effect-eye-tracking-technology-based-visual-scanning-training-on

Effect of Eye-Tracking Technology-Based Visual Scanning Training on Unilateral Spatial Neglect after Stroke

This study aimed to explore the effect of eye-tracking technology-based visual scanning training on recovery from unilateral spatial neglect after stroke. ...

Capital Medical University

China Rehabilitation Research Center

To evaluate the effects of hyperglycemia and glimepiride on proliferation, differentiation and mineralization of rat mandibular osteoblasts to verify the hypothesis of dental implant administration.

[Effects of glimepiride on proliferation, differentiation and mineralization of rat mandibular osteoblasts in hyperglycemia].

Our previous studies demonstrated that glimepiride enhanced the proliferation and differentiation of osteoblasts and led to activation of the PI3K/Akt pathway. Recent genetic evidence shows that endothelial nitric oxide synthase (eNOS) plays an important role in bone homeostasis. In this study, we further elucidated the roles of eNOS, PI3K and Akt in bone formation by osteoblasts induced by glimepiride in a high glucose microenvironment. We demonstrated that high glucose (16.5 mM) inhibits the osteogenic differentiation potential and proliferation of rat osteoblasts. Glimepiride activated eNOS expression in rat osteoblasts cultured with two different concentrations of glucose. High glucose-induced osteogenic differentiation was significantly enhanced by glimepiride. Down-regulation of PI3K P85 levels by treatment with LY294002 (a PI3K inhibitor) led to suppression of P-eNOS and P-AKT expression levels, which in turn resulted in inhibition of RUNX2, OCN and ALP mRNA expression in osteoblasts induced by glimepiride at both glucose concentrations. ALP activity was partially inhibited by 10 µM LY294002. Taken together, our results demonstrate that glimepiride-induced osteogenic differentiation of osteoblasts occurs via eNOS activation and is dependent on the PI3K/Akt signaling pathway in a high glucose microenvironment.

Glimepiride promotes osteogenic differentiation in rat osteoblasts via the PI3K/Akt/eNOS pathway in a high glucose microenvironment.

While linear ubiquitin plays critical roles in multiple cell signaling pathways, few substrates have been identified. Global profiling of linear ubiquitin substrates represents a significant challenge because of the low endogenous level of linear ubiquitination and the background interference arising from highly abundant ubiquitin linkages (e.g. K48- and K63-) and from the non-specific attachment of interfering proteins to the linear polyubiquitin chain. We developed a bio-orthogonal linear ubiquitin probe by site-specific encoding of a norbornene amino acid on ubiquitin (NAEK-Ub). This probe facilitates covalent labeling of linear ubiquitin substrates in live cells and enables selective enrichment and identification of linear ubiquitin-modified proteins. Given the fact that the frequent overexpression of the linear linkage-specific deubiquitinase OTULIN correlates with poor prognosis in glioblastoma, we demonstrated the feasibility of the NAEK-Ub strategy by identifying and validating substrates of linear ubiquitination in patient-derived glioblastoma stem-like cells (GSCs). We identified STAT3 as a bona fide substrate of linear ubiquitin, and showed that linear ubiquitination negatively regulates STAT3 activity by recruitment of the phosphatase TC-PTP to STAT3. Furthermore, we demonstrated that preferential expression of OTULIN in GSCs restricts linear ubiquitination on STAT3 and drives persistent STAT3 signaling, and thereby maintains the stemness and self-renewal of GSCs.

A bio-orthogonal linear ubiquitin probe identifies STAT3 as a direct substrate of OTULIN in glioblastoma.

Cuproptosis-a novel cell death mechanism-is an innovative strategy for tumor therapy. However, the insufficient efficacy of cuproptosis, primarily owing to the low sensitivity of tumor cells to Cu ions, remains a major challenge. In this study, we design TiCuMOF@PEG@l-Arg@TPP (TCPAT) nanoparticles to facilitate self-sensitized cuproptosis for anti-tumor therapy through the dual upregulation of p53. TiMOF serves as a microwave sensitizer by generating reactive oxygen species (ROS). Notably, the uniformly distributed Cu ions within the MOF serve as co-catalysts to provide reactive sites that enhance ROS generation. Additionally, the ROS generated are utilized to oxidize l-arginine, thus resulting in the release of nitric oxide (NO), which has a long half-life and diffusion distance, thereby enabling it to penetrate deep into the tumor regions that are typically inaccessible to ROS. Furthermore, TCPAT not only induces cuproptosis but also leverages the efficiently generated ROS and cascade-released NO for the dual upregulation of p53. This upregulation subsequently inhibits glycolysis, increases cellular sensitivity to Cu ions, and facilitates self-sensitized cuproptosis. Consequently, the self-sensitized cuproptosis strategy, dependent on the efficient generation of ROS, presents a promising avenue for tumor therapy based on cuproptosis mechanisms.

Article	Year
[Effects of glimepiride on proliferation, differentiation and mineralization of rat mandibular osteoblasts in hyperglycemia]. Shanghai kou qiang yi xue = Shanghai journal of stomatology\| PubMed ID: 23708031	2013
Glimepiride promotes osteogenic differentiation in rat osteoblasts via the PI3K/Akt/eNOS pathway in a high glucose microenvironment. PloS one\| PubMed ID: 25391146	2014
A bio-orthogonal linear ubiquitin probe identifies STAT3 as a direct substrate of OTULIN in glioblastoma. Nucleic acids research\| PubMed ID: 36660824	2023
Dual-upregulation of p53 for self-sensitized cuproptosis via microwave dynamic and NO gas therapy. Journal of colloid and interface science\| PubMed ID: 40154167	2025

Bin Gu

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