigned to receive the vaccine (8 µg on day 0 [n=84] or 4 µg on days 0 and 14 [n=84], days 0 and 21 [n=84], or days 0 and 28 [n=84]) or placebo on the same schedules (n=112). At least one adverse reaction within the first 7 days was reported in 76 (23%) of 336 vaccine recipients (33 [39%], 8 µg day 0; 18 [21%], 4 µg days 0 and 14; 15 [18%], 4 µg days 0 and 21; and ten [12%], 4 µg days 0 and 28). One placebo recipient in the 4 µg days 0 and 21 group reported grade 3 fever, but was self-limited and recovered. All other adverse reactions were mild or moderate in severity. The most common systematic adverse reaction was fever (one [1%], 8 µg day 0; one [1%], 4 µg days 0 and 14; three [4%], 4 µg days 0 and 21; two [2%], 4 µg days 0 and 28). The vaccine-elicited neutralising antibody titres on day 28 were significantly greater in the 4 µg days 0 and 14 (169·5, 95% CI 132·2-217·1), days 0 and 21 (282·7, 221·2-361·4), and days 0 and 28 (218·0, 181·8-261·3) schedules than the 8 µg day 0 schedule (14·7, 11·6-18·8; all p<0·001). INTERPRETATION: The inactivated SARS-CoV-2 vaccine, BBIBP-CorV, is safe and well tolerated at all tested doses in two age groups. Humoral responses against SARS-CoV-2 were induced in all vaccine recipients on day 42. Two-dose immunisation with 4 µg vaccine on days 0 and 21 or days 0 and 28 achieved higher neutralising antibody titres than the single 8 µg dose or 4 µg dose on days 0 and 14. FUNDING: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.

9.
Vaccine ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33041100

RESUMO

Recent studies have revealed that the interface of gp120 and gp41 and some parts of gp41 are also critical epitopes for elicitation of broadly neutralizing antibodies. Therefore, potential trimeric gp41 or gp140 immunogen candidates are needed. Previously, we developed a trimer motif MTQ and demonstrated that it could help formation of trimeric gp120 and gp140 proteins. In the present study, we immunized Balb/c mice using trimeric gp41-expressing plasmid for prime and monomeric gp41 or trimeric gp140 protein as well as a mutant (Q577A) for boost. The antibody responses in the context of regimens with various immunization intervals and DNA adjuvants including praziquantel (PZQ), cimetidine (CIM), and amiloride (AML) were evaluated. We found that these three adjuvants were not enough to elicit remarkable specific Abs after gp41 DNA immunization, while AML could significantly promote humoral immune responses after protein boosts. Long immunization interval could induce the specific binding Abs earlier and higher and maintain a high level of Abs in the following 27 weeks after final protein boost. Moreover, two times of protein boosts with DNA adjuvant and a longer time interval achieved a higher titer of specific Abs than three times of protein boosts with a shorter time interval. Q577A mutant was benefit for trimeric gp140 boost in the production of binding Abs but harmful to inducing neutralizing Abs, while this mutant in monomeric gp41 presented the opposite trend which may be associated with the immunogen structures. This study highlights the significance of DNA adjuvant Amiloride and long immunization interval in promoting antibody responses and provides new insights into effective HIV immunization regimen design in the future.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33044052

RESUMO

AIMS: Interleukin-35 (IL-35), a novel anti-inflammatory cytokine, has recently been implicated in tumor development, progression, and survival. However, the relationship between serum IL-35 levels and gastric cancer (GC) is inconclusive. Here, we performed this study to clarify the role of serum level of IL-35 in GC patients. METHODS: We enrolled 180 GC patients and 170 healthy controls and used enzyme-linked immunosorbent assay to detect serum IL-35 levels. The clinical relevance between IL-35 and clinical pathology parameters was assessed. Univariate and multivariate logistic regressions were used to determine the feasibility of IL-35 as a clinical biomarker. RESULTS: We observed that serum IL-35 levels were significantly higher in GC patients (17.559 ± 13.266 pg/mL) than in healthy controls (8.077 ± 3.801 pg/mL, P < .001). High serum IL-35 levels were significantly associated with clinical stage (P = .048) and Helicobacter pylori (HP) infection (P < .001). The Kaplan-Meier survival analysis indicated that patients in the high-IL-35 group had poor overall survival (OS) and progression-free survival (PFS) (median OS: 26.0 vs 36.0 months, P < .001; median PFS: 18.0 vs.26.0 months, P = .044). Multivariate analyses demonstrated that serum IL-35 was an independent prognostic factor for GC (OS: hazard ratio [HR] = 1.031 [95% CI, 1.017-1.045], P < .001; PFS: HR = 1.029 [95% CI, 1.015-1.043], P < .001). CONCLUSIONS: High serum IL-35 levels are associated with poor disease prognosis in GC patients, and it may be become a new and promising biomarker for prognosis of gastric cancer.

12.
Gut ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037055

RESUMO

OBJECTIVE: Factors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined. DESIGN: We conducted a nested case-control study among participants aged 18-64 in the IBM MarketScan Commercial Database (2006-2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs. RESULTS: MetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50-64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (ptrend <0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50-64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09). CONCLUSIONS: Metabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.

13.
J Mass Spectrom ; : e4659, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33047383

RESUMO

The antiparasitic agent ivermectin offers more promises to treat a diverse range of diseases. However, a comprehensive proteomic analysis of ivermectin-treated ovarian cancer (OC) cells has not been performed. This study sought to identify ivermectin-related proteomic profiling and molecular network alterations in human OC cells. Stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics was used to study the human OC TOV-21G cells. After TOV-21G cells underwent 10 passages in SILAC-labeled growth media, TOV-21G cells were treated with 10 ml of 20 µmol/L ivermectin in cell growing medium for 24 h. The SILAC-labeled proteins were digested with trypsin; tryptic peptides were identified with mass spectrometry (MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to mine signaling pathway alterations with ivermectin-related proteins in TOV-21G cells. Gene ontology (GO) analysis was used to explore biological functions of ivermectin-related proteins, including biological processes (BPs), cellular components (CCs), and molecular functions (MFs). The protein-protein interaction network was analyzed with molecular complex detection (MCODE) to identify hub modules. In total, 4,447 proteins were identified in ivermectin-treated TOV-21G cells. KEGG analysis revealed 89 statistically significant signaling pathways. Interestingly, the clustering analysis of these pathways showed that ivermectin was involved in various cancer pathogenesis processes, including modulation of replication, RNA metabolism, and translational machinery. GO analysis revealed 69 statistically significant CCs, 87 MFs, and 62 BPs. Furthermore, MCODE analysis identified five hub modules, including 147 hub molecules. Those hub modules involved ribosomal proteins, RNA-binding proteins, cell-cycle progression-related proteins, proteasome subunits, and minichromosome maintenance proteins. These findings demonstrate that SILAC quantitative proteomics is an effective method to analyze ivermectin-treated cells, provide the first ivermectin-related proteomic profiling and molecular network alterations in human OC cells, and provide deeper insights into molecular mechanisms and functions of ivermectin to inhibit OC cells.

14.
Anal Methods ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33047756

RESUMO

Carbon dots (CDs) with blue fluorescence were synthesized using indole-3-butyric acid and l-tryptophan using a one-step hydrothermal method. The CDs were further employed as a fluorescent sensor with high selectivity for colorimetric and ratiometric detection of tetracycline (TC) in water. The limit of detection (LOD) was found to be 0.33 µM for TC with R2 = 0.98387. Besides, the CDs could be applied in practical water samples and showed good recovery.

15.
FASEB J ; 34(9): 12932-12945, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33000523

RESUMO

We previously demonstrated that Tetraticopeptide 4 (TTC4) inhibited apoptosis in vascular endothelial cells (VEC) deprived of serum and fibroblast growth factor 2 (FGF-2). In this study, we aimed to resolve the mechanism of TTC4 inhibiting VEC apoptosis. TTC4, predicted as a HSP70 co-chaperone protein, may regulate the fate of cells by affecting the activity of HSP70, however, there is no experimental evidence showing the interaction of TTC4 and HSP70. Using Co-immunoprecipitation (Co-IP), we demonstrated that TTC4 interacted with HSP70. If HSP70 was knockdown, TTC4 no longer suppressed apoptosis. Furthermore, we found ABO, an inhibitor of annexin A7 (ANXA7) GTPase, could promote the interaction of TTC4 and HSP70 and the translocation of ANXA7 to lysosome. At the same time, ABO inhibited the interaction of HSP70 and ANXA7. Moreover, Akt, as a downstream effector of HSP70 was upregulated, and ANXA7 translocating to lysosome protected the stability of lysosomal membrane. Here, we discovered a special mechanism by which TTC4 inhibited apoptosis via HSP70 in VECs. On the one hand, increasing TTC4 and HSP70 interaction upregulated Akt that inhibited apoptosis. On the other hand, decreasing HSP70 and ANXA7 interaction promoted the translocation of ANXA7 to lysosome, which inhibited apoptosis through protecting the lysosomal membrane stability.

16.
Ecotoxicol Environ Saf ; 207: 111384, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33011457

RESUMO

Light intensity is one of the ecological factors that appreciably affects the metabolism of Scylla paramamosain during overwintering. This study adopted the isobaric tag for relative and absolute quantitation (iTRAQ) method to investigate metabolic changes of S. paramamosain under three illumination levels (0, 1.43 and 40.31 µmol m-2·s-1) for four months during indoor overwintering. The iTRAQ identified 3282 proteins, among which 267 exhibited significant differential expression (122 upregulated and 145 downregulated) in the low light group, and 299 with significant differential expression (252 upregulated and 47 downregulated) in the high light group. Analysis of these results showed that there were different metabolic regulatory patterns under different light intensities. Low light is more conducive to the survival of S. paramamosain, which needs to produce and consume relatively less energy to sustain physiological activities. Thus, the essential proteins associated with physiological activities were significantly upregulated, while those related to energy production were significantly downregulated. In contrast, high light exerts a certain stress on the survival of S. paramamosain and required more energy to cope with this stress, which forced a significant upregulation of proteins related to stress response and energy production. The findings of this study highlighted the metabolic regulatory mechanisms of S. paramamosain under different light intensities.

17.
Cancer Epidemiol ; 69: 101801, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33017728

RESUMO

OBJECTIVE: To evaluate the performance of low-dose computed tomography (LDCT) on lung cancer screening in high-risk populations in Sichuan. METHODS: From April 2014 to July 2018, LDCT was performed annually on 3185 subjects aged 50-74 years who had smoked ≥ 20 pack-years (or subjects having quit smoking within 5 years). Information about all deaths and lung cancer diagnoses were obtained by active investigation, or passive matching to disease surveillance system. RESULTS: The screening population had a median age of 60 years. 62.4 % of which were current smokers and had smoked 30 pack-years. After participating in the baseline screening, the compliance rates of subjects consecutively completing one round, two rounds, three rounds, and four rounds of annual screening were 67.22 %, 52.84 %, 43.24 %, and 40.04 %, respectively. The positive rates in baseline and annual screening were 6.53 % and 5.79 %, respectively. During the 5 rounds, a total of 9522 person-times were screened by LDCT with a screening sensitivity of 89.13 % (95 % CI: 76.96-95.27), specificity of 94.36 % (95 % CI: 93.88-94.81), positive predictive value of 7.13 % (95 % CI: 5.30-9.53), and negative predictive value of 99.94 % (95 % CI: 99.87-99.98). There were no statistically significant performance differences between baseline and annual screening. The difference in the proportion of screen-detected stage I lung cancer between baseline screening and annual screening was not statistically significant, neither. CONCLUSION: The application of LDCT on lung cancer screening in high-risk populations shows favorable compliance and a high screening performance in the project area of Sichuan,China.

18.
Chemosphere ; 264(Pt 1): 128500, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035954

RESUMO

Carbide slag may pollute the environment because it is difficult to handle. In this paper, carbide slag without pretreatment served as the new source of calcium and was added to bituminous coal for gasification experiments to realize waste utilization. The gasification experiment after adding carbide slag to bituminous coal enhances H2 production, which reduced the activation energy of the gasification reaction. The results show that the catalytic effect on steam gasification was evident when the carbide slag was added to Mongolian bituminous coal. The coal char at reaction temperature was prepared and characterized by X-ray diffraction (XRD), Raman, Scanning electron microscope (SEM), Transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and FT-IR spectroscopy. The carbon structure evolution and calcium structure changes of coal char under reaction temperature were studied, and the influence of coal char structure changes on gasification performance was analyzed. The results show that in the coal char added with carbide slag, the oxygen-containing functional groups generated by the polycondensation reaction interacted with calcium to form a calcium-oxygen-carbon complex. The existence of this structure not only leads to the highly uniform dispersion of CaO in the char but also hinders the graphitization process of the char. Highly dispersed CaO and disordered carbon structure significantly improved the reactivity of bituminous coal steam gasification. Si and Al in the bituminous coal affected the dispersion of Ca during steam gasification.

19.
J Colloid Interface Sci ; 583: 579-585, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-33038607

RESUMO

The design and construction of advanced electrode materials is important to the development of high-performance electrochemical energy storage devices. In this paper, V-doped 1T MoS2 nanosheets with a large layer spacing are grown on carbon cloth (CC) via a one-step hydrothermal method. The resulting material features abundant edge sites and active centers, and its large layer spacing facilitates the interlayer shuttle of Na+. Doping with V buffers the volume change and maintains the integrity of MoS2. The layered structure of the composite featuring CC as a conductive substrate effectively prevents the agglomeration of MoS2 during the electrochemical process. When used as an anode material for a Na+ battery, the material displays a high first-cycle irreversible discharge specific capacity of 1234.9 mAh g-1. A specific capacity of 453.2 mAh g-1 is obtained after 100 cycles at a current density of 200 mA g-1. This work provides an effective and eco-friendly route toward obtaining superior MoS2 electrodes for high-performance Na+ storage.

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