Discovery of HC-7366: An Orally Bioavailable and Efficacious GCN2 Kinase Activator.

A series of activators of GCN2 (general control nonderepressible 2) kinase have been developed, leading to HC-7366, which has entered the clinic as an antitumor therapy. Optimization resulted in improved permeability compared to that of the original indazole hinge binding scaffold, while maintaining potency at GCN2 and selectivity over PERK (protein kinase RNA-like endoplasmic reticulum kinase). The improved ADME properties of this series led to robust compound exposure in both rats and mice, allowing HC-7366 to be dosed in xenograft models, demonstrating that activation of the GCN2 pathway by this compound leads to tumor growth inhibition.

Risk factors for 90-day all-cause mortality in post-operative central nervous system infections (PCNSIs): A retrospective study of 99 patients in China.

Post-operative central nervous system infections (PCNSIs) are serious complications of craniotomy. Many factors, including patient-related, surgical, and postoperative factors, affect the survival of patients with PCNSIs. Timely and effective implementation of antibiotics targeting pathogenic bacteria is crucial to reduce mortality.

Inhibition of microRNA-29b suppresses oxidative stress and reduces apoptosis in ischemic stroke.

MicroRNAs (miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. MicroRNA-29b (miR-29b) plays a broad and critical role in brain homeostasis. In this study, we tested the function of miR-29b in animal and cell models by inhibiting miR-29b expression.

Development of a novel method to evaluate sialylation of glycoproteins and analysis of gp96 sialylation in Hela, SW1990 and A549 cell lines.

Background: Glycoproteins play a critical role in the cellular activities of eukaryotes. Sialic acid is typically the outermost monosaccharide of glycolipids and glycoproteins, and is necessary for normal development.

Results: A strategy based on avidin-biotin affinity was established to enrich sialylated glycoproteins from HeLa cervical carcinoma, SW1990 pancreatic adenocarcinoma, and A549 lung adenocarcinoma cells.

A novel approach for fluorescent visualization of glycyrrhetic acid on a cell with a quantum dot.

Glycyrrhetic acid (GA), a pentacyclic triterpenoid derivative obtained from hydrolysis of glycyrrhizic acid, was found to have synergistic anti-asthmatic effects with the β2-adrenergic receptor (β2AR) agonist via the β2AR-mediated pathway. This study visualized the location of GA on a human cell expressing β2AR via chemical biological approaches. A CdTe/ZnS quantum dot modified with an alkynyl group (QD-AL) was first synthesized, and an azide-terminal GA (ATGA) was also prepared.

Qingfei Xiaoyan Wan alleviates asthma through multi-target network regulation.

Background: Qingfei Xiaoyan Wan (QFXY), a traditional Chinese formula, is widely used for relieving cough, asthma, upper respiratory tract infection, bronchitis, pneumonia, and etc. in clinic. Comparing with other anti-asthma drugs, it is characterised with moderate and persistent efficacy as well as few side effects, however, the underlying action mechanism still remains elusive.

Preparation of functionalized alkynyl magnetic microspheres for the selective enrichment of cell glycoproteins based on click chemistry.

Functionalized alkynyl polyvinyl alcohol magnetic microspheres (PVA MMs) were developed for the specific enrichment of sialic acid-rich glycoproteins by click chemistry. The capture capability for proteins was evaluated through a novel dual-labeled bovine serum albumin (BSA) that utilizes fluorescence resonance energy transfer (FRET). The PVA MM parameters, including the size and coverage of functionalized groups, were optimized by response surface methodology.

Cell surface glycoprotein profiling of cancer cells based on bioorthogonal chemistry.

Bioorthogonal chemistry refers to chemical reactions that can occur within a living system without altering native biochemical processes. Applications of this concept extend to studies on a group of biomolecules that includes glycans, proteins, and lipids. In this study, a strategy for isolating cell surface glycoproteins and based on bioorthogonal chemistry was employed to identify new cancer-related glycoproteins.

Preparation of cellulose magnetic microspheres with "the smallest critical size" and their application for microbial immunocapture.

The goal of this paper is to introduce a universal method for quantitative control of the particle size of magnetic cellulose microspheres (MCMS) and to produce an optimal antibody absorption capability as an aid in the research of new applications of MCMS in immunomagnetic capture. In this study, "the smallest critical size theory" (TSCS) was proposed, tested, and confirmed by IgG-carrying capability measurements, magnetic response analysis, immunomagnetic capture, and PCR identification of bacteria. A Gaussian expression was proposed and used to guide the preparation of MCMS of the smallest critical size (SCS).

The synergistic anti-asthmatic effects of glycyrrhizin and salbutamol.

Aim: To investigate the efficacy of glycyrrhizin (GL) combined with salbutamol (SA) as an anti-asthma therapy.

Methods: Rat lung beta2-adrenergic receptor (beta(2)-AR) mRNA level was measured by real-time RT PCR. Intracellular cAMP accumulation was evaluated with a reporter gene assay.

Preparation of novel magnetic cellulose microspheres via cellulose binding domain-streptavidin linkage and use for mRNA isolation from eukaryotic cells and tissues.

We have developed micron-sized magnetic cellulose microspheres (MCMS), biospecifically coated with streptavidin (SA) using a novel cellulose binding domain and SA fusion protein, to harvest mRNA from eukaryotic cells and tissues. Biospecific connection between SA and MCMS exhibited significant advantages compared with traditional chemical coupling, including convenient and simple preparation, elimination of toxic compounds, and highly efficient extraction of a pure target molecule. To confirm compatibility, mRNA isolated from cell or tissue samples was used for amplification of housekeeping genes (GAPDH and beta-actin) and specific target genes (two fragments V(H) and V(L) from the variable fragments of IgG and the gene encoding GLP-1 receptor).

Development, characterization, and evaluation of a fusion protein of a novel glucagon-like peptide-1 (GLP-1) analog and human serum albumin in Pichia pastoris.

Glucagon-like peptide-1 (GLP-1) has considerable potential as a possible therapeutic agent for type-2 diabetes. Unfortunately, this glucoincretin is short lived due to degradation by dipeptidyl-peptidase IV and rapid clearance by renal filtration. In this study, we attempted to extend GLP-1 action through the attachment of a lysine residue at the N-terminal of GLP-1 (named KGLP-1), and to make a fusion protein with human serum albumin (HSA) in Pichia pastoris.

Identification of antiviral mimetic peptides with interferon alpha-2b-like activity from a random peptide library using a novel functional biopanning method.

Aim: To screen for interferon (IFN) alpha-2b mimetic peptides with antiviral activity.

Methods: Selecting IFN receptor-binding peptides from a phage-display heptapeptide library using a novel functional biopanning method. This method was developed to identify peptides with activity against vesicular stomatitis virus (VSV) inducing cytopathic effects on WISH cells.