Advancing Proteolysis Targeting Chimera (PROTAC) Nanotechnology in Protein Homeostasis Reprograming for Disease Treatment.

Proteolysis targeting chimeras (PROTACs) represent a transformative class of therapeutic agents that leverage the intrinsic protein degradation machinery to modulate the hemostasis of key disease-associated proteins selectively. Although several PROTACs have been approved for clinical application, suboptimal therapeutic efficacy and potential adverse side effects remain challenging. Benefiting from the enhanced targeted delivery, reduced systemic toxicity, and improved bioavailability, nanomedicines can be tailored with precision to integrate with PROTACs which hold significant potential to facilitate PROTAC nanomedicines (nano-PROTACs) for clinical translation with enhanced efficacy and reduced side effects.

Design, synthesis, and biological evaluation of 5-(1H-indol-5-yl)isoxazole-3-carboxylic acids as novel xanthine oxidase inhibitors.

Xanthine oxidase (XO) is a key enzyme for the production of uric acid in the human body. XO inhibitors (XOIs) are clinically used for the treatment of hyperuricemia and gout, as they can effectively inhibit the production of uric acid. Previous studies indicated that both indole and isoxazole derivatives have good inhibitory effects against XO.

Controlled Release of Growth Factor from Heparin Embedded Poly(aldehyde guluronate) Hydrogels and Its Effect on Vascularization.

To deliver growth factors controllably for tissue regeneration, poly(aldehyde guluronate) (PAG) was obtained from alginate and covalently cross-linked with aminated gelatin (AG) to form PAG/AG hydrogel as a growth factors carrier. The prepared hydrogel exhibits a slow degradation rate and excellent cytocompatibility. Heparin was conjugated with gelatin and embedded into the hydrogel to reserve and stabilize growth factors.

Protective effects of areca nut polyphenols on hypoxic damage of rat pulmonary microvascular endothelial cells.

Objective: To investigate the protective effects of areca nut polyphenols on hypoxic damage of rat pulmonary microvascular endothelial cells (PMVECs).

Methods: Malondialdehyde and superoxide dismutase (SOD) were used to determine the optimal modeling of lung hypoxic injury cells. CCK-8 method was used to detect cell viability for determining the effective dose of areca nut polyphenols.

Research Progress of Epigenetic Modification on the Regulation of Transporters Under Hypoxia.

Epigenetic modification refers to the heritable changes caused by chromosomal changes without changing the DNA sequence. Epigenetics runs through the entire growth and differentiation process of the body, which causes varied diseases. Hypoxia is a physiological astate of lowered partial oxygen partial pressure that affects cell and tissue function.

Research Progress on the Mechanism of Intestinal Barrier Damage and Drug Therapy in a High Altitude Environment.

The plateau is a typical extreme environment with low temperature, low oxygen and high ultraviolet rays. The integrity of the intestinal barrier is the basis for the functioning of the intestine, which plays an important role in absorbing nutrients, maintaining the balance of intestinal flora, and blocking the invasion of toxins. Currently, there is increasing evidence that high altitude environment can enhance intestinal permeability and disrupt intestinal barrier integrity.

Exploration of -Arylsulfonyl-indole-2-carboxamide Derivatives as Novel Fructose-1,6-bisphosphatase Inhibitors by Molecular Simulation.

A series of -arylsulfonyl-indole-2-carboxamide derivatives have been identified as potent fructose-1,6-bisphosphatase (FBPase) inhibitors (FBPIs) with excellent selectivity for the potential therapy of type II diabetes mellitus. To explore the structure-activity relationships (SARs) and the mechanisms of action of these FBPIs, a systematic computational study was performed in the present study, including three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, pharmacophore modeling, molecular dynamics (MD), and virtual screening. The constructed 3D-QSAR models exhibited good predictive ability with reasonable parameters using comparative molecular field analysis ( = 0.

[Evaluation of regional wall movement abnormalities in coronary artery disease by quantitative tissue velocity imaging].

Objective: To evaluate the clinical value of quantitative tissue velocity imaging (QTVI) in detection of regional wall movement abnormalities in patients with coronary artery disease (CAD).

Methods: The segmental left ventricular wall motion velocity was measured in 45 normal subjects and 48 patients with CAD, and the parameters of QTVI were analyzed between the two groups.

Results: Velocity decrement and wave form alterations were shown in abnormal segmental movements in the CAD group.