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1.
J Cell Biochem ; 121(1): 363-370, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31209933

RESUMO

BACKGROUND: This study aimed to explore the roles of endothelial nitric oxide synthase (eNOS) in the control of metastasis of infection with endothelial dysfunction, as well as the roles of -786T>C polymorphism in eNOS promoter in the control of metastasis of endothelial function. METHOD: In-silicon analysis and luciferase assay were used to identify the location of -786>C on the promoter of eNOS. Subsequently, real-time PCR and Western-blot were used to determine the expression level of eNOS. Ultrasound examination was used to detect baseline brachial artery diameter and flow-mediated dilation of patients in different treat groups. RESULTS: -786T>C was located on the promoter of eNOS, and the luciferase activity of cells transfected with -786-C allele was much higher than empty vector, while even higher subsequent to transfection of -786-T allele. In addition, the result of ultrasound examination showed that the baseline brachial artery diameter was comparable between patients genotyped as TT, TC and CC, while the flow-mediated dilation of patients genotyped as TC was much higher compared with CC group, and the flow-mediated dilation of patients genotyped as TT even higher than TC group. We found eNOS messenger RNA and protein with TT genotype was significantly higher compared with other genotypes. And the production of NO was remarkably higher in TT groups compared with TC and CC, while the production of NO in TC and CC groups were similar. CONCLUSION: These findings indicated that down-expression of -786T>C located on the promoter of eNOS is associated with an increased risk of endothelial dysfunction.

2.
J Pharm Biomed Anal ; 177: 112888, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31563758

RESUMO

Metabolomics measurements of seminal plasma are widely used in diagnosis and finding of molecular mechanisms of male infertility. However, so far the limitation of metabolome coverage of analytical methods hinders comprehensive metabolite biomarker finding. Moreover, the widely used case-control comparison is not enough to unveil the detailed correlations of the metabolic changes with different sperm abnormalities. In this work, we aimed to have comprehensive metabolic profiling of seminal plasma to find the metabolomics difference between healthy controls and infertility case samples with different semen abnormities by liquid chromatography-mass spectrometry (LC-MS) detection with previously established new sample preparation procedure. Among 624 detected metabolite features, 63 potential biomarkers in various metabolite classes were found for infertility in seminal plasma by multivariate analysis. Interestingly, different infertility forms have different potential biomarkers with few in common, and most of potential biomarkers were found in oligo-astheno-teratospermia samples. To further find the association of the metabolomic changes with specific sperm abnormality, sperm parameters including sperm concentration, sperm deformity rate and sperm motility were also collected, and multivariate linear regression was used to find correlations between sperm parameters and potential biomarkers. Finally, levels of 17 metabolites were found to be significantly correlated with sperm parameters. Most of correlations agreed with previously reported mechanisms of infertility, such as correlation of acylcarnitines with sperm concentration and sperm deformity, and correlation of some antioxidants with sperm deformity rate and sperm motility. Some correlations were reported for the first time, such as negative correlations of isopentenyl pyrophosphate, 2-phosphoglyceric acid and γ-glutamyl-Se-methylselenocysteine with sperm deformity rate, and negative correlation of creatine riboside with sperm concentration. All the potential biomarkers were involved in 14 metabolic pathways playing important role in energy production, antioxidation, hormone regulation and sperm membrane. These results proved previously reported molecular mechanism (such as oxidative stress and energy production) and also gave new possible clues to the pathology of male infertility, which will benefit future etiology, diagnosis and treatment of male infertility.

3.
Front Biosci (Landmark Ed) ; 25: 710-721, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585913

RESUMO

Adenosine deaminase acting on RNA1 (ADAR1) is an RNA editing enzyme that modulates the replication of several viruses. Here, we provide evidence showing that ADAR1 stimulates hepatitis B virus (HBV) DNA replication in hepatocellular carcinoma cell lines that are transiently or stably-transfected with HBV. We show that overexpression of ADAR1 promotes the replication of all four HBV genotypes (A, B, C, and D). Furthermore, analysis by mutagenesis shows that RNA editing region, and to a lesser content, RNA binding region of ADAR is responsible for the promotion of replication. Together, these data show that ADAR1 stimulates HBV replication.

4.
Talanta ; 206: 120176, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514900

RESUMO

Nd2O3 nanoparticle grafted graphene nanocomposite (NOGG) was synthesized by sonochemical treatment of an ethanolic dispersion of Nd2O3 nanoparticle and graphene. All the synthesized materials were characterized by XRD, FESEM, TEM, and BET. The NOGG has a high specific surface area (272 m2g-1) with narrowly distributed pores with diameter centered at 2.8, 6.0 and 7.50 nm. A composite paste electrode of 1:1 (w/w) NOGG and graphite was showed better electrochemical properties. The NOGG/GP electrode showed all around better electrocatalytic activity towards Adrenaline (AD) and Tyrosine (TY) than TRG/GP and bare GP electrode. According to cyclic voltammograms, AD and TY oxidized irreversibly through adsorption control process. DPV peak currents were measured at 378 ±â€¯15 mV and 787 ±â€¯15 mV for determination AD and TY respectively using the NOGG/GP electrode as the peak intensities were highest at those potentials. Under the optimized experimental condition, the determination ranges for AD and TY showed two linear ranges, those were 0.1-5-130 µM and 0.1-3-120 µM, respectively. A detection limit of AD and TY was measured (m-LOD) to be 50 nM and 40 nM, respectively. The modified electrode was reproducible, selective, highly sensitive and also employed for analysis of AD and TY in biological and pharmaceutical samples with excellent recovery.

5.
Chemosphere ; 239: 124811, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726522

RESUMO

China has been suffering from endemic fluorosis for the past 30 years. This study investigated fluoride concentrations in 10 districts of Tianjin, China, to illustrate their spatial distribution characteristics and potential human health risks. The results showed fluoride concentration of 0.01-6.30 mg L-1 with a mean value of 0.99 mg L-1, and 78.82% of water fluoride reaches the standard for drinking water (1.5 mg L-1). Higher fluoride levels were recorded in deep well pumps supply zones, and more potential changes in fluoride occurred was positively correlated with pH in groundwater. Mean value of fluoride in drinking water in 10 districts followed the order of WQ > BC > JZ > NH > BD > BH > JN > JH > DL > XQ. Estimations of non-carcinogenic risk for drinking water indicated that mean hazard quotient values of fluoride for combined pathways (i.e., oral ingestion and dermal absorption) were >1.0 for all age groups of WQ and BC. The results also showed that the estimated risk primarily came from the ingestion pathway. Risk levels for children varied obviously, generally in the order of 1-4y > 4-7y > 7-9y (years old). In the central tendency center and reasonable maximum exposure conditions, estimated risks were 1.25, 1.12, 0.771 and 3.66, 3.29, 2.27, respectively. The results supply material information for health authorities in fluorosis areas to put forward more efficient policies to control the endemic diseases. Attention should be paid to the formulation of health promotion strategies and measures to reduce fluoride intake in order to protect the health of residents.

6.
J Hazard Mater ; 383: 121188, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31525684

RESUMO

New carbon-doped ferric zinc oxide sorbents were fabricated to capture the environment carcinogen tobacco specific nitrosamines (TSNA) efficiently in solution, following new adsorption model of electrostatic attraction instead of traditional geometric constraints. The influence of ferric content on the structure-property of the sorbents was systemically studied with XRD, N2 adsorption-desorption and SEM methods combined with the adsorption of TSNA in different solutions. New sorbent captured 99% of 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) in simulated surface water and 40% of TSNA in the tobacco extract solution, more than activated carbon or zeolites. Ferric ZnO sorbent took about 15 min to reach the adsorption equilibrium in the NNK or Pb(Ⅱ) solution, faster than NaZSM-5 zeolite. Moreover, the adsorbed NNK on ferric ZnO sorbent decomposed at mild conditions for the first time, providing a new way to control environment pollution.

7.
J Cell Physiol ; 235(2): 1197-1208, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31270811

RESUMO

Chemotherapy is the first-line treatment option for patients with lung cancer. However, therapeutic resistance occurs through an incompletely understood mechanism. Our research wants to investigate the influence of Caveolin-1 (Cav-1) on the therapeutic sensitivity of lung cancer in vitro. Results in this study demonstrated that Cav-1 levels were markedly inhibited in A549 lung cancer cells after exposure to cisplatin. Knockdown of caveolin further enhanced cisplatin-triggered cancer death in A549 cells. The functional investigation demonstrated that Cav-1 inhibition amplified the mitochondrial stress signaling induced by cisplatin, as evidenced by the mitochondrial reactive oxygen species burst, cellular metabolic disruption, mitochondrial membrane potential reduction, and mitochondrial caspase-9-related apoptosis activation. At the molecular level, cav-1 augmented cisplatin-mediated mitochondrial damage by inhibiting Parkin-related mitochondrial autophagy. Mitophagy activation effectively attenuated the promotive impact of Cav-1 knockdown on mitochondrial damage and cell death. Furthermore, our data indicated that Cav-1 affected Parkin-related mitophagy by activating the Rho-associated coiled-coil kinase 1 (ROCK1) pathway; inhibition of the ROCK1 axis prevented cav-1 knockdown-mediated cell death and mitochondrial damage. Taken together, our results provide ample data illuminate the necessary action exerted by Cav-1 on affecting cisplatin-related therapeutic resistance. Silencing of Cav-1 inhibited Parkin-related mitophagy, thus amplifying cisplatin-mediated mitochondrial apoptotic signaling. This finding identifies the Cav-1/ROCK1/Parkin/mitophagy axis as a potential target to overcome cisplatin-related resistance in lung cancer cells.

8.
Virology ; 539: 92-103, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31706164

RESUMO

Hepatitis B virus (HBV) X protein (HBx) has been reported to counteract the innate immune responses through interfering with the pattern recognition receptors signaling activated by retinoic acid-inducible gene-I (RIG-I)-mitochondrial antiviral signaling protein (MAVS). Here, we showed that, compared to the HBx derived from genotype (gt) A, C and D, HBx of gtB exhibited more potent inhibitory activity on the RIG-I-MAVS-mediated interferon-ß promoter activation. Functional analysis of the genotype-associated differences in amino acid sequence and the reciprocal mutation experiments in transient-transfection and infection cell models revealed that HBx with asparagine (N) and glutamic acid (E) at 118-119 positions inhibited RIG-I signaling and interacted with MAVS more efficiently than that with lysine (K) and aspartic acid (D). An impaired RIG-I-induced MAVS aggregation was observed in the presence of HBx-118N119E while MAVS-TRAF3 interaction was not affected. These results implicated that HBx gene heterogeneity may affect the innate immune responses to HBV infection.

9.
Opt Express ; 27(21): 30280-30286, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684277

RESUMO

Double optical gating (DOG) technique was implemented with a two-cycle, 1.7 µm driving field to generate isolated attosecond pulses in the 100-250 eV spectrum range. The strong ellipticity dependency of the high harmonics from the 1.7 µm driving field makes polarization based gating method very efficient. When a second harmonic (SH) field is introduced, complete gating can be achieved with less ionization from the leading edge of the driving field, which yields supercontinua with a pulse energy of 0.3 nJ. We perform an attosecond streaking measurement to confirm the generation of isolated attosecond pulses.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31685424

RESUMO

Two novel ruthenium(II) polypyridyl complexes, namely, [Ru(dmp)2(CAPIP)](ClO4)2 (Ru(II)-1) and [Ru(dmp)2(CFPIP)](ClO4)2 (Ru(II)-2), which respectively contain (E)-2-(2-(furan-2-yl)vinyl)-1H-imidazo[4,5-f][1,10]phen-anthroline (CAPIP) and (E)-2-(4-fluorostyryl)-1H-imidazo[4,5-f][1,10]phenanthroline. (CFPIP), were first designed and characterized (dmp = 2,9-dimethyl-1,10-phenanthroline). DNA binding experiments indicated that Ru(II) complexes interact with CT DNA through intercalative mode. In addition, the complexes Ru(II)-1 and Ru(II)-2, showed remarkable cell cytotoxicity, giving the respective IC50 values of 4.1 ±â€¯1.4 µM and 6.1 ±â€¯1.4 µM on the A549 cancer cells. These values indicated higher activity than CAPIP, CFPIP, cisplatin (8.2 ±â€¯1.4 µM) and other corresponding Ru(II) polypyridyl complexes. Furthermore, the Ru(II) complexes could arrive the cytoplasm through the cell membrane and accumulate in the mitochondria. Significantly, complexes Ru(II)-1 and Ru(II)-2 induced A549 cells apoptosis was mediated by increase of ROS levels and dysfunction of mitochondria, and resulted in cell cycle arrest and increased anti-migration activity on A549 cells. Overall, these results indicated that complexes Ru(II)-1 and Ru(II)-2 could be suitable candidates for further investigation as a chemotherapeutic agent in the treatment of tumors.

11.
Histol Histopathol ; : 18181, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31688946

RESUMO

Ewing's sarcoma (ES) is a small cell malignant tumor that occurs in the bone of children or adolescents. ES can also occur in extraskeletal organs, such as the pancreas, thyroid, liver, proximal phalanx, and, rarely, cervix. Only 15 published case reports have discussed ES arising in the cervix. We report a 76-year-old woman who had groin mass. ES was diagnosed in accordance with morphological and immunohistochemical maps. Fluorescence in situ hybridization and RT-PCR (reverse transcription PCR) revealed ESWR1 gene rearrangement and fusion gene formation (EWS-FLI-1), both of which confirmed the diagnosis of ES. Although the patient underwent surgical resection, the patient died without chemotherapy and radiotherapy. This case is the first one to involve a patient aged over 70 years and the fifth one to show metastasis occurrence.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31718979

RESUMO

Identifying and detecting similar target cations through combining "turn on" and "turn off" fluorescence mechanism is effective and challenging. Now a new colorimetric and ON-OFF-ON fluorescent probe N'-((7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene)-3-hydroxy-2-naphthohydrazide (L) was reported, which could detect Cu2+ and Co2+ in phosphate buffered CH3CH2OH-H2O solvent system. With the assistance of glutathione and pH adjustment, a unique ON-OFF-ON fluorescence detection strategy could be achieved for distinguishing Cu2+ and Co2+. The emission of probe could recover from the L-Cu2+ and L-Co2+ system by addition of GSH or adjusting pH value to 4, respectively, which is due to the abolishment of paramagnetic Cu2+/Co2+. Based on fluorescence titration experiments, the limit of detection was determined as 3.84 × 10-9 M and 4.55 × 10-9 M for Cu2+ and Co2+, respectively. Meanwhile, the detection limit reached 6.21 × 10-8 M for Cu2+ and 6.96 × 10-8 M for Co2+ according to absorbance signal output. Fast recognition of Cu2+/Co2+ can be achieved by obvious color changes from green to colorless under UV light, as well as from yellow to orange-red in room light. The binding mode of L toward Cu2+ and Co2+ have been systematically studied by Job's plot analysis, ESI-MS, IR and density functional theory calculations. Most strikingly, further practical applications of the probe L in fluorescence imaging were investigated in MCF-7 cells and zebrafish due to its low cytotoxicity and good optical properties, suggesting that L could serve as a fluorescent sensor for tracking Cu2+ and Co2+in vivo.

13.
Clin Lab ; 65(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710426

RESUMO

BACKGROUND: Reliable reference intervals (RIs) for the serum creatinine (SCr), assayed by Jaffe's method and categorized in small intervals, are still lacking in elderly population. The study aims to establish RIs for SCr with Jaffe's method in healthy geriatric population of China. METHODS: Eight hundred twenty cases from six representative geographical regions in China (including 369 male cases and 374 female cases) of apparently healthy Chinese elderly aged 60 - 90 years were recruited. SCr were analyzed by an ARCHITECT c8000 biochemical analyzer with Jaffe's method, and RIs for Scr with Jaffe's method were determined following CLSI C28-A3 guidelines using a nonparametric method. RESULTS: In apparently healthy Chinese geriatric population of China, the RIs for Scr with Jaffe's method were 69.4 ~ 113.1, 74.1 ~ 122.1, 75.2 ~ 126.9 µmol/L, respectively, for males aged 61 - 70, 71 - 80, 81 - 90 years and 60.7 ~ 91.6, 62.2 ~ 102.5, 86.5 ~ 107.2 µmol/L, respectively, for females aged 61 - 70, 71 - 80, 81 - 90 years. CONCLUSIONS: The RIs for Scr using Jaffe's method were established within apparently healthy geriatric Chinese population according to CLSI C28-A3 document, providing a reference for clinical practice.

14.
J Clin Lab Anal ; : e23034, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31713264

RESUMO

OBJECTIVE: This study aimed to explore the association of integrin α7 with clinicopathological characteristics and overall survival (OS) in clear cell renal cell carcinoma (ccRCC) patients. METHODS: 179 ccRCC patients who underwent nephrectomy were included in this retrospective study. Tumor tissue and paired adjacent tissue specimens of patients were obtained. Immunohistochemistry assay was performed to detect integrin α7 expression. OS was calculated with the median follow-up duration of 91.0 months (range: 3.0-116.0 months). RESULTS: Integrin α7 was highly expressed in tumor tissue compared to paired adjacent tissue (P < .001), and tumor integrin α7 high expression was correlated with higher pathological grade (P = .004), increased T stage (P = .017), and advanced TNM stage (P = .033). Kaplan-Meier curve showed that patients with integrin α7 high expression (mean OS = 69.8, 95%CI: 60.5-79.1 months) presented with worse OS compared to patients with integrin α7 low expression (mean OS = 101.8, 95%CI: 96.0-107.7 months; P < .001). Multivariate Cox's regression analysis further disclosed that tumor integrin α7 high expression independently predicted poor OS (P < .001). CONCLUSION: Integrin α7 is upregulated and correlates with higher pathological grade, increased T stage, and advanced TNM stage, meanwhile it also acts as a valuable prognostic factor for worse survival in ccRCC patients.

15.
Transbound Emerg Dis ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714018

RESUMO

H7 subtype avian influenza virus infection is an emerging zoonosis in some Asian countries and an important avian disease worldwide. A rapid and simple test is needed to confirm infection in suspected cases during disease outbreaks. In this study, we developed a reverse transcription recombinase-aided amplification assay for the detection of H7 subtype avian influenza virus. Assays were performed at a single temperature (39°C) and the results were obtained within 20 min. The assay showed no cross-detection with Newcastle disease virus or infectious bronchitis virus, which are the other main respiratory viruses affecting birds. The analytical sensitivity was 102 RNA copies per reaction at a 95% probability level according to probit regression analysis, with 100% specificity. Compared with published reverse transcription quantitative real-time polymerase chain reaction assays, the κ value of the reverse transcription recombinase-aided amplification assay in 342 avian clinical samples was 0.988 (p < .001). The sensitivity for avian clinical sample detection was 100% (95%CI, 90.40%-100%) and the specificity was 99.96% (95%CI, 97.83%-99.98%). These results indicated that our reverse transcription recombinase-aided amplification assay may be a valuable tool for detecting avian influenza H7 subtype virus.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31697199

RESUMO

Background: The reported rate of surgical site infection (SSI) in breast surgery is often higher than expected. Using antibiotic prophylaxis to reduce SSI is debatable because of the risk of developing bacteria resistance and the cost burden. In this study, we evaluated the effectiveness of antibiotic prophylaxis in breast surgery and the factors predisposing patients to SSI. Methods: A retrospective-prospective (ambispective) study was conducted in the Department of Breast Surgery, Qilu Hospital, P.R. China. The retrospective antibiotic-using group was composed of patients found to have breast cancer between January 2008 and October 2010. The prospective non-antibiotic-using group was composed of patients identified between November 2010 and November 2013. Pre-operative, peri-operative, and post-operative clinical data were analyzed. Results: The SSI rate of the non-prophylaxis and prophylaxis groups was 1.1% (11/1,022) and 1.2% (12/1,034), respectively. Neoadjuvant chemotherapy was related to SSI in the non-prophylaxis group (p = 0.026). Staphylococcus aureus was the predominant microorganism responsible for SSI, without obvious resistance to a widely used first-generation cephalosporin. Conclusions: Peri-operative antibiotic prophylaxis is of no significant value in preventing SSI in breast cancer surgery. Our results indicated that neoadjuvant chemotherapy might be a risk factor doe SSI, but further research is needed because of the sample size disparity between infected and uninfected groups.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31697230

RESUMO

A novel bacterium, designated TRM 44457T, belonging to the genus Streptomyces, was isolated from soil sampled in cotton fields in Xinjiang, PR China. Comparative 16S rRNA gene sequence analysis indicated that strain TRM 44457T was phylogenetically most closely related to Streptomyces laurentii LMG 19959T (99.38 % sequence similarity); however, strain TRM 44457T had a relatively low DNA-DNA relatedness value with S. laurentii LMG 19959T as determined by calculating the average nucleotide identity value (84.42 %). Strain TRM 44457T possessed ll-diaminopimelic acid as the diagnostic cell-wall diamino acid, MK-9 (H6) and MK-9 (H10) as the major menaquinone. The polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphotidylinositol, phosphatidylinositol mannosides and an unidentified phospholipid. The major fatty acids were anteiso-C15:0, iso-C16:0, anteiso-C17:0, iso-C15:0, C16:0, iso-C17:0, cyclo-C17:0 and anteiso-C17:1ω9c. The genomic DNA G+C content was 72.6 mol%. Based on the evidence from this polyphasic study, strain TRM 44457T represents a novel species of the Streptomyces, for which the name Streptomyces roseicoloratus is proposed. The type strain is TRM 44457T (=KCTC 39904T=CCTCC AA 2016040T).

18.
Theranostics ; 9(24): 7122-7139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695757

RESUMO

Background: Acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) such as erlotinib is a major challenge to achieve an overall clinical benefit of the targeted therapy. Recently, aldehyde dehydrogenase 1 (ALDH1) induction has been found to render lung adenocarcinomas resistant to EGFR-TKIs, and targeting ALDH1A1 becomes a novel strategy to overcome resistance. However, the molecular mechanism underlying such effect remains poorly understood. Methods: Comprehensive assays were performed in a panel of lung adenocarcinoma cell lines and xenografts that acquired resistance to erlotinib. Cancer phenotype was evaluated by cell viability, apoptosis, migration, and epithelial-mesenchymal transition analysis in vitro, tumorsphere formation analysis ex vivo, and tumor growth and dissemination analysis in vivo. Reactive oxygen species (ROS) and reactive carbonyl species (RCS) were detected based on fluorescent oxidation indicator and liquid chromatography coupled to mass spectrometry, respectively. Protein target was suppressed by RNA interference and pharmacological inhibition or ecto-overexpressed by lentivirus-based cloning. Gene promoter activity was measured by dual-luciferase reporting assay. Results: Knockdown or pharmacological inhibition of ALDH1A1 overcame erlotinib resistance in vitro and in vivo. ALDH1A1 overexpression was sufficient to induce erlotinib resistance. Metabolomic analysis demonstrated lower ROS-RCS levels in ALDH1A1-addicted, erlotinib-resistant cells; in line with this, key enzymes for metabolizing ROS and RCS, SOD2 and GPX4, respectively, were upregulated in these cells. Knockdown of SOD2 or GPX4 re-sensitized the resistant cells to erlotinib and the effect was abrogated by ROS-RCS scavenging and mimicked by ROS-RCS induction. The ALDH1A1 overexpressed cells, though resisted erlotinib, were more sensitive to SOD2 or GPX4 knockdown. The ALDH1A1 effect on erlotinib resistance was abrogated by ROS-RCS induction and mimicked by ROS-RCS scavenging. Detection of GPX4 and SOD2 expression and analysis of promoter activities of GPX4 and SOD2 under the condition of suppression or overexpression of ALDH1A1 demonstrated that the RCS-ROS-metabolic pathway was controlled by the ALDH1A1-GPX4-SOD2 axis. The ROS-RCS metabolic dependence mechanism in ALDH1A1-induced resistance was confirmed in vivo. Analysis of public databases showed that in patients undergoing chemotherapy, those with high co-expression of ALDH1A1, GPX4, and SOD2 had a lower probability of survival. Conclusions: ALDH1A1 confers erlotinib resistance by facilitating the ROS-RCS metabolic pathway. ALDH1A1-induced upregulation of SOD2 and GPX4, as well as ALDH1A1 itself, mitigated erlotinib-induced oxidative and carbonyl stress, and imparted the TKI resistance. The elucidation of previously unrecognized metabolic mechanism underlying erlotinib resistance provides new insight into the biology of molecular targeted therapies and help to design improved pharmacological strategies to overcome the drug resistance.

19.
Math Biosci Eng ; 16(6): 7510-7525, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31698626

RESUMO

Impressed current cathodic protection (ICCP) was widely applied for the corrosion control of reinforced concrete. During the ICCP treatment, the anodic reactions happened on the primary anode surface may induce acidification and subsequently pH drop in the vicinity of the anode, leading to damage of the external anode mortar. In this study, the relationship between the applied current (simulating ICCP treatment) on the Ti mesh anode and pH alterations in simulated concrete pore (SCP) solution (with/without chlorides) was investigated. It was found that the applied current slightly reduced the corrosion resistance of Ti mesh; this negative effect was more pronounced in the presence of chlorides. The pH value of SCP solution near Ti mesh anode decreased when the external current was applied. The consumption rate of OH- ion was higher in the chloride-containing SCP solution. A mathematical model was proposed between the electric charge quantity (Q) and OH- concentration (cOH-) in SCP solution near Ti mesh anode. This model is a useful tool to quantitatively identify the acidification damage induced by impressed current from the perspective of pH alternation near Ti mesh anode.

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