Development and Validation of a HPLC-MS/MS Method for the Determination of Compound 13b in Rat Plasma and Its Application to a Pharmacokinetic Study.

Compound 13b, a newly identified anthraquinone derivative, has demonstrated potent efficacy against the Zika virus. To explore the bioavailability and pharmacokinetic properties of compound 13b, a robust and sensitive HPLC-MS/MS method was established and verified to determine its plasma concentration in rats. Sample preparation involved protein precipitation using acetonitrile with testosterone as an internal standard.

PPARα regulates YAP protein levels and activity by affecting its ubiquitination modification.

Background: Peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in liver physiological and pathological processes. Yes-associated protein (YAP) is a key effector in regulating cell growth and organ size. Ubiquitination is known to modulate YAP protein expression, stability, and nuclear localization.

Schisandrol B alleviates depression-like behavior in mice by regulating bile acid homeostasis in the brain-liver-gut axis via the pregnane X receptor.

Background: Depression is a widely recognized neuropsychiatric disorder. Recent studies have shown a potential correlation between bile acid disorders and depression, highlighting the importance of maintaining bile acid balance for effective antidepressant treatment. Schisandrol B (SolB), a primary bioactive compound from Schisandra chinensis (Turcz.

Development and Validation of a Sensitive LC-MS/MS Method for Determination of Lenvatinib and Its Major Metabolites in Human Plasma and Its Application in Hepatocellular Carcinoma Patients.

Lenvatinib has been demonstrated effective in advanced hepatocellular carcinoma (HCC), but the pharmacokinetic-pharmacodynamics behavior of lenvatinib and its metabolites remains unclear. To investigate the pharmacokinetic-pharmacodynamics behavior of lenvatinib and its active metabolites in advanced HCC patients, it is important to develop a simple and rapid method to analyze the exposures of lenvatinib and its metabolites in human samples. Here, we established and validated a simple and rapid method for determining lenvatinib and its three major metabolites, descyclopropyl lenvatinib (M1), O-demethyl lenvatinib hydrochloride (M2), and lenvatinib N-Oxide (M3) by liquid chromatography-tandem mass spectrometry method.

Pregnane X receptor activation promotes hematopoiesis during liver regeneration by inducing proliferation of hematopoietic stem and progenitor cells in mice.

Liver regeneration is a complex process that involves the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs). Pregnane X receptor (PXR), also known as NR1I2, is an important regulator for liver enlargement and regeneration. However, the role of PXR activation in hematopoiesis during liver regeneration remains unclear.

Pregnane X receptor activation induces liver enlargement and regeneration and simultaneously promotes the metabolic activity of CYP3A1/2 and CYP2C6/11 in rats.

Human pregnane X receptor (PXR) is critical for regulating the expression of key drug-metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent-specific PXR agonist pregnenolone-16α-carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two-thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver.

Gut Microbiota Affects Mouse Pregnane X Receptor Agonist Pregnenolone 16α-Carbonitrile-Induced Hepatomegaly by Regulating Pregnane X Receptor and Yes-Associated Protein Activation.

Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis, and the gut microbiota is closely linked to liver physiologic and pathologic status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota contributes to PXR-induced hepatomegaly and the involved mechanisms remain unclear.

PXR triggers YAP-TEAD binding and Sirt2-driven YAP deacetylation and polyubiquitination to promote liver enlargement and regeneration in mice.

Pregnane X receptor (PXR) plays an important role in the regulation of metabolic homeostasis. Yes-associated protein (YAP) is a critical regulator of liver size and liver regeneration. Recently, we reported that PXR-induced liver enlargement and regeneration depend on YAP signalling, but the underlying mechanisms remain unclear.

Time-Dependent Distribution of Hydroxychloroquine in Cynomolgus Macaques Using Population Pharmacokinetic Modeling Method.

To evaluate the biodistribution of hydroxychloroquine (HCQ) in cynomolgus macaques and receive dynamic quantitative relationship between plasma, blood, and lung tissue concentration using the population pharmacokinetic modeling method, seventeen cynomolgus macaques were divided into six groups according to different HCQ dosing regimens over 5 days. The monkeys were euthanized, and blood, plasma, urine, feces and ten tissues were collected. All the samples were prepared by protein precipitation and analyzed by HPLC-MS/MS detection.

Therapeutic effect of transmembrane TAT-tCNTF via Erk and Akt activation using and models of Alzheimer's disease.

Suppressing Alzheimer's disease (AD) progression via its pathological characteristics, namely senile plaques and neurofibrillary tangles, is an efficient treatment approach. Numerous studies have indicated that ciliary neurotrophic factor (CNTF) not only promotes neuronal growth and maintains cell survival but also significantly reduces amyloid beta (Aβ) aggregation and deposition. In this study, transactivator of transcription (TAT) was linked to truncated ciliary neurotrophic factor (tCNTF) and expressed as a fusion protein, TAT-tCNTF, to overcome the transmembrane inability of CNTF.

Association analysis of SNPs present in plasma with adverse events and population pharmacokinetics in Chinese sunitinib treated patients with renal cell carcinoma.

Background: Sunitinib is a tyrosine kinase inhibitor with effective therapeutic outcomes in patients with renal-cell carcinoma. The study were to analyze the association of single-nucleotide polymorphisms present in cell-free DNA and pharmacokinetics with sunitinib treatment-emergent adverse events in Chinese patients with renal-cell carcinoma.

Materials And Methods: We genotyped 8 keys SNPs in 6 candidate genes.