Targeting renal OATs to develop renal protective agent from traditional Chinese medicines: Protective effect of Apigenin against Imipenem-induced nephrotoxicity.

Imipenem (Imp) is a widely used broad-spectrum antibiotic. However, renal adverse effects limit its clinical application. We previously reported that organic anion transporters (OATs) facilitated the renal transport of Imp and contributed its nephrotoxicity.

A conjugated mTOR/MEK bifunctional inhibitor as potential polypharmacological anticancer agent: the prototype compound discovery.

mTOR/MEK bifunctional inhibitors have the potential to surmount the drug resistance aroused from cross talk between PI3K/Akt/mTOR (PAM) and Ras/MEK/ERK pathways. Herein, we report the discovery of a conjugated dual-targeted molecule, compound , as the prototype mTOR/MEK bifunctional inhibitor. It exhibited moderately high inhibitory activity against mTOR and MEK1 with IC values of 0.

Microwave roasting of blast furnace slag for carbon dioxide mineralization and energy analysis.

For both the waste treatment of large quantities of blast furnace (BF) slag and carbon dioxide (CO) that are discharged in ironworks, mineral carbonation by BF slag was proposed in this decade. However, it has not been widely used due to its high energy consumption and low production efficiency. In this study, a microwave roasting method was employed to mineralize CO with BF slag, and the process parameters for the sulfation and energy consumption were investigated.

Organic anion transporters also mediate the drug-drug interaction between imipenem and cilastatin.

This study aimed to clarify that organic anion transporters (OATs) mediate the drug-drug interaction (DDI) between imipenem and cilastatin. After co-administration with imipenem, the plasma concentrations and the plasma concentration-time curve () of cilastatin were significantly increased, while renal clearance and cumulative urinary excretion of cilastatin were decreased. At the same time, imipenem significantly inhibited the uptake of cilastatin in rat kidney slices and in human OAT1 (hOAT1)-HEK293 and human OAT3 (hOAT3)-HEK293 cells.

Fenretinide-polyethylene glycol (PEG) conjugate with improved solubility enhanced cytotoxicity to cancer cell and potent efficacy.

Fenretinide (4-HPR), a synthetic retinoid, has shown its antitumor activity in many tumor types with low cytotoxicity to normal cells and high clinical safety. However, the low water solubility limits its further biological applications. To increase solubility, 4-HPR was conjugated with methoxy polyethylene glycol carboxylic acid (mPEG-COOH) by an ester linkage between the phenol hydroxyl of 4-HPR and the carboxyl of mPEG-COOH.

The AKT/GSK3-Mediated Slug Expression Contributes to Oxaliplatin Resistance in Colorectal Cancer via Upregulation of ERCC1.

Although oxaliplatin serves as one of the first-line drugs prescribed for treating colorectal cancer (CRC), the therapeutic effect is disappointing due to drug resistance. So far, the molecular mechanisms mediating oxaliplatin resistance remain unclear. In this study, we found the chemoresistance in oxaliplatin-resistant HCT116 cells (HCT116/OXA) was mediated by the upregulation of ERCC1 expression.

Denoise magnitude diffusion magnetic resonance images via variance-stabilizing transformation and optimal singular-value manipulation.

Although shown to have a great utility for a wide range of neuroscientific and clinical applications, diffusion-weighted magnetic resonance imaging (dMRI) faces a major challenge of low signal-to-noise ratio (SNR), especially when pushing the spatial resolution for improved delineation of brain's fine structure or increasing the diffusion weighting for increased angular contrast or both. Here, we introduce a comprehensive denoising framework for denoising magnitude dMRI. The framework synergistically combines the variance stabilizing transform (VST) with optimal singular value manipulation.

Dynamic wrinkling pattern exhibiting tunable fluorescence for anticounterfeiting applications.

A dynamic surface pattern with a topography and fluorescence in response to environmental stimulus can enable information recording, hiding, and reading. Such patterns are therefore widely used in information security and anticounterfeiting. Here, we demonstrate a dynamic dual pattern using a supramolecular network comprising a copolymer containing pyridine (P4VP-nBA-S) and hydroxyl distyrylpyridine (DSP-OH) as the skin layer for bilayer wrinkling systems, in which both the wrinkle morphology and fluorescence color can be simultaneously regulated by visible light-triggered isomerization of DSP-OH, or acids.

Mixed micelles of TPGS and Soluplus for co-delivery of paclitaxel and fenretinide: and anticancer study.

Fenretinide (4-HPR), as a semi-synthetic retinoid, has apoptosis-promoting effects as a single agent and chemotherapy synergist . When a human ovarian cancer cells line (A2780s) was treated with both PTX and 4-HPR, there was a synergistic anti-cancer effect demonstrated with a average combination index of 0.44.

Molecular pharmacokinetic mechanism of the drug-drug interaction between genistein and repaglinide mediated by P-gp.

This study was devised to investigate if P-glycoprotein (P-gp) mediated the drug-drug interaction (DDI) between genistein and repaglinide. When genistein was added, the plasma concentrations of repaglinide in rats were increased. The maximum plasma concentration (Cmax) of repaglinide increased from 70.

Heterologous Expression of from L. Promotes Flowering in L.

Methyl-CpG-binding domain (MBD) proteins have diverse molecular and biological functions in plants. Most studies of MBD proteins in plants have focused on the model plant L. Here we cloned from the willow L.

Piperacillin enhances the inhibitory effect of tazobactam on β-lactamase through inhibition of organic anion transporter 1/3 in rats.

To assess the mechanism of the pharmacokinetic interaction between piperacillin and tazobactam, renal excretion and pharmacokinetic studies of piperacillin/tazobactam were investigated in normal and bacteremia rats. A bacteremia model was established to investigate the pharmacokinetic properties of piperacillin and tazobactam under different conditions. Renal slices were taken to examine the uptake of piperacillin and tazobactam.

Structurally novel PI3Kδ/γ dual inhibitors characterized by a seven-membered spirocyclic spacer: The SARs investigation and PK evaluation.

Herein, we communicate our recent medicinal chemistry efforts which have culminated in a series of PI3Kδ/γ dual inhibitors structurally featuring a seven-membered spirocyclic spacer. Compound 26, the most potent one among them, exhibited superior PI3Kδ inhibitory activity (IC = 1.0 nM) to that of the approved PI3Kδ inhibitor Idelalisib.

CRISPR/Cas12a technology combined with immunochromatographic strips for portable detection of African swine fever virus.

African swine fever virus (ASFV), the aetiological agent of African swine fever (ASF), causes lethal haemorrhagic fever in domestic pigs with high mortality and morbidity and has devastating consequences on the global swine industry. On-site rapid and sensitive detection of ASFV is key to the timely implementation of control. In this study, we developed a rapid, sensitive and instrument-free ASFV detection method based on CRISPR/Cas12a technology and lateral flow detection (named CRISPR/Cas12a-LFD).

Applications of cerebrospinal fluid circulating tumor DNA in the diagnosis of gliomas.

Objective: The 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) was revised to include molecular biomarkers as diagnostic criteria. However, conventional biopsies of gliomas were spatially and temporally limited. This study aimed to determine whether circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) could provide more comprehensive diagnostic information to gliomas.

Targeting of miR-96-5p by catalpol ameliorates oxidative stress and hepatic steatosis in LDLr-/- mice via p66shc/cytochrome C cascade.

Hepatic steatosis and oxidative stress are considered to be the sequential steps in the development of non-alcoholic fatty liver disease (NAFLD). We previously found that catalpol, an iridoid glucoside extracted from the root of Romania glutinosa L, protected against diabetes-induced hepatic oxidative stress. Here, we found that the increased expression of p66shc was observed in NAFLD models and catalpol could inhibit p66shc expression to ameliorate NAFLD effectively.

Protective effect of cilastatin against diclofenac-induced nephrotoxicity through interaction with diclofenac acyl glucuronide via organic anion transporters.

Background And Purpose: Diclofenac is a widely used nonsteroidal anti-inflammatory drug. However, adverse effects in the kidney limit its clinical application. The present study was aimed to evaluate the potential effect of cilastatin on diclofenac-induced acute kidney injury and to clarify the potential roles of renal organic anion transporters (OATs) in the drug-drug interaction between cilastatin and diclofenac.

JAK3 inhibitors based on thieno[3,2-d]pyrimidine scaffold: design, synthesis and bioactivity evaluation for the treatment of B-cell lymphoma.

JAK3 is predominantly expressed in hematopoietic cells and has been a promising therapeutic target for the treatment of B-cell lymphoma. In this study, a new class of thieno[3,2-d]pyrimidines harboring acrylamide pharmacophore were synthesized as potent covalent JAK3 inhibitors (IC < 10 nM). Among them, 9a and 9 g displayed the strongest inhibitory potency against JAK3 kinase activity, with IC values of 1.

Surgical Navigation System for Low-Dose-Rate Brachytherapy Based on Mixed Reality.

This article presents a personalized mixed reality (MR) surgical assistance system for brachytherapy. Using a novel, modified multi-information fusion method, the fusion of virtual organs and a preoperative plan for an actual patient and the real-time tracking of surgical tools were achieved. Using the quaternion-based iterative closest point (QICP) algorithm and a hand-eye calibration method, the preoperative plan can be fused into individual patients.

Hierarchical 3D Patterns with Dynamic Wrinkles Produced by a Photocontrolled Diels-Alder Reaction on the Surface.

Three-dimensional (3D) reconfigurable patterns with dynamic morphologies enable the on-demand control of surface properties, such as optical, wetting, and adhesive properties, to achieve smart surfaces. Here, a simple yet general strategy is developed for fabricating 3D patterns with reversible wrinkles on the surface, in which a Diels-Alder (D-A) reaction in the top layer, which consists of a reversible cross-linked polymer network composed of a furan-containing copolymer (PSFB) and bismaleimide (BMI), can be spatially controlled by the photodimerization of BMI. When a photomask is used during irradiation with ultraviolet (UV) light, selective photodimerization of the maleimide leads to the diffusion of maleimide from the unexposed region to the exposed region, resulting in the generation of a diffused relief pattern.

Different changes in granulocyte-colony stimulating factor and its correlation with inflammatory biomarkers in patients after traumatic brain injury.

Objective: This study analyzed changes in granulocyte-colony stimulating factor (G-CSF) and its correlation with leukocyte and neutrophil counts in patients after traumatic brain injury (TBI).

Methods: Sixty TBI patients were included retrospectively. The serum levels of G-CSF, tumor necrosis factor-α (TNF-α), and peripheral leukocyte and neutrophil counts at different time points were measured and analyzed, and the 6-month functional outcomes were monitored.

Phosphocreatine Improves Cardiac Dysfunction by Normalizing Mitochondrial Respiratory Function through JAK2/STAT3 Signaling Pathway and .

Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications in patients with diabetes. Accumulating evidence has demonstrated that DCM is thoroughly related to mitochondrial energy impairment and increases the generation of reactive oxygen species (ROS). Therefore, an ongoing study is developing strategies to protect cardiac mitochondria from diabetic complications, especially from hyperglycemia.

Synthesis and biological activity of thieno[3,2-d]pyrimidines as potent JAK3 inhibitors for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a serious and fatal lung disease, with a median survival of only 3-5 years from diagnosis. Janus kinase 3 (JAK3) has a well-established role in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis (RA) and autoimmune-related pulmonary fibrosis. In this study, through the use of a conformationally-constrained design strategy, a series of thieno[3,2-d]pyrimidines were synthesized as potent JAK3 inhibitors for the treatment of IPF.