Jianchang Qian

Introduction Ziprasidone is primarily metabolized by CYP3A4, an enzyme with genetic variability and susceptibility to inhibition or induction. This study explored the functional variability of CYP3A4 in ziprasidone metabolism, focusing on drug interactions and genetic polymorphisms. Methods The metabolic inhibition and kinetic properties of zipras...

CYP3A, a key member of the cytochrome P450 (CYP450) superfamily, is integral to drug metabolism, processing a substantial portion of medications. Their role in drug metabolism is particularly prominent, as CYP3A4 and CYP3A5 metabolize approximately 30–50% of known drugs. The genetic polymorphism of CYP3A4/5 is significant inter-individual variabili...

Objectives To investigate the interaction between tramadol and representative tyrosine kinase inhibitors, and to study the inhibition mode of drug-interaction. Methods Liver microsomal catalyzing assay was developed. Sprague-Dawley rats were administrated tramadol with or without selected tyrosine kinase inhibitors. Samples were prepared and ultra...

To investigate the pharmacokinetic and pharmacodynamic profiles of volunteers carrying CYP2D6 genotypes with unknow metabolic phenotypes, a total of 22 volunteers were recruited based on the sequencing results. Peripheral blood and urine samples were collected at specific time points after oral administration of metoprolol. A validated high-perform...

Protein tyrosine kinases (RTKs) modulate a wide range of pathophysiological events in several non-malignant disorders, including diabetic complications. To find new targets driving the development of diabetic cardiomyopathy (DCM), we profiled an RTKs phosphorylation array in diabetic mouse hearts and identified increased phosphorylated fibroblast g...

Amino acid variants in protein may result in deleterious effects on enzymatic activity. In this study we investigate the DNA variants on activity of CYP2B6 gene in a Chinese Han population for potential use in precision medicine. All exons in CYP2B6 gene from 1483 Chinese Han adults (Zhejiang province) were sequenced using Sanger sequencing. The ef...

Background Inflammation and metabolic disorders are important factors in the occurrence and development of obesity complications. In this study, we investigated the protective effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, Cyy-287, on mice fed a high-fat diet (HFD). Methods The mice were randomly separated into four...

Aim: This study was conducted to determine the metabolic phenotypes of newly discovered CYP2D6 genotypes. Methods: Totally, 22 volunteers were recruited in the study. The peripheral blood and urine were collected at the indicated time after orally administration of 100 mg metoprolol. After sample preparation, a validated HPLC method was employed to...

This study aimed to investigate the interactions between icotinib/apatinib and oxycodone in rats and to unveil the underlying mechanism. An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine oxycodone and its demethylated metabolite simultaneously. In vivo , Sprague–Dawley (...

This study aimed to evaluate the effects of cytochrome P450 3A4 (CYP3A4) gene polymorphism and drug interaction on the metabolism of blonanserin. Human recombinant CYP3A4 was prepared using the Bac-to-Bac baculovirus expression system. A microsomal enzyme reaction system was established, and drug-drug interactions were evaluated using Sprague-Dawle...

Since the combination of anticancer drugs and opioids is very common, apatinib and tramadol are likely to be used in combination clinically. This study evaluated the effects of apatinib on the pharmacokinetics of tramadol and its main metabolite O-desmethyltramadol in Sprague-Dawley (SD) rats and the inhibitory effects of apatinib on tramadol in ra...

Aim: Ibuprofen is the most commonly used analgesic. CYP polymorphisms are mainly responsible for the differences in drug metabolism among individuals. Variations in the ability of populations to metabolize ibuprofen can lead to drug exposure events. The aim of this study was to evaluate the effects of CYP2C19 and CYP3A4 polymorphisms on ibuprofen...

The objective of this study was to determine the effect of flavonoids on midostaurin disposition considering co-administration and metabolic enzyme gene polymorphism. Enzymatic incubation assays were performed in vitro, while in vivo experiments were conducted in Sprague-Dawley rats. The analytes were determined via UPLC-MS/MS. We found that myrice...

The aim of this study is to investigate the effects of CYP3A4 genetic polymorphisms on the metabolism of cyclosporine (CsA) in vitro and identify drugs that interact with CsA. An enzymatic incubation system was developed to evaluate the kinetic parameters of CYP3A4 on CsA catalysis. A total of 132 drugs were screened to identify potential drug–drug...

In this study, we investigated the effect of type 1 diabetes mellitus on the modulation of the activities of CYP450s in dynamics by a UHPLC-MS/MS method. The diabetic rat model was constructed by an intraperitoneal single injection of streptozotocin. Fasting blood glucose levels >16.7 mmol/L were considered as diabetic. The rats were given a cockta...

In recent decades, EGFR-targeted tyrosine kinase inhibitors (TKIs) have been proven to be an effective therapy for EGFR-mutant non-small cell lung cancer (NSCLC). However, resistance to EGFR-TKIs limits their clinical application. In the present study, we investigate the antitumor effect and underlying mechanism of a novel pyrimidine-2,4-diamine de...

Purpose To investigate the pharmacokinetic profile and pharmacodynamics characterization of volunteers who carries newly discovered CYP2D6 genotypes. Methods Totally, 22 volunteers were recruited in the study. The peripheral blood and urine were collected at the indicated time after orally administration of metoprolol. After sample preparation, a...

This study aimed 1) to investigate the influence of CYP2D6 variants on the catalyzing of fluvoxamine, and 2) to study the interaction between fluvoxamine and apatinib. An enzymatic reaction system was setup and the kinetic profile of CYP2D6 in metabolizing fluvoxamine was determined. In vivo, drug-drug interaction was investigated using Sprague–Daw...

Heme, as an essential component of hemoproteins, is a prosthetic co-factor found in many cells, which is essential for physiologically vital oxygen transport. However, extracellular or circulatory heme is cytotoxic and triggers inflammation. Although the proinflammatory role of heme has been reported to be associated with Toll-like receptor 4 (TLR4...

Background: Elevated Ang II (angiotensin II) level leads to a range of conditions, including hypertensive kidney disease. Recent evidences indicate that FGFR1 (fibroblast growth factor receptor 1) signaling may be involved in kidney injuries. In this study, we determined whether Ang II alters FGFR1 signaling to mediate renal dysfunction. Methods:...

The aim of this study was to 1) investigate the effects of 27 CYP3A4 variants on the metabolism of osimertinib and 2) study the interactions between osimertinib and others as well as the underlying mechanism. A recombinant human CYP3A4 enzymatic incubation system was developed and employed to determine the kinetic profile of CYP3A4 variants. Ultra-...

Myeloid differential protein-2 (MD2) has been shown to play a critical role in the progression of diabetic cardiomyopathy (DCM). This study aims to explore the non-inflammatory mechanisms mediated by MD2 in DCM and to test the therapeutic effects of MD2 inhibitor C30 on DCM. Streptozotocin (STZ) was used to construct DCM model in wild-type and MD2...

Background and objective Valsartan is widely used for the treatment of moderate hypertension. However, previous studies have found that efficacy of the valsartan depends on the dose and intake. Cytochrome P450 (CYP) 2C9 metabolizes ∼15% of the clinical drugs. Genetic polymorphisms of CYP2C9 markedly affect the safety and effectiveness of many drugs...

Introduction Cytochrome P450 (CYP) is a key monooxygenase superfamily mediating the elimination of anti-hypertensive drugs. Genetic polymorphisms of CYP would lead to differential drug efficacy. Building relationships between genotype–phenotype will benefit individual medical treatment of hypertension. Areas covered The review systematically summa...

Aim Elevated inflammatory signaling has been shown to play an important role in diabetic kidney disease (DKD). We previously developed a new anti-inflammatory compound LG4. In the present study, we have tested the hypothesis that LG4 could prevent DKD by suppressing inflammation and identified the underlying mechanism. Methods Streptozotocin-induc...

Diabetic nephropathy (DN) is a chronic inflammatory renal disease induced by hyperglycemia. Recent studies have implicated cyclin-dependent kinase 9 (CDK9) in inflammatory responses and renal fibrosis. In this study, we explored a potential role of CDK9 in DN by using cultured mouse mesangial cell line SV40 MES-13 and streptozotocin-induced type 1...

Diabetic nephropathy is the leading cause of renal failure worldwide. Elevated inflammatory signaling has been shown to lead to deterioration of renal function in human and experimental diabetes. We recently developed a salviadione derivative (compound 15a) that prevented microbial lipopolysaccharide-induced inflammatory responses, which are largel...

Aim We aimed to systematically examine the effects of enzymatic activity of 38 human CYP2C9 alleles and 21 human CYP3A4 alleles, including wild-type CYP2C9.1 and CYP3A4.1, which contain the 24 CYP2C9 novel alleles (*36–*60) and 6 CYP3A4 novel alleles (*28–*34) newly found in the Chinese population, on sildenafil metabolism through in vitro experime...

Ethnopharmacological relevance Kaempferia rhizome is a famous traditional herbal medical in tropical and subtropical areas. Kaempferol (KPF) is one of the main bioactive compounds in Kaempferia rhizome, with anti-oxidant/anti-inflammatory effects demonstrated in various disease models, including cancers, obesity and diabetes. Aim of the study Infl...

Objective In this study, we aimed to investigate the potential interaction of apatinib and buspirone and underlying mechanism. Methods UPLC‐MS/MS assay was applied to determine the concentrations of buspirone and its main metabolites (1‐PP and 6‐OH buspirone) after incubated with liver microsomes. Moreover, the connection of in vitro and in vivo w...

Hyperglycemia activates toll-like receptor 4 (TLR4) to induce inflammation in diabetic cardiomyopathy (DCM). However, the mechanisms of TLR4 activation remain unclear. Here we examine the role of myeloid differentiation 2 (MD2), a co-receptor of TLR4, in high glucose (HG)- and diabetes-induced inflammatory cardiomyopathy. We show increased MD2 in h...

Diabetic kidney disease (DKD) is considered a chronic inflammatory renal disease induced by hyperglycemia. Therefore, even meticulous control of blood glucose levels cannot prevent the progression of DKD efficiently. Management of the inflammatory response could be one of the most promising strategies for treatment. We previously validated an imida...

Anlotinib is a novel inhibitor of receptor kinase tyrosine with multitargets and has a broad spectrum of inhibitory action on tumor angiogenesis and growth. A simple and rapid UHPLC-MS/MS bioanalytical method was validated for the determination of anlotinib in rat plasma, using imatinib as an internal standard. An Acquity BEH C18 column was used to...

Background: Angiotensin II (Ang II)-induced chronic inflammation and oxidative stress often leads to irreversible vascular injury, in which the endothelial to mesenchymal transition (EndMT) in the endothelial layers are involved. Schisandrin B (Sch B), a natural product isolated from traditional Schisandra chinensis, has been reported to exert vas...

An efficient protocol for highly chemoselective introduction of dithiocarbamate groups to nitrogen position of indoles with bis(dialkylaminethiocarbonyl)disulfides was achieved by employing t-BuOK as a promoter. Based on this methodology, twenty nine novel indole-dithiocarbamate compounds were prepared in moderate to excellent yields at room temper...

Purpose: We aimed to investigate efficacy and mechanism of MTI-31 (LXI-15029), a novel mTORC1/mTORC2 inhibitor currently in human trial (NCT03125746), in non-small cell lung cancer (NSCLC) models of multiple driver mutations and tyrosine kinase inhibitor (TKI)-resistance. Experimental design: Gene depletion, inhibitor treatment, immunological, f...

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), pose a major clinical challenge. The major driving force in this syndrome is pulmonary inflammation. Recent studies have shown that the naturally occurring flavonoid kaempferol (KPF) reduces endotoxin-induced inflammatory responses in mice. However, the mechani...

A novel series of di-carbonyl analogs of curcumin (DACs) were prepared and evaluated for their anti-inflammatory properties. Preliminary results showed that a vast majority of compounds tested in this study could effectively suppress LPS-induced production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Structure-activity relationships of...

Corydalis decumbens , a Traditional Chinese Medicine, has been widely used for the alternative and/or complementary therapy of hypertension, arrhythmias rheumatoid arthritis, sciatica, stroke, hemiplegia, paraplegia, and vascular embolism. The aim of this study was to determinate the potential effects of Corydalis decumbens on the five cytochrome P...

Diabetic nephropathy (DN) is a progressive kidney disease due to glomerular capillary damage in diabetic patients, with inflammation and oxidative stress implicated as crucial pathogenic factors. There is an urgent need to develop effective therapeutic drug. Natural medicines are rich resources for active lead compounds. They would provide new oppo...

Background Diabetes mellitus is a well-known risk factor for the development of heart failure. Inflammation and oxidative stress play a key role in the development of diabetic cardiomyopathy (DCM), and this nexus represents an attractive target to combat this disease. Naturally occurring flavonoid luteolin exhibits both anti-inflammatory and antiox...

Triple negative breast cancer (TNBC) is an aggressive subgroup of human breast cancer. In this study, we have examined the potential of Schisandrin B (Sch B), a bioactive chemical compound found in Schisandra chinensis, against TNBC. We used MDA-MB-231, BT-549, and MDA-MB-468 TNBC cells and immunodeficient mice to study the effect of Sch B. Our res...

Inflammation is a key factor in the pathogenesis of ALI. Therefore, suppression of inflammatory response could be a potential strategy to treat LPS-induced lung injury. Osthole, a natural coumarin extract, has been reported to protect against acute kidney injury through an anti-inflammatory mechanism, but its effect on ALI is poorly understood. In...

PurposeSuppression of inflammation and oxidative stress is an attractive strategy to against diabetic cardiomyopathy (DCM). Kaempferol (KPF) exerts both anti-inflammatory and antioxidant pharmacological properties. However, little is known about the effect of KPF on protecting myocardial injury in diabetes. The present study aimed to investigate th...

Table S1. Primers used for real‐time qPCR assay. Figure S1. The effects of 6b treatment on the profiles of body weight, blood glucose and insulin in STZ‐induced diabetic mice. Figure S2. The effects of 6b on H9c2 viability. Figure S3. The effects of 6b on cardiomyocyte size in STZ‐induced diabetic mice. Figure S4. 6b attenuates NF‐κB nucleus tr...

Inflammation and oxidative stress play a crucial role in the development of diabetic cardiomyopathy (DCM). We previously had synthesized an Aza resveratrol–chalcone derivative 6b, of which effectively suppressing lipopolysaccharide (LPS)-induced inflammatory response in macrophages. This study aimed to investigate the potential protective effect of...

The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF e...

The mechanistic target of rapamycin (mTOR) is a rational target for cancer treatment. While the mTORC1-selective rapalogs have shown significant benefits in the clinic, antitumor response may be further improved by inhibiting both mTORC1 and mTORC2. Herein, we established target profile of a novel mTOR kinase inhibitor (mTOR-KI) MTI-31 and employed...

The mechanistic target of rapamycin (mTOR) is a major regulator of cell growth and is frequently dysregulated in cancer. While mTOR complex-1 (mTORC1) is a validated cancer target, the role of mTOR complex-2 (mTORC2) remains less defined. Here, we reveal mTORC2 as a critical regulator of breast cancer metabolism. We showed that hyperphosphorylation...

Antagonizing MDM2 and MDMX to activate the tumor suppressor protein p53 is an attractive therapeutic paradigm for the treatment of glioblastoma multiforme (GBM). However, challenges remain with respect to the poor ability of p53 activators to efficiently cross the blood-brain barrier and/or blood-brain tumor barrier and to specifically target tumor...

Aim: The purpose of this study was to determine the genetic polymorphisms of the CYP2D6 gene and to elucidate the allele distribution pattern in the Chinese Han population. Materials & methods: We used PCR and bidirectional sequencing methods to analyze all nine exons of the CYP2D6 gene in 2129 unrelated, healthy Chinese Han subjects from two ge...

Genetic polymorphisms of CYP2C9 significantly influence the pharmacokinetics and pharmacodynamics of some drugs, which might result in adverse drug effects and therapeutic failure. Several studies have been performed on CYP2C9 genetic polymorphisms in Han Chinese populations. However, these studies only focused on two commonly investigated alleles,...

Aim: This study aims to systematically investigate the genetic polymorphisms of the CYP2C19 gene and provide accurate data of the allele distribution pattern in the Chinese Han population. Materials & methods: We amplified all nine exons of the CYP2C19 gene in 2127 unrelated healthy Chinese Han subjects from two geographical locations (Zhejiang...

A sensitive and accurate isotope-diluted LC-MS/MS method was developed for determination of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn), derived from DNA, and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), derived from RNA, in various tissue specimens obtained from normal SAMR1 and senescence-accelerated SAMP8 mice. An age-dependent accumulation of o...

  Colorectal cancer is one of the most rapidly increasing cancers in the world, and accumulation of alterations in oncogenes, tumour suppressor genes and mismatch repair (MMR) genes contributes to colorectal tumorigenesis. Thus, we investigated the alterations of 14 microsatellite loci adjacent to MMR genes, p53, adenomatous polyposis coli (APC) an...

To develop a high performance liquid chromatography method for the simultaneous determination of cortisone and cortisol in rat serum and apply it for pharmacokinetics. After addition of pir-fenidone as internal standard (IS), a liquid-liquid extraction with ethylacetate was employed for the sample preparation. Samples were separated on Zorbax SB-C1...