VEGF-B is a novel mediator of endoplasmic reticulum stress which induces angiogenesis in the heart without VEGFR1 or NRP activities via RGD-binding integrins.

Vascular endothelial growth factor B186 (VEGF-B186), a ligand for VEGF receptor 1 (VEGFR1) and neuropilin (NRP), promotes vascular growth in healthy and ischemic myocardium. However, the mechanisms and signaling of VEGF-B186 to support angiogenesis have remained unclear. We studied the effects of VEGF-B186 and its variant, VEGF-B186R127S, which cannot bind to NRPs, using VEGFR1 tyrosine kinase knockout (TK) mice to explore the mechanism of VEGF-B186 in promoting vascular growth.

A novel paracetamol derivative alleviates lipopolysaccharide-induced neuroinflammation.

Neuroinflammation has been implicated as a pathological contributor to several neurodegenerative disorders. Increasing evidence suggests that paracetamol (PCM, acetaminophen) has unappreciated anti-neuroinflammatory properties. However, PCM possesses hepatotoxicity in higher dosages, which are needed for achieving therapeutic concentrations in the brain.

The L-type amino acid transporter 1 enhances drug delivery to the mouse pancreatic beta cell line (MIN6).

l-type amino acid transporter 1 (LAT1) is a membrane transporter responsible for carrying large, neutral l-configured amino acids as well as appropriate (pro)drugs into a cell. It has shown a great potential to improve drug delivery across the blood-brain barrier and to increase cell uptake into several brain and cancer cell types. However, besides the brain, the LAT1-utilizing compounds are also delivered more efficiently into the pancreas in vivo.

Functionalization strategy of carboxymethyl cotton gauze fabrics with zeolitic imidazolate framework-67 (ZIF-67) as a recyclable material for biomedical applications.

The accumulation of uremic toxins in the human body poses a deadly risk because it causes chronic kidney disease. To increase the effectiveness of hemodialysis and raise the survival rate, these toxins must be effectively removed from the bloodstream. Developing effective materials for removing these dangerous substances requires a thorough understanding of the interactions between an adsorbent and the uremic toxins.

Transporter Protein Expression of Corneal Epithelium in Rabbit and Porcine: Evaluation of Models for Ocular Drug Transport Study.

The transcorneal route is the main entry route for drugs to the intraocular parts, after topical administration. The outer surface, the corneal epithelium (CE), forms the rate-limiting barrier for drug permeability. Information about the role and protein expression of drug and amino acid transporter proteins in the CE is sparse and lacking.

Physiologically based pharmacokinetics modeling and transporter proteomics to predict systemic and local liver and muscle disposition of statins.

Statins are used to reduce liver cholesterol levels but also carry a dose-related risk of skeletal muscle toxicity. Concentrations of statins in plasma are often used to assess efficacy and safety, but because statins are substrates of membrane transporters that are present in diverse tissues, local differences in intracellular tissue concentrations cannot be ruled out. Thus, plasma concentration may not be an adequate indicator of efficacy and toxicity.

Decoration of viscose fibers with silver nanoparticle-based titanium-organic framework for use in environmental applications.

To effectively remove pharmaceuticals, nitroaromatic compounds, and dyes from wastewater, an efficient multifunctional material was created based on silver nanoparticles (Ag) and MIL-125-NH (MOF) immobilized on viscose fibers (VF) as a support substrate. Firstly, silver nanoparticles (Ag) were immobilized on the surface of viscose fibers (VF) via in situ synthesis using trisodium citrate (TSC) as a reducing agent to create (VF-Ag). Then, VF and VF-Ag were decorated with the titanium metal-organic framework MIL-125-NH (MOF) to create VF-MOF and VF-Ag-MOF.

Amino acid derivative of probenecid potentiates apoptosis-inducing effects of vinblastine by increasing oxidative stress in a cancer cell-specific manner.

Many chemotherapeutic drugs suffer from multidrug resistance (MDR). Efflux transporters, namely ATP-binding cassettes (ABCs), that pump the drugs out of the cancer cells comprise one major reason behind MDR. Therefore, ABC inhibitors have been under development for ages, but unfortunately, without clinical success.

Specific transport of temozolomide does not override DNA repair-mediated chemoresistance.

Temozolomide (TMZ) a DNA alkylating agent, is the standard-of-care for brain tumors, such as glioblastoma multiforme (GBM). Although the physicochemical and pharmacokinetic properties of TMZ, such as chemical stability and the ability to cross the blood-brain barrier (BBB), have been questioned in the past, the acquired chemoresistance has been the main limiting factor of long-term clinical use of TMZ. In the present study, an L-type amino acid transporter 1 (LAT1)-utilizing prodrug of TMZ (TMZ-AA, 6) was prepared and studied for its cellular accumulation and cytotoxic properties in human squamous cell carcinoma, UT-SCC-28 and UT-SCC-42B cells, and TMZ-sensitive human glioma, U-87MG cells that expressed functional LAT1.

Formulating of the sustained release of Tebuconazole pesticide using chitosan aerogel reinforced NFC/CaCO nanocomposite.

Chitosan-based aerogels were fabricated through utilizing of nanofibrillated cellulose (NFC)/CaCO composites. Chitosan aerogel and extra three aerogels loaded different concentrations of NFC/CaCO were investigated to explore their release efficiency of Tebuconazole pesticides. Results obtained from ATR-FTIR showed a remarkable decline of the characterized chitosan hydroxyl group peak prolonging with appearance of new peaks assigned to the inclusion of inorganic calcium element.

Altering distribution profile of palbociclib by its prodrugs.

Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is currently used clinically for treating hormone receptor-positive and human epidermal growth factor receptor 2 negative breast cancer. Additionally, it has the potential to be utilized in the treatment of various tumors, including malignant glioblastoma. Previous research has indicated that palbociclib is a substrate for two efflux transporters, P-glycoprotein (P-gp; MDR1) and breast cancer-resistant protein (BCRP), which restrict the brain exposure of palbociclib.

Targeting Glial Cells by Organic Anion-Transporting Polypeptide 1C1 (OATP1C1)-Utilizing l-Thyroxine-Derived Prodrugs.

OATP1C1 (organic anion-transporting polypeptide 1C1) transports thyroid hormones, particularly thyroxine (T), into human astrocytes. In this study, we investigated the potential of utilizing OATP1C1 to improve the delivery of anti-inflammatory drugs into glial cells. We designed and synthesized eight novel prodrugs by incorporating T and 3,5-diiodo-l-tyrosine (DIT) as promoieties to selected anti-inflammatory drugs.

Self-crosslinked polyvinyl alcohol/cellulose nanofibril cryogels loaded with synthesized aminophosphonates as antimicrobial wound dressings.

Microbial infection is the most common obstacle in the wound healing process, leading to wound healing impairment and complications and ultimately increasing morbidity and mortality. Due to the rising number of pathogens evolving resistance to the existing antibiotics used for wound care, alternative approaches are urgently required. In this study, α-aminophosphonate derivatives as antimicrobial agents were synthesized and incorporated into self-crosslinked tri-component cryogels composed of fully hydrolyzed polyvinyl alcohol (PVA-F), partially hydrolyzed polyvinyl alcohol (PVA-P), and cellulose nanofibrils (CNFs).

Sodium-Dependent Neutral Amino Acid Transporter 2 Can Serve as a Tertiary Carrier for l-Type Amino Acid Transporter 1-Utilizing Prodrugs.

Membrane transporters are the key determinants of the homeostasis of endogenous compounds in the cells and their exposure to drugs. However, the substrate specificities of distinct transporters can overlap. In the present study, the interactions of l-type amino acid transporter 1 (LAT1)-utilizing prodrugs with sodium-coupled neutral amino acid transporter 2 (SNAT2) were explored.

Aminopeptidase B can bioconvert L-type amino acid transporter 1 (LAT1)-utilizing amide prodrugs in the brain.

A prodrug approach is a powerful method to temporarily change the physicochemical and thus, pharmacokinetic properties of drugs. However, in site-selective targeted prodrug delivery, tissue or cell-specific bioconverting enzyme is needed to be utilized to release the active parent drug at a particular location. Unfortunately, ubiquitously expressed enzymes, such as phosphatases and carboxylesterases are well used in phosphate and ester prodrug applications, but less is known about enzymes selectively expressed, e.

Enhanced drug delivery by a prodrug approach effectively relieves neuroinflammation in mice.

Aims: Neuroinflammation is a prominent hallmark in several neurodegenerative diseases (NDs). Halting neuroinflammation can slow down the progression of NDs. Improving the efficacy of clinically available non-steroidal anti-inflammatory drugs (NSAIDs) is a promising approach that may lead to fast-track and effective disease-modifying therapies for NDs.

L-type Amino Acid Transporter 1 Utilizing Ferulic Acid Derivatives Show Increased Drug Delivery in the Mouse Pancreas Along with Decreased Lipid Peroxidation and Prostaglandin Production.

Oxidative stress and pathological changes of Alzheimer's disease (AD) overlap with metabolic diseases, such as diabetes mellitus (DM). Therefore, tackling oxidative stress with antioxidants is a compelling drug target against multiple chronic diseases simultaneously. Ferulic acid (FA), a natural antioxidant, has previously been studied as a therapeutic agent against both AD and DM.

Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery.

One of the major reasons why central nervous system (CNS)-drug development has been challenging in the past, is the barriers that prevent substances entering from the blood circulation into the brain. These barriers include the blood-brain barrier (BBB), blood-spinal cord barrier (BSCB), blood-cerebrospinal fluid barrier (BCSFB), and blood-arachnoid barrier (BAB), and they differ from each other in their transporter protein expression and function as well as among the species. The quantitative expression profiles of the transporters in the CNS-barriers have been recently revealed, and in this review, it is described how they affect the pharmacokinetics of compounds and how these expression differences can be taken into account in the prediction of brain drug disposition in humans, an approach called pharmacoproteomics.

Comparison of Experimental Strategies to Study l-Type Amino Acid Transporter 1 (LAT1) Utilization by Ligands.

l-Type amino acid transporter 1 (LAT1), expressed abundantly in the brain and placenta and overexpressed in several cancer cell types, has gained a lot of interest in drug research and development, as it can be utilized for brain-targeted drug delivery, as well as inhibiting the essential amino acid supply to cancer cells. The structure of LAT1 is today very well-known and the interactions of ligands at the binding site of LAT1 can be modeled and explained. However, less is known of LAT1's life cycle within the cells.

Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP).

Efflux transporters, namely ATP-binding cassette (ABC), are one of the primary reasons for cancer chemoresistance and the clinical failure of chemotherapy. Ganciclovir (GCV) is an antiviral agent used in herpes simplex virus thymidine kinase (HSV-TK) gene therapy. In this therapy, HSV-TK gene is delivered together with GCV into cancer cells to activate the phosphorylation process of GCV to active GCV-triphosphate, a DNA polymerase inhibitor.

In Situ Photopolymerization of Acrylamide Hydrogel to Coat Cellulose Acetate Nanofibers for Drug Delivery System.

In this study we developed electrospun cellulose acetate nanofibers (CANFs) that were loaded with a model non-steroidal anti-inflammatory drug (NSAID) (ibuprofen, Ib) and coated with poly(acrylamide) (poly-AAm) hydrogel polymer using two consecutive steps: an electrospinning process followed by photopolymerization of AAm. Coated and non-coated CANF formulations were characterized by several microscopic and spectroscopic techniques to evaluate their physicochemical properties. An analysis of the kinetic release profile of Ib showed noticeable differences due to the presence or absence of the poly-AAm hydrogel polymer.

Molecular characteristics supporting l-Type amino acid transporter 1 (LAT1)-mediated translocation.

l-Type amino acid transporter 1 (LAT1) is an interesting protein due to its peculiar expression profile. It can be utilized not only as a carrier for improved or targeted drug delivery, e.g.

Alginate, gelatin, and carboxymethyl cellulose coated nonwoven fabrics containing antimicrobial AgNPs for skin wound healing in rats.

Nonwoven fabrics containing silver nanoparticles (AgNPs) are widely utilized to assist management of infected wounds and those at risk of infection. However, such materials have varied responses due to their chemical nature. Herein we investigated the correlation between the concentration of AgNPs taken up by nonwoven viscose material and antibacterial activity in a simulated wound fluid model against two bacterial models (i.

Exploring the Biochemical Foundations of a Successful GLUT1-Targeting Strategy to BNCT: Chemical Synthesis and Evaluation of the Entire Positional Isomer Library of -Carboranylmethyl-Bearing Glucoconjugates.

Boron neutron capture therapy (BNCT) is a noninvasive binary therapeutic modality applicable to the treatment of cancers. While BNCT offers a tumor-targeting selectivity that is difficult to match by other means, the last obstacles preventing the full harness of this potential come in the form of the suboptimal boron delivery strategies presently used in the clinics. To address these challenges, we have developed delivery agents that target the glucose transporter GLUT1.