The transcriptional regulator VarN contributes to Salmonella Typhimurium growth in macrophages and virulence in mice.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major intracellular pathogen of humans and animals and its survival and growth in macrophages is essential for its pathogenicity. The S.

Synthesis of a Novel Series of Amino Acid Prodrugs Based on Thienopyridine Scaffolds and Evaluation of Their Antiplatelet Activity.

The thienopyridines class of drugs used as P2Y receptor antagonists plays a vital role in antiplatelet therapy. To further optimized this compound class, we designed and synthesized a series of amino acid prodrugs of 2-hydroxytetrahydrothienopyridine. All compounds were then evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats and then ED and bleeding time of the most potent compounds were compared with commercial drugs.

An integrated approach to uncover quality marker underlying the effects of Alisma orientale on lipid metabolism, using chemical analysis and network pharmacology.

Background: Quality control of traditional Chinese medicines is currently a great concern, due to the correlation between the quality control indicators and clinic effect is often questionable. According to the "multi-components and multi-targets" property of TCMs, a new special quality and bioactivity evaluation system is urgently needed.

Purpose: Present study adopted an integrated approach to provide new insights relating to uncover quality marker underlying the effects of Alisma orientale (AO) on lipid metabolism.

Identify super quality markers from prototype-based pharmacokinetic markers of Tangzhiqing tablet (TZQ) based on in vitro dissolution/ permeation and in vivo absorption correlations.

Background: A quality marker (Q-marker) is defined as an inherent chemical compound that is used for the quality control of a drug. Its biological activities are closely related to safety and therapeutic effects. Generally, a multiple-component herbal medicine may have many Q-markers.

Transcriptomic Study Reveals Recovery of Impaired Astrocytes Contribute to Neuroprotective Effects of Danhong Injection Against Cerebral Ischemia/Reperfusion-Induced Injury.

Danhong Injection (DHI) is widely used in clinics for treating cardiovascular and cerebrovascular diseases in China. However, the mode of action of DHI for neuroprotection remains unclear. In the present study, we deemed to investigate the effects of DHI on a rat model of cerebral ischemia/reperfusion injury (IRI) with an emphasis on its regulated gene profile obtained from microarray assays.

Quality transitivity and traceability system of herbal medicine products based on quality markers.

Background: Due to a variety of factors to affect the herb quality, the existing quality management model is unable to evaluate the process control. The development of the concept of "quality marker" (Q-marker) lays basis for establishing an independent process quality control system for herbal products.

Hypothesis/purpose: To ensure the highest degree of safety, effectiveness and quality process control of herbal products, it is aimed to establish a quality transitivity and traceability system of quality and process control from raw materials to finished herbal products.

The method of quality marker research and quality evaluation of traditional Chinese medicine based on drug properties and effect characteristics.

Background: Quality of traditional Chinese medicine (TCM) plays a critical role in industry of TCM. Rapid development of TCM pharmaceutical areas is, however, greatly limited, since there are many issues not been resolved, concerning the quality study of TCM.

Hypothesis/purpose: Core concept of TCM quality as well as the characteristics of TCM was discussed, in order to guide the quality research and evaluation of TCM, further improve the level of TCM quality control.

Identification of quality markers of Yuanhu Zhitong tablets based on integrative pharmacology and data mining.

Background: The quality evaluation of traditional Chinese medicine (TCM) formulations is needed to guarantee the safety and efficacy. In our laboratory, we established interaction rules between chemical quality control and biological activity evaluations to study Yuanhu Zhitong tablets (YZTs). Moreover, a quality marker (Q-marker) has recently been proposed as a new concept in the quality control of TCM.

A quality marker study on salvianolic acids for injection.

Background: The quality of Chinese medicine (CM) has being an active and challenging research area for CM. Prof. Chang-Xiao Liu et al first proposed the concept of quality marker (Q-Marker) for the quality evaluation and control on CM.

Discovery and identification of quality markers of Chinese medicine based on pharmacokinetic analysis.

Background: Quality control of Chinese medicine (CM) is an effective measure to ensure the safety and efficacy of CM in clinical practice, which is also a key factor to restrict the modernization process of CM. Various chemical components exist in CM and the determination of several chemical components is the main approach for quality control of vast majority of CM in the present. However, many components determined lack not only specificity, but also biological activities.

The comparative pharmacokinetic study of Yuanhu Zhitong prescription based on five quality-markers.

Background: According to the compatibility theory, therapeutic effects of Chinese medicine prescription are generally attributed to the synergism of multi-herbs. Quality-markers, as the crucial effective components, play a key role in the interaction of compatibility. Pharmacokinetic studies could illustrate the interaction between multiple components in dynamics perspective.

The pharmacokinetics study of ginkgolide A, B and the effect of food on bioavailability after oral administration of ginkgolide extracts in beagle dogs.

Ginkgolides are the primarily active components in Ginkgo products that are popular worldwide. However, few studies have evaluated the bioavailability of ginkgolides and the effects of food on it after oral administration of ginkgolides. In this article, pharmacokinetics and absolute bioavailability of the primary components in ginkgolide extracts were evaluated in beagle dogs.

Quality markers based on biological activity: A new strategy for the quality control of traditional Chinese medicine.

Background: The quality and quality evaluation system of traditional Chinese medicine (TCM) are crucial in the safety and effectiveness assessment of TCM. However, they are also the major bottlenecks that restrict the quality control of TCM. Given the nature of Chinese medicine and the limitations of science and technology, the quality evaluation of TCM involves a few difficulties.

From quality markers to data mining and intelligence assessment: A smart quality-evaluation strategy for traditional Chinese medicine based on quality markers.

Background: The quality of traditional Chinese medicine (TCM) forms the foundation of its clinical efficacy. The standardization of TCM is the most important task of TCM modernization. In recent years, there has been great progress in the quality control of TCM.

Determination of human insulin in dog plasma by a selective liquid chromatography-tandem mass spectrometry method: Application to a pharmacokinetic study.

A simple, sensitive and selective LC-MS/MS method for quantitative analysis of human insulin was developed and validated in dog plasma. Insulin glargine was used as the internal standard. After a simple step of solid-phase extraction, the chromatographic separation of human insulin was achieved by using InertSustain Bio C18 column with a mobile phase of acetonitrile containing 1% formic acid (A)-water containing 1% formic acid (B).

Nanoparticles induced by embedding self-assembling cassette into glucagon-like peptide 1 for improving in vivo stability.

The multiple physiologic characteristics of glucagon-like peptide 1 (GLP-1) make it a promising drug candidate for treating type 2 diabetes mellitus. However, the half-life of GLP-1 is short as a result of degradation by dipeptidyl peptidase IV and renal clearance. Stabilizing GLP-1 is therefore critical for its use in drug development.

Pharmacokinetics, tissue distribution, and excretion of FGF-21 following subcutaneous administration in rats.

As one of the fibroblast growth factor (FGF) superfamily, FGF-21 has been extensively investigated for its functions and roles since its discovery. It has been demonstrated to be one of the key regulators for glucose and lipid metabolism, and exhibits beneficial effects on cardiovascular disease. However, studies focusing on its pharmacokinetic behavior in vivo as a novel therapeutic agent have not been reported.

Effect of recombinant human prourokinase on thrombolysis in a rabbit model of thromboembolic stroke.

The aim of the present study was to investigate the efficacy of recombinant human prourokinase (rhPro-UK) on thromboembolic stroke in rabbits. A total of 210 rabbits were used in experiments. The 180 thromboembolic stroke rabbits were divided into three therapeutic time windows with six groups in each time window (n=10).

Systematic Structure-Activity Relationship (SAR) Exploration of Diarylmethane Backbone and Discovery of A Highly Potent Novel Uric Acid Transporter 1 (URAT1) Inhibitor.

In order to systematically explore and better understand the structure-activity relationship (SAR) of a diarylmethane backbone in the design of potent uric acid transporter 1 (URAT1) inhibitors, 33 compounds (- and -) were designed and synthesized, and their in vitro URAT1 inhibitory activities (IC) were determined. The three-round systematic SAR exploration led to the discovery of a highly potent novel URAT1 inhibitor, , which was 200- and 8-fold more potent than parent lesinurad and benzbromarone, respectively (IC = 0.035 μM against human URAT1 for vs.

Semisynthesis and Biological Evaluation of Oleanolic Acid 3-O-β-d-Glucuronopyranoside Derivatives for Protecting H9c2 Cardiomyoblasts against H₂O₂-Induced Injury.

A series of novel oleanolic acid 3---d-glucuronopyranoside derivatives have been designed and synthesized. Biological evaluation has indicated that some of the synthesized compounds exhibit moderate to good activity against H₂O₂-induced injury in rat myocardial cells (H9c2). Particularly, derivative 28--isobutyl ursolic amide 3---d-galactopyranoside () exhibited a greater protective effect than the positive control oleanolic acid 3---d-glucuronopyranoside, indicating that it possesses a great potential for further development as a cardiovascular disease modulator by structural modification.

The Clinical Pharmacokinetics and Pharmacodynamics of Warfarin When Combined with Compound Danshen: A Case Study for Combined Treatment of Coronary Heart Diseases with Atrial Fibrillation.

Warfarin is used as anticoagulant and Compound Danshen prescription (CDP) is able to promote blood circulation. The combination might produce a synergic effect for patients of coronary heart diseases (CHDs) with atrial fibrillation (AF). Whether the combination increases the bleeding risk of warfarin is unclear, so the effects of Compound Danshen dripping pill (CDDP) on the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of warfarin was investigated in patients.

Glycyrrhetic Acid Derivative TY501 Protects Against Lithocholic Acid-Induced Cholestasis.

The aim of the study is to investigate the protective effects of TY501 against LCA-induced cholestasis in mice and to explore the potential mechanisms. It was demonstrated that TY501(5, 15 or 45 mg/kg, i.g.

Integrated pharmacokinetics of ginsenosides after intravenous administration of YiQiFuMai powder injection in rats with chronic heart failure by UFLC-MS/MS.

YiQiFuMai powder injection (YQFM), derived from the classical traditional Chinese medicine (TCM) formula Shengmai San, is a modern preparation widely used to combat cardiovascular diseases, chronic heart failure (CHF) for example, in clinical practice in China. Ginsenosides are the major components of YQFM, which are responsible for its therapeutic effect. In this research, we developed a rapid, sensitive and simple method for simultaneous determination of ten ginsenosides from YQFM in CHF rat plasma with ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS).

Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy.

The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma's, monoclonal antibodies (mAbs) have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue.

Novel cationic lipid nanoparticles as an ophthalmic delivery system for multicomponent drugs: development, characterization, in vitro permeation, in vivo pharmacokinetic, and molecular dynamics studies.

The purpose of this study was to prepare, optimize, and characterize a cationic lipid nanoparticle (CLN) system containing multicomponent drugs using a molecular dynamics model as a novel method of evaluating formulations. Puerarin (PUE) and scutellarin (SCU) were used as model drugs. CLNs were successfully prepared using melt-emulsion ultrasonication and low temperature-solidification technique.