Citations

ABSTRACT Reliable assessment of infarct severity is essential in experimental stroke research, yet commonly used approaches such as 2,3,5‐triphenyltetrazolium chloride (TTC) staining and magnetic resonance imaging require additional tissue processing, specialized equipment, or substantial time and cost. In this study, we developed and validated a rapid visual Infarct Score to determine infarct volume and evaluate neuroprotective efficacy in rat middle cerebral artery occlusion (MCAO) models. A retrospective analysis was performed using data from 315 male Sprague–Dawley rats, including TTC‐derived infarct volume, visual Infarct Score, neurological deficit scores, and body weight changes. The Infarct Score demonstrated the strongest correlation with infarct volume among individual indicators in both nontreatment (Rho = 0.71) and treatment cohorts (Rho = 0.68). We further developed a Comprehensive Score by integrating the Infarct Score with the Longa 5‐point score at 48 h, which showed the highest overall correlation with infarct volume (Rho = 0.75 in both cohorts) and strong discrimination of infarct severity (AUC = 0.90). Interrater reliability analysis demonstrated excellent agreement among independent raters (intraclass correlation coefficient = 0.89; Kendall's W = 0.83, both p < 0.001). Neuroprotective interventions, including therapeutic hypothermia, nitroglycerin, and remote ischemic conditioning combined with physical exercise, significantly reduced infarct volume, Infarct Score, Comprehensive Score, neurological deficits, and weight loss. These findings indicate that the Infarct Score offers a rapid, practical, and cost‐effective method for infarct assessment, whereas the Comprehensive Score further improves the predictive accuracy and may serve as a useful tool for evaluating stroke severity and treatment outcomes in preclinical studies.

Freezing of gait (FOG) is a complex and highly disabling motor symptom that frequently affects patients with Parkinson’s disease (PD), especially in the middle and late stages. Although traditionally associated with motor deficits, accumulating evidence suggests that FOG is also strongly influenced by non-motor domains, including cognitive dysfunction and emotional disturbances. The prefrontal cortex (PFC), a key hub for executive functions, attention, and emotional regulation, has been increasingly implicated in the pathophysiology of FOG. Structural and functional abnormalities in the PFC, particularly in the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (MPFC), have been reported in PD patients with FOG. This narrative review aims to summarize current evidence on the role of the prefrontal cortex in the development and modulation of freezing episodes, focusing on neuroimaging findings. Clarifying the contribution of frontal lobe dysfunction to FOG may inform therapeutic strategies targeting frontostriatal circuits to improve mobility and quality of life in PD patients. This is a narrative review and does not employ formal systematic review methodology.

ABSTRACT Peritoneal fibrosis is one of the main causes of peritoneal dysfunction and withdrawal of patients from peritoneal dialysis (PD). Our previous study has shown that high‐glucose dialysis solution promotes glycolysis in peritoneal mesothelial cells, leading to mesothelial‐to‐mesenchymal transition (MMT) and peritoneal fibrosis. However, the molecular mechanisms remain unclear. Using single‐cell RNA sequencing (scRNA‐seq) analysis of cells from the effluent of patients undergoing PD from our previous study, we found that pyruvate kinase isozymes M2 (PKM2), a key rate‐limiting enzyme of glucose metabolism, was significantly upregulated in the mesothelial cells of patients with long‐term peritoneal dialysis (LPD). Using co‐immunoprecipitation, chromatin immunoprecipitation assay, and gene silencing techniques, we revealed that PKM2 promotes the expression of transcription factor SNAI2 by acetylating histone H3K9 (H3K9ac), thereby promoting the occurrence of MMT and hence peritoneal fibrosis. l ‐cysteine, a known PKM2 inhibitor, blocked these responses and prevented PD‐induced peritoneal fibrosis. These results could provide a novel therapeutic strategy for treating peritoneal fibrosis.

BACKGROUNDProstate cancer (PCa) is the most commonly diagnosed male cancer in the United States and is a hormone‐driven disease. Androgens have been recognized as a major promoter of PCa development and progression. However, the mechanism of androgen action in PCa, especially in PCa cell invasion and metastasis remains largely unclear. SMAD ubiquitination regulatory factor‐1 (SMURF1) is a C2‐WW‐HECT‐domain E3 ubiquitin ligase that plays important roles in cancer cell metastasis. Whether there is a relationship between androgens and SMURF1 expression is not known.METHODSThe effect of androgens on the expression of SMURF1 in PCa cell lines was examined by Western blot analyses and reverse transcription‐polymerase chain reaction (RT‐PCR). Gene transfection was performed by electroporation to manipulate the expression levels of proteins studied. The binding of AR to the SMURF1 gene enhancer was determined by chromatin immunoprecipitation (ChIP) assay. Cell migration and invasion was measured by wound healing and Matrigel invasion assays, respectively.RESULTSWe found that expression of SMURF1 is upregulated by androgens in PCa cell lines and that this effect of androgens is mediated through the androgen receptor (AR). We further showed that androgens regulate SMURF1 expression at transcriptional level and provided evidence that AR transcriptionally activates SMURF1 by binding to its enhancer that contains a canonical half androgen responsive element (ARE). Finally, we demonstrated that SMURF1 is important for androgen‐induced invasion of PCa cells.CONCLUSIONSWe demonstrate for the first time that SMURF1 is a bona fide target gene of the AR. Our findings also suggest a potential role of SMURF1 in PCa metastasis. Prostate 75: 561–572, 2015. © 2015 Wiley Periodicals, Inc.