ABSTRACT
Iron deficiency (ID) is common in patients with acute myocardial infarction (AMI). It is unknown whether patients with AMI combined with ID will benefit from iron supplementation therapy. This study aimed to assess the relationship between iron therapy and mortality in AMI patients. Retrospective analysis was performed in subjects screened from the Medical Information Mart in Intensive Care-IV database. The data were obtained from ICU patients admitted to Beth Israel Deaconess Medical Center between 2008 and 2019. The patients were divided into two groups according to iron treatment exposure. Propensity score matching (PSM) was performed in the original cohort at a 1:1 ratio. Univariate and multivariate analyses were performed to adjust for confounding factors. The primary outcome was 28-day mortality. A total of 426 patients were included in this study. After 1:1 PSM, 208 patients were analyzed. Iron treatment was associated with a lower risk of 28-day mortality (9 deaths (8.65%) in the iron treatment group vs. 21 deaths (20.19%) in the non-iron treatment group; HR = 0.39; 95% CI = 0.17-0.89; p = 0.025) and in-hospital mortality (4 deaths (3.85%) in the iron treatment group vs. 12 deaths (11.54%) in the non-iron treatment group; OR, 0.15; 95% CI, 0.03-0.74; p = 0.029). Iron treatment was associated with reduced 28-day mortality in patients with AMI combined with ID. Iron treatment had no significant effect on the length of hospitalization or the length of ICU stay. Prospective studies are needed to verify this conclusion.
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BACKGROUND: Warfarin is a common oral anticoagulant, and its effects vary widely among individuals. Numerous dose-prediction algorithms have been reported based on cross-sectional data generated via multiple linear regression or machine learning. This study aimed to construct an information fusion perturbation theory and machine learning prediction model of warfarin blood levels based on clinical longitudinal data from cardiac surgery patients. METHODS AND MATERIAL: The data of 246 patients were obtained from electronic medical records. Continuous variables were processed by calculating the distance of the raw data with the moving average (MA ∆vki(sj)), and categorical variables in different attribute groups were processed using Euclidean distance (ED Ç∆vk(sj)Ç). Regression and classification analyses were performed on the raw data, MA ∆vki(sj), and ED Ç∆vk(sj)Ç. Different machine-learning algorithms were chosen for the STATISTICA and WEKA software. RESULTS: The random forest (RF) algorithm was the best for predicting continuous outputs using the raw data. The correlation coefficients of the RF algorithm were 0.978 and 0.595 for the training and validation sets, respectively, and the mean absolute errors were 0.135 and 0.362 for the training and validation sets, respectively. The proportion of ideal predictions of the RF algorithm was 59.0%. General discriminant analysis (GDA) was the best algorithm for predicting the categorical outputs using the MA ∆vki(sj) data. The GDA algorithm's total true positive rate (TPR) was 95.4% and 95.6% for the training and validation sets, respectively, with MA ∆vki(sj) data. CONCLUSIONS: An information fusion perturbation theory and machine learning model for predicting warfarin blood levels was established. A model based on the RF algorithm could be used to predict the target international normalized ratio (INR), and a model based on the GDA algorithm could be used to predict the probability of being within the target INR range under different clinical scenarios.
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The growth of InGaAs quantum wells (QWs) epitaxially on InP substrates is of great interest due to their wide application in optoelectronic devices. However, conventional molecular beam epitaxy requires substrate temperatures between 400 and 500 °C, which can lead to disorder scattering, dopant diffusion, and interface roughening, adversely affecting device performance. Lower growth temperatures enable the fabrication of high-speed optoelectronic devices by increasing arsenic antisite defects and reducing carrier lifetimes. This work investigates the low-temperature epitaxial growth of InAs/GaAs short-period superlattices as an ordered replacement for InGaAs quantum wells, using migration-enhanced epitaxy (MEE) with low growth temperatures down to 200-250 °C. The InAs/GaAs multi-quantum wells with InAlAs barriers using MEE grown at 230 °C show good single crystals with sharp interfaces, without mismatch dislocations found. The Raman results reveal that the MEE mode enables the growth of (InAs)4(GaAs)3/InAlAs QWs with excellent periodicity, effectively reducing alloy scattering. The room temperature (RT) photoluminescence (PL) measurement shows the strong PL responses with narrow peaks, revealing the good quality of the MEE-grown QWs. The RT electron mobility of the sample grown in low-temperature MEE mode is as high as 2100 cm2/V∗s. In addition, the photoexcited band-edge carrier lifetime was about 3.3 ps at RT. The high-quality superlattices obtained confirm MEE's effectiveness for enabling advanced III-V device structures at reduced temperatures. This promises improved performance for applications in areas such as high-speed transistors, terahertz imaging, and optical communications.
ABSTRACT
The low-temperature-grown InGaAs (LT-InGaAs) photoconductive antenna has received great attention for the development of highly compact and integrated cheap THz sources. However, the performance of the LT-InGaAs photoconductive antenna is limited by its low resistivity and mobility. The generated radiated power is much weaker compared to the low-temperature-grown GaAs-based photoconductive antennas. This is mainly caused by the low abundance of excess As in LT-InGaAs with the conventional growth mode, which inevitably gives rise to the formation of As precipitate and alloy scattering after annealing. In this paper, the migration-enhanced molecular beam epitaxy technique is developed to grow high-quality (InAs)m/(GaAs)n short-period superlattices with a sharp interface instead of InGaAs on InP substrate. The improved electron mobility and resistivity at room temperature (RT) are found to be 843 cm2/(V·s) and 1648 ohm/sq, respectively, for the (InAs)m/(GaAs)n short-period superlattice. The band-edge photo-excited carrier lifetime is determined to be ~1.2 ps at RT. The calculated photocurrent intensity, obtained by solving the Maxwell wave equation and the coupled drift-diffusion/Poisson equation using the finite element method, is in good agreement with previously reported results. This work may provide a new approach for the material growth towards high-performance THz photoconductive antennas with high radiation power.
ABSTRACT
Alzheimer's disease (AD) is the leading cause of dementia and is rapidly becoming one of the most costly, fatal diseases, which is typically discovered in the late stage of molecular pathology, at which point medication intervention is irreversible. As a result, there is an urgent need for a low-cost, least-invasive way of screening cognitive impairment, with the goal of identifying persons at risk of AD. Mild cognitive impairment (MCI) has been described as a transitional state between normal cognitive aging and AD. Early detection and timely tracking of MCI can to some extent prevent the progression towards AD. We found a population in Northwestern China has a comparatively high prevalence of MCI. Continued education, consistent exercise, and a secure financial situation can all help older people maintain cognitive function. Due to the critical role of circulating microRNAs in intercellular signaling and the perturbations thereof, their investigation has assumed paramount significance in elucidating various pathological conditions. Numerous investigations have substantiated the significance of circulating miRNAs specifically in MCI. Here, we evaluated miR-483-5p (Area Under the Curve (AUC) is 0.901, sensitivity 79.2 % and specificity 100 %) and miR-502-5p (AUC is 0.872, sensitivity 79.2 % and specificity 83.3 %), which were derived from plasma exosomes and maintained at high levels in elderly people with MCI, could be employed as promising noninvasive biomarkers.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , MicroRNAs , Humans , Aged , MicroRNAs/genetics , Biomarkers , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/genetics , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Aging/geneticsABSTRACT
BACKGROUND AND OBJECTIVES: Due to the high individual variability of anticoagulant warfarin, this study aimed to investigate the effects of vitamin K concentration and gut microbiota on individual variability of warfarin in 246 cardiac surgery patients. METHODS: The pharmacokinetics and pharmacodynamics (PKPD) model predicted international normalized ratio (INR) and warfarin concentration. Serum and fecal samples were collected to detect warfarin and vitamin K [VK1 and menaquinone-4 (MK4)] concentrations and gut microbiota diversity, respectively. In addition, the patient's medical records were reviewed for demographic characteristics, drug history, and CYP2C9, VKORC1, and CYP4F2 genotypes. RESULTS: The PKPD model predicted ideal values of 62.7% for S-warfarin, 70.4% for R-warfarin, and 76.4% for INR. The normal VK1 level was 1.34±1.12 nmol/ml (95% CI: 0.33-4.08 nmol/ml), and the normal MK4 level was 0.22±0.18 nmol/ml (95% CI: 0.07-0.63 nmol/ml). The MK4 to total vitamin K ratio was 16.5±9.8% (95% CI: 4.3-41.5%). The S-warfarin concentration of producing 50% of maximum anticoagulation and the half-life of prothrombin complex activity tended to increase with vitamin K. Further, Prevotella and Eubacterium of gut microbiota identified as the main bacteria associated with individual variability of warfarin. The results suggest that an increase in vitamin K concentration can decrease anticoagulation, and gut microbiota may influence warfarin anticoagulation through vitamin K2 synthesis. CONCLUSION: This study highlights the importance of considering vitamin K concentration and gut microbiota when prescribing warfarin. The findings may have significant implications for the personalized use of warfarin. Further research is needed to understand better the role of vitamin K and gut microbiota in warfarin anticoagulation.
Subject(s)
Cardiac Surgical Procedures , Gastrointestinal Microbiome , Humans , Warfarin/pharmacology , Vitamin K , Cytochrome P450 Family 4/genetics , Vitamin K Epoxide Reductases/genetics , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , GenotypeABSTRACT
Rabbit anti-thymocyte globulin (rATG) has been widely used to prevent graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The therapeutic window of rATG is narrow, and it may increase the risk of relapse, viral reactivation, delayed immune reconstitution and GvHD when overexposed or underexposed. Therefore, a reliable method for detecting the rATG concentration in human serum by flow cytometry was established and fully validated for therapeutic drug monitoring. In this method, Jurkat T cells were used to capture active rATG in human serum, and PE-labeled donkey anti-rabbit IgG was used as a secondary antibody. The method showed good specificity, selectivity and excellent linearity at concentration of 0.00300-20.0â¯AU/mL. The intra- and interday precision values were all within 20% at four concentration levels for the analyte. The stock solutions of rATG showed no significant degradation after storage at ambient temperature for 8â¯h and at -â¯80⯰C for 481 days. No significant degradation of rATG in serum was observed at ambient temperature for 6â¯h, during six freezethaw cycles and at -â¯80⯰C for at least 373 days. This method was fully validated and successfully applied to monitor active rATG concentration in serum of patients with haploid-identical hematopoietic stem cell transplantation.
Subject(s)
Antilymphocyte Serum , Graft vs Host Disease , Humans , Antilymphocyte Serum/therapeutic use , Drug Monitoring , Flow Cytometry , Graft vs Host Disease/drug therapy , Graft vs Host Disease/prevention & control , Jurkat CellsABSTRACT
An energy-restricted weight-loss approach has limitations when it used in the elderly, especially because of muscle loss. We aimed to assess the effects of whey protein (WP) or WP hydrolysate (WPH) combined with an energy-restricted diet (ERD) on weight reduction and muscle preservation in older women with overweight and obesity. A total of 60 women were randomized to the control (ERD), WP (ERD + 20 g/d WP) or WPH (ERD + 20 g/d WPH) group, using a 1:1:1 allocation ratio. After an 8-week intervention, body composition, gut microbiota, and serum metabolomics changes were compared among the three groups. The reductions in body weight (−1.11 ± 1.11 vs. −2.34 ± 1.35, p < 0.05), BMI (−0.46 ± 0.45 vs. −0.97 ± 0.54, p < 0.05), and body fat (−0.70 ± 0.92 vs. −2.45 ± 1.65, p < 0.01) were higher in the WPH group than in the control group. Body fat (%) was significantly decreased in the two protein groups. Fat-free mass did not significantly change among the three groups. Serum metabolomics showed that the tricarboxylic acid cycle pathway was upregulated in the WPH group. No significant changes in microbiota were observed among the groups. In conclusion, WP or WPH supplementation combined with an energy-restricted diet benefits older women during weight loss. WPH was more effective, possibly due to increased energy metabolism.
Subject(s)
Dietary Supplements , Weight Loss , Humans , Female , Aged , Whey Proteins , Body Composition , DietABSTRACT
Aim: The 20(S)-ginsenoside Rh2 (Rh2) is being developed as a new antitumor drug. However, to date, little is known about the kinetics of its deglycosylation metabolite (protopanoxadiol) (PPD) following Rh2 administration. The aim of this work was to 1) simultaneously characterise the pharmacokinetics of Rh2 and PPD following intravenous and oral Rh2 administration, 2) develop and validate a mechanism-based pharmacokinetic model to describe the deglycosylation kinetics and 3) predict the percentage of Rh2 entering the systemic circulation in PPD form. Methods: Plasma samples were collected from rats after the I.V. or P.O. administration of Rh2. The plasma Rh2 and PPD concentrations were determined using HPLC-MS. The transformation from Rh2 to PPD, its absorption, and elimination were integrated into the mechanism based pharmacokinetic model to describe the pharmacokinetics of Rh2 and PPD simultaneously at 10 mg/kg. The concentration data collected following a 20 mg/kg dose of Rh2 was used for model validation. Results: Following Rh2 administration, PPD exhibited high exposure and atypical double peaks. The model described the abnormal kinetics well and was further validated using external data. A total of 11% of the administered Rh2 was predicted to be transformed into PPD and enter the systemic circulation after I.V. administration, and a total of 20% of Rh2 was predicted to be absorbed into the systemic circulation in PPD form after P.O. administration of Rh2. Conclusion: The developed model provides a useful tool to quantitatively study the deglycosylation kinetics of Rh2 and thus, provides a valuable resource for future pharmacokinetic studies of glycosides with similar deglycosylation metabolism.
ABSTRACT
Warfarin is a common first line anticoagulant with a narrow therapeutic window. Because of the large blood volume needed, previous warfarin determination methods were not applicable to small animals, such as mice. To reduce the number of small animals used needed, we developed and validated a sensitive rapid assay for the simultaneous detection of warfarin enantiomers in mouse dried blood spot (DBS) samples. Analytes were extracted by tert-butyl methyl ether and then separated by a chiral Cellulose-1 column with a mobile phase of 75% acetonitrile (containing 0.1% formic acid). The total chromatographic run time was 3 min. Negative mode electrospray ionization was used for MS/MS detection, where the monitored ion transitions were m/z 307.1 â 161.0 and 341.1 â 284.0 for warfarin and coumachlor (internal standard) respectively. The calibration curves were linear with a correlation coefficient of ≥0.994 for both enantiomers over a concentration range of 10-1000 ng/mL. The satisfactory accuracy and adequate reproducibility of both warfarin enantiomers were validated in terms of intra- and interday precision with mouse DBS cards. The samples were stable at room temperature for at least 14 days. The validated method was applied to a pharmacokinetic study in mice.
Subject(s)
Tandem Mass Spectrometry , Warfarin , Animals , Calibration , Chromatography, High Pressure Liquid/methods , Dried Blood Spot Testing/methods , Mice , Reproducibility of Results , Tandem Mass Spectrometry/methodsABSTRACT
AIM: This trial (NCT04013048) investigated the metabolite profiles, mass balance and pharmacokinetics of fuzuloparib, a novel poly (ADP-ribose) polymerase inhibitor, in subjects with advanced solid cancers. METHODS: A single dose of 150 mg [14 C]fuzuloparib was administered to five subjects with advanced solid cancers. Blood, urine and faecal samples were collected, analysed for radioactivity and unchanged fuzuloparib, and profiled for metabolites. The safety of the medicine was assessed during the study. RESULTS: The maximum concentrations (Cmax ) of the total radioactivity (TRA) and unchanged fuzuloparib in plasma were 5.39 µg eq./mL and 4.19 µg/mL, respectively, at approximately 4 hours post dose. The exposure (AUC0-t ) of fuzuloparib accounted for 70.7% of the TRA in plasma, and no single metabolite was observed accounting for more than 10% of the plasma TRA. The recovery of TRA in excreta was 103.3 ± 3.8% in 288 hours, including 59.1 ± 9.9% in urine and 44.2 ± 10.8% in faeces. Sixteen metabolites of fuzuloparib were identified, including mono-oxidation (M1), hydrogenation (M2), di-oxidation (M3), trioxidation (M4), glucuronidation (M5, M7, M8) and de-ethylation (M6) products, and there was no specific binding between these metabolites and blood cells. Aliphatic hydroxylated fuzuloparib (M1-1) was the primary metabolite in the excreta, accounting for more than 40% of the dose for subjects. There were no serious adverse events observed in the study. CONCLUSION: Fuzuloparib was widely metabolized and excreted completely through urine and faeces in subjects with advanced solid cancer. Unchanged fuzuloparib was indicated to be the primary drug-related compound in circulation. [14 C]fuzuloparib was well-tolerated at the study dose.
Subject(s)
Antineoplastic Agents , Neoplasms , Adenosine Diphosphate/analysis , Administration, Oral , Antineoplastic Agents/adverse effects , Feces/chemistry , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Poly(ADP-ribose) Polymerase Inhibitors/analysis , Ribose/analysisABSTRACT
In this study, a sensitive and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous analysis of cytarabine (ara-C), cytarabine monophosphate (ara-CMP), cytarabine diphosphate (ara-CDP) and cytarabine triphosphate (ara-CTP) in the cytosol and nucleus. The separation of analytes and endogenous interferents was achieved in 8 min on a hypercarb column (2.1 mm × 100 mm, 3 µm) by using a gradient elution with 95% acetonitrile and aqueous 5 mM hexylamine with 0.4% (v/v) diethylamine adjusted to pH 10. The analytes were detected with both negative and positive electrospray ionization in multiple reaction monitoring (MRM) mode. The calibration curve demonstrated good linearity ranging from 5 to 750 nM for ara-C, 50-7500 nM for ara-CMP, 20-3000 nM for ara-CDP and 1-150 nM for ara-CTP in the cytosol. In the nucleus, good linearity was achieved over a concentration range of 1-100 nM for ara-C, 5-500 nM for ara-CMP, 2.5-250 nM for ara-CDP and 0.5-50 nM for ara-CTP. Intra- and interbatch accuracies and precisions met the standards of validation. The matrix effect, recovery and stability were also within acceptable ranges. After incubation with 10 µM ara-C for 3 h, the levels of ara-C, ara-CMP, ara-CDP and ara-CTP in the cytosol and nucleus of HL-60 cells and HL-60/ara-C cells were determined. Most of the metabolites were found within the quantitation range. The results showed that the nuclear ara-CTP level was significantly different than the intracellular ara-CTP level between HL-60 and HL-60/ara-C cells.
Subject(s)
Arabinofuranosylcytosine Triphosphate , Cytarabine , Arabinofuranosylcytosine Triphosphate/analysis , Arabinofuranosylcytosine Triphosphate/metabolism , Chromatography, High Pressure Liquid/methods , Cytosol/metabolism , Diphosphates , Humans , Tandem Mass SpectrometryABSTRACT
Background and aims: Surgical site infection is a common complication after surgery. Periprocedural antibiotics are necessary to prescribe for preventing or treating infections. The present study aimed to explore the effect of intravenous antibiotics on gut microbiota and menaquinone biosynthesis in patients, especially in elderly patients undergoing cardiac surgery. Methods: A total of 388 fecal samples were collected from 154 cardiac surgery patients. The V3-V4 hypervariable region of the bacterial 16S rRNA gene was amplified and sequenced on a MiSeq PE300. The gut microbiota diversity of samples was analyzed in terms of α- and ß-diversity at the OTU level. The different groups were classified according to antibiotics in combinations and single antibiotics. PICRUSt2 was used for preliminary prediction of the gut microbiota function for menaquinone biosynthesis. Results: The intravenously administered antibiotics which are excreted via bile represents the main antibiotics that could disturb the gut microbiota's composition in cardiac surgery patients, especially for elderly patients. The effect of antibiotics on gut microbiota is produced after antibiotics treatments over one week. The recovery of gut microbiota to the state of pre-antibiotics may require over two weeks of antibiotics withdrawal. Sex factor doesn't represent as an influencer in gut microbiota composition. Long-term use of cefoperazone-sulbactam may affect coagulation function. Conclusions: The composition of the gut microbiota had a significant change post-intravenous antibiotics treatment in cardiac surgery patients. The richness and diversity of gut microbiota are increased in elderly patients.
Subject(s)
Cardiac Surgical Procedures , Gastrointestinal Microbiome , Humans , Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , RNA, Ribosomal, 16S/genetics , Vitamin K 2/pharmacology , Feces/microbiologyABSTRACT
[This corrects the article DOI: 10.3389/fphar.2021.658998.].
ABSTRACT
Siegesbeckia orientalis L. (SO) is a commonly used Chinese medicinal herb. It has long been used as a remedy in traditional Chinese medicine (TCM) for symptoms that resemble inflammatory joint disorders. However, it is slightly toxic. According to the TCM theory, processing can reduce the toxicity of the herbs. Here, we performed metabolomics to determine whether processing with rice wine reduces the toxicity of raw SO, and to explore the mechanisms underlying the raw SO-induced toxicity and the toxicity-reducing effect of processing. Our results showed that raw SO has long-term toxicity in rats. It significantly elevated the serum level of LDH and caused histopathological damages in the lung tissues. It is worth noting that the LDH level in the PSO group was lower than that in the raw SO group, and the damages in lung tissues were relatively mild in PSO-treated rats, suggesting that processing reduces the pulmonary toxicity of the raw. Moreover, a total of 32 significantly changed metabolites were identified. Based on the MetaboAnalyst pathway analysis, we found that two characteristic metabolic pathways including alanine, aspartate and glutamate metabolism and glycerophospholipid metabolism were only changed in the raw SO group, while histidine metabolism was only changed in the PSO group, which suggests that induction of oxidative stress contributes to raw SO-induced pulmonary toxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on how raw SO induces pulmonary toxicity and how the toxicity can be reduced by processing. This study not only provides scientific justifications for the traditional processing theory of SO, but also helps to optimize the processing protocol and the clinical drug combination of SO.
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INTRODUCTION: The composition of microorganisms is closely related to human health. Antibiotic use during pregnancy may have adverse effects on the neonatal gut microbiome and subsequently affect infant health development, leading to childhood atopy and allergic diseases, intestinal, metabolic and brain disorders, and infection. AREAS COVERED: This review includes the effect of maternal antibiotic use during pregnancy on potential diseases in animals and human offspring. EXPERT OPINION: Exposure to antibiotics during pregnancy alters offspring outcomes. Alterations in the microbiome may potentially lower the risk of a range of problems and may also be a novel therapeutic target in children later in life.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Gastrointestinal Microbiome/drug effects , Prenatal Exposure Delayed Effects/physiopathology , Animals , Anti-Bacterial Agents/adverse effects , Child , Female , Humans , Infant , Infant, Newborn , Maternal Exposure/adverse effects , Pregnancy , Prenatal Exposure Delayed Effects/microbiologyABSTRACT
Bazi Bushen capsule (BZBS), as a Chinese medicine used to relieve fatigue, has been proven effective for the treatment of atherogenesis through antilipid effects. To investigate the potential mechanism of BZBS in the anti-atherosclerotic effect, Ovx/ApoE-/- mice were applied to investigate the anti-atherosclerotic efficiency and potential mechanism of BZBS. Therapeutic effect was evaluated based on the number of CD68+ and CD3+ cells, the level of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and the ratio of cleaved caspase-3/caspase-3, as well as increasing ratio of Bcl2/Bax. Human umbilical vein endothelial cells (HUVECs) were chosen to evaluate the role of GPER1. Treatment with BZBS reduced lipid deposition by reducing the numbers of CD68+ and CD3+ cells, the level of ICAM-1 and VCAM-1, and the ratio of cleaved caspase-3/caspase-3, and increasing the ratio of Bcl2/Bax as compared with the control group. In si-GPER1-treated HUVECs, the anti-apoptotic effect of BZBS was decreased. This study revealed that BZBS exhibited a clear effect against atherogenesis via GPER1-dependent anti-inflammatory and anti-apoptotic mechanisms. We believe that this manuscript is informative and useful for researchers pursuing the related alleviation of post-menopausal AS via anti-inflammatory and anti-apoptotic mechanisms.