Development of a UHPLC-MS/MS method for the quantification of Pristinamycin ⅠA and ⅡA in beagle dog plasma and its pharmacokinetic application.

The aim of this study was to develop and fully validate a sensitive and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantification of pristinamycin ⅠA (PⅠA) and pristinamycin ⅡA (PⅡA) in plasma of beagle dogs after oral administration of pristinamycin tablets. PⅠA, PⅡA and quinupristin (internal standard, IS) were separated on an Agilent Eclipse Plus C column (2.1 mm × 100 mm, 3.

Pharmacodynamic and Toxicity Studies of 6-Isopropyldithio-2'-guanosine Analogs in Acute T-Lymphoblastic Leukemia.

(1) Background: The research group has developed a new small molecule, 6-Isopropyldithio-2'-deoxyguanosine analogs-YLS004, which has been shown to be the most sensitive in acute T-lymphoblastic leukemia cells. Moreover, it was found that the structure of Nelarabine, a drug used to treat acute T-lymphoblastic leukemia, is highly similar to that of YLS004. Consequently, the structure of YLS004 was altered to produce a new small molecule inhibitor for this study, named YLS010.

Sustained growth factor delivery from bioactive PNIPAM-grafted-chitosan/heparin multilayers as a tool to promote growth and migration of cells.

Delivery of growth factors (GFs) is challenging for regulation of cell proliferation and differentiation due to their rapid inactivation under physiological conditions. Here, a bioactive polyelectrolyte multilayer (PEM) is engineered by the combination of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and glycosaminoglycans to be used as reservoir for GF storage. PNIPAM-grafted-chitosan (PChi) with two degrees of substitution (DS) are synthesized, namely LMW* (DS 0.

Spontaneous Internal Electric Field in Heterojunction Boosts Bifunctional Oxygen Electrocatalysts for Zinc-Air Batteries: Theory, Experiment, and Application.

Heterojunctions are a promising class of materials for high-efficiency bifunctional oxygen electrocatalysts in both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). However, the conventional theories fail to explain why many catalysts behave differently in ORR and OER, despite a reversible path ( O ⇋ OOH⇋ O⇋ OH). This study proposes the electron-/hole-rich catalytic center theory (e/h-CCT) to supplement the existing theories, it suggests that the Fermi level of catalysts determines the direction of electron transfer, which affects the direction of the oxidation/reduction reaction, and the density of states (DOS) near the Fermi level determines the accessibility for injecting electrons and holes.

A recyclable stereoauxiliary aminocatalyzed strategy for one-pot synthesis of indolizine-2-carbaldehydes.

Indolizine-carbaldehydes with the easily modifiable carbaldehyde group are important synthetic targets as versatile precursors for distinct indolizines. However, the efficient one-pot construction of trisubstituted indolizine-2-carbaldehydes represents a long-standing challenge. Herein, we report an unprecedented recyclable stereoauxiliary aminocatalytic approach via aminosugars derived from biomass, which enable the efficient one-pot synthesis of desired trisubstituted indolizine-2-carbaldehydes via [3+2] annulations of acyl pyridines and α,β-unsaturated aldehyde.

Studies on the interaction of five triazole fungicides with human renal transporters in cells.

The widespread use of triazole fungicides in agricultural production poses a potential risk to human health. This study investigates the interaction of five triazole fungicides, i.e.

Metabolism and pharmacokinetic study of deuterated osimertinib.

Osimertinib is a highly selective third-generation irreversible inhibitor of epidermal growth factor receptor mutant, which can be utilized to treat non-small cell lung cancer. As the substrate of cytochrome P450 enzyme, it is mainly metabolized by the CYP3A enzyme in humans. Among the metabolites produced by osimertinib, AZ5104, and AZ7550, which are demethylated that is most vital.

Synthesis of Thermoresponsive PNIPAM-Grafted Cellulose Sulfates for Bioactive Multilayers via Layer-by-Layer Technique.

The robust thermoresponsive and bioactive surfaces for tissue engineering by combining poly--isopropylacrylamide (PNIPAM) and cellulose sulfate (CS) remain highly in demand but not yet realized. Herein, PNIPAM-grafted cellulose sulfates (PCSs) with diverse degrees of substitution ascribed to sulfate groups (DS) are synthesized for the first time. Higher sulfated PCS2 generally forms larger aggregates than lower sulfated PCS1 at their cloud point temperatures (TCP) of around 33 °C, whereas PCS1 leads to larger aggregates at body temperature (37 °C).

Engineering of Stable Cross-Linked Multilayers Based on Thermo-Responsive PNIPAM--Chitosan/Heparin to Tailor Their Physiochemical Properties and Biocompatibility.

The thermo-responsive poly(-isopropylacrylamide) (PNIPAM) is ubiquitously applied in controlled drug release and tissue engineering. However, the lack of bioactivity of PNIPAM restricts its use in cell-containing systems being a thermo-responsive adhesive substratum with no regulating effect on cell growth and differentiation. In this study, integrating PNIPAM with chitosan into PNIPAM--chitosan (PNIPAM-Chi) allows a layer-by-layer assembly with bioactive heparin to fabricate PNIPAM-modified polyelectrolyte multilayers (PNIPAM-PEMs).

Blockade LAT1 Mediates Methionine Metabolism to Overcome Oxaliplatin Resistance under Hypoxia in Renal Cell Carcinoma.

Hypoxic microenvironment and metabolic dysregulation of tumor impairs the therapeutic efficacy of chemotherapeutic drugs, resulting in drug resistance and tumor metastasis, which has always been a challenge for the treatment of solid tumors, including renal cell carcinoma (RCC). Herein, starting from the evaluation of methionine metabolism in RCC cells, we demonstrated that the increased methionine accumulation in RCC cells was mediated by L-type amino acid transporter 1 (LAT1) under hypoxia. Glutathione (GSH), as a methionine metabolite, would attenuate the therapeutic efficacy of oxaliplatin through chemical chelation.

Fenbendazole and its synthetic analog interfere with HeLa cells' proliferation and energy metabolism via inducing oxidative stress and modulating MEK3/6-p38-MAPK pathway.

Fenbendazole, a broad-spectrum anti-parasitic drug, can be a potential anti-tumor agent. In this study, we synthesized and purified its derivative, analog 6, intending to achieve improved efficacy in cancer cells and decreased toxicity in normal cells. To evaluate in vitro anti-tumor activities of fenbendazole and analog 6 in different cancer cell lines, a CCK-8 assay was performed, and we found that human cervical cancer HeLa cells were more sensitive to analog 6 than to fenbendazole.

Direct nitrogen interception from chitin/chitosan for imidazo[1,5-]pyridines.

A catalyst-free one-pot methodology that enables direct nitrogen interception of chitosan/chitin for imidazo[1,5-]pyridines was developed. This strategy features direct synthesis of important deuterated imidazo[1,5-]pyridines and tridentate ligands. In particular, a broad group of previously inaccessible products including saturated 1-alkylimidazo[1,5-]pyridines are unprecedently synthesized by this protocol.

Anomeric Stereoauxiliary Cleavage of the C-N Bond of d-Glucosamine for the Preparation of Imidazo[1,5-a]pyridines.

The targeted cleavage of the C-N bonds of alkyl primary amines in sustainable compounds of biomass according to a metal-free pathway and the conjunction of nitrogen in the synthesis of imidazo[1,5-a]pyridines are still highly challenging. Despite tremendous progress in the synthesis of imidazo[1,5-a]pyridines over the past decade, many of them can still not be efficiently prepared. Herein, we report an anomeric stereoauxiliary approach for the synthesis of a wide range of imidazo[1,5-a]pyridines after cleaving the C-N bond of d-glucosamine (α-2° amine) from biobased resources.

targeted delivery of antibodies into cancer cells with pH-responsive cell-penetrating poly(disulfide)s.

Cell-penetrating poly(disulfide)s (CPDs) are promising vehicles for cytosolic delivery of proteins. However, currently available arginine-rich CPD has rarely been reported for systemic delivery due to its "always" positive charge. Herein, we developed pH-responsive CPD that executes tumor targeting delivery protonation of imidazole groups within the acidic tumor microenvironment.

Dealkalization and Leaching Behavior of Fe, Al, Ca, and Si of Red Mud by Waste Acid from Titanium White Production.

Dealkalization is the necessary step for the multipurpose use of red mud (RM), and acid leaching is a productive method to realize the dealkalization of RM. Most researches focus on recovering metals from the highly alkaline waste by pure acid leaching or stabilization by dealkalization. In this study, according to the strong alkalinity of RM and strong acidity of the waste acid from titanium dioxide production, the waste acid was used for the dealkalization of RM.

Pharmacokinetics and brain distribution studies of 6-hydroxykynurenic acid and its structural modified compounds.

Objectives: 6-Hydroxykynurenic acid (6-HKA) is an organic acid component in extracts of Ginkgo biloba leaves and acts as a major contributor to neurorestorative effects, while its oral bioavailability was low. Therefore, using prodrug method to improve the bioavailability and brain content of 6-HKA is significant.

Methods: Three structural modified compounds of 6-HKA were synthesized, and ultra performance liquid chromatography-tandem mass spectrometry methods for quantification of these structural modified compounds in rat plasma and rat brain homogenate were established and comprehensively validated.

The characterisation of the metabolism and transport of 6-hydroxykynurenic acid, an important constituent of extracts.

6-Hydroxykynurenic acid (6-HKA) is a nitrogen-containing phenolic acid compound in leaves. The pharmacological activities of 6-HKA have been reported and shown that 6-HKA has the potential to become a therapeutic drug and may play an important role in the treatment of nervous system diseases. However, there are few studies on the drug metabolism and transport of 6-HKA.

6-Dithio-2'-deoxyguanosine analogs induce reactive oxygen species-mediated tumor cell apoptosis via bi-targeting thioredoxin 1 and telomerase.

Thioredoxin 1 (Trx1) and telomerase play key roles in the development and progression process of most tumors, and they both are promising drug therapy targets. We have, for the first time, discovered that Trx1 and telomerase had a dual-target synergistic effect. Based on that results, we designed a series of 6-dithio-2'-deoxyguanosine analogs (named as YLS00X) and verified whether they can inhibit Trx1 and telomerase simultaneously.

Recent Progress on Cellulose-Based Ionic Compounds for Biomaterials.

Glycans play important roles in all major kingdoms of organisms, such as archea, bacteria, fungi, plants, and animals. Cellulose, the most abundant polysaccharide on the Earth, plays a predominant role for mechanical stability in plants, and finds a plethora of applications by humans. Beyond traditional use, biomedical application of cellulose becomes feasible with advances of soluble cellulose derivatives with diverse functional moieties along the backbone and modified nanocellulose with versatile functional groups on the surface due to the native features of cellulose as both cellulose chains and supramolecular ordered domains as extractable nanocellulose.

The failure of DAC to induce OCT2 expression and its remission by hemoglobin-based nanocarriers under hypoxia in renal cell carcinoma.

Human organic cation transporter 2 (OCT2) is the most abundant and important uptake transporter involved in the renal excretion of cationic drugs. Abnormal hypermethylation- mediated silencing of OCT2 results in oxaliplatin resistance in renal cell carcinoma (RCC). The epigenetic activation of OCT2 by decitabine (DAC) reversed this resistance in normoxic conditions.

Thermoresponsive polymers and their biomedical application in tissue engineering - a review.

Thermoresponsive polymers hold great potential in the biomedical field, since they enable the fabrication of cell sheets, in situ drug delivery and 3D-printing under physiological conditions. In this review we provide an overview of several thermoresponsive polymers and their application, with focus on poly(N-isopropylacrylamide)-surfaces for cell sheet engineering. Basic knowledge of important processes like protein adsorption on surfaces and cell adhesion is provided.

Upregulation of miR-489-3p and miR-630 inhibits oxaliplatin uptake in renal cell carcinoma by targeting OCT2.

Renal cell carcinoma (RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment.

The inhibition mechanism of the uptake of lamivudine via human organic anion transporter 1 by Stellera chamaejasme L. extracts.

Stellera chamaejasme L. is a traditional Chinese medicine with a long history to treat stubborn skin ulcer, and it also has antiviral and antitumor effects. Neochamaejasmine B (NCB), Neochamaejasmine A (NCA) and Chamaechromone (CMC) are the major components in dried roots of Stellera chamaejasme L.

Influence of organic anion transporter 1/3 on the pharmacokinetics and renal excretion of ginkgolides and bilobalide.

Ethnopharmacological Relevance: The major terpene lactones of ginkgo biloba extract (GBE) include ginkgolide A, B, C and bilobalide are used for the protection of cardiovascular, cerebrovascular and neurodegenerative diseases. Terpene lactones are orally bioavailable and predominantly eliminated via the renal pathway. However, information on the transporters involved in the pharmacokinetics (PK) and renal excretion of terpene lactones is limited.