Synergistic effect of regorafenib with aminoglycosides in ferroptosis-mediated liver injury.

Background: Combination therapy of anticancer drugs with antibacterial agents has numerous advantages, but these may develop adverse drug events that were rarely studied. Specifically, regorafenib (REGO) mediates ferroptosis and causes liver injury when used in combination with aminoglycosides (AGs); however, this interaction remains unexplored.

Methodology: The study was conducted using both and assays involving Sprague-Dawley (SD) rats and HepG2/Huh7 to investigate ferroptosis-associated liver injury.

Inhibition of CYP1B1 by miR-200b-3p increases the sensitivity of paclitaxel in hepatocellular carcinoma treatment.

Liver cancer ranks as the third leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90 % of primary liver cancer cases. Elevated expression of drug-metabolizing enzyme CYP1B1 in HCC has been identified as a potential contributor to primary paclitaxel (PTX) resistance. This study demonstrated that miR-200b-3p suppresses CYP1B1 expression in HCC cells.

Bi-targeting of thioredoxin 1 and telomerase by thiotert promotes cell death of myelodysplastic syndromes and lymphoma.

Thioredoxin1 (TRX1) and telomerase are both attractive oncology targets that are tightly implicated in tumor initiation and development. Here, we reported that the 6-dithio-2-deoxyguanosine analog thiotert exhibits an effective cytotoxic effect on myelodysplastic syndromes (MDS) cell SKM-1 and lymphoma cell U-937. Further studies confirmed that thiotert effectively disrupts cellular redox homeostasis, as evidenced by elevated intracellular reactive oxygen species (ROS) levels, increased MnSOD, accelerated DNA impairment, and activated apoptosis signal.

A reliable LC-MS/MS method for the quantification of natural amino acids in human plasma and its application in clinic.

A simple and fast LC-MS/MS method was developed and validated for simultaneous quantification of 20 L-amino acids (AAs) in human plasma. Chromatographic separation was achieved on an Agilent AdvanceBio Hilic column within 15 min via gradient elution with an aqueous solution containing 5 mM ammonium formate, 5 mM ammonium acetate and 0.1 % formic acid and an organic mobile phase containing 0.

Nervonic acid protects against oligodendrocytes injury following chronic cerebral hypoperfusion in mice.

Chronic cerebral hypoperfusion (CCH) has been acknowledged as a potential contributor to cognitive dysfunction and brain injury, causing progressive demyelination of white matter, oligodendrocytes apoptosis and microglia activation. Nervonic acid (NA), a naturally occurring fatty acid with various pharmacological effects, has been found to alleviate neurodegeneration. Nonetheless, evidence is still lacking on whether NA can protect against neurological dysfunction resulting from CCH.

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.

Regulation mechanism of endoplasmic reticulum stress on metabolic enzymes in liver diseases.

The endoplasmic reticulum (ER) plays a pivotal role in protein folding and secretion, Ca storage, and lipid synthesis in eukaryotic cells. When the burden of protein synthesis and folding required to be handled exceeds the processing capacity of the ER, the accumulation of misfolded/unfolded proteins triggers ER stress. In response to short-term ER stress, the unfolded protein response (UPR) is activated to allow cells to survive.

SND1 Regulates Organic Anion Transporter 2 Protein Expression and Sensitivity of Hepatocellular Carcinoma Cells to 5-Fluorouracil.

Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world. Inadequate efficacy of 5-fluorouracil (5-FU) on HCC could be related to low expression of human organic anion transporter 2 (OAT2). However, the knowledge of downregulation of OAT2 in HCC remains limited.

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.

Design and analysis of self-priming extension DNA hairpin probe for miRNA detection based on a unified dynamic programming framework.

MicroRNAs (miRNAs) are potential biomarkers for cancer diagnosis and prognosis, methods for detecting miRNAs with high sensitivity, selectivity, and stability are urgently needed. Various nucleic acid probes that have traditionally been for this purpose suffer several drawbacks, including inefficient signal-to-noise ratios and intensities, high cost, and time-consuming method establishment. Computing tools used for investigating the thermodynamics of DNA hybridization reactions can accurately predict the secondary structure of DNA and the interactions between DNA molecules.

DR30318, a novel tri-specific T cell engager for Claudin 18.2 positive cancers immunotherapy.

Background: Claudin 18.2 (CLDN18.2) is a highly anticipated target for solid tumor therapy, especially in advanced gastric carcinoma and pancreatic carcinoma.

Dual targeting agent Thiotert inhibits the progression of glioblastoma by inducing ER stress-dependent autophagy.

Glioblastoma (GBM) is the most aggressive and lethal type of tumor in the central nervous system, characterized by a high incidence and poor prognosis. Thiotert, as a novel dual targeting agent, has potential inhibitory effects on various tumors. Here, we found that Thiotert effectively inhibited the proliferation of GBM cells by inducing G2/M cell cycle arrest and suppressed the migratory ability in vitro.

VARIDT 3.0: the phenotypic and regulatory variability of drug transporter.

The phenotypic and regulatory variability of drug transporter (DT) are vital for the understanding of drug responses, drug-drug interactions, multidrug resistances, and so on. The ADME property of a drug is collectively determined by multiple types of variability, such as: microbiota influence (MBI), transcriptional regulation (TSR), epigenetics regulation (EGR), exogenous modulation (EGM) and post-translational modification (PTM). However, no database has yet been available to comprehensively describe these valuable variabilities of DTs.

Physiologically Based Pharmacokinetic Modeling for Prediction of 5-FU Pharmacokinetics in Cancer Patients with Hepatic Impairment After 5-FU and Capecitabine Administration.

Purpose: 5-fluorouracil (5-FU) and its prodrug capecitabine are commonly prescribed anti-tumor medications. We aimed to establish physiologically based pharmacokinetic (PBPK) models of capecitabine-metabolites and 5-FU-metabolites to describe their pharmacokinetics in tumor and plasma of cancer patients with liver impairment.

Methods: Models including the cancer compartment were developed in PK-Sim® and MoBi® and evaluated by R programming language with 25 oral capecitabine and 18 intravenous 5-FU studies for cancer patients with and without liver impairment.

MiR-183-5p promotes renal cell carcinoma metastasis by targeting TET1.

Ten-eleven translocation 1 (TET1) is a member of the DNA demethylase family that regulates the methylation level of the genome. Dysregulation of TET1 in renal cell carcinoma (RCC) may be associated with RCC progression, but the mechanism of TET1 down-regulation in RCC is not yet known. MiR-183-5p is up-regulated in various tumor tissues and acts as an oncogene.

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.

A duplex-specific nuclease (DSN) and catalytic hairpin assembly (CHA)-mediated dual amplification method for miR-146b detection.

A novel method for detecting miRNA has been developed using a combination of duplex-specific nuclease signal amplification (DSNSA) and a catalytic hairpin assembly (CHA). In this work, a biotinylated trigger release (BTR) probe with a biotin group at the 3'-end and a CHA reaction sequence trigger as an initiator (catalyst I) at the 5'-end was designed to hybridize target miRNA. The DSN enzyme was introduced to initiate the DSNSA.

Oligomerization of the HBV/HDV functional receptor NTCP expressed in Sf9 insect cell.

Background: Sodium taurocholate co-transportering polypeptide (NTCP, SLC10A1) is a vital bile acid transporter and the functional receptor of hepatitis B and D virus. The oligomerization of NTCP is important for the structural study of its interaction with HBV preS1 peptide.

Methods: Recombinant NTCPs were expressed in Sf9 host cell using baculoviruses.

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.