Quantification of Gut Microbiota Dysbiosis-Related Organic Acids in Human Urine Using LC-MS/MS.

Urine organic acid contains water-soluble metabolites and/or metabolites—derived from sugars, amino acids, lipids, vitamins, and drugs—which can reveal a human’s physiological condition. These urine organic acids—hippuric acid, benzoic acid, phenylacetic acid, phenylpropionic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyl acetic acid, 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenyl propionic acid, and 3-indoleacetic acid—were the eligible candidates for the dysbiosis of gut microbiota. The aim of this proposal was to develop and to validate a liquid chromatography−tandem mass spectrometry (LC-MS/MS) bioanalysis method for the nine organic acids in human urine.

Evidence of the need for modified well-stirred model in vitro to in vivo extrapolation.

In vitro to in vivo extrapolation (IVIVE), an approach for hepatic clearance (CL) prediction used worldwide, remains controversial due to systematic underprediction. Among the various probable factors, the original assumption of the hepatic mathematical model (i.e.

A substructure-based screening approach to uncover N-nitrosamines in drug substances.

Drug substances are at risk of contamination with N-nitrosamines (NAs), well-known carcinogenic agents, during synthesis processes and/or long-term storage. Therefore, in this study, we developed an efficient data-based screening approach to systemically assess marketed products and investigated its scalability for benefiting both regulatory agencies and pharmaceutical industries. A substructure-based screening method employing DataWarrior, an open-source software, was established to evaluate the risks of NA impurities in drug substances.

Evolution of Cryoglobulinemia in Direct-Acting Antiviral-Treated Asian Hepatitis C Patients With Sustained Virological Responses: A 4-Year Prospective Cohort Study.

Background: How cryoglobulinemia evolves after sustained virological response (SVR) following direct-acting antiviral (DAA) treatment in Asian hepatitis C virus (HCV)-infected patients remains elusive.

Methods: A prospective cohort study was conducted in 422 Taiwanese patients (358 completed DAA therapy and 353 experienced SVRs). Serum cryoglobulins were surveyed at baseline and every 3-6 months posttherapy.

Microwave- and Ultrasound-Assisted Extraction of Cucurbitane-Type Triterpenoids from L. Cultivars and Their Antiproliferative Effect on SAS Human Oral Cancer Cells.

Cucurbitane-type triterpenoids are a major class of bioactive compounds present in bitter melon. In the present study, six different cultivars of bitter melon were extracted by using microwave- or ultrasound-assisted techniques to identify the prominent method that can extract the majority of cucurbitane-type triterpenoids. A UHPLC-MS/MS (ultra-high-performance liquid chromatography tandem mass spectrometry) system was used for the identification and quantification of ten cucurbitane-type triterpenoids.

Ethnobotanical Survey on Bitter Tea in Taiwan.

In Taiwan, herbal tea is considered a traditional medicine and has been consumed for hundreds of years. In contrast to regular tea, herbal teas are prepared using plants other than the regular tea plant, Camellia sinensis (L.) Kuntze.

Decoupled Glucose and Lipid Metabolic Recovery after Viral Clearance in Direct-Acting Antiviral-Treated HCV Patients: A 3-Year Prospective Cohort Study.

Background/aim: The recovery pattern of hepatitis C virus (HCV)-associated metabolic alteration after sustained virological response (SVR) following direct-acting antivirals (DAAs) remains elusive.

Methods: A prospective cohort study of chronic HCV-infected (CHC) patients (n = 415) receiving DAAs (n = 365) was conducted. Metabolic profiles were examined in SVR patients (n = 360) every 3-6 months after therapy and compared with those of sex- and age-matched controls (n = 470).

Critical role of triglycerides for adiponectin levels in hepatitis C: a joint study of human and HCV core transgenic mice.

Background: Both hepatitis C virus (HCV) infection and adiponectin are critically involved in metabolism. The reversal and associations of altering adiponectin levels after sustained virological responses (SVRs) following direct-acting antivirals (DAA) in HCV-infected patients remained elusive.

Methods: A joint study was conducted in a prospective cohort of 427 HCV-infected patients and a line of HCV core transgenic mice.

Precisely adjusting the hepatic clearance of highly extracted drugs using the modified well-stirred model.

Hepatic clearance has been widely studied for over 50 yr. Many models have been developed using either theoretical or empirical tests to predict drug metabolism. The well-stirred, parallel-tube, and dispersion metabolic models have been extensively discussed.

Use of urinary hippuric acid and o-/p-/m-methyl hippuric acid to evaluate surgical smoke exposure in operating room healthcare personnel.

Toluene and xylene are common components of surgical smoke, whereas hippuric acid (HA) and methylhippuric acid (MHA) are the products of toluene and xylene metabolism in humans, respectively. HA and MHA can be used as indicators to evaluate the exposure hazards of toluene and xylene. In this study, we used liquid chromatography tandem mass spectrometry (LC-MS/MS) to simultaneously analyze the HA, o-/m-/p-MHA, and creatinine contents in the urine of healthcare personnel.

Gallic Acid Ameliorated Impaired Lipid Homeostasis in a Mouse Model of High-Fat Diet-and Streptozotocin-Induced NAFLD and Diabetes through Improvement of -oxidation and Ketogenesis.

Gallic acid (GA) is a simple polyphenol found in food and traditional Chinese medicine. Here, we determined the effects of GA administration in a combined mouse model of high-fat diet (HFD)-induced obesity and low-dose streptozotocin (STZ)-induced hyperglycemia, which mimics the concurrent non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes pathological condition. By combining the results of physiological assessments, pathological examinations, metabolomic studies of blood, urine, liver, and muscle, and measurements of gene expression, we attempted to elucidate the efficacy of GA and the underlying mechanism of action of GA in hyperglycemic and dyslipidemic mice.

Sources and components of volatile organic compounds in breast surgery operating rooms.

Objectives: The composition and concentration distribution of volatile organic compounds (VOCs) in surgical smoke had seldomly been reported. This study aimed to investigate the profile of VOCs and their concentration in surgical smoke from breast surgery during electrocautery in different tissues, electrosurgical units, and electrocautery powers.

Methods: Thirty-eight surgical smoke samples from 23 patients performed breast surgery were collected using evacuated stainless steel canisters.

An Ethnobotanical Study on Qīng-Căo-Chá Tea in Taiwan.

Herbal tea, a beverage prepared from a variety of plant materials excluding the leaves of the tea plant (L.) Kuntze of the family Theaceae, for a long time, has been consumed by most Chinese people for preventive and/or therapeutic health care. Usually, it is brewed or prepared as a decoction of local plants in water.

Effects of processing adjuvants on traditional Chinese herbs.

Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs).

Major achievements of evidence-based traditional Chinese medicine in treating major diseases.

A long history of use and extensive documentation of the clinical practices of traditional Chinese medicine resulted in a considerable number of classical preparations, which are still widely used. This heritage of our ancestors provides a unique resource for drug discovery. Already, a number of important drugs have been developed from traditional medicines, which in fact form the core of Western pharmacotherapy.

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance.

Background: The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation.

Methods: A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center.

Results: Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy.

Link between plasminogen activator inhibitor-1 and cardiovascular risk in chronic hepatitis C after viral clearance.

The pathophysiological implications of plasminogen activator inhibitor-1 (PAI-1) in HCV infection remain obscure. This prospective study evaluated 669 HCV patients, of whom 536 had completed a course of anti-HCV therapy and had pre-, peri- and post-therapy measurements of various profiles, including PAI-1 levels. Multivariate analysis demonstrated, before anti-HCV-therapy, platelet count and PAI-1-rs1799889 genotype were associated with PAI-1 levels.

Improving the Concentrations of the Active Components in the Herbal Tea Ingredient, Uraria crinita: The Effect of Post-harvest Oven-drying Processing.

Uraria crinita is widely used as a popular folk drink; however, little is known about how the post-harvest operations affect the chemical composition and bioactivity of UC. We assessed three drying methods (Oven-drying, Air-drying, Sun-drying), as well as the Oven-drying temperature using metabolomics approaches and bioactivity assays. The samples processed at 40 degree show a greater effect on the levels of estrogen receptor-alpha activity and nuclear factor erythroid 2-related factor 2 activity, anti-oxidative activity, and cyclooxygenase-2 inhibition compared with the other samples.

Pentoxifylline ameliorates non-alcoholic fatty liver disease in hyperglycaemic and dyslipidaemic mice by upregulating fatty acid β-oxidation.

Nonalcoholic fatty liver disease (NAFLD), which includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis, is characterised by abnormal fat accumulation in the liver in the absence of excessive alcohol intake. In patients with type 2 diabetes (T2D), concurrent NAFLD might increase the risk of chronic kidney disease and the mortality rate. Although several studies have examined the effectiveness of pentoxifylline (PTX) in NAFLD treatment, no results are available to verify the effectiveness of PTX in treating T2D associated with NAFLD.

Chinese herbal medicines promote hippocampal neuroproliferation, reduce stress hormone levels, inhibit apoptosis, and improve behavior in chronically stressed mice.

Ethnopharmacological Relevance: An efficacious antidepressant without unwanted side effects is need urgently at present. This study aimed to investigate whether treatment with four Chinese herbal medicines (CHMs), namely Radix Astragali, Saposhnikovia divaricate (SD), Eucommia ulmoides Oliv. bark (EU), and Corydalis yanhusuo W.

Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study.

The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects.

Blockade of KCa3.1 potassium channels protects against cisplatin-induced acute kidney injury.

Tubular cell apoptosis significantly contributes to cisplatin-induced acute kidney injury (AKI) pathogenesis. Although KCa3.1, a calcium-activated potassium channel, participates in apoptosis, its involvement in cisplatin-induced AKI is unknown.

Using Visualized Matrix Effects to Develop and Improve LC-MS/MS Bioanalytical Methods, Taking TRAM-34 as an Example.

Matrix effects (MEs) continue to be an obstacle in the development of the LC-MS/MS method, with phospholipids being the major cause of MEs. Changing the mobile phase has been a common strategy to reduce MEs; however, the underlying mechanism is unclear. "In-source multiple-reaction monitoring" (IS-MRM) for glycerophosphocholines (PCs) has been commonly applied in many bioanalytical methods.

Gallic acid ameliorated impaired glucose and lipid homeostasis in high fat diet-induced NAFLD mice.

Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more "holistic view" approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA.