Development, validation, and clinical application of a UPLC-MS/MS method for omadacycline determination in human serum.

Background: Omadacycline is the first aminomethyl-tetracycline variety to successfully enter clinical applications. To support regular therapeutic drug monitoring (TDM) in clinical practice, an ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed that would allow omadacycline quantification in human serum.

Methods: Proteins were precipitated from serum samples using methanol.

Development, Validation, and Clinical Application of an Ultra-High-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for the Determination of 10 Antituberculosis Drugs in Human Serum.

Introduction: Linezolid, moxifloxacin, rifapentine, rifabutin, cycloserine, clofazimine, bedaquiline, levofloxacin, prothionamide, and ethionamide are commonly used second-line antituberculosis (anti-TB) drugs. To support therapeutic drug monitoring in regular clinical practice, the authors sought to develop a method based on ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) that would allow for the simultaneous quantification of multiple second-line anti-TB drugs in human serum.

Methods: Analytes were extracted from human serum by protein precipitation.

Mechanism underlying linezolid-induced peripheral neuropathy in multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) remains a main global health concern as there is no comprehensive therapeutic intervention yet and numerous adverse effects follow the therapeutic process. In recent years, linezolid has been frequently used for treating MDR-TB. However, peripheral neuropathy associated with linezolid has reduced patient compliance.

Downregulation of the farnesoid X receptor promotes colorectal tumorigenesis by facilitating enterotoxigenic Bacteroides fragilis colonization.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the world. The downregulation of farnesoid X receptor (FXR) is frequently founded in CRC patients. The current study found that the decreased expression of FXR in colorectal cancer leads to disorders of bile acids (BAs) metabolism.

LncRNA regulation: New frontiers in epigenetic solutions to drug chemoresistance.

Long-noncoding RNAs (lncRNAs) have been shown to participate in sensitizing or de-sensitizing cancer cells to chemical drugs during cancer therapeutics. Notably, a plethora of lncRNAs have been confirmed to be associated with epigenetic controllers and regulate histone protein modification or DNA methylation states in the process of gene transcription. This correlation between lncRNAs and epigenetic regulators can induce the expression of core genes to trigger drug resistance.

Progress and trends on the analysis of nucleic acid and its modification.

Nucleic acid is a collective term of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), and it is an essential substance in all known life forms. As numerous of studies have shown that nucleic acids can be used as therapeutic agents and the abnormality of various nucleic acid and its modification level has been proven to be closely bound up with changes in diseases such as cancer, the development of analytical methods for the nucleic acid and its modification has become one of the research hotspots in the field of life sciences. Compared with classical nucleic acid detection methods such as Northern blotting, Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) and Polymerase Chain Reaction (PCR), novel analytical methods based on nanomaterials, nucleic acid amplification strategies and biosensors can better satisfy the needs for sensitivity and simplicity in current clinical diagnosis.

Metabolic interactions between flumatinib and the CYP3A4 inhibitors erythromycin, cyclosporine, and voriconazole.

Flumatinib, indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, is a structural analog of imatinib and has shown higher potency than imatinib as a BCR-ABL inhibitor. In this paper, the metabolic profile of flumatinib was studied. It was found that CYP3A4 and CYP2C8 were the main cytochrome P450 enzyme substyles catalyzing the metabolism of flumatinib, and CYP3A4 has a stronger metabolic ability for flumatinib than CYP2C8.

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.

Epigenetic Mechanisms Underlying Organic Solute Transporter Repression in Colorectal Cancer.

Colorectal cancer (CRC) is known to be the third most common cancer disease and the fourth-leading cause of cancer-related deaths worldwide. Bile acid, especially deoxycholic acid and lithocholic acid, were revealed to play an important role during carcinogenesis of CRC. In this study, we found organic solute transporter (OST), an important subunit of a bile acid export transporter OST-OST, was noticeably downregulated in CRC.