Ginkgo biloba extracts protect human retinal Müller glial cells from t-BHP induced oxidative damage by activating the AMPK-Nrf2-NQO-1 axis.

Objectives: Retinal Müller glial cell loss is almost involved in all retinal diseases, especially diabetic retinopathy (DR). Oxidative stress significantly contributes to the development of Müller glial cell loss. Ginkgo biloba extracts (GBE) have been reported to possess antioxidant property, beneficial in treating human retinal diseases.

Small Molecule Inhibitors of Programmed Cell Death Ligand 1 (PD-L1): A Patent Review (2019-2021).

Introduction: The blockade of immune checkpoints, especially the PD-1/PD-L1 pathway with therapeutic antibodies, has shown success in treating cancers in recent years. Seven monoclonal antibodies (mAbs) targeting PD-1 or PD-L1 have been approved by FDA. However, mAbs exhibit several disadvantages as compared to small molecules such as poor permeation, high manufacturing costs, immunogenicity as well as lacking oral bioavailability.

Compritol solid lipid nanoparticle formulations enhance the protective effect of betulinic acid derivatives in human Müller cells against oxidative injury.

Müller cells maintain homeostatic functions in the retina. Their dysfunction leads to irreversible retinal diseases. Oxidative injury is a leading cause of retinal cytotoxicity.

Procyanidin B2 and rutin in Ginkgo biloba extracts protect human retinal pigment epithelial (RPE) cells from oxidative stress by modulating Nrf2 and Erk1/2 signalling.

Oxidative stress plays an important role in the pathogenesis of human retinal diseases. Ginkgo biloba products are widely consumed herbal supplements that contain ingredients with anti-oxidant potentials. However, the active agents in ginkgo biloba extracts (GBE) are unclear.

The Potential Application of Pentacyclic Triterpenoids in the Prevention and Treatment of Retinal Diseases.

Retinal diseases are a leading cause of impaired vision and blindness but some lack effective treatments. New therapies are required urgently to better manage retinal diseases. Natural pentacyclic triterpenoids and their derivatives have a wide range of activities, including antioxidative, anti-inflammatory, cytoprotective, neuroprotective, and antiangiogenic properties.

Impaired Transport Activity of Human Organic Anion Transporters (OATs) and Organic Anion Transporting Polypeptides (OATPs) by Wnt Inhibitors.

The Wnt/β-catenin signaling pathway is dysregulated in diseases and Wnt inhibitors like PRI-724 are in clinical development. This study evaluated the regulatory actions of PRI-724 and other Wnt inhibitors on the transport activity of human renal Organic anion transporters (OATs) and Organic anion transporting polypeptides (OATPs). The substrate uptake by OAT4 and OATP2B1 was markedly decreased by PRI-724 (V/K: ∼26% and ∼17% of corresponding control), with less pronounced decreases in OAT1, OAT3 and OAT1A2.

The involvement of human organic anion transporting polypeptides (OATPs) in drug-herb/food interactions.

Organic anion transporting polypeptides (OATPs) are important transporter proteins that are expressed at the plasma membrane of cells, where they mediate the influx of endogenous and exogenous substances including hormones, natural compounds and many clinically important drugs. OATP1A2, OATP2B1, OATP1B1 and OATP1B3 are the most important OATP isoforms and influence the pharmacokinetic performance of drugs. These OATPs are highly expressed in the kidney, intestine and liver, where they determine the distribution of drugs to these tissues.

Betulinic acid derivatives can protect human Müller cells from glutamate-induced oxidative stress.

Müller cells are the predominant retinal glial cells. One of the key roles of Müller cells is in the uptake of the neurotransmitter glutamate and in its conversion to glutamine. Müller cell dysfunction due to oxidative stress elicited by high glutamate concentrations can lead to toxicity, which promote the pathogenesis of retinal diseases like diabetic retinopathy and glaucoma.

A derivative of betulinic acid protects human Retinal Pigment Epithelial (RPE) cells from cobalt chloride-induced acute hypoxic stress.

The Retinal Pigment Epithelium (RPE) is a monolayer of cells located above the choroid. It mediates human visual cycle and nourishes photoreceptors. Hypoxia-induced oxidative stress to RPE is a vital cause of retinal degeneration such as the Age-related Macular Degeneration.

The 5'-AMP-Activated Protein Kinase Regulates the Function and Expression of Human Organic Anion Transporting Polypeptide 1A2.

The organic anion transporting polypeptides (OATPs) are important membrane proteins that mediate the cellular uptake of drugs and endogenous substances. OATP1A2 is widely distributed in many human tissues that are targeted in drug therapy; defective OATP1A2 leads to altered drug disposition influencing therapeutic outcomes. 5'-AMP-activated protein kinase (AMPK) signaling plays an important role in the pathogenesis of the metabolic syndrome characterized by an increased incidence of type II diabetes and nonalcoholic fatty liver disease.

Demonstration of In Vitro Host-Guest Complex Formation and Safety of para-Sulfonatocalix[8]arene as a Delivery Vehicle for Two Antibiotic Drugs.

The macrocycle para-sulfonatocalix[8]arene, sCX[8], was examined with 2 antibiotic drugs, ciprofloxacin (CIP) and isoniazid. The drugs were shown to form complexes with sCX[8] using proton nuclear magnetic resonance, thermogravimetric analysis, fluorescence spectroscopy, and molecular modeling. Both drugs form 1:1 hydrated (HO: 13%-14% w/w) host-guest complexes, with sCX[8] binding around the pyridine ring of isoniazid, and around the piperazine and cyclopropane rings of CIP.

Tubulin inhibitors: pharmacophore modeling, virtual screening and molecular docking.

Aim: To construct a quantitative pharmacophore model of tubulin inhibitors and to discovery new leads with potent antitumor activities.

Methods: Ligand-based pharmacophore modeling was used to identify the chemical features responsible for inhibiting tubulin polymerization. A set of 26 training compounds was used to generate hypothetical pharmacophores using the HypoGen algorithm.

Characterization of a fluorescence probe based on gold nanoclusters for cell and animal imaging.

A facile approach to synthesize gold nanoclusters (Au NCs) with bluish green fluorescence using histidine as both reductant and capping agent was reported. The UV-visible absorption and photoluminescence spectra measurement was performed to explore its optical properties under different circumstances (preparing condition, temperature, pH, storing time). Then, MPA, a NIR organic dye, was conjugated to Au NCs (Au-MPA) for in vivo fluorescence imaging application.

Functional and molecular characterization of rat intestinal prolidase.

Genetic deficiency of prolidase can lead to severe problems in child development, including mental retardation. However, the exact pathogenesis of the disease is unclear. To understand the enzyme's physiologic functions, we studied the regulation of rat intestinal prolidase.