Chondroitin sulfate (CS) is a major component of the extracellular matrix found to be abnormally accumulated in several types of cancer tissues. Previous studies have indicated that CS synthases and modification enzymes are frequently elevated in human gliomas and are associated with poor prognosis. However, the underlying mechanisms of CS in cancer progression and approaches for interrupting its functions in cancer cells remain largely unexplored. Here, we have found that CS was significantly enriched surrounding the vasculature in a subset of glioma tissues, which was akin to the perivascular niche for cancer-initiating cells. Silencing or overexpression of the major CS synthase, chondroitin sulfate synthase 1 (CHSY1), significantly regulated the glioma cell invasive phenotypes and modulated integrin expression. Furthermore, we identified CD44 as a crucial chondroitin sulfate proteoglycan (CSPG) that was modified by CHSY1 on glioma cells, and the suppression of CS formation on CD44 by silencing the CHSY1-inhibited interaction between CD44 and integrin β1 on the adhesion complex. Moreover, we tested the CS-specific binding peptide, resulting in the suppression of glioma cell mobility in a fashion similar to that observed upon the silencing of CHSY1. In addition, the peptide demonstrated significant affinity to CD44, promoted CD44 degradation, and suppressed integrin β1 expression in glioma cells. Overall, this study proposes a potential regulatory loop between CS, CD44, and integrin β1 in glioma cells, and highlights the importance of CS in CD44 stability. Furthermore, the targeting of CS by specific binding peptides has potential as a novel therapeutic strategy for glioma.

Dementia with Lewy bodies (DLB) is characterized by neuronal deficits andα-synuclein inclusions in the brain. Ceftriaxone (CEF), aβ-lactam antibiotic, has been suggested as a therapeutic agent in several neurodegenerative disorders for its abilities to counteract glutamate-mediated toxicity and to blockα-synuclein polymerization. By using manganese-enhanced magnetic resonance imaging (MEMRI) and immunohistochemistry, we measured the effects of CEF on neuronal activity andα-synuclein accumulation in the brain in a DLB rat model. The data showed that CEF corrected neuronal density and activity in the hippocampal CA1 area, suppressed hyperactivity in the subthalamic nucleus, and reducedα-synuclein accumulation, indicating that CEF is a potential agent in the treatment of DLB.

Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care.

Craniofacial bone deficiencies caused by trauma or disease pose clinical challenges as the shape of the damaged area varies between people. Although bone grafts are effective, they face issues such as poor drug retention and potential immune responses. PLA scaffolds possess therapeutic potential owing to their size, mechanical properties, stability, and biocompatibility. However, PLA scaffolds inherently lack bioactive molecules necessary to promote osteogenesis. HSPG2, also known as perlecan (Pln), are a basement membrane-specific GAG-containing core protein. Pln is a reservoir for heparin-binding growth factors, such as FGF, through GAG chains in domain I. For these reasons, we designed an HSPG2-coated PLA scaffold to enhance FGF delivery and promote cranial bone regeneration. Our results suggested an ideal scaffold with a 0.3 mm pore size and 60% porosity, enabling MG63 cell proliferation and osteogenesis. HSPGs help modulate FGF signaling during MG63 cell differentiation, motivating further studies on the microenvironment involved in neo-bone formation. We used 3D-printed PLA scaffolds coated with HSPG2 to create an osteoconductive environment. Advanced quantitative tests, computed tomography, and confocal microscopy confirmed the efficacy of the scaffold in reducing cranial bone-gap distances. Customized PLA scaffolds repaired diverse bone defects and regulated FGF delivery via HSPG2/FGF signaling, consequently promoting cranial bone regeneration. This study demonstrated promising applications for the treatment of cranial bone defects.