Ursodeoxycholic acid may protect from severe acute respiratory syndrome coronavirus 2 Omicron variant by reducing angiotensin-converting enzyme 2.

The SARS-CoV-2 caused COVID-19 pandemic has posed a global health hazard. While some vaccines have been developed, protection against viral infection is not perfect because of the urgent approval process and the emergence of mutant SARS-CoV-2 variants. Here, we employed UDCA as an FXR antagonist to regulate ACE2 expression, which is one of the key pathways activated by SARS-CoV-2 Delta variant infection.

Role of Danggui Buxue Decoction for the prevention and treatment of cardiovascular and pulmonary diseases.

Cardiovascular and pulmonary diseases have become the major disease endangering people's physical and mental health because of its high morbidity and mortality. Danggui Buxue Decoction, a noteworthy classical prescription, is composed of astragali radix and angelicae sinensis radix at a ratio of 5꞉1. It is a prescription for tonifying both vital energy and blood and has the effect of dredging collaterals.

Effects of plateau hypoxia on pharmacokinetic parameters and cerebral-blood distribution of levetiracetam in rats.

Objectives: Plateau hypoxia exposure causes changes in pharmacokinetic parameters and cerebral-blood distribution of drugs, including many substrates of P-glycoprotein (P-gp). Levetiracetam, a kind of antiepileptic drugs, is a substrate of P-gp. Whether plateau hypoxia exposure changes its pharmacokinetic characteristics and cerebral-blood distribution remains unclear.

Role of Physiologically Based Biopharmaceutics Modeling (PBBM) in Fed Bioequivalence Study Waivers: Regulatory Outlook, Case Studies and Future Perspectives.

Over the past few decades, physiologically based biopharmaceutics modeling (PBBM) has demonstrated its utility in both new drug and generic product development. Applications of PBBM for fed bioequivalence study waivers is an upcoming area. Recently Innovation & Quality (IQ) consortium demonstrated utility of PBBM to avoid repeat food effect studies for new drugs.

[The research progress of high altitude environment-associated chronic obstructive pulmonary disease and therapeutic drugs].

The plateau environment is characterized by low oxygen, low air pressure, low temperature, and strong ultraviolet rays, etc. Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic lung disease. High altitude environment increases COPD prevalence, clinical manifestation and mortality.

Physiologically Based Pharmacokinetics Modeling in Biopharmaceutics: Case Studies for Establishing the Bioequivalence Safe Space for Innovator and Generic Drugs.

For successful oral drug development, defining a bioequivalence (BE) safe space is critical for the identification of newer bioequivalent formulations or for setting of clinically relevant in vitro specifications to ensure drug product quality. By definition, the safe space delineates the dissolution profile boundaries or other drug product quality attributes, within which the drug product variants are anticipated to be bioequivalent. Defining a BE safe space with physiologically based biopharmaceutics model (PBBM) allows the establishment of mechanistic in vitro and in vivo relationships (IVIVR) to better understand absorption mechanism and critical bioavailability attributes (CBA).

Effects of Altitude and Duration of Differing Levels of Hypoxic Exposure on Hypoxia-Inducible Factor-1α in Rat Tissues.

Li, Xiao-lin, Wei-gang Wang, Mao-xing Li, Tian-long Liu, Xiu-yu Tian, and Lan Wu. Effects of altitude and duration of differing levels of hypoxic exposure on hypoxia-inducible factor-1α in rat tissues. .

Hydroxytyrosol Alleviated Hypoxia-Mediated PC12 Cell Damage through Activating PI3K/AKT/mTOR-HIF-1 Signaling.

Background: Hypoxia exerts pressure on cells and organisms, and this pressure can occur under both pathological and nonpathological conditions. There are many reports confirmed that hydroxytyrosol has good in vitro antioxidant activity, while the research about hydroxytyrosol on hypoxia-mediated cell damage is still unclear.

Purpose: The aim of this study was to investigate the effect and mechanism of hydroxytyrosol on hypoxia-mediated cell damage.

Nanotechnology-Assisted Metered-Dose Inhalers (MDIs) for High-Performance Pulmonary Drug Delivery Applications.

Purpose: Respiratory disorders pose a major threat to the morbidity and mortality to public health. Here we reviewed the nanotechnology based pulmonary drug delivery using metered dose inhalers.

Methods: Major respiratory diseases such as chronic obstructive pulmonary diseases (COPD), asthma, acute lower respiratory tract infections, tuberculosis (TB) and lung cancer.

Effect of aqueous extract of Astragalus membranaceus on behavioral cognition of rats living at high altitude.

Objective: To investigate the effect of aqueous extract of Astragalus membranaceus on cognitive ability of rats living at high altitude.

Methods: Rats were exposed to a simulated highaltitude hypobaric hypoxia chamber. The behavior of rats was tested by eight-arm maze.

Crocetin: A Systematic Review.

Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to exist in several medicinal plants, the desiccative ripe fruit of the cape jasmine belonging to the Rubiaceae family, and stigmas of the saffron plant of the Iridaceae family. According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties.

8u, a pro-apoptosis/cell cycle arrest compound, suppresses invasion and metastasis through HSP90α downregulating and PI3K/Akt inactivation in hepatocellular carcinoma cells.

8u, an acridine derivative, has been proved effective anti-hepatocarcinoma effect, while the underlying mechanism remains unclear. Here, metabolomics and proteomics approaches were applied to study its anti-cancer mechanism and explore its effect on HepG2 cells' invasion and metastasis abilities. The results showed that 8u significantly suppressed HepG2 cells migration and enhanced cell-to-cell junctions.

Surface-printed microdot array chips coupled with matrix-assisted laser desorption/ionization mass spectrometry for high-throughput single-cell patterning and phospholipid analysis.

Rationale: Single-cell analysis is very important in several research fields for the heterogeneity of individual cells, which has been well accepted. However, restricted by the size and low content of a single cell, current studies have encountered challenges in high-throughput, high-space resolution and sensitivity, and multicomponent analysis. A methodology of a surface-printed microdot array chip coupled with matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) is presented in this study for high-throughput single-cell patterning and phospholipid analysis.

Development of a blood-brain barrier model in a membrane-based microchip for characterization of drug permeability and cytotoxicity for drug screening.

Since most of the central nervous system (CNS) drug candidates show poor permeability across the blood-brain barrier (BBB), development of a reliable platform for permeability assay will greatly accelerate drug discovery. Herein, we constructed a microfluidic BBB model to mimic drug delivery into the brain to induce cytotoxicity at target cells. To reconstitute the in vivo BBB properties, human cerebral microvessel endothelial cells (hCMEC/D3) were dynamically cultured in a membrane-based microchannel.

Application of metabolomics to investigate the antitumor mechanism of flavopiridol in MCF-7 breast cancer cells.

Flavopiridol is reported to have potent antitumor effects by inhibition of cyclin-dependent kinases (CDKs). However, most studies of flavopiridol focus on specific genes and kinases, so the antitumor mechanism needs further elucidation at the metabolic level. In the present study, an UPLC/Q-TOF MS metabolomics approach was used to investigate its antiproliferative effects on MCF-7 breast cancer cells.

Study of Phospholipids in Single Cells Using an Integrated Microfluidic Device Combined with Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry.

Single-cell trapping and high-throughput mass spectrometry analysis remain challenging now. Current technologies for single-cell analysis have several limitations, such as throughput, space resolution, and multicomponent analysis. In this study, we demonstrate, for the first time, the combination of microfluidic chip and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for high-throughput and automatic single-cell phospholipids analysis.

Molecular interaction study of flavonoid derivative 3d with human serum albumin using multispectroscopic and molecular modeling approach.

Human serum albumin (HSA) has been developed as a model protein to study drug-protein interaction. In the present work, the interaction between our synthesized flavonoid derivative 3d (possessing potent antitumor activity against HepG2 cells) and HSA was investigated using fluorescence spectroscopy, circular dichroism spectroscopy, UV-vis spectroscopy and molecular modeling approach. Fluorescence spectroscopy showed that the fluorescence of HSA can be quenched remarkably by 3d under physiological condition with a slight shift of maximum fluorescence emission bands from 360nm to 363nm.

Stability-Indicating UPLC Method for Tramadol HCl Impurities in the Tramadol Injection after Dilution by Infusion Fluids (5% Dextrose and 0.9% Sodium Chloride).

A novel, rapid, and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated as per ICH guidelines for the determination of tramadol HCl impurities in the tramadol HCl injection after reconstitution by infusion fluids (5% dextrose and 0.9% sodium chloride). The tramadol HCl injection is for the treatment of patients with moderate-to-severe pain.

3,5-disubstituted thiadiazine-2-thiones: new cell-cycle inhibitors.

Two series, a and b, of 3-cyclopentyl or (3-cyclohexyl)-5-substituted-3,4,5,6-tetrahydro-2H-1,3,5-thiadiazine-2-thiones (THTT) 2a-9a and 3b, 4b, 6b-9b, were synthesized to develop new cell cycle inhibitors. Variable and promising in vitro antiproliferative activities were shown with the synthesized THTT derivatives. Compound 5a with a 5-cyclopentyl group on position-3 and a glutamine residue on position-5 of the THTT moiety showed maximum activity (IC(50) = 8.

Dissimilar chromatographic systems to indicate and identify antioxidants from Mallotus species.

The genus of Mallotus contains several species commonly used as traditional medicines in oriental countries. A data set containing 39 Mallotus samples, differing in species, cultivation conditions, harvest season and/or part of the plant was used to develop fingerprints on two dissimilar chromatographic systems. An exploratory analysis with principal component analysis (PCA) was performed on both data sets individually.

Mucoadhesive polymeric hydrogels for nasal delivery of acyclovir.

The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated.

1,5-Benzodioxepin derivatives as a novel class of muscarinic M3 receptor antagonists.

The structure-activity relationships of novel 1,5-benzodioxepin derivatives as muscarinic M(1)-M(3) receptor antagonists are reported. Some of these compounds were found to possess high binding affinity for the muscarinic M(3) receptor and potent effect on rhythmic increase in bladder pressure in unanesthetized rats following oral administration. These compounds displayed selectivity for the bladder over the salivary gland.