Design and Antimalarial Evaluation of Polydopamine-Modified Methyl Artelinate Nanoparticles.

Targeted nanodrug delivery systems are highly anticipated for the treatment of malaria. It is known that can induce new permeability pathways (NPPs) on the membrane of infected red blood cells (iRBCs) for their nutrient uptake. The NPPs also enable the uptake of nanoparticles (NPs) smaller than 80 nm.

2-Monoacylglycerol Mimetic Liposomes to Promote Intestinal Lymphatic Transport for Improving Oral Bioavailability of Dihydroartemisinin.

Purpose: Reducing the first-pass hepatic effect via intestinal lymphatic transport is an effective way to increase the oral absorption of drugs. 2-Monoacylglycerol (2-MAG) as a primary digestive product of dietary lipids triglyceride, can be assembled in chylomicrons and then transported from the intestine into the lymphatic system. Herein, we propose a biomimetic strategy and report a 2-MAG mimetic nanocarrier to target the intestinal lymphatic system via the lipid absorption pathway and improve oral bioavailability.

Co-delivery of doxorubicin-dihydroartemisinin prodrug/TEPP-46 nano-liposomes for improving antitumor and decreasing cardiotoxicity in B16-F10 tumor-bearing mice.

In order to reduce the cardiotoxicity of doxorubicin (DOX) and improve its antitumor effect, dihydroartemisinin (DHA) and DOX prodrug (DOX-S-DHA) synthesized via a single sulfur bond was used with TEPP-46 to prepare nano-liposomes (DOX-S-DHA@TEPP-46 Lips). In which, TEPP-46 was expected to exert p53 bidirectional regulation to promote the synergistic antitumor effect of DOX and DHA while reducing cardiotoxicity. DOX-S-DHA@TEPP-46 Lips exhibited uniform particle size, good stability, and excellent redox-responsive activity.

Genetically predicted 486 blood metabolites concerning risk of systemic lupus erythematosus: a Mendelian randomization study.

Metabolic abnormalities constitute a significant characteristic of systemic lupus erythematosus (SLE). We utilised a two-sample Mendelian randomisation (MR) study to evaluate the potential causal association between 486 blood metabolites and SLE. Exposure data at the metabolite level were extracted from 7824 European Genome-wide association studies (GWAS).

Novel multi-component crystals of berberine with improved pharmaceutical properties.

As an extremely popular natural product, berberine (BER) is mainly used for gastroenteritis and diarrhoea caused by bacteria. Research has also revealed the potent and extensive pharmacological properties of BER including its anti-arrhythmic, anti-tumour, anti-inflammatory and hypoglycemic activities and so on; therefore, BER is a promising drug for further development. However, its commercial form with hydrochloride exhibits poor stability and solubility, which are detrimental to its clinical therapeutic effects.

Docetaxel prodrug and hematoporphyrin co-assembled nanoparticles for anti-tumor combination of chemotherapy and photodynamic therapy.

To realize the synergistic anti-tumor effect of chemotherapy and photodynamic therapy, the mono sulfide-modified docetaxel (DTX) prodrugs (DSD) provided by our laboratory and hematoporphyrin (HP) were used to physically prepare co-assembled nanoparticles (DSD/HP NPs) by nano-precipitation. For the first time, this study showed its characteristics, anti-tumor activity, pharmacokinetic behavior in rats, distribution, and pharmacodynamic effects on 4T1 tumor-bearing Bal b/c mice. DSD/HP NPs optimized by single-factor and response surface optimization had several distinct characteristics.

Bacteriological Profile and Antimicrobial Susceptibility Patterns of Gram-Negative Bloodstream Infection and Risk Factors Associated with Mortality and Drug Resistance: A Retrospective Study from Shanxi, China.

Objective: The aim of this study was to analyze the epidemiological of gram-negative bloodstream infection (GNBSI) and establish a risk prediction model for mortality and acquiring multidrug resistant (MDR), the extended spectrum beta-lactamases (ESBLs) producing and carbapenem-resistant (CR) GNBSI.

Methods: This retrospective study covered five years from January 2015 to December 2019. Data were obtained from Hospital Information System (HIS) and microbiology department records.

Construction of reduction-sensitive heterodimer prodrugs of doxorubicin and dihydroartemisinin self-assembled nanoparticles with antitumor activity.

Doxorubicin (DOX) is used as a first-line chemotherapeutic drug, whereas dihydroartemisinin (DHA) also shows a certain degree of antitumor activity. Disulfide bonds (-SS-) in prodrug molecules can be degraded in highly reducing environments. Thus, heterodimer prodrugs of DOX and DHA linked by a disulfide bond was designed and subsequently prepared as reduction-responsive self-assembled nanoparticles (DOX-SS-DHA NPs).

Design of red blood cell membrane-cloaked dihydroartemisinin nanoparticles with enhanced antimalarial efficacy.

Targeting delivery and prolonging action duration of artemisinin drugs are effective strategies for improving antimalarial treatment outcomes. Here, dihydroartemisinin (DHA) loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PDNs) were prepared and further cloaked with red blood cell (RBC) membranes via electrostatic interactions to yield RBC membrane-cloaked PDNs (RPDNs). The prepared RPDNs displayed a notable "core-shell" structure, with a negative surface charge of -29.

Xanthohumol Induces ROS through NADPH Oxidase, Causes Cell Cycle Arrest and Apoptosis.

Reactive oxygen species (ROS) are either toxic in excess or essential for redox signalling at the physiological level, which is closely related to the site of generation. Xanthohumol (XN) is an important natural product of hops ( L.) and was reported to induce ROS in mitochondria.

Examination of the differences between sulforaphane and sulforaphene in colon cancer: A study based on next-generation sequencing.

Sulforaphane and sulforaphene are isothiocyanate compounds derived from cruciferous vegetables that have demonstrated antiproliferative properties against colon cancer. However, the underlying mechanism of action of these two compounds has yet to be elucidated. The aim of the present study was to examine the effects of sulforaphane and sulforaphene on colon cancer using next-generation sequencing (NGS).

Murine pharmacokinetics and antimalarial pharmacodynamics of dihydroartemisinin trimer self-assembled nanoparticles.

Currently, conjugation of artemisinin-derived dimers, trimers, and tetramers is a viable strategy for developing new effective antimalarial candidates. Furthermore, nanotechnology is an effective means to achieve intravenous administration of hydrophobic drugs. In this paper, an ester-linked dihydroartemisinin trimer (DHA) was synthesized and further prepared as self-assembled nanoparticles (DHANPs) by a one-step nanoprecipitation method.

Performance Evaluation of Warfarin Dose Prediction Algorithms and Effects of Clinical Factors on Warfarin Dose in Chinese Patients.

Background: The clinical utility of warfarin dose prediction algorithms remains controversial, our purpose is to evaluate the performance of warfarin dose prediction algorithms and the effects of clinical factors on warfarin dose in Chinese patients.

Methods: Clinical data of 217 patients who received warfarin treatment were used to assess 6 warfarin dose prediction algorithms (OHNO, IWPC [International Warfarin Pharmacogenetics Consortium], HUANG, KIM, BRESS, and MIAO). The predicted dose (PD) was compared with the warfarin optimal dose (WOD, defined as the dose that maintains the international normalized ratio within the target range of 2.

Choline and PEG dually modified artemether nano delivery system targeting intra-erythrocytic and its pharmacodynamics .

Objective: The choline derivative (CD) and polyethylene-glycol (PEG) dually modified artemether (ARM) nanostructured lipid carriers (CD-PEG-ARM-NLC) have been designed to prolong the circulation of ARM in blood, as well as to develop targeting for new permeability pathways (NPPs) and erythrocyte choline carriers (ECCs) that are expressed on the infected erythrocyte membrane.

Significance: The CD-PEG-ARM-NLC constructed in this study was found to be able to target endoerythrocytic by increasing the drug concentration and residence time in the infected erythrocytic microenvironment and minimizing toxicity and side effects.

Methods: CD-PEG-ARM-NLC was prepared using high-pressure homogenization followed by physicochemical characterization.

Identification of sulforaphane regulatory network in hepatocytes by microarray data analysis based on GEO database.

For the past several years, more and more attention has been paid to the exploration of traditional medicinal plants. Further studies have shown that more dietary consumption of cruciferous vegetables can prevent the occurrence of tumor, indicating the potential applications in the chemoprevention of cancer. Sulforaphane (SFN) has been identified by the National Cancer Institute as a candidate for chemopreventive research; it is one of several compounds selected by the National Cancer Institute's Rapid Access to Preventive Intervention Development Program and is currently in use.

Auto-Induction of Intestinal First-Pass Effect Related Time-Dependent Pharmacokinetics of Artemisinin Rather than Dihydroartemisinin.

Artemisinin (ART) drugs showed declining plasma concentrations after repeated oral dosing, known as time-dependent pharmacokinetics (PK). ART and dihydroartemisinin (DHA) were adopted as representatives to evaluate the roles of first-pass effects and systemic metabolism in time-dependent PK by comparison of oral versus intravenous administration and 1 dose versus 5 consecutive doses PK in rats and dogs, respectively. The hepatic extraction ratio (ER) and the intestinal elimination changes were further investigated in rats to distinguish the roles of hepatic first-pass effect or intestinal first-pass effect.

Solvates of acotiamide hydrochloride: characterization and phase transformation.

Five novel crystals of acotiamide hydrochloride (AH) with solvates dimethyl formide (DMF), dimethyl sulfoxide (DMSO), ethyl acetate (EA) and water (W) [1AH-1W-1DMF, 1AH-1DMSO-I, 1AH-1DMSO-II, 1AH-1W-1DMSO and 2AH-2DMSO-1EA] were characterized using single-crystal X-ray diffraction, powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy. The five crystals can be divided into four distinct structural types based on analysis of their similarities; 1AH-1W-1DMF and 1AH-1W-1DMSO are isostructural. The benzene rings in 1AH-1DMSO-I, 1AH-1DMSO-II and 2AH-2DMSO-1EA can rotate 180°, and the intramolecular hydrogen bond changes from an OH.

Surface-enhanced Raman Spectroscopy Coupled with Dispersive Solid-phase Extraction for the Rapid Detection of Tricyclazole Residues in Rice and Brassica campestris L. ssp. chinensis var. utilis Tsen.

An efficient methodology has been developed to determine the tricyclazole residue in matrix based on surface-enhanced Raman scattering (SERS) coupled with dispersible matrix solid-phase extraction. After pretreatment and test conditions optimization, peaks at 1373 and 1317 cm in the SERS spectrum were respectively selected as quantitative peaks for rice and Brassica campestris L. ssp.

[Method for rapid synchronization of different growth cycles of Plasmodium falciparum in vitro and application in differential gene expression profile of 3D7 after dihydroartemisinin treatment].

Plasmodium culture in vitro is often used as an antimalarial drug evaluation model, but the lifecycle of P. falciparum culture in vitro tends to be disordered, which affects the research and evaluation of antimalarial drug mechanism in vitro. By combining magnetic bead separation method with sorbitol synchronization method, a synchronization method was constructed to quickly acquire different lifecycles of P.

and evaluation of dihydroartemisinin prodrug nanocomplexes as a nano-drug delivery system: characterization, pharmacokinetics and pharmacodynamics.

To develop new, more effective and lower toxicity antitumor dihydroartemisinin (DHA) nanocomplexes, a DHA prodrug synthesized in this study was used to prepare DHA prodrug self-assembled nanocomplexes (DHANPs) by molecular self-assembly technology. The optimization, pharmacokinetics and and antitumor efficiency of DHANPs were assessed. The results showed that the entrapment efficiency, drug loading, particle size and zeta potential of the optimized formulation were 92.

Construction and anti-tumor activities of disulfide-linked docetaxel-dihydroartemisinin nanoconjugates.

Co-delivery of anti-tumor agents with outstanding stimulus-triggered drug release in tumor cells, especially with the aid of nanotechnology, provided the possibility to enhance delivery efficiency for targeting tumor cells and antitumor efficacy. In this paper, docetaxel-dihydroartemisinin nanoconjugates linked by disulfide bond were designed to increase co-delivery and anti-tumor efficacy. Docetaxel and dihydroartemisinin were synthesized using two-step reaction and furtherly assembled to nanoconjugates.

antimalarial activity and pharmacokinetics of artelinic acid-choline derivative liposomes in rodents.

It is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method.

Delivery of Antisense Oligonucleotide LOR-2501 Using Transferrin-conjugated Polyethylenimine-based Lipid Nanoparticle.

Background/aim: Efficient delivery of antisense oligonucleotide (ASO) by nanoparticle vectors is critical for its clinical application. The aim of this study was to design and evaluate a novel ASO vector TPSH-LP consisting of a reduction-sensitive cationic polymer PEI-SS-HA (PSH), lipids and transferrin (Tf) as a targeting ligand.

Materials And Methods: PSH was synthesized based on PEI 25 kDa.

Antimalarial activity and metabolism of dihydroartemisinin-derived dimer.

The dihydroartemisinin-derived dimer (DHA dimer) was synthesized, and its antimalarial activities were evaluated both in vitro and in vivo. The dimer IC value of 0.51 ± 0.

Construction and cellular uptake evaluation of redox-responsive docetaxel prodrug self-assembled nanoparticles.

Docetaxel (DTX) solution has some serious adverse side effects. A redox-responsive DTX prodrug synthesized in our laboratory was used to prepare DTX prodrug self-assembled nanoparticles (DSNPs) with the method of nanoprecipitation. This study aimed at optimizing the formulation to develop stable preparation for the delivery of DTX.