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1.
Thromb Haemost ; 120(4): 647-657, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32289862

RESUMO

Heparanase (HPSE) is an endo-ß-D-glucuronidase that cleaves heparan sulfate and hence participates in remodeling of the extracellular matrix, leading to release of cytokines that are immobilized by binding to heparan sulfate proteoglycans (HSPGs), and consequently activating signaling pathways. This function of HPSE is correlated to its expression level that is normally very low in majority of the tissues. Exceptionally, human platelets express high level of HPSE, suggesting a unique physiological role in this cell. Using K562 cell line, we found a progressive increase of HPSE during the megakaryocytic differentiation. Analysis of a series of megakaryocytic differentiation-related heparin-binding proteins (HBPs) in the cell culture medium revealed an exclusive positive correlation between the level of interleukin 6 (IL-6) and HPSE expression. IL-6 modulated megakaryocytic differentiation through activation of STAT3. Further, we demonstrated that overexpression of HPSE potentiates megakaryocytic differentiation, whereas elimination of HPSE led to a delayed differentiation. This function of HPSE is associated with its activity, as overexpression of inactive HPSE had no effect on IL-6 production and megakaryocytic differentiation. The role of HPSE is further supported by the observation in an umbilical cord blood CD34+ cells megakaryocytic differentiation model. Our data propose a novel role for HPSE in platelets production by a HPSE/IL-6/STAT3 positive feedback loop that specifically regulates megakaryocytes maturation.

2.
Biomed Res Int ; 2020: 6097516, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32185211

RESUMO

We here investigated the impact of mechanical ventilation (MV) time on ferroptosis in a rat renal ischemia/reperfusion injury (IRI) model. Thirty-two male adult Sprague Dawley rats were divided into four groups (n = 8/group): the sham group, IRI group, IRI+MV-4 h group, and IRI+MV-12 h group. Rats in the IRI group were subjected to 45 min bilateral renal ischemia. Rats in the IRI+MV groups were additionally mechanically ventilated with tracheal intubation after 45 min bilateral renal ischemia. Morphological changes associated with kidney injury and ferroptosis were assessed by hematoxylin and eosin staining and electron microscopy. Levels of the central regulator of ferroptosis, glutathione peroxidase 4 (GPX4), and lipid peroxidation markers 4-hydroxynonenal (4HNE) and superoxide dismutase 2 (SOD2) were determined in the kidney tissue by western blotting. Glutathione (GSH) levels were assessed in the serum and kidney homogenate. Scr levels in the IRI+MV-12 h group were significantly higher than those in the sham, IRI, and IRI+MV-4 h groups (all P < 0.001). Electron microscopy revealed the most pronouncedly abnormal mitochondrial morphology, suggestive of ferroptosis, in the IRI+MV-12 h group. The GPX4 and SOD2 protein levels progressively decreased in the following order: sham group > IRI group > IRI+MV-4 h group > IRI+MV-12 h group (P < 0.05 for all comparisons). By contrast, the 4HNE levels progressively increased in the kidney, with the highest values in the IRI+MV-12 h group (P < 0.05, vs. the IRI group and vs. the IRI+MV-4 h group). Further, the GSH levels in the serum and kidney homogenates were significantly reduced in the IRI+MV-12 h group (P < 0.01, vs. IRI group and vs. the IRI+MV-4 h group). A significant positive correlation was observed between the serum and kidney GSH levels (r 2 = 0.542, P = 0.03). These observations suggested that prolonged MV may exacerbate renal function failure, already initiated by IRI, by ferroptosis. Depletion of GSH may contribute to this effect, which requires further investigation.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 296-299, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027292

RESUMO

OBJECTIVE: To establise the bank of platelet donors with the human platelet antigen (HPA) 1-6, 15 genes so as to provide the HPA-matched platelets for the patients. METHODS: The HPA genotyping of platelets donors and patients with platelet antibody positive confirmed by sercening was performed by using the SSP-PCR; the efficacy of transfusing the HPA-matched platelets for 37 cases platelet antibody positive was analyzed. RESULTS: The most common genotype in platelet donors were HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b, followed by HPA-1a/1a-2a/2a-3a/3a-4a/4a-5a/5a-6a/6a-15a/15b; the most common genotype in 53 cases of platelet antibody positive confirened by screening were HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b. Among 37 patients with platelet antibody positive confirened by screeming, 28 showed that the transfusion of HPA-matched platelets was effective with statistically significant difference in comparison with random transfusion group. The HPA-3, HPA-15 were the main factors leading to polymorphisms. CONCLUSION: HPA-3 and HPA-15 are polymorphic, which should be focused on. HPA-matched platelets can improve the efficiency of platelet transfusion, and avoid the waste of blood resources. The genotypes of platelet donors can basically meet the requirements for common genotype transfusion.


Assuntos
Plaquetas , Antígenos de Plaquetas Humanas , Doadores de Sangue , Frequência do Gene , Genótipo , Humanos , Polimorfismo Genético
4.
PLoS One ; 15(1): e0227862, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995595

RESUMO

BACKGROUND: The effect of phase-change material blood containers on the quality of stored red blood cells (RBCs) transported in the Qinghai-Tibet Plateau remains to be studied. STUDY DESIGN AND METHODS: RBCs stored in a phase-change material blood container were transported from Chengdu to Tibet and then back to Chengdu. The detection time points were the 1st day of fresh-collected RBCs (group 1), the 14th day of resting refrigerated storage (group 2), and the 14th day of plateau transportation under refrigerated storage in the container (group 3). RBC counts, hemoglobin (HGB) content, free hemoglobin (FHb) content, blood biochemical indexes, hemorheologic indexes and 2,3-DPG content were detected. RESULTS: Compared with group 2, RBC counts and HGB were decreased, and the mean corpuscular volume (MCV), FHb and K+ content were increased in group 3. The glucose consumption and lactic acid production were significantly increased in groups 2 and 3. Compared with group 2, the 2,3-DPG content and whole blood viscosity were decreased in group 3. After resting refrigerated storage and plateau transportation, the RBC quality still met the national standard (GB18469-2012 whole blood and component blood quality requirements). CONCLUSION: The phase-change material blood container can be maintained at a constant temperature under plateau environmental conditions, ensuring that the quality of the stored RBCs is compliant with GB18469-2012 whole blood and component blood quality requirements.


Assuntos
Preservação de Sangue/instrumentação , Eritrócitos/química , Manejo de Espécimes/instrumentação , Transportes , 2,3-Difosfoglicerato/sangue , Contagem de Eritrócitos , Glucose/metabolismo , Sistema Hematopoético/metabolismo , Hemoglobinas/metabolismo , Humanos , Ácido Láctico/sangue , Tibet
5.
Nanotechnology ; 31(18): 18LT01, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31978905

RESUMO

The electrical breakdown is a bottleneck preventing AgNW networks from being used in high-current electronics such as transparent heaters or similar applications. The process of failure confirms that Joule-heating plays a key role in the formation of cracks perpendicular to the voltage direction. To improve the transfer of Joule heating, solution-processed ZnO nanoparticles were deposited on a gravure printed AgNW random network with good transparency. The AgNW-ZnO nanocomposites show better heating uniformity at higher temperatures because of their improved thermal conductivity. A 57.7% higher power density was obtained without failure, as well as the improved maximum average temperature rise from 72.2 °C to 97.9 °C, after the AgNW was composited with ZnO. This work opens up a new method to study AgNW failures for applications in high-current electronics.

6.
Respir Care ; 65(1): 45-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31551283

RESUMO

BACKGROUND: To investigate patient-ventilator interaction during different levels of noninvasive proportional assist ventilation (PAV) compared with noninvasive pressure support ventilation (PSV). METHODS: Fifteen subjects with severe COPD and hypercapnia were consecutively recruited. After the baseline assessment of unassisted spontaneous breathing, 3 levels of ventilatory support were applied. The proportional assist (PA) and pressure support (PS) levels were set by subject comfort. PA-, PS- or PA+, PS+ were set at 25% more or less of PA or PS (PA- = 75% PA, PA+ = 125% PA, PS- = 75% PS, PS+ = 125% PS). Each level lasted at least 20 min. To demonstrate the patient-ventilator interaction, the neural respiratory drive, respiratory muscle effort, flow signal, and airway pressure were simultaneously monitored. RESULTS: The expiratory cycle delay (time between the termination of the diaphragm electromyogram [EMGdi] signal and the end of the inspiratory flow) progressively increased with increasing assist level in both modes. However, compared with PSV, the expiratory cycle delay was significantly longer in each assist level during noninvasive PAV. The runaway phenomenon was observed in PA+. The time between the peak EMGdi signal and the maximum value of the flow signal and the time difference between the peak EMGdi signal and the maximum value of inspiratory pressure were significantly increased with the increasing assist level of PAV. CONCLUSIONS: The expiratory cycle delay of noninvasive PAV was significantly longer than that of noninvasive PSV in the subjects with COPD with respiratory failure. During the levels of PAV, the lag time between neural respiratory drive and airway pressurization was significantly increased and the "runaway" phenomenon may be observed. (ClinicalTrials.gov registration NCT01782768.).

7.
Adv Sci (Weinh) ; 6(22): 1901490, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763148

RESUMO

With the rapid progress of organic solar cells (OSCs), improvement in the efficiency of large-area flexible OSCs (>1 cm2) is crucial for real applications. However, the development of the large-area flexible OSCs severely lags behind the growth of the small-area OSCs, with the electrical loss due to the large sheet resistance of the electrode being a main reason. Herein, a high conductive and high transparent Ag/Cu composite grid with sheet resistance <1 Ω sq-1 and an average visible light transparency of 84% is produced as the transparent conducting electrode of flexible OSCs. Based on this Ag/Cu composite grid electrode, a high efficiency of 12.26% for 1 cm2 flexible OSCs is achieved. The performances of large-area flexible OSCs also reach 7.79% (4 cm2) and 7.35% (9 cm2), respectively, which are much higher than those of the control devices with conventional flexible indium tin oxide electrodes. Surface planarization using highly conductive PEDOT:PSS and modification of the ZnO buffer layer by zirconium acetylacetonate (ZrAcac) are two necessary steps to achieve high performance. The flexible OSCs employing Ag/Cu grid have excellent mechanical bending resistance, maintaining high performance after bending at a radius of 2 mm.

8.
Bosn J Basic Med Sci ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31668144

RESUMO

Diabetic nephropathy (DN) is the most common complication of diabetes and is prone to kidney failure. Dihydromyricetin (DHM) has been reported to have a variety of pharmacological activities. This study aims to explore the effect of DHM on DN and the underlying molecular mechanism. An in vivo DN rat model was established. The degree of renal interstitial fibrosis (RIF) was detected by hematoxylin-eosin (HE) staining, Masson's trichrome staining, and immunohistochemistry (IHC). In vitro, NRK-52E cells were divided into four groups: normal glucose (NG), high glucose (HG), HG+DHM, and HG+rapamycin (autophagy inhibitor). The levels of autophagy- and fibrosis-related proteins were analyzed by western blotting. The expression of miR-155-5p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) and their relationship were assessed by quantitative reverse transcription (qRT)-PCR and dual luciferase reporter gene assay. Our results showed that RIF was increased in DN rat model and in HG-induced NRK-52E cells. DHM treatment attenuated the increased RIF and also increased autophagy. MiR-155-5p expression was increased, while PTEN expression was decreased in DN rat and cell model, and DHM reversed both effects. Dual luciferase assay showed that PTEN was the target gene of miR-155-5p. DHM inhibited HG-induced fibrosis and promoted autophagy by inhibiting miR-155-5p expression in NRK-52E cells. In addition, DHM promoted autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, DHM promotes autophagy and attenuates RIF by regulating the miR-155-5p/PTEN signaling and PI3K/AKT/mTOR signaling pathway in DN.

9.
Chem Res Toxicol ; 32(8): 1469-1486, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31353895

RESUMO

Cisplatin is one of the most widely used chemotherapeutic agents for various solid tumors in the clinic due to its high efficacy and broad spectrum. The antineoplastic activity of cisplatin is mainly due to its ability to cross-link with DNA, thus blocking transcription and replication. Unfortunately, the clinical use of cisplatin is limited by its severe, dose-dependent toxic side effects. There are approximately 40 specific toxicities of cisplatin, among which nephrotoxicity is the most common one. Other common side effects include ototoxicity, neurotoxicity, gastrointestinal toxicity, hematological toxicity, cardiotoxicity, and hepatotoxicity. These side effects together reduce the life quality of patients and require lowering the dosage of the drug, even stopping administration, thus weakening the treatment effect. Few effective measures exist clinically against these side effects because the exact mechanisms of various side effects from cisplatin remain still unclear. Therefore, substantial effort has been made to explore the complicated biochemical processes involved in the toxicology of cisplatin, aiming to identify effective ways to reduce or eradicate its toxicity. This review summarizes and reviews the updated advances in the toxicological research of cisplatin. We anticipate to provide insights into the understanding of the mechanisms underlying the side effects of cisplatin and designing comprehensive therapeutic strategies involving cisplatin.

10.
Front Pharmacol ; 10: 736, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333458

RESUMO

[This corrects the article DOI: 10.3389/fphar.2019.00195.].

11.
Molecules ; 24(10)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091778

RESUMO

The clinically widely-used anticancer drug, cisplatin, binds strongly to DNA as a DNA-damaging agent. Herein, we investigated the interaction of cisplatin with a 15-mer single-stranded C,T-rich oligodeoxynucleotide, 5'-CCTT4CTT7G8C9T10TCTCC-3' (ODN15), using ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) in conjunction with tandem mass spectrometry (top-down MS). Top-down MS analysis with collision-induced dissociation (CID) fragmentation of the mono-platinated and di-platinated ODN15 provided abundant and informative Pt-containing or Pt-free a/[a - B], w and internal fragments, allowing the unambiguous identification of T4, T7, C9, and T10 as the platination sites on the cisplatin-ODN15 adducts. These results revealed that, in addition to the well-established guanine site, the unexpected thermodynamic binding of cisplatin to cytosine and thymine bases was also evident at the oligonucleotide level. Furthermore, the binding models of cisplatin with cytosine and thymine bases were built as the Pt coordinated to cytosine-N(3) and thymine-N(3) with displacement of the proton or tautomerization of thymine. These findings contribute to a better understanding of the mechanism of action of cisplatin and its preference for gene loci when the drug binds to cellular DNA, and also demonstrate the great potential and superiority of FT-ICR MS in studying the interactions of metallodrugs with large biomolecules.


Assuntos
Cisplatino/farmacologia , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/metabolismo , Citosina/metabolismo , Modelos Moleculares , Espectrometria de Massas em Tandem , Timina/metabolismo
12.
Front Pharmacol ; 10: 195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30971915

RESUMO

Resveratrol (Res) is a multi-functional polyphenol compound that has protective functions in cardiovascular and neurodegenerative diseases. This study aimed to determine the effect of Res on osteogenic differentiation and bone mineralization in zebrafish (Danio rerio) with dexamethasone (Dex)-induced bone damage. Our results showed that Dex exposure (15 µmol/l) decreased the green fluorescence areas and the integrated optic density (IOD) values in the skull bones of zebrafish larvae of the TG(SP7:EGFP) strain in a dose-dependent manner (p < 0.01). Furthermore, Dex exposure decreased the alizarin red S-stained areas (bone mineralization area) in the skeleton and spinal bones of zebrafish larvae of the AB strain in a dose-dependent manner (p < 0.01). By contrast, Res treatment (150 µmol/l) significantly increased both the green fluorescence and bone mineralization area in Dex-exposed zebrafish larvae. Thus, our data show that Res improves bone mineralization after glucocorticoid-induced bone damage in a zebrafish model. Res may be a candidate drug for the prevention of osteoporosis.

13.
J Int Med Res ; 47(6): 2394-2403, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30991866

RESUMO

OBJECTIVE: To compare the full age spectrum (FAS) equation with the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in predicting glomerular filtration rate (GFR) in patients with obstructive nephropathy. METHODS: Adult patients with obstructive nephropathy who had undergone a GFR measurement using technetium-99m diethylenetriaminepentaacetic acid radioisotope renography were enrolled in the study. The measured GFR was taken as the reference value. Bias, precision and accuracy were compared between the three equations. Kappa test and the Bland-Altman method were used to evaluate the classification and the agreement. Receiver operating characteristic (ROC) curve analysis was used to describe the diagnostic accuracy of each equation. RESULTS: A total of 327 patients were enrolled. The P30 value for the FAS equation was 60.2% in the overall study cohort. The FAS equation had the highest diagnostic accuracy (ROCAUC = 0.87, 95% confidence interval [CI] 0.84, 0.91) compared with the MDRD equation (ROCAUC = 0.86, 95% CI 0.82, 0.89). The median bias of the FAS equation was significantly higher than that of the MDRD equation (8.7 versus 7.6 ml/min/1.73 m2, respectively). CONCLUSIONS: Despite the drawbacks associated with each equation, the FAS equation was probably closer to ideal to estimate GFR in patients with obstructive nephropathy.


Assuntos
Taxa de Filtração Glomerular , Conceitos Matemáticos , Modelos Teóricos , Insuficiência Renal Crônica/fisiopatologia , Obstrução Ureteral/complicações , Adolescente , Adulto , Creatinina/sangue , Comportamento Alimentar , Feminino , Seguimentos , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal Crônica/etiologia , Estudos Retrospectivos , Adulto Jovem
14.
Anal Chem ; 91(9): 6035-6042, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30990031

RESUMO

A new proteomic strategy combining functionalized magnetic nanoparticle affinity probes with mass spectrometry was developed to capture and identify proteins specifically responding to 1,2-d(GpG) intrastrand cisplatin-cross-linked DNA, the major DNA lesion caused by cisplatin and thought to induce apoptosis. A 16-mer oligodeoxynucleotide (ODN) duplex and its cisplatin-cross-linked adduct were immobilized on magnetic nanoparticles via click reaction, respectively, to fabricate negative and positive affinity probes which were very stable in cellular protein extracts due to the excellent bio-orthogonality of click chemistry and the inertness of covalent triazole linker. Quantitative mass spectrometry results unambiguously revealed the predominant binding of HMGB1 and HMGB2, the well-established specific binders of 1,2-cisplatin-cross-linked DNA, to the cisplatin-cross-linked ODN, thus validating the accuracy and reliability of our strategy. Furthermore, 5 RNA or single-stranded DNA binding proteins, namely, hnRNP A/B, RRP44, RL30, RL13, and NCL, were demonstrated to recognize specifically the cisplatinated ODN, indicating the significantly unwound ODN duplex by cisplatin cross-linking. In contrast, the binding of a transcription factor TFIIFa to DNA was retarded due to cisplatin damage, implying that the cisplatin lesion stalls DNA transcription. These findings promote understanding in the cellular responses to cisplatin-damaged DNA and inspire further precise elucidation of the action mechanism of cisplatin.

15.
Sci Rep ; 9(1): 6452, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015608

RESUMO

We aimed to evaluate the alteration of diagnosis of individual expert and multidisciplinary discussion (MDD) team in the longitudinal diagnostic assessment of idiopathic interstitial pneumonia (IIP). The retrospective analysis included 56 patients diagnosed as IIP by The First Affiliated Hospital of Guangzhou Medical University with follow-up visits during Jan 1st to Aug 31st 2014. Each expert was provided information in a sequential manner and was asked to assign an individual diagnosis and an MDD diagnosis after group discussion. The level of agreement among individual experts and between different visits was calculated by kappa and the agreement between individual specialist and MDD team with different consensus levels was measured by weighted-kappa coefficients. Follow-up data changed the original clinical diagnosis and MDD diagnosis in 24.1% and 10.7% of all cases, respectively, and clinician and MDD consensus level in 55.4% and 25.0%, respectively. The diagnostic performance of individual clinicians or radiologist was closer to that of the MDD compared with the pathologist, and follow-up further increased the agreement. The longitudinal evaluation of patients with IIP improved the inter-observer agreement in a multidisciplinary team. The performance of individual clinicians or radiologist was approaching the accuracy of multidisciplinary team when provided with follow-up data.

16.
Kidney Blood Press Res ; 44(2): 222-232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30921805

RESUMO

BACKGROUND/AIMS: The study aimed at investigating the impact of serum magnesium (Mg) baseline level and its variability on mortality in maintenance hemodialysis (MHD) patients. METHODS: Eligible patients receiving regular MHD at Ningbo No. 2 Hospital between January 2009 and August 2016 were enrolled and follow-ups were conducted afterwards until death or transplantation. General information, laboratory results, and outcomes of subjects were collected. The relationship between baseline serum Mg level, its coefficient of variation (CV), and all-cause mortality and cardiovascular disease mortality were assessed, respectively. Subjects were divided into groups in 2 manners: by serum Mg level (lower Mg group: serum Mg <1.00 mmol/L, higher Mg group: serum Mg ≥1.00 mmol/L) and by serum Mg CV (high variation group: CV ≥0.149 mmol/L, middle variation group: 0.114 mmol/L ≤ CV < 0.149 mmol/L, and low variation group: CV <0.114 mmol/L). RESULTS: 169 MHD patients were recruited in the study, with mean serum Mg 1.00 ± 0.18 mmol/L, average age 60.20 ± 15.64 years, and median dialysis duration 37.00 (18.30, 77.97) months. During the follow-up, 69 (40.83%) patients died, 24 (34.78%) of which died due to cardiovascular disease. Comparing the two groups, patients in the lower Mg group had a higher all-cause mortality (50.00 vs. 29.33%, p = 0.007). The multivariate Cox regression analysis suggested that lower Mg level was an independent factor for all-cause mortality as well as cardiovascular mortality (HR = 13.268, 95% CI 6.234-28.237, p < 0.001; HR = 12.702, 95% CI 3.737-43.174, p < 0.001, respectively). However, there were no significant statistical differences of all-cause and cardiovascular mortality among these three groups concerning Mg variation. And in the univariate and multivariate Cox regression analysis, serum magnesium CV was not the independent factor for all-cause mortality and cardiovascular mortality. CONCLUSIONS: The lower baseline serum magnesium level was associated with all-cause and cardiovascular mortality in MHD patients. However, the variability of magnesium level was not independently associated with the risk of death and further studies need to be conducted.


Assuntos
Falência Renal Crônica/mortalidade , Magnésio/sangue , Diálise Renal , Idoso , Doenças Cardiovasculares/mortalidade , Causas de Morte , Feminino , Seguimentos , Humanos , Falência Renal Crônica/complicações , Magnésio/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais
17.
Rapid Commun Mass Spectrom ; 33(10): 951-958, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30812058

RESUMO

RATIONALE: The binding ratio of metal complexes with cysteinyl thiols in proteins plays an important role in deciphering the mechanisms of action of therapeutic metal complexes, but its analysis is still a significant challenge. In this work, a quantitative mass spectrometry method is developed to determine the binding ratio of metal-based anticancer complexes with cysteines in human copper chaperone protein Atox1. METHODS: A novel strategy based on a thiol-specific stable isotopic labelling reagent was developed to determine the binding ratio of metal-based anticancer complexes, namely cisplatin and organometallic ruthenium complex [(η6 -biphenyl)RuCl(en)]PF6 (en = ethylenediamine), with the cysteinyl residues of Atox1. RESULTS: Both cisplatin and the ruthenium complex were reactive not only to Cys15 and/or Cys18, the copper(I) binding site of Atox1, but also to Cys44. The binding ratios of the ruthenium complex with the cysteinyl residues were much higher than those of cisplatin. However, the addition of copper(I) could markedly increase the binding ratios of cysteinyl residues of Atox1 with cisplatin, but not with the ruthenium complex. CONCLUSIONS: This strategy can not only precisely determine the binding ratios of metal complexes to protein thiols, but also be helpful in distinguishing thiol-binding sites from other binding sites of metal complexes in proteins. We expect wide application of this method to the research of covalent/coordinative interactions between metal complexes and protein thiols.


Assuntos
Antineoplásicos/química , Cisplatino/química , Cobre/química , Espectrometria de Massas/métodos , Metalochaperonas/química , Rutênio/química , Sítios de Ligação , Cisteína/química , Humanos , Modelos Moleculares , Ligação Proteica , Compostos de Sulfidrila/química
18.
Metallomics ; 11(3): 546-555, 2019 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-30693924

RESUMO

Peroxiredoxins (Prxs) are a family of ubiquitous antioxidant proteins and the inhibition of Prxs would elevate the reactive oxygen species level so as to induce cancer cell death. The interactions of organometallic ruthenium arene anticancer complexes with proteins play important roles in their mechanisms of action. Herein, we demonstrate that Ru complexes [(η6-arene)Ru(en)Cl]+ (en = ethylenediamine, arene = p-cymene (1), biphenyl (2) and 9,10-dihydrophenanthrene (3)) can inhibit the enzymatic activity of human peroxiredoxin I (Prx-I) in an order of 1 > 3 > 2. Mass spectrometric (MS) analysis revealed that 1-3 coordinated to the catalytic site Cys173 of Prx-I, and partially induced the oxidation of the thiolate to sulfenate. Quantitative MS analysis demonstrated that the higher level of the ruthenation of Cys173 is correlated with the higher inhibitory potency of the Ru complexes against Prx-I, suggesting their binding to Cys173 accounts for their inhibition towards Prx-I.

19.
Org Lett ; 21(4): 1161-1164, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30694686

RESUMO

The first catalytic asymmetric Diels-Alder reaction of 3-vinylindole and nitroolefin is described. In the promotion of organocatalyst 3j, structurally diverse 1-nitro-hydrocarbazoles are produced in moderate-to-good yields and high-to-excellent enantioselectivities. All of these products are obtained as a single diastereoisomer. The 1-nitro-hydrocarbazole compounds can be converted into 1-amino-hydrocarbazole derivatives and structurally complex ring-fused indoles enantioseletively. Possible transition states were investigated by control experiments and DFT calculations.

20.
ACS Appl Mater Interfaces ; 11(2): 2243-2253, 2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30576120

RESUMO

Zinc oxide (ZnO) is one of the most extensively used electron-transporting layers (ETLs) in organic solar cells. However, owing to numerous surface defects and mismatched energy bands with the photoactive layer, light-soaking process is usually required to achieve a high device performance for the ZnO-based cells. Herein, we reported the synthesis of N,S-doped carbon quantum dots (N,S-CQDs) by a simple hydrothermal treatment using ascorbic acid and ammonium persulfate as reagents. As characterized by high-resolution transmission electron microscopy and X-ray diffraction, the synthesized CQDs were found to be 2-7 nm in dimensions, having a graphite-structured core and amorphous carbon on the shell. Fourier transform infrared and X-ray photoelectron spectroscopy analyses confirmed that these CQDs are highly nitrogen- and sulfur-doped, which leads to efficient (with a quantum yield of 33%) downconversion and excitation-dependent photoluminescence character. Application of these N,S-CQDs as surface modifier for ZnO layer in inverted organic solar cells was investigated. Results indicate that the cells with N,S-CQDs-decorated ZnO ETL showed higher power conversion efficiency without S-shaped kink in the current density-voltage curves. The performance improvement and the elimination of light-soaking effect for ZnO:N,S-CQDs cells are attributed to the ZnO surface defect passivation by N,S-CQDs, as confirmed by fluorescence spectroscopy and scanning Kelvin probe microscopy. The cells with N,S-CQDs-modified ZnO ETL showed a high power conversion efficiency of 9.31%, which is higher than the reference ZnO cells. The current work provides a feasible way to achieve shell element-doped CQDs for specific application in organic electronic devices.

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