LC-HRMS methods for the quantification of two artemisinin drugs and their metabolites in rat blood and plasma.

As first-line antimalarials used in the artemisinin combination therapy, artemisinin drugs exert their action inside red blood cells. However, the blood pharmacokinetic characteristics of artemisinin drugs have not been fully revealed owing to their built-in chemical instability initiated by Fe released from hemoglobin, with limited information on their metabolites. In this study, liquid chromatography tandem high-resolution mass spectrometric (LC-HRMS) methods were developed for the quantification of two representative artemisinin drugs (artemisinin, ART; dihydroartemisinin, DHA) and their respective metabolite (deoxyartemisinin, D-ART; dihydroartemisinin glucuronide, DHA-Glu) in rat blood/plasma.

The antiplasmodial activity of the carboxylic acid metabolite of piperaquine and its pharmacokinetic profiles in healthy volunteers.

Background: The long-acting antimalarial drug piperaquine can be metabolized into the carboxylic acid metabolite (PQM). However, the clinical relevance of PQM remains unclear.

Objectives: The pharmacodynamics/pharmacokinetics of PQM were studied.

Protein Dynamics Mediated by Cardiolipin in Bacteria.

Bacterial proteins targeting the appropriate subcellular sites are the base for their proper function. Several studies have shown that the anionic phospholipid cardiolipin (CL), a conical lipid preferring negative membrane curvature, modulates the lipid bilayers' structure, which impacts the activity of their resident proteins. Due to the favor of negative membrane curvature, CL is not randomly distributed in the bacterial plasma membrane.

Transcriptome Profiling of Male Adult .

Background: The pathogen of angiostrongyliasis is the parasite and the transcriptome profiling of the male adult was unclear. We aimed to understand how the male adults adapt, so the expression profile of adult males was analyzed.

Methods: In order to improve the understanding of the transcriptome of adult males, RNA from three groups of male adult was extracted and reverse transcribed to construct cDNA libraries.

The Effect of Retroconversion Metabolism of -oxide Metabolites by Intestinal Microflora on Piperaquine Elimination in Mice, as well as in Humans Predicted Using a PBPK Model.

Background: Piperaquine (PQ) and its pharmacologically active metabolite PQ -oxide (PM1) can be metabolically interconverted via hepatic cytochrome P450 and FMO enzymes.

Objectives: The reductive metabolism of PM1 and its further -oxidation metabolite (PM2) by intestinal microflora was evaluated, and its role in PQ elimination was also investigated.

Methods: The hepatic and microbial reduction metabolism of PM1 and PM2 was studied .

Corrigendum: Ultrasonic washing as an abiotic elicitor to induce the accumulation of phenolics of fresh-cut red cabbages: Effects on storage quality and microbial safety.

[This corrects the article DOI: 10.3389/fnut.2022.

Ultrasonic washing as an abiotic elicitor to induce the accumulation of phenolics of fresh-cut red cabbages: Effects on storage quality and microbial safety.

Ultrasonic washing has been proved to be an abiotic elicitor to induce the accumulation of phenolics in some fruit and vegetables. However, the feasibility of ultrasonic washing on the accumulation of phenolics in fresh-cut red cabbages has not yet been reported. Therefore, the effects of ultrasonic washing on the phenolics and related phenolic metabolism enzymes of fresh-cut red cabbages, as well as quality and microbial safety during cold storage, were investigated.

Geniposide attenuates postischemic long-term potentiation via GluN2A.

N-Methyl-D-aspartate receptor (NMDAR)-induced antioxidation is a significant cause of neuronal injury after ischemic stroke. In a previous work, we verified the neuroprotective roles of geniposide during tMCAO in vivo. However, it remains unknown whether geniposide ameliorates injury to hippocampal neurons during Ischemic Long Term Potentiation (iLTP) induction in vitro.

A scalable and reproducible preparation for the antitumor protein TLC, a human-derived telomerase inhibitor.

Telomerase, which is overexpressed in approximately 90% of liver cancer cells, is an ideal target for anti-liver cancer therapy. LPTS, a putative liver tumor suppressor, is the only human-derived protein that can bind telomerase directly and inhibit the extension of telomere activity. Our previous studies demonstrated that TAT-LPTS-LC (TLC), a recombinant protein fused by the C-terminal 133-328 fragment of LPTS and TAT peptides, could be delivered into cells to inhibit telomerase-positive hepatoma cell growth in vitro and in vivo with very low toxicity.

The immunoenhancement effects of sea buckthorn pulp oil in cyclophosphamide-induced immunosuppressed mice.

In this study, the immunomodulatory effect of sea buckthorn (SBT) pulp oil was elucidated in immunosuppressed Balb/c mice induced by cyclophosphamide (CTX). The results showed that SBT pulp oil could reverse the decreasing trend of body weight, thymus/spleen index and hematological parameters induced by CTX. Compared with immunosuppressive mice induced by CTX, SBT pulp oil could enhance NK cytotoxicity, macrophage phagocytosis, and T lymphocyte proliferation, and regulate the proportion of T cell subsets in mesenteric lymph nodes (MLN), and promote the production of secretory immunoglobulin A (sIgA), IFN-γ, IL-2, IL-4, IL-12 and TNF-α in the intestines.

Colon cancer-associated transcript-1 enhances glucose metabolism and colon cancer cell activity in a high-glucose environment and .

Background: Our study aims to investigate the effect of colon cancer-associated transcript-1 (CCAT-1) on colon cancer cells' activity and metabolism under different glucose environments and .

Methods: The levels of proliferation, migration, glucose, lactic acid, glucose metabolism-related enzymes, apoptosis genes, epithelial-mesenchymal transition (EMT) marker proteins, and PI3K/Akt/C-MYC pathway in -silenced SW620 cells cultured with different glucose levels were tested. Twenty BALB/C nude mice with hyperglycemia or normal blood sugar were transplanted with -silenced SW620 cells, blood glucose levels, lactic acid, insulin, and volume of transplanted tumor cells, the expression of EMT marker proteins, and PI3K/Akt/C-MYC pathway was detected.

Glycine attenuates cerebrovascular remodeling via glycine receptor alpha 2 and vascular endothelial growth factor receptor 2 after stroke.

As a dual-acting neurotransmitter, glycine plays critical roles in cerebral ischemia by activating both glycine receptors (GlyRs) and N-methyl-D-aspartate acid receptors (NMDARs). However, the involvement of glycine receptor alpha 2 (GlyRa2) in cerebral ischemia has not been explored. The objective of this study was to determine the mechanism of action of GlyRa2 in cerebrovascular remodeling.

Identification of the association of CD28 CD244 Tc17/IFN-γ cells with chronic hepatitis C virus infection.

CD8 T cells play multiple and complex immunological roles including antiviral, regulatory, and exhaustive effects in hepatitis C virus (HCV) infected patients. Some CD8 T-cell subsets were confirmed to be closely related to HCV infection such as T , T , T RA, Tc17, and CD8 Treg. Herein, we report a new subset of interleukin (IL)-17/interferon (IFN)-γ producing CD8 T (Tc17/IFN-γ) cells that markedly correlate with CD28 CD244 cells, IL-17 levels, and HCV RNA in HCV patients.

Decision-making among the substitute decision makers in intensive care units: An investigation of decision control preferences and decisional conflicts.

Aims: To explore decision control preferences and decisional conflicts and to analyse their association among the surrogate decision makers in the intensive care unit.

Design: The study carried out a cross-sectional survey among the surrogates.

Methods: The participants were 115 surrogate decision makers of critical patients, from August to September 2019.

Discovery of a natural fluorescent probe targeting the Plasmodium falciparum cysteine protease falcipain-2.

The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an attractive antimalarial target. Here, we discovered that the natural compound NP1024 is a nonpeptidic inhibitor of FP-2 with an IC value of 0.44 μmol L.

Constitutively expressed MHC class Ib molecules regulate macrophage M2b polarization and sepsis severity in irradiated mice.

Macrophages can change their physiology in response to microenvironmental signals. This differentiation into classically activated M1 or alternatively activated M2 macrophages is known as polarization. In this study, we isolated bone marrow-derived macrophages from β2m-deficient (deficient in both MHC class Ia and Ib) and K D -deficient (deficient only in MHC class Ia) mice and found that β2m-deficient macrophages showed a significantly lower M2b polarization efficiency.

The anti-aging effects of Gracilaria lemaneiformis polysaccharide in Caenorhabditis elegans.

The anti-aging activity of marine macroalgae Gracilaria lemaneiformis polysaccharide (GP) on Caenorhabditis elegans was evaluated by observing the lifespan, reproduction, pharyngeal pumping and stress response of worms. Moreover, quantitative fluorescence of polyglutamic acid and nuclear localization of DAF-16 were observed. The results showed that GP treatment enhanced the mean lifespan by over 16.

Synthesis, Design, and Structure⁻Activity Relationship of the Pyrimidone Derivatives as Novel Selective Inhibitors of Dihydroorotate Dehydrogenase.

The inhibition of dihydroorotate dehydrogenase (DHODH) potentially represents a new treatment option for malaria, as relies entirely on a de novo pyrimidine biosynthetic pathway for survival. Herein, we report a series of pyrimidone derivatives as novel inhibitors of DHODH. The most potent compound, , showed high inhibition activity against DHODH (IC = 23 nM), with >400-fold species selectivity over human dihydroorotate dehydrogenase (DHODH).

Metabolism of Piperaquine to Its Antiplasmodial Metabolites and Their Pharmacokinetic Profiles in Healthy Volunteers.

As a partner antimalarial for artemisinin drug-based combination therapy (ACT), piperaquine (PQ) can be metabolized into two major metabolites, including piperaquine -oxide (M1) and piperaquine ,-dioxide (M2). To better understand the antimalarial potency of PQ, the antimalarial activity of the PQ metabolites (M1 and M2) was studied (in strains 3D7 and Dd2) and (in the murine species ) in this study. The recrudescence and survival time of infected mice were also recorded after drug treatment.

Transcriptomic Analysis Reveals Genes Mediating Salt Tolerance through Calcineurin/CchA-Independent Signaling in .

Adaptation to changes in the environment is crucial for the viability of all organisms. Although the importance of calcineurin in the stress response has been highlighted in filamentous fungi, little is known about the involvement of ion-responsive genes and pathways in conferring salt tolerance without calcium signaling. In this study, high-throughput RNA-seq was used to investigate salt stress-induced genes in the parent, Δ, and ΔΔ strains of , which differ greatly in salt adaption.

MHC class II peptides induce CD8CD44Ly49 regulatory T cells in C57BL/6 mice.

CD8 regulatory T cells (Tregs) play an important role in regulating peripheral immune tolerance. However, difficulties in the characterization of CD8 Tregs that lack suitable markers have a considerably limited research in this area. Moreover, the induction and effector mechanisms of CD8 Tregs remain unclear.