Medical & Pharmaceutical Industry Tech & Dev Center

Betaine, a methylated glycine derivative, shows promise in treating neuropsychiatric and neurological disorders, but its mechanisms remain unclear. This study investigates betaine's concentration-dependent effects on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex slices and calcium influx in cultured cortical neurons. We further assessed subtype specificity using HEK293 cells stably expressing GluN1/GluN2A, GluN1/GluN2B, or GluN1/GluN2C NMDA receptor subtypes, measuring calcium flux and single-channel activity. In cortical slices, betaine alone did not alter EFPs but, when co-applied with glutamate, significantly increased EFP frequency and amplitude. Conversely, co-application with glutamate and glycine markedly reduced EFPs. Similarly, in cultured cortical neurons, betaine enhanced NMDA receptor-dependent calcium influx with glutamate alone but attenuated it when both glutamate and glycine were present. In HEK293 cells, betaine exhibited dual modulatory effects on NMDA receptor-mediated calcium influx, varying with GluN2 subtype and glutamate/glycine concentrations. Cell-attached patch-clamp recordings confirmed that betaine with glutamate induced NMDA receptor currents, which were reduced by glycine co-application. Molecular docking and dynamics simulations proposed that betaine binds effectively to the glycine-binding site on the GluN1 subunit, with stable interactions. These findings identify betaine as a context-dependent modulator of NMDA receptors via its interaction with the glycine-binding site, offering a novel mechanism that may underlie its therapeutic potential in disorders involving NMDA receptor dysfunction.

Colorectal cancer (CRC) is one of the deadliest cancers worldwide and long-term survival is not guaranteed in metastatic disease despite current multidisciplinary therapies. A new compound 2,3,5,4'-Tetrahydroxystilbene (TG1), derived from THSG (2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-Glucoside), has been developed, and its anticancer ability against CRC is verified in this study.

HCT116, HT-29, and DLD-1 were treated with TG1 and the IC₅₀ was measured using a sulforhodamine B assay. A Xenograft mouse model was used to monitor tumor growth. Apoptosis and autophagy, induced by TG1 in CRC cells, were examined. RNA-sequencing analysis of CRC cells treated with TG1 was performed to discover underlying pathways and mechanisms.

The results demonstrated that treatment with TG1 inhibited CRC proliferation in vitro and in vivo and induced apoptotic cell death, which was confirmed by Annexin V-FITC/PI staining and Western blotting. Additionally, TG1 treatment increased the level of autophagy in cells. RNA-sequencing and GSEA analyses revealed that TG1 was associated with MYC and the induction of ferroptosis. Furthermore, the ferroptosis inhibitor Bardoxolone abrogated the cytotoxic effect of TG1 in CRC cells, indicating that ferroptosis played a crucial role in TG1-induced cytotoxicity.

These findings suggest that TG1 might be a potential and potent compound for clinical use in the treatment of CRC by inhibiting proliferation and inducing ferroptosis through the MYC pathway.

Self-expanding sinus stents are often used in functional endoscopic sinus surgery to treat inflamed sinuses. The PROPEL self-expanding sinus stent offers mechanical support to the sinus cavity to prevent restenosis. The stent is made of a bioabsorbable material (PLGA) that disappears after wound healing. However, complications such as foreign body sensation and severe stent migration/expulsion have been reported after implantation. Little is known about the contact characteristics of self-expanding sinus stents from when the stent is crimped into the insertion device through to deployment into the sinus cavity. This current study developed a test platform to analyze the biomechanical behavior of the stent during this process. Three common bioabsorbable materials, PLGA, PCL and Mg alloy, were evaluated to understand how the choice of material affects the biomechanical characteristics of self-expanding sinus stents. The results showed that the material can have a considerable influence on the contact characteristics during crimping and deployment. When crimped, the PLGA and Mg alloy stents showed much higher plastic strain and contact stress than the PCL stent. When deployed, the PCL stent had the largest contact area (4.3 mm²) and the lowest contact pressure (0.1 MPa) on the inner surface of the sinus canal. The results indicate that PCL could be a suitable choice for self-expanding sinus stents. This current study provides a method for observing the biomechanical characteristics of sinus stents during stent crimping and deployment.