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Antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a group of chronic multisystem autoimmune diseases with substantial mortality and morbidity and frequent relapses. The complexity of the disease condition and treatment‐related adverse reactions as well as infections play important roles in the poor outcomes. Unfortunately, the subjective symptoms and objective indicators are not fully parallel, and manifestations between disease activity and treatment‐related adverse reactions are often similar. Here, we describe a case of pulmonary mucormycosis in an old female patient with AAV to highlight these challenges. [ABSTRACT FROM AUTHOR]

Current evidence shows that herbal medicines could be beneficial for the treatment of various diseases. However, the complexities present in chemical compositions of herbal medicines are currently an obstacle for the progression of herbal medicines, which involve unclear bioactive compounds, mechanisms of action, undetermined targets for therapy, non‐specific features for drug metabolism, etc. To overcome those issues, metabolomics can be a great to improve and understand herbal medicines from the small‐molecule metabolism level. Metabolomics could solve scientific difficulties with herbal medicines from a metabolic perspective, and promote drug discovery and development. In recent years, mass spectrometry‐based metabolomics was widely applied for the analysis of herbal constituents in vivo and in vitro. In this review, we highlight the value of mass spectrometry‐based metabolomics and metabolism to address the complexity of herbal medicines in systems pharmacology, and to enhance their biomedical value in biomedicine, to shed light on the aid that mass spectrometry‐based metabolomics can offer to the investigation of its active ingredients, especially, to link phytochemical analysis with the assessment of pharmacological effect and therapeutic potential. © 2019 Wiley Periodicals, Inc. Mass Spec Rev [ABSTRACT FROM AUTHOR]

Apremilast (AP) {systematic name: ( S)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4-acetamidoisoindoline-1,3-dione} is an inhibitor of phosphodieasterase-4 (PDE4) and is indicated for the treatment of adult patients with active psoriatic arthritis. The ability of AP to form solvates has been investigated and three solvatomorphs of AP, namely, the AP ethyl acetate hemisolvate, C22H24N2O7S·0.5C4H8O2, the AP toluene hemisolvate, C22H24N2O7S·0.5C7H8, and the AP dichloromethane monosolvate, C22H24N2O7S·CH2Cl2, were obtained. The three AP solvatomorphs were characterized by X-ray powder diffraction, thermogravimetric analysis and differential scanning calorimetry. Single-crystal X-ray diffraction was used to analyze the structures, crystal symmetry, packing modes, stoichiometry and hydrogen-bonding interactions of the solvatomorphs. In addition, dissolution analyses were performed to study the dissolution rates of different AP solvatomorph tablets in vitro and to make comparisons with commercial apremilast tablets (produced by Celgene); all three solvatomorphs showed similar dissolution rates and similar values of the similarity factor f2 in a comparison of their dissolution profiles. [ABSTRACT FROM AUTHOR]

Aims/Introduction Irisin is a newly identified myokine that can promote energy expenditure. Previous studies showed that circulating urotensin II ( UII) levels were increased in diabetes, and UII could inhibit the glucose transport in skeletal muscle in diabetic mice and aggravated insulin resistance. We presumed that irisin levels are associated with UII in diabetic patients. Materials and Methods A total of 71 patients with type 2 diabetes and 40 healthy subjects were recruited. Blood and urinary irisin concentrations were measured by using enzyme-linked immunosorbent assay, and UII concentrations were measured by bioelectrical impedance analysis. Every participant's body composition was analyzed by bioelectrical impedance. Results The serum irisin levels were significantly lower in diabetic patients than that of controls, whereas serum UII levels were significantly higher in diabetic patients than that in that of controls. Serum irisin levels were negatively associated with circulating UII, hemoglobin A1c and the natural logarithm transformation of urinary albumin excretion, whereas serum irisin was positively associated with estimated glomerular filtration rate, and low-density lipoprotein cholesterol and urinary irisin were positively associated with urinary UII. Furthermore, circulating irisin is positively associated with muscle mass, whereas circulating UII is negatively associated with muscle mass in diabetic patients. Hemoglobin A1c and circulating UII are independent determinants of circulating irisin by multiple regression analysis. Conclusions The present results provide the clinical evidence of an association between irisin and UII in diabetic patients. Hemoglobin A1c and circulating UII are independent determinants of circulating irisin. Our results hint that UII and high glucose might inhibit the release of irisin from skeletal muscle in diabetic patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Root cortex of Paeonia suffruticosa Andrews (Paeoniaceae), known as Moutan Cortex (MC), is known to have anti-allergic and anti-inflammatory properties. However, the constituents absorbed into blood after oral administration of MC remain unknown. A sensitive and rapid method by ultra-high-pressure liquid chromatography-electrospray ionization-quadrupole-time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS) technology and the MetaboLynxTM software combined with multiple data processing approach (Mdpa) was established to investigate the absorbed constituents in rats after oral administration of MC, providing unique high-throughput capabilities for drug metabolism study. A hyphenated electrospray ionization and quadrupole-time-of-flight analyzer was used for the determination of accurate mass of the fragment ion in negative mode, with excellent MS mass accuracy and enhanced data acquisition. This rapid automated analysis method was successfully applied for screening and identification of the constituents absorbed and metabolized studies of MC after oral administration to rats. A total of 46 peaks were obtained from MC, 41 of which were tentatively characterized. In the VIP-plot of orthogonal partial least-squares discriminant analysis, 23 interesting ions in serum samples were extracted, and 16 parent components and seven metabolites were detected in vivo. The integrative serum pharmacochemistry technique, UPLC-ESI-Q-TOF-MS, and Mdpa method were successfully applied for rapid discovery of multiple components from MC. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The limited selection of immunosuppressants in the clinic hampers the efficient management of immune disorders such as rejections after organ transplantations. However, the search for new immunosuppressive compounds remains random and creates inevitably financial and laborious wastes. Herein, we present an immunity-inspired discovery strategy that rationally allows an efficient identification of immunosuppressive compounds from the endophyte culture, as exemplified by the new peptide trichomide A. This compound exerts its immunosuppressive action more selectively than cyclosporin A. It was found that trichomide A decreases the expression of Bcl-2, increases the expression of Bax, and has a small or negligible effect on the expressions of p-Akt, CD25, and CD69. Our study strengthens the idea that the cross-kingdom similarity in immunity among living things could provide a shorter route towards the identification of natural products valuable for the development of new immunosuppressants. [ABSTRACT FROM AUTHOR]

ABSTRACT This study aimed to investigate the in vivo behaviors of the main components in traditional Chinese medicine (TCM) fomulae. The plasma pharmacokinetics, tissue distribution and excretion of the main component-schisandrin in rats after oral administration of a classical TCM prescription, shengmaisan (SMS), were studied by a developed and validated UPLC-MS/MS method. The separation of schisandrin was achieved on a UPLC HSS T3 column with a mobile phase consisting of acetonitrile and water at a flow rate of 0.5 mL/min by linear gradient elution. The MS/MS detection was carried out by monitoring the fragmentation of m/ z 415.22 → 384.26 for schisandrin on a triple quadrupole mass spectrometer. The result showed that the method was suitable for the quantification of schisandrin in plasma, tissue and excreta samples with satisfactory selectivity, precision, accuracy, sensitivity, linearity and recovery. Pharmacokinetic results showed a rapid absorption phase with the mean Tmax of 0.17 h and a relatively slow elimination proceeding with a half-life ( T1/2) of 5.24 ± 1.28 h. The tissue distribution showed the maximum concentration distributions of schisandrin after oral administration of SMS were in the order of small intestine > large intestine > lung > liver > kidney > spleen > heart > brain. Only 0.005-0.006% of schisandrin was recovered in feces and was not detected in urine. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Liuwei Dihuang Wan (LDW), a classic Chinese medicinal formula, has been used to improve or restore declined functions related to aging and geriatric diseases, such as impaired mobility, vision, hearing, cognition, and memory. It has attracted increasing attention as one of the most popular and valuable herbal medicines. However, the systematic analysis of the chemical constituents of LDW is difficult and thus has not been well established. In this paper, a rapid, sensitive, and reliable ultra-performance LC with ESI quadrupole TOF high-definition MS method with automated MetaboLynx analysis in positive and negative ion mode was established to characterize the chemical constituents of LDW. The analysis was performed on a Waters UPLC™ HSS T3 using a gradient elution system. MS/MS fragmentation behavior was proposed for aiding the structural identification of the components. Under the optimized conditions, a total of 50 peaks were tentatively characterized by comparing the retention time and MS data. It is concluded that a rapid and robust platform based on ultra-performance LC with ESI quadrupole TOF high-definition MS has been successfully developed for globally identifying multiple constituents of traditional Chinese medicine prescriptions. This is the first report on the systematic analysis of the chemical constituents of LDW. [ABSTRACT FROM AUTHOR]

Shuanghuanglian formula ( SF) is a combination of Flos lonicerae japonicae, Radix scutellariae, and Fructus forsythiae, commonly used to treat viral or bacterial infections. However, the constituents absorbed into the blood after oral administration of SF are difficult to determine and thus remain unclear. Here, we report the application of an accurate background subtraction and multiple data processing approach ( Bs- Mpa) for the comprehensive detection of compounds of SF in vivo. A sensitive and reliable ultra-performance LC coupled with ESI quadrupole TOF MS ( UPLC- ESI- Q- TOF- MS) approach coupled with Bs- Mpa, which is implemented in the Strip tool from UP LC to remove nonrelated ion signals from accurate mass LC- MS data, was established to characterize the chemical constituents and rat metabolites of SF. In the loading plot of the principal component analysis, 68 ions of interest were extracted from blood samples, among them, 39 absorbed prototype components of SF and 29 metabolites were identified in vivo. It is concluded that the integrative Bs- Mpa method can be successfully applied for the rapid discovery of multiple components from a traditional Chinese medicine. The above challenge was addressed by using the proposed Bs- Mpa method and it was particularly suitable for applying to the global characterization of the constituents or metabolites in rat blood after oral administration of other well-known formulae. [ABSTRACT FROM AUTHOR]

Molecular biomarkers could detect biochemical changes associated with disease processes. The key metabolites have become an important part for improving the diagnosis, prognosis, and therapy of diseases. Because of the chemical diversity and dynamic concentration range, the analysis of metabolites remains a challenge. Assessment of fluctuations on the levels of endogenous metabolites by advanced NMR spectroscopy technique combined with multivariate statistics, the so-called metabolomics approach, has proved to be exquisitely valuable in human disease diagnosis. Because of its ability to detect a large number of metabolites in intact biological samples with isotope labeling of metabolites using nuclei such as H, C, N, and P, NMR has emerged as one of the most powerful analytical techniques in metabolomics and has dramatically improved the ability to identify low concentration metabolites and trace important metabolic pathways. Multivariate statistical methods or pattern recognition programs have been developed to handle the acquired data and to search for the discriminating features from biosample sets. Furthermore, the combination of NMR with pattern recognition methods has proven highly effective at identifying unknown metabolites that correlate with changes in genotype or phenotype. The research and clinical results achieved through NMR investigations during the first 13 years of the 21st century illustrate areas where this technology can be best translated into clinical practice. In this review, we will present several special examples of a successful application of NMR for biomarker discovery, implications for disease diagnosis, prognosis, and therapy evaluation, and discuss possible future improvements. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Lipid metabolism has a significant function in the central nervous system and Alzheimer's disease (AD) is an age‐related senile disease characterized by central nerve degeneration. The pathological development of AD is closely related to lipid metabolism disorders. To reveal the influence of Kai‐Xin‐San (KXS) on lipid metabolism in APP/PSI transgenic mice and potential therapeutic targets for treating AD, brain tissue samples were collected and analyzed by high‐throughput lipidomics based on UPLC–Q/TOF‐MS. The collected raw data were processed by multivariate data analysis to discover the potential biomarkers and lipid metabolic profiles. Compared with the control wild‐type mouse group, nine potential lipid biomarkers were found in the AD model group, of which seven were up‐regulated and two were down‐regulated. Orally administrated KXS can reverse the changes in these potential biomarkers. Compared with the model group, a total of six differential metabolites showed a recovery trend and may be potential targets for KXS to treat AD. This study showed that high‐throughput lipidomics can be used to discover the perturbed pathways and lipid biomarkers as potential targets to reveal the therapeutic effects of KXS. [ABSTRACT FROM AUTHOR]

The article presents a summary of Cochrane systematic review of randomized controlled trials (RCT) or cluster randomized controlled trials which have an impact on the use of the telephone in delivering HIV test results and post-test counseling. The reviewers consider homeless youths and youth at high risk for contracting HIV infection as study participants who were offered counseling and oral HIV testing. The implications of the review for public health nursing research are discussed.