Regulation, targets and functions of CHK.

Src family kinases (SFKs) play pivotal roles in multiple signaling pathways (Yeatman, 2004). SFK activity is inhibited by phosphorylation at its C-terminal tyrosine, by CSK (C-terminal Src kinase) and CHK (CSK-homologous kinase). CHK expression is restricted to normal hematopoietic cells, brain, and colon tissues.

CS1003, a novel human and mouse cross-reactive PD-1 monoclonal antibody for cancer therapy.

The programmed cell death protein 1 (PD-1) is an immune-checkpoint that negatively regulates the immune system and a key mechanism that tumors utilize to escape from immune surveillance. PD-1 antibodies can block the interaction of PD-1 with its ligands (PD-L1 and PD-L2), restore T cells activation, and elicit antitumor activity. In this paper, we reported a novel PD-1 monoclonal antibody (mAb) CS1003, which is a humanized IgG4 PD-1 mAb generated by conventional hybridoma technology, and currently being developed in multiple clinical trials as monotherapy or in combination with other anticancer agents.

Lithium adduct as precursor ion for sensitive and rapid quantification of 20 (S)-protopanaxadiol in rat plasma by liquid chromatography/quadrupole linear ion trap mass spectrometry and application to rat pharmacokinetic study.

A novel, rapid and sensitive liquid chromatography/quadrupole linear ion trap mass spectrometry [LC-ESI-(QqLIT)MS/MS] method was developed and validated for the quantification of protopanaxadiol (PPD) in rat plasma. Oleanolic acid (OA) was used as internal standard (IS). A simple protein precipitation based on acetonitrile (ACN) was employed.

Material basis of Chinese herbal formulas explored by combining pharmacokinetics with network pharmacology.

The clinical application of Traditional Chinese medicine (TCM), using several herbs in combination (called formulas), has a history of more than one thousand years. However, the bioactive compounds that account for their therapeutic effects remain unclear. We hypothesized that the material basis of a formula are those compounds with a high content in the decoction that are maintained at a certain level in the system circulation.

Quantification of neutral human milk oligosaccharides by graphitic carbon high-performance liquid chromatography with tandem mass spectrometry.

Defining the biological roles of human milk oligosaccharides (HMOS) requires an efficient, simple, reliable, and robust analytical method for simultaneous quantification of oligosaccharide profiles from multiple samples. The HMOS fraction of milk is a complex mixture of polar, highly branched, isomeric structures that contain no intrinsic facile chromophore, making their resolution and quantification challenging. A liquid chromatography-mass spectrometry (LC-MS) method was devised to resolve and quantify 11 major neutral oligosaccharides of human milk simultaneously.

Determination of bakkenolide A in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study.

A sensitive rapid analytical method was established and validated to determine the bakkenolide A (BA) in rat plasma. This method was further applied to assess the pharmacokinetics of BA in rats receiving a single dose of BA. Liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode was used in the method, and costundide was used as internal standard.

A sensitive method for determination of platycodin d in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study.

Platycodin D (PD), a major component isolated from the root of Platycodon grandiflorum, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated to determine the PD in rat plasma. This method was further applied to assess the pharmacokinetics of PD in rats following administration of a single dose.

Capillary electrophoresis of acidic oligosaccharides from human milk.

Interest in defining the array of oligosaccharides of human milk has been increasing. Pathogens that bind glycans on their host mucosal surfaces may be inhibited by human milk oligosaccharides. It has been postulated that acidic oligosaccharides in human milk may inhibit binding by pathogens that bind acidic glycans in the gut, but testing this hypothesis requires their reliable quantification in milk.

A sensitive method for determination of salvianolic acid A in rat plasma using liquid chromatography/tandem mass spectrometry.

Salvianolic acid A (SAA), a major effective constituent of Salvia miltiorrhizas, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated for SAA in rat plasma, which was further applied to assess the pharmacokinetics of SAA in rats receiving a single oral dose of SAA. The method used liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode with chloramphenicol as the internal standard.

Hydrocortisone modulates cholera toxin endocytosis by regulating immature enterocyte plasma membrane phospholipids.

Background & Aims: Diarrheal disease is a major cause of morbidity and mortality in infants and children worldwide. Evidence has indicated immature human enterocytes and their interaction with bacteria and enterotoxins may account for the noted increased susceptibility of neonates to diarrhea. Our aim was to characterize the developmental difference in cholera toxin (CT)-GM1-mediated endocytosis.

Simultaneous quantification of sialyloligosaccharides from human milk by capillary electrophoresis.

The acidic oligosaccharides of human milk are predominantly sialyloligosaccharides. Pathogens that bind sialic acid-containing glycans on their host mucosal surfaces may be inhibited by human milk sialyloligosaccharides, but testing this hypothesis requires their reliable quantification in milk. Sialyloligosaccharides have been quantified by anion exchange high-performance liquid chromatography (HPLC), reverse- or normal-phase HPLC, and capillary electrophoresis (CE) of fluorescent derivatives; in milk, these oligosaccharides have been analyzed by high pH anion exchange chromatography with pulsed amperometric detection and, in our laboratory, by CE with detection at 205nm.

A sensitive method for the detection and quantification of ginkgo flavonols from plasma.

Extracts from Ginkgo biloba leaves (family Ginkgoaceae) have antioxidant and free radical scavenging effects, largely attributed to the flavonols, which are a major class of functional components in ginkgo extracts. In order to facilitate analysis of systemic exposure to ginkgo-derived products in animals and/or humans, we developed a liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based method that is capable of routinely monitoring plasma levels of ginkgo flavonols. We used an initial acidic hydrolysis step to convert the plasma ginkgo flavonol conjugates into their aglycone forms [quercetin (QCT), kaempferol (KMF) and isorhamnetin (ISR)] prior to EtOAc-based extraction and subsequent LC/MS/MS-based analysis.

Determination of saikosaponin derivatives in Radix bupleuri and in pharmaceuticals of the chinese multiherb remedy xiaochaihu-tang using liquid chromatographic tandem mass spectrometry.

Saikosaponins are bioactive oleanane saponins derived from the Chinese medicinal herb Radix bupleuri ("chaihu" in Chinese). An LC-MS/MS-based method has been developed for characterization and quantification of 15 saikosaponin derivatives (saikosaponin a, saikosaponin b(1), saikosaponin g, saikogenin A, saikogenin H, saikosaponin c, saikosaponin h, saikosaponin i, prosaikogenin C(2), prosaikogenin B(2), saikogenin C, saikogenin B, saikosaponin d, saikosaponin b(2), and saikogenin D) in one chromatographic run. Optimization of the ionization process was performed with electrospray and atmospheric pressure chemical ionization techniques in both positive and negative ion modes.