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Kinnunen, M.

Publications and source records attributed to Kinnunen, M..

2 recordsLinked to original sources

Obstructive Sleep Apnea Syndrome Disrupts Glymphatic-Related Physiological Brain Pulsations

BackgroundObstructive sleep apnea (OSA) affects over one billion people and increases neurodegenerative risk. Brain vasomotor, respiratory, and cardiac pulsations are thought to drive glymphatic clearance during sleep, yet OSAs effect on these pulsations remains poorly understood. MethodsWe studied 20 healthy controls (HC; 39.7{+/-}8.0 y) and 12 patients with OSA (PWOSA; 53.0{+/-}11.0 y) using a four wavelength (690-980 nm) functional near-infrared spectroscopy (fNIRS) measuring oxygenated, deoxygenated and total hemoglobin, water and cerebrospinal fluid (HbO, HbR, HbT, H2O, CSF). Polar devices provided heart rate variability (HRV). Spectral power, coherence and phase transfer entropy analysis was performed for very low frequency (VLF), respiratory, and cardiac bands from 30 min sleep segments and event-based whole-night analysis assessed autonomic responses. ResultsOSA patients exhibited lower fNIRS spectral entropy for HbO, HbT, H2O & CSF (p<0.05), with increased VLF and respiratory band power across all concentrations (HbO, HbR, HbT, H2O & CSF, p<0.05). Signal coherence was reduced in respiratory and cardiac bands. Phase transfer entropy revealed disrupted directional coupling toward HbR (cardiac) and CSF-to-HbO (respiratory). HRV showed parallel VLF amplification (p <0.05), elevated heart rate during event-free and respiratory-event periods (p<0.001) and reduced Root Mean Square of Successive Differences (RMSSD, 32.5 vs 43.0 ms, p<0.001). Hypoxic burden correlated with cardiac band power of HbO, HbT and CSF (r>0.73). ConclusionsOSA reorganizes cortical pulsatile dynamics - reducing complexity, amplifying low frequency power and suppfdsfsdfsdfsdisrupting directed coupling. This state may compromise sleep-related glymphatic clearance. fNIRS-based spectral analysis offers a promising bedside tool for monitoring brain pulsatility.

physiology↗

PROX1 transcription factor is a master regulator of myogenic and oncogenic features of rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is an aggressive pediatric soft tissue cancer in need for novel therapies. Here we show that the PROX1 transcription factor, which is essential for normal myoblast differentiation, is highly expressed in RMS tumors. We demonstrate that PROX1 is needed for RMS cell stemness and growth in vitro, and for RMS tumor formation in mouse xenograft models. In addition, we unveil that PROX1 is an essential for myogenic properties in RMS. PROX1 depletion reprogrammed the RMS transcriptome to resemble benign mesenchymal stem cells and repressed many of the previously identified RMS effector transcripts and myogenic genes. By using proximity labeling and mass spectrometry, we found that PROX1 interacts with the NuRD and CoREST complexes containing class I HDACs. Our studies reveal a major role of PROX1-HDAC interaction in RMS and give insights that inhibiting this interaction could be a promising therapeutic approach.

cancer biology↗