Sulfated alginate oligosaccharide exerts antitumor activity and autophagy induction by inactivating MEK1/ERK/mTOR signaling in a KSR1-dependent manner in osteosarcoma.

Alginate oligosaccharide (AOS) has the function to inhibit tumor progression and the sulfated modification can enhance the antitumor activity. To date, the function and mechanism of sulfated AOS (AOS-SO4) in tumors remain largely elusive. We prepared AOS by the enzymatic degradation of alginate, collected AOS-SO4 by sulfating following the canonical procedure. Using these materials, in vitro assays showed that both AOS and AOS-SO4 elicited antitumor effects in osteosarcoma cells. Sulfated modification significantly enhanced the antitumor activity. In addition, AOS-SO4 had obvious effects on cell cycle arrest, apoptosis, and autophagy induction in vitro and in vivo. Mechanistically, we observed that AOS-SO4 treatment triggered proapoptotic autophagy by inhibiting MEK1/ERK/mTOR signaling. The ERK activator reversed AOS-SO4-induced autophagy. More importantly, we found that KSR1 interacted with MEK1 and functioned as a positive regulator of MEK1 protein in osteosarcoma cells. High KSR1 expression was significantly associated with poor survival in osteosarcoma patients. Together, these results suggest that AOS-SO4 has a better antitumor effect in osteosarcoma by inhibiting MEK1/ERK/mTOR signaling, which is KSR1-dependent; thus, AOS-SO4 can be a new potential therapeutic candidate for the treatment of osteosarcoma.

Brain hothubs and dark functional networks: correlation analysis between amplitude and connectivity for Broca's aphasia.

Source localization and functional brain network modeling are methods of identifying critical regions during cognitive tasks. The first activity estimates the relative differences of the signal amplitudes in regions of interest (ROI) and the second activity measures the statistical dependence among signal fluctuations. We hypothesized that the source amplitude-functional connectivity relationship decouples or reverses in persons having brain impairments. Five Broca's aphasics with five matched cognitively healthy controls underwent overt picture-naming magnetoencephalography scans. The gamma-band (30-45 Hz) phase-locking values were calculated as connections among the ROIs. We calculated the partial correlation coefficients between the amplitudes and network measures and detected four node types, including hothubs with high amplitude and high connectivity, coldhubs with high connectivity but lower amplitude, non-hub hotspots, and non-hub coldspots. The results indicate that the high-amplitude regions are not necessarily highly connected hubs. Furthermore, the Broca aphasics utilized different hothub sets for the naming task. Both groups had dark functional networks composed of coldhubs. Thus, source amplitude-functional connectivity relationships could help reveal functional reorganizations in patients. The amplitude-connectivity combination provides a new perspective for pathological studies of the brain's dark functional networks.

Hyoid-complex elevation and stimulation technique restores swallowing function in patients with lateral medullary syndrome: Two case reports.

BACKGROUND: A swallowing disorder may occur following a brainstem stroke, especially one that occurs in the swallowing centers. Lateral medullary syndrome (referred to as LMS), a rare condition in which a vascular event occurs in the territory of the posterior inferior cerebellar artery or the vertebral artery, has been reported to lead to more severe and longer lasting dysphagia. CASE SUMMARY: We report two patients with dysphagia due to LMS and propose a novel technique named hyoid-complex elevation and stimulation technique (known as HEST). The two patients had no other functional incapacity back into life, but nasogastric feeding was the only possible way for nutrition because of severe aspirations. Swallowing function was evaluated by functional oral intake scale, modified water swallow test, surface electromyographic signal associated with video fluorography swallowing study to assess the situation of aspiration, pharyngeal residue, pharyngeal peristalsis, upper esophageal opening and the ability of deglutition. Both patients were treated with the HEST method for dysphagia and recovered quickly. CONCLUSION: HEST is effective for shortening the in-hospital time and improving the quality of life for patients with dysphagia who suffer from LMS and likely other strokes.