ABSTRACT
Clinical annotations for the actionable pharmacogenetic variants affecting the efficacy of cardiovascular drugs have been collected, yet their impacts on elderly patients with coronary artery disease (CAD) undergoing polypharmacy remain uncertain. We consecutively enrolled 892 elderly patients (mean age 80.7 ± 5.2) with CAD and polypharmacy. All the included patients underwent genotyping for 13 variants in 10 pharmacogenes (CYP2C19, CYP2C9, CYP4F2, CYP2D6, VKORC1, SLCO1B1, APOE, ACE, ADRB1, and MTHFR), which have the clinical annotations for 12 drugs that are commonly prescribed for patients with CAD. We found that 80.3% of the elderly CAD patients had at least one drug-gene pair associated with a therapeutical drug change. After adjusting for covariates, the number of drug-gene pairs was independently associated with a decreased risk of both major cardiovascular events (MACEs) (adjusted hazard ratio [HR]: 0.803, 95% confidence interval [CI]: 0.683-0.945, p = 0.008) and all-cause mortality (adjusted HR: 0.848, 95% CI: 0.722-0.996, p = 0.045), but also with an increased risk of adverse drug reactions (ADRs) (adjusted HR: 1.170, 95% CI: 1.030-1.329, p = 0.016). The Kaplan-Meier survival curves showed that compared to patients without a drug-gene pair, a significantly lower risk of MACEs could be observed in patients with a drug-gene pair during a 4-year follow-up (HR: 0.556, 95% CI: 0.325-0.951, p = 0.013). In conclusion, the carrier status of the actionable drug-gene pair is predictive for the clinical outcomes in elderly patients with CAD and polypharmacy. Implementing early or preemptive pharmacogenetic panel-guided polypharmacy holds the potential to enhance clinical outcomes for these patients.
ABSTRACT
The recycling of spent lithium-ion batteries (LIBs) can not only reduce the potential harm caused by solid waste piles to the local environment but also provide raw materials for manufacturing new batteries. Flotation is an alternative approach to achieve the selective separation of cathode and anode active materials from spent LIBs. However, the presence of organic binder on the surface of hydrophilic lithium transition-metal oxides results in losses of cathode materials in the froth phase. In this study, plasma treatment was utilized to remove organic layers from cathode and anode active materials. Firstly, the correlations between plasma treatment parameters (e.g., input power, air flowrate, and treatment time) were explored and the contact angles of cathode and anode active materials were investigated by the response surface methodology. Secondly, differences in the flotation recoveries of cathode and anode active materials were enhanced with plasma modification prior to flotation, which is consistent with the contact angle measurement. Finally, the plasma-modification mechanisms of hydrophobicity of cathode and anode active materials were discussed according to Fourier Transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses. The proposed method could be a promising tool to enhance the flotation separation efficiency of cathode and anode active materials for the recycling of spent LIBs.
Subject(s)
Electric Power Supplies , Electrodes , Hydrophobic and Hydrophilic Interactions , Lithium , Recycling , Lithium/chemistry , Recycling/methods , Photoelectron Spectroscopy , Spectroscopy, Fourier Transform Infrared , Electronic WasteABSTRACT
Two-dimensional (2D) heterojunction nanomaterials offer exceptional physicochemical and catalytic properties, thanks to their special spatial electronic structure. However, synthesizing morphologically uniform 2D platinum (Pt)-based metallic nanomaterials with diverse crystalline phases remains a formidable challenge. In this study, we have achieved the successful synthesis of advanced 2D platinum-tellurium heterojunction nanosheet assemblies (Ptx-PtTe2 HJNSAs, x = 0, 1, 2), seamlessly integrating both trigonal PtTe2 (t-PtTe2) and cubic Pt (c-Pt) phases. By enabling efficient electron transport and leveraging the specific electron density present at the heterojunction, the Pt2-PtTe2 HJNSAs/C demonstrated exceptional formic acid oxidation reaction (FAOR) activity and stability. Specifically, the specific and mass activities reached 8.4 mA cm-2 and 6.1 A mgPt-1, which are 46.7 and 50.8 times higher than those of commercial Pt/C, respectively. Impressively, aberration-corrected high-angle annular dark field scanning transmission electron microscopy (AC-HAADF-STEM) revealed a closely packed arrangement of atomic layers and a coherent intergrowth heterogeneous structure. Density functional theory (DFT) calculations further indicated that rearrangement of electronic structure occurred on the surface of Pt2-PtTe2 HJNSAs resulting in a more favorable dehydrogenation pathway and excellent CO tolerance, beneficial for performance improvement. This work inspires the targeted exploration of Pt-based nanomaterials through 2D heterostructure design, leading to an important impact on fuel cell catalysis and beyond.
ABSTRACT
Colloids can potentially affect the efficacy of traditional acid mine drainage (AMD) treatment methods such as precipitation and filtration. However, it is unclear how colloids affect antimony (Sb) migration in AMD, especially when natural organic matter (NOM) is present. To conduct an in-depth investigation on the formation and migration behavior of NOM, iron (Fe), Sb and NOM-Fe-Sb colloids in AMD, experiments were performed under simulated AMD conditions. The results demonstrate significant variations in the formation of NOM-Fe-Sb colloids (1-3-450 nm) as the molar ratio of carbon to iron (C/Fe) increases within acidic conditions (pH = 3). Increasing the C/Fe molar ratio from 0.1 to 1.2 resulted in a decrease in colloid formation but an increase in particulate fraction. The distribution of colloidal Sb, Sb(III), and Fe(III) within the NOM-Fe-Sb colloids decreased from 68 % to 55 %, 72 % to 57 %, and 68 % to 55 %, respectively. Their distribution in the particulate fraction increased from 28 % to 42 %, 21 % to 34 %, and 8 % to 27 %. XRD, FTIR, and SEM-EDS analyses demonstrated that NOM facilitates the formation and crystallization of Fe3O4 and FeSbO4 crystalline phases. The formation of the colloids depended on pH. Our results indicate that NOM-Fe-Sb colloids can form when the pH ≤ 4, and the proportion of colloidal Sb fraction within the NOM-Fe-Sb colloids increased from 9 % to a maximum of 73 %. Column experiments show that the concentration of NOM-Fe-Sb colloids reaches its peak and remains stable at approximately 3.5 pore volumes (PVs), facilitating the migration of Sb in the porous media. At pH ≥ 5, stable NOM-Fe-Sb colloids do not form, and the proportion of colloidal Sb fraction decreases from 7 % to 0 %. This implies that as pH increases, the electrostatic repulsion between colloidal particles weakens, resulting in a reduction in the colloidal fraction and an increase in the particulate fraction. At higher pH values (pH ≥ 5), the repulsive forces between colloidal particles nearly disappear, promoting particle aggregation. The findings of this study provide important scientific evidence for understanding the migration behavior of NOM-Fe-Sb colloids in AMD. As the pH gradually shifts from acidic to near-neutral pH during the remediation process of AMD, these results could be applied to develop new strategies for this purpose.
ABSTRACT
BACKGROUND: ß1-blockers could improve clinical outcomes in patients with coronary artery disease by lowering the heart rate, blood pressure, and myocardial contractility. Moreover, recent studies have suggested that ß1-blockers may also have the potential to reduce bleeding risk. OBJECTIVES: This study aimed to evaluate the association between ß1-blockers and bleeding risk in the patients prescribed with potent dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI). METHODS: Patients with ACS or undergoing PCI treated by DAPT of ticagrelor and aspirin were consecutively recruited. Follow-up for all eligible patients was conducted for 1 year. Major bleeding outcomes were defined as events that were type ≥2 based on the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 1,113 eligible ticagrelor-treated patients were recruited. During the 1-year follow-up interval, 142 (12.6%) patients experienced BARC ≥2 bleedings including 23 patients (2.1%) suffering BARC ≥3 bleedings, with the most common site of bleeding located in the gastrointestinal tract. ß1-blockers treatment was associated with a lower risk of BARC ≥2 bleedings (11.2% vs. 23.3%, adjusted HR: 0.42, 95% CI: 0.28-0.62, P < 0.01). Moreover, metoprolol (11.1% vs. 23.3%, adjusted HR: 0.56, 95% CI: 0.37-0.83, P < 0.01) and bisoprolol (11.3% vs. 23.3%, adjusted HR: 0.56, 95% CI: 0.33-0.96, P = 0.04) had similar effects on the reduction of bleeding risk. CONCLUSION: ß1-blockers might be beneficial for the reduction of bleeding risk in potent dual antiplatelet therapy patients with ACS or undergoing PCI.
ABSTRACT
Ultrasound has emerged as a promising technique for improving the mineral flotation performance. However, limited research exists regarding the influence of different ultrasound types on the flotation process. Specifically, the impact of combined ultrasound and the comparison of horn- and bath-type ultrasounds on flotation have not been fully investigated. To address this knowledge gap, a comprehensive study to explore the effects of different ultrasonic pretreatments on the flotation of flake graphite was conducted. A Box-Behnken design is employed to analyze the effects of combined ultrasound on graphite flotation. By characterizing the properties of graphite samples before and after the ultrasonic treatment, the aim is to elucidate the mechanism underlying the impact of ultrasound on graphite flotation. The experimental results indicated that the ultrasonic cavitation intensity exerted a significant influence on the graphite flotation recovery. Both horn- and bath- type ultrasounds contributed to flotation, but horn-type ultrasound demonstrated a more pronounced effect, leading to a 7% increase in flotation recovery, whereas bath-type ultrasound resulted in only a 2% increase. Furthermore, the cavitation intensity of combined ultrasound was found to be higher than that of single-frequency ultrasound in the same duration. However, the performance of graphite flotation was better with short duration combined ultrasound pretreatment, while the opposite trend was observed for a long duration ultrasound pretreatment. These findings may inform the development of more efficient and effective ultrasonic pretreatments for flotation separation processes.
ABSTRACT
In this study, discarded mushroom-stick, which is widely available, was selected as a precursor to prepare MnO2-modified biochar (MBC) for Sb(III) removal. Several characterisation methods (SEM, BET, XPS, FT-IR, and XRD) were used to explore the mechanisms of antimony adsorption onto MBC. The results showed that MBC is a mesoporous material with a fluffy structure and a higher specific surface area (23.56 and 32.09 m2·g-1) than PBC600 (13.62 m2·g-1), exhibiting superior and stable adsorption capacities for Sb(III) (50.30 mg·g-1 for 1/30MBC600 and 64·12 mg·g-1 for 1/20MBC600) across a wide pH range (pH 4-8). X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) spectroscopy analyses indicated that the main oxides and functional groups involved in the adsorption were manganese oxides and hydroxyl groups. Forty-four per cent of the adsorbed Sb(III) was oxidised to Sb(V) by manganese oxides or hydroxyl groups both on the surface of biochar and in solution. According to adsorption kinetics and isotherms, the adsorption process of Sb(III) is chemisorption, which includes monolayer and multilayer heterogeneous chemisorption processes. To sum up, MBC is an excellent adsorbent for the capture of Sb(III) from contaminated water with strong potential for future application.
Subject(s)
Agaricales , Water Pollutants, Chemical , Adsorption , Charcoal/chemistry , Hydrogen-Ion Concentration , Kinetics , Manganese , Manganese Compounds/chemistry , Oxides/chemistry , Spectroscopy, Fourier Transform Infrared , Water , Water Pollutants, Chemical/chemistryABSTRACT
The interfacial properties of surfactant solutions are closely related to the micellization of surfactants. Temperature, salt type and concentration, pH, and other parameters affecting the micellization of surfactants have all been extensively investigated previously. However, the effect of dissolved gas on surfactant micellization and associated interfacial properties' transformations is not completely understood yet. In this study, sodium oleate (NaOl) was chosen as the research object, and the role of gas/gas nucleation in NaOl micellization was systematically investigated. The results indicated that the solution changed to be more turbid and the dissolved oxygen content increased after NaOl solutions were subjected to compression-decompression treatments. Meanwhile, the surface tension of the NaOl solution was altered, which was more pronounced when the concentration of NaOl was close to the critical micelle concentration. Given that the surface tension was a good indicator of the assembly and distribution state of the soluble monomers and insoluble micelles of NaOl, interactions between nucleated bubbles originating from the gas nucleation and NaOl molecules were unveiled through the analysis of the size distribution and zeta potential of sub-micro- and nanoscale particles in bulk solutions. Finally, possible micellization models of NaOl molecules, fully considering the role of gas/gas nucleation, were proposed under varying NaOl concentration conditions.
Subject(s)
Micelles , Oleic Acid , Surface Tension , Surface-Active AgentsABSTRACT
Purpose: Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist and lead to a much higher risk of mortality in the elderly population. The aim of this study was to investigate whether the CHA2DS2-VASc score could predict the risk of death in elderly patients with CAD and AF. Methods: Hospitalized patients aged ≥65 years with a diagnosis of CAD and AF were recruited consecutively. Patients were divided into 5 groups according to the CHA2DS2-VASc score (≤2, =3, =4, =5, and ≥6). At least a 1-year follow-up was carried out for the assessment of all-cause death. Results: A total of 1,579 eligible patients were recruited, with 582 all-cause deaths (6.86 per 100 patient-years) occurring during a follow-up of at least 1 year. With the increase in the CHA2DS2-VASc score, the 1-year and 5-year survival rate decreased (96.4% vs. 95.7% vs. 94.0% vs. 86.5% vs. 85.7%, respectively, P < 0.001; 78.4% vs. 68.9% vs. 64.6% vs. 55.5% vs. 50.0%, respectively, P < 0.001). Compared with the patients with CHA2DS2-VASc score <5, for patients with CHA2DS2-VASc score ≥5, the adjusted hazard ratio for death was 1.78 (95% CI: 1.45-2.18, P < 0.001). The predictive values of the CHA2DS2-VASc score ≥5 for in-hospital (C-index = 0.66, 95% CI: 0.62-0.69, P < 0.001), 1-year (C-index = 0.65, 95% CI: 0.63-0.67, P < 0.001) and 5-year (C-index = 0.60, 95% CI: 0.59-0.61, P < 0.001) death were in comparable. Conclusion: In elderly patients with concomitant CAD and AF, the CHA2DS2-VASc score can be used to predict death with moderate accuracy.
ABSTRACT
The CHADS2 and CHA2DS2-VASc scores were initially developed to assess the risk of stroke or systemic embolism in patients with atrial fibrillation (AF). Recently, these two scoring systems have been demonstrated to predict long- and short-term cardiovascular (CV) outcomes in many patient cohorts. However, to the best of our knowledge, their prognostic value has not been fully elucidated in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This study aimed to investigate the association of CHADS2 and CHA2DS2-VASc scores with CV outcomes in such patients.We included a total of 915 ACS patients undergoing PCI in this study. CHADS2 and CHA2DS2-VASc scores were calculated from data collected before discharge. The primary endpoint was defined as a composite of major adverse CV events (MACE) including overall death, nonfatal stroke, nonfatal myocardial infarction (MI) and unplanned repeat revascularization. We assessed MACE's relationship to CHADS2 and CHA2DS2-VASc scores using Cox proportional-hazard regression analyses.Mean follow-up duration was 918 days. MACE occurred in 167 (18.3%) patients. A higher CHADS2 score was associated with reduced event-free survival (EFS) from MACE (logrank test, Pâ=â.007) with differences potentiated if stratified by CHA2DS2-VASc score (logrank test, Pâ<â.001). Univariate analysis showed that both CHADS2 and CHA2DS2-VASc scores were good predictors of MACE. In the multivariate Cox proportional-hazard regression analysis, CHA2DS2-VASc score (hazard ratio [HR], 1.15; 95% confidence interval [CI] 1.04-1.27; Pâ=â.007) remained a useful predictor of MACE; however, CHADS2 score was no longer associated with increased risk of MACE. C-statistics for CHA2DS2-VASc score, GRACE (Global Registry of Acute Coronary Events) hospital discharge risk score (GRACE Score) and SYNTAX (Synergy between PCI with TAXUS and Cardiac Surgery) Score II (SS II) in predicting MACE were 0.614, 0.598, and 0.609, respectively.CHA2DS2-VASc score was an independent and significant predictor of MACE in ACS patients undergoing PCI, and its discriminatory performance was not inferior to those of GRACE Score and SS II.
Subject(s)
Acute Coronary Syndrome/therapy , Cardiovascular Diseases/mortality , Patient Discharge/statistics & numerical data , Percutaneous Coronary Intervention/adverse effects , Acute Coronary Syndrome/mortality , Aftercare , Aged , Atrial Fibrillation/complications , Cardiovascular Diseases/epidemiology , Embolism/epidemiology , Embolism/etiology , Female , Humans , Male , Middle Aged , Myocardial Infarction/epidemiology , Patient Discharge/trends , Percutaneous Coronary Intervention/methods , Predictive Value of Tests , Prognosis , Research Design , Retrospective Studies , Risk Assessment , Stroke/epidemiology , Stroke/etiologyABSTRACT
BACKGROUND: The triglyceride glucose (TyG) index, a simple surrogate estimate of insulin resistance, has been demonstrated to predict cardiovascular (CV) disease morbidity and mortality in the general population and many patient cohorts. However, to our knowledge, the prognostic usefulness of the TyG index after percutaneous coronary intervention (PCI) in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) has not been determined. This study aimed to evaluate the association of the TyG index with adverse CV outcomes in patients with T2DM and ACS who underwent PCI. METHODS: The TyG index was calculated using the formula ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The primary endpoint was the composite of all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, or unplanned repeat revascularization. The association between the TyG index and adverse CV outcomes was assessed by Cox proportional hazards regression analysis. RESULTS: In total, 776 patients with T2DM and ACS who underwent PCI (mean age, 61 ± 10 years; men, 72.2%) were included in the final analysis. Over a median follow-up of 30 months, 188 patients (24.2%) had at least 1 primary endpoint event. The follow-up incidence of the primary endpoint rose with increasing TyG index tertiles. The multivariate Cox proportional hazards regression analysis adjusted for multiple confounders revealed a hazard ratio for the primary endpoint of 2.17 (95% CI 1.45-3.24; P for trend = 0.001) when the highest and lowest TyG index tertiles were compared. CONCLUSIONS: The TyG index was significantly and positively associated with adverse CV outcomes, suggesting that the TyG index may be a valuable predictor of adverse CV outcomes after PCI in patients with T2DM and ACS.
Subject(s)
Acute Coronary Syndrome/therapy , Blood Glucose/analysis , Diabetes Mellitus, Type 2/blood , Percutaneous Coronary Intervention , Triglycerides/blood , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/mortality , Aged , Biomarkers/blood , Cause of Death , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Female , Humans , Insulin Resistance , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Salbutamol (SAL), one of the prohibited veterinary drugs, has been proven to be harmful to animals, but very few studies reported the underlying mechanism of actions and the effects after SAL intake. In this study, Ba-Ma minipigs were used as the animal model to demonstrate the impacts of SAL residues on blood lipid and the lung bronchial structures and the regulation of gene expression and gut microorganism population. The results showed that (1) SAL decreased the indexes of serum lipid and organ, (2) SAL widely retained in various tissues and organs, (3) the lung bronchial expanded under the influence of SAL, (4) the gene expression of growth-related ghrelin has increased, and (5) the residues of SAL affected the composition of gut microorganism population, which could be associated with the mechanism of action of SAL on pig. The findings suggest that SAL could be harmful to minipigs by altering the blood lipid, bronchial morphology, gastric mucosal gene expression, and the gut microorganism population.
ABSTRACT
Currently, little is known regarding the predictive utility of aortic arch calcification (AAC) for clinical outcomes in patients with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI). The present study was designed to investigate the predictive performance of AAC as detected by chest x-ray for clinical outcomes among ACS patients undergoing PCI.A total of 912 patients who were diagnosed as ACS and treated with PCI were included in this prospective, cohort study. All study participants received chest x-rays on admission, and a semiquantitative 4-point scale was used to assess the extent of AAC. The primary end point was defined as a composite of major adverse cardiovascular events (MACE) comprising death, nonfatal stroke, nonfatal myocardial infarction, and unplanned repeat revascularization. The key secondary end point was the composite of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction. The prognostic values of AAC were assessed in multivariate Cox-proportional hazards regression analyses adjusted for major confounders.The mean follow-up duration was 917 days and, during the follow-up period, MACE occurred in 168 (18.4%) patients. Kaplan-Meier analyses revealed significantly higher incidences of the primary and key secondary end points in patients with higher AAC grades (log-rank test; all Pâ<â.001). Multivariate Cox-proportional hazards regression analyses showed that, in comparison to AAC grade 0, the hazard ratios of AAC grades 1, 2, and 3 for predicting MACE were 1.63 (95% confidence interval [CI] 0.99-2.67), 2.15 (95% CI 1.27-3.62), and 2.88 (95% CI 1.41-5.86), respectively. The C-index of the variables, including peripheral arterial disease and serum levels of triglyceride for predicting MACE, was 0.644 (95% CI 0.600-0.687) versus 0.677 (95% CI 0.635-0.719) when AAC grades were also included; the continuous net reclassification improvement was 16.5% (8.7%-23.4%; Pâ<â.001).The extent of AAC as detected by chest x-ray is an independent predictor of MACE among ACS patients undergoing PCI. Further research is warranted to evaluate whether specific treatment strategies that are established based on AAC extent are needed for optimal risk reduction in relevant patient populations.
Subject(s)
Acute Coronary Syndrome , Aorta, Thoracic , Percutaneous Coronary Intervention , Vascular Calcification , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/mortality , Acute Coronary Syndrome/surgery , Aged , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/pathology , China/epidemiology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Percutaneous Coronary Intervention/statistics & numerical data , Predictive Value of Tests , Prognosis , Prospective Studies , Radiography, Thoracic/methods , Radiography, Thoracic/statistics & numerical data , Risk Adjustment/methods , Risk Factors , Vascular Calcification/diagnosis , Vascular Calcification/epidemiologyABSTRACT
[This corrects the article DOI: 10.1155/2017/8246420.].
ABSTRACT
The effects of Apostichopus japonicus enzymatic hydrolysate on the regulation of dyslipidemia, pathoglycemia, and transcription changes in kidney tissues of db/db mice were evaluated. In this study, the symptoms of diabetes in db/db mice were alleviated after 10 weeks of treatments with low (db/db + LD group) and high dose (db/db + HD group) of Apostichopus japonicus enzymatic hydrolysate, and the high dose treatment showed a better antidiabetic effect. Compared with the db/db group, the fasting blood glucose levels (36.84 ± 7.82 vs 25.18 ± 6.84 mmol/L, P < 0.01), the urine glucose levels (45.44 ± 3.93 vs 22.66 ± 5.58 mmol/L, P < 0.01), and the serum insulin sensitivity index (-4.65 ± 0.43 vs -4.74 ± 0.75, P > 0.05) in the db/db + HD group were decreased, whereas the fasting plasma insulin (3.12 ± 1.08 vs 5.54 ± 1.82 µg/L, P < 0.01) and the serum insulin resistance index (5.01 ± 2.02 vs 5.96 ± 2.49, P < 0.05) were increased. Subsequently, the kidney transcription profiles were measured in the db/db group and db/db + HD group via microarray, and the results show that Apostichopus japonicus hydrolysate induced differential expression of 77 genes. Among these genes, the down-regulation of genes ntrK1 and ptpN5 played vital roles, as this effect induced the further down-regulation of neurotrophin tyrosine kinase, protein tyrosine phosphatase, and other transcription factors, which are involved in the classical mitogen-activated protein kinases (MAPK) and p38MAPK signaling pathways. The inhibited MAPK and p38MAPK signaling pathways are involved in glycometabolism and the control of lipid metabolism, and they regulate the occurrence and development of diabetic nephropathy.
Subject(s)
Diabetes Mellitus, Experimental/diet therapy , Gene Expression Regulation , Kidney/physiology , Stichopus , Animals , Diabetes Mellitus, Experimental/genetics , Dietary Supplements , Hydrolysis , Insulin/blood , Kidney/physiopathology , Mice, Transgenic , Peptides/analysis , Peptides/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Stichopus/chemistryABSTRACT
Astilbin, a flavonoid compound, was isolated from the rhizome of Smilax glabra Roxb. (with red cross-section) grown in Guizhou Province, China. We accessed its effect and potential mechanism on attenuation of the inflammatory response in CFA-induced AA rats. Our results showed that daily oral administration of astilbin at 5.3 mg/kg reduced joint damage in the hind paw of AA rats. Accordingly, astilbin exhibited remarkable inhibitory effects on TNF-α, IL-1ß, and IL-6 mRNA expression. Significant decrease of serum cytokine levels of TNF-α, IL-1ß, and IL-6 was also observed in astilbin-treated AA rats compared to the vehicle-treated AA rats. The reduced expression of these cytokines was associated with protein activity suppression of three key molecular targets in the pathogenesis of RA, including IKKß, NF-κB p65 subunit, and TLR adaptor MyD88. Furthermore, the therapeutic effects of astilbin on the inhibition of cytokines production as well as the reduction of inflammatory response in AA rats are close to a commonly used antirheumatic drug, leflunomide. Collectively, our data suggest that the action mechanism of astilbin, as an anti-inflammatory agent for RA treatment, is associated with modulating the production of proinflammatory cytokines and inhibiting the expression of key elements in NF-κB signaling pathway mediated by TLR.
ABSTRACT
BACKGROUND: The quality of the materials used in Chinese medicine (CM) is generally assessed based on an analysis of their chemical components (e.g., chromatographic fingerprint analysis). However, there is a growing interest in the use of color metrics as an indicator of quality in CM. The aim of this study was to investigate the accuracy and feasibility of using color metrics and chemical fingerprint analysis to determine the quality of Smilacis Glabrae Rhizoma (Tufuling) (SGR). The SGR samples were divided into two categories based on their cross-sectional coloration, including red SGR (R-SGR) and white SGR (W-SGR). METHODS: Forty-three samples of SGR were collected and their colors were quantized based on an RGB color model using the Photoshop software. An ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QTOF MS) system was used for chromatographic fingerprint analysis to evaluate the quality of the different SGR samples. Hierarchical cluster analysis and dimensional reduction were used to evaluate the data generated from the different samples. Pearson correlation coefficient was used to evaluate the relationship between the color metrics and the chemical compositions of R-SGR and W-SGR. RESULTS: The SGR samples were divided into two different groups based on their cross-sectional color, including color A (CLA) and B (CLB), as well as being into two separate classes based on their chemical composition, including chemical A (CHA) and B (CHB). Standard fingerprint chromatograms were for CHA and CHB. Statistical analysis revealed a significant correlation (Pearson's r = -0.769, P < 0.001) between the color metrics and the results of the chemical fingerprint analysis. CONCLUSIONS: The SGR samples were divided into two major clusters, and the variations in the colors of these samples reflected differences in the quality of the SGR material. Furthermore, we observed a statistically significant correlation between the color metrics and the quality of the SGR material.
ABSTRACT
Manganese (Mn) as an environmental risk factor of Parkinson's disease (PD) is considered to cause manganism. Mitophagy is thought to play a key role in elimination the injured mitochondria. The goal of this paper was to explore whether the PINK1/Parkin-mediated mitophagy is activated and its role in Mn-induced mitochondrial dysfunction and cell death in SH-SY5Y cells. Here, we investigated effects of MnCl2 on ROS generation, mitochondrial membrane potential (MMP/ΔΨm) and apoptosis by FACS and examined PINK1/Parkin-mediated mitophagy by western-blotting and the co-localization of mitochondria and acidic lysosomes. Further, we explore the role of mitophagy in Mn-induced apoptosis by inhibition the mitophagy by knockdown Parkin level. Results show that MnCl2 dose-dependently caused ΔΨm decrease, ROS generation and apoptosis of dopaminergic SH-SY5Y cells. Moreover, Mn could induce mitophagy and PINK1/Parkin-mediated pathway was activated in SH-SY5Y cells. Transient transfection of Parkin siRNA knockdown the expressing level of parkin inhibited Mn-induced mitophagy and aggravated apoptosis of SH-SY5Y cells. In conclusion, our study demonstrated that Mn may induce PINK1/Parkin-mediated mitophagy, which may exert significant neuro-protective effect against Mn-induced dopaminergic neuronal cells apoptosis.
Subject(s)
Manganese/toxicity , Mitophagy , Protein Kinases/genetics , Ubiquitin-Protein Ligases/genetics , Apoptosis/drug effects , Apoptosis/genetics , Apoptosis/physiology , Cell Death/drug effects , Cell Line, Tumor , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitophagy/drug effects , Mitophagy/genetics , Mitophagy/physiology , Reactive Oxygen Species/metabolismABSTRACT
To screen potential biomarkers of benzo(a)pyrene (BaP)-induced lung cancer, the proteomic profiles of BaP-transformed 16HBE cell line T-16HBE-C1 cells serum-free culture supernatant and xenografted nude mice sera were compared with those of 16HBE group by utilizing label-free quantitative proteomic strategy. By employing nano-LC-MS/MS technology followed by MaxQuant and Perseus processing, 489 differentially expressed proteins were identified between T-16HBE-C1 and 16HBE cells serum-free culture supernatant, and 49 significantly up-regulated proteins were identified in T-16HBE-C1 xenografted nude mice sera. Three proteins neuropilin-2 (NRP2), clusterin (CLU) and A-kinase anchor protein 12 (AKAP12) were up-regulated in the serum-free culture supernatant of T-16HBE-C1 cells. These 3 human proteins were present in the sera of nude mice xenografted with T-16HBE-C1 cells, but were undetectable in mice xenografted with 16HBE cells. The proteomic results of NRP2 and AKAP12 were confirmed by Western blotting and enzyme-linked immunosorbent assays, respectively. Moreover, the serum NRP2 levels were significantly elevated at the 4th day after tumor cell implantation and showed good positive correlation with tumor growth characterized by tumor volume. In conclusion, serum NRP2, CLU and AKAP12 could be potential biomarkers of BaP-induced lung cancer. The proteomic results will gain deeper insights into the mechanisms of BaP-induced carcinogenesis.
Subject(s)
Benzo(a)pyrene , Lung Neoplasms/chemically induced , Lung Neoplasms/diagnosis , Lung/pathology , A Kinase Anchor Proteins/analysis , A Kinase Anchor Proteins/blood , Animals , Biomarkers, Tumor/analysis , Biomarkers, Tumor/blood , Cell Line, Transformed , Clusterin/analysis , Clusterin/blood , Humans , Lung Neoplasms/blood , Mice, Inbred BALB C , Mice, Nude , Neuropilin-2/analysis , Neuropilin-2/blood , ProteomicsABSTRACT
This study aimed to simultaneously determine the contents of astilbin and engeletin in dong medicine "sunl gaems" of Guizhou origin by quantitative analysis of multi-components by single marker (QAMS), with astilbin as the internal standard substance. On UPLC and HPLC chromatograms, different models of instruments were used to investigate relative correction factors (RCF), in order to discuss the interoperability of RCFs established in different chromatographic systems. The engeletin content was calculated based on the established RCFs and compared by the one point external standard method and the external standard working curve method, in order to verify the accuracy of QAMS. According to the result, in different chromatograms, the ratios between RCF and retention time of engeletin and astilbin had a good reproducibility, with RSD between 2.0% and 1.8%, both were less than 3%. The relative differences among results of QAMS, the external standard working curve method of dong medicine "sunl gaems" ranged between 1.6% and 3.9%, with RSD between 2.02%-0.80% in line with relevant requirements and Pearson correlation coefficient at 0.9998 (P <0.01). The findings showed that QAMS was an accurate, reliable and highly reproducible method to determine the contents of astilbin and engeletin in dong medicine "sunl gaems" of Guizhou origin and so could be used to control the inherent quality of the herb.