Predictors for Upper-Limb Functional Recovery Trajectory in Individuals Receiving Stroke Rehabilitation: A Secondary Analysis of Data from Randomized Controlled Trials.

BACKGROUND: The objective of the study was to determine predictors for upper-limb functional recovery trajectory after occupational therapy in a population with chronic stroke. METHODS: In this retrospective secondary analysis, Fugl-Meyer Assessment-Upper Extremity (FMA-UE) scores before and after intervention and at the 3-month follow-up were used to divide 105 participants with chronic stroke into three groups of recovery trajectories: fast (participants who reached an improvement of 7 after intervention), extended (those who reached an improvement of 7 at follow-up), and limited (those who did not reach an improvement of 7) recovery. Comparisons among the three groups were made in demographics, stroke characteristics, and baseline assessment scores. Logistic regression analyses were performed to determine predictors for group membership. RESULTS: Time after onset of stroke and the baseline scores of FMA-UE, Stroke Impact Scale-Hand (SIS-Hand), Wolf Motor Function Test (WMFT)-Quality, WMFT-Time scores, Motor Activity Log-Amount of Use (MAL-AOU), and Motor Activity Log-Quality of Movement (MAL-QOM) scores were significantly different among the three groups. Univariate logistic regressions confirmed that SIS-Hand, WMFT-Quality, WMFT-Time, MAL-AOU, and MAL-QOM were significant predictors for both the fast versus limited recovery group membership and the extended versus limited group membership. Time after stroke onset and baseline FMA-UE were additional predictors for the fast versus limited recovery group membership. CONCLUSION: These findings may assist healthcare professionals in making optimal therapeutic decisions and in informing clients and caregivers about the outcomes of stroke recovery.

L-Carnitine reduces reactive oxygen species/endoplasmic reticulum stress and maintains mitochondrial function during autophagy-mediated cell apoptosis in perfluorooctanesulfonate-treated renal tubular cells.

We previously reported that perfluorooctanesulfonate (PFOS) causes autophagy-induced apoptosis in renal tubular cells (RTCs) through a mechanism dependent on reactive oxygen species (ROS)/extracellular signal-regulated kinase. This study extended our findings and determined the therapeutic potency of L-Carnitine in PFOS-treated RTCs. L-Carnitine (10 mM) reversed the effects of PFOS (100 µM) on autophagy induction and impaired autophagy flux. Furthermore, it downregulated the protein level of p47Phox, which is partly related to PFOS-induced increased cytosolic ROS in RTCs. Moreover, L-Carnitine reduced ROS production in mitochondria and restored PFOS-impeded mitochondrial function, leading to sustained normal adenosine triphosphate synthesis and oxygen consumption and reduced proton leakage in a Seahorse XF stress test. The increased inositol-requiring enzyme 1α expression by PFOS, which indicated endoplasmic reticulum (ER) stress activation, was associated with PFOS-mediated autophagy activation that could be attenuated through 4-phenylbutyrate (5 mM, an ER stress inhibitor) and L-Carnitine pretreatment. Therefore, by reducing the level of IRE1α, L-Carnitine reduced the levels of Beclin and LC3BII, consequently reducing the level of apoptotic biomarkers including Bax and cleaving PARP and caspase 3. Collectively, these results indicate that through the elimination of oxidative stress, extracellular signal-regulated kinase activation, and ER stress, L-Carnitine reduced cell autophagy/apoptosis and concomitantly increased cell viability in RTCs. This study clarified the potential mechanism of PFOS-mediated RTC apoptosis and provided a new strategy for using L-Carnitine to prevent and treat PFOS-induced RTC apoptosis.

Histone deacetylase inhibitor MPT0B291 suppresses Glioma Growth in vitro and in vivo partially through acetylation of p53.

Background: Histone deacetylase (HDAC) inhibitors have emerged as a new class of anti-tumor agents for various types of tumors, including glioblastoma. Methods and results: We found that a novel HDAC inhibitor, MPT0B291, significantly reduced the cell viability and increased cell death of human and rat glioma cell lines, but not in normal astrocytes. We also demonstrated that MPT0B291 suppressed proliferation by inducing G1 phase cell cycle arrest and increased apoptosis in human and rat glioma cell lines by flow cytometry and immunocytochemistry. We further investigated the anti-tumor effects of MPT0B291 in xenograft (mouse) and allograft (rat) models. The IVIS200 images and histological analysis indicated MPT0B291 (25 mg/kg, p. o.) reduced tumor volume. Mechanistically, MPT0B291 increased phosphorylation and acetylation/activation of p53 and increased mRNA levels of the apoptosis related genes PUMA, Bax, and Apaf1 as well as increased protein level of PUMA, Apaf1 in C6 cell line. The expression of cell cycle related gene p21 was also increased and Cdk2, Cdk4 were decreased by MPT0B291. Conclusion: Our study highlights the anti-tumor efficacy of a novel compound MPT0B291 on glioma growth.