β-Catenin Preserves the Stem State of Murine Bone Marrow Stromal Cells Through Activation of EZH2

During bone marrow stromal cell (BMSC) differentiation, both Wnt signaling and the development of a rigid cytoskeleton promote commitment to the osteoblastic over adipogenic lineage. β-catenin plays a critical role in the Wnt signaling pathway to facilitate downstream effects on gene expression. We show that β-catenin was additive with cytoskeletal signals to prevent adipogenesis, and β-catenin knockdown promoted adipogenesis even when the actin cytoskeleton was depolymerized. β-catenin also prevented osteoblast commitment in a cytoskeletal-independent manner, with β-catenin knockdown enhancing lineage commitment. Chromatin immunoprecipitation (ChIP)-sequencing demonstrated binding of β-catenin to the promoter of enhancer of zeste homolog 2 (EZH2), a key component of the polycomb repressive complex 2 (PRC2) complex that catalyzes histone methylation. Knockdown of β-catenin reduced EZH2 protein levels and decreased methylated histone 3 (H3K27me3) at osteogenic loci. Further, when EZH2 was inhibited, β-catenin's anti-differentiation effects were lost. These results indicate that regulating EZH2 activity is key to β-catenin's effects on BMSCs to preserve multipotentiality. © 2020 American Society for Bone and Mineral Research.     

Does abnormal interhemispheric inhibition play a role in mirror dystonia?

The presence of mirror dystonia (dystonic movement induced by a specific task performed by the unaffected hand) in the dominant hand of writer's cramp patients when the nondominant hand is moved suggests an abnormal interaction between the 2 hemispheres. In this study we compare the level of interhemispheric inhibition (IHI) in 2 groups of patients with writer's cramp, one with the presence of a mirror dystonia and the other without as well as a control group. The level of bidirectional IHI was measured in wrist muscles with dual‐site transcranial magnetic stimulation with a 10‐millisecond (short IHI) and a 40‐millisecond (long IHI) interstimulus interval during rest and while holding a pen in 9 patients with mirror dystonia 7 without mirror dystonia, and 13 controls. The group of patients without mirror dystonia did not differ from the controls in their IHI level. In contrast, IHI was significantly decreased in the group of patients with mirror dystonia in comparison with the group without mirror dystonia and the controls in both wrist muscles of both the dystonic and unaffected hand whatever the resting or active condition (P = 0.001). The decrease of IHI level in the group of patients with mirror dystonia was negatively correlated with the severity and the duration of the disease: the weaker the level of IHI, the more severe was the disease and the longer its duration. Interhemispheric inhibition disturbances are most likely involved in the occurrence of mirror dystonia. This bilateral deficient inhibition further suggests the involvement of the unaffected hemisphere in the pathophysiology of unilateral dystonia. © 2013 International Parkinson and Movement Disorder Society     

Case report: peritoneal sarcoidosis in an unusual location

A 48-year-old woman underwent surgery for a lesion seen on ultrasound and interpreted as a uterine myoma. The surgery revealed multiple nodules that had seeded on the omentum, peritoneum, and ovaries. The macroscopic interpretation was either metastasis or tuberculosis. The biopsy showed noncaseating granulomas, and a diagnosis of peritoneal sarcoidosis was reported. The AFB (acid fast bacillus) and L?wenstein-Jensen culture were negative. She was treated with methylprednisolone for 1 year for pulmonary sarcoidosis progression, with a resulting decrease in her DLCO (diffusing lung capacity for carbon monoxide). Computed tomography showed only a slight decrease in the multiple nodules and cysts. She is currently symptom-free.     

The role of DJ-1 in the oxidative stress cell death cascade after stroke

Oxidative stress is closely associated with secondary cell death in many disorders of the central nervous system including stroke,Parkinson’s disease,Alzheimer’s disease.Among many aberrant oxidative stress-associated proteins,DJ-1 has been associated with the oxidative stress cell death cascade primarily in Parkinson’s disease.Although principally expressed in the cytoplasm and nucleus,DJ-1 can be secreted into the serum under pathological condition.Recently,a close pathological association between DJ-1 and oxidative stress in stroke has been implicated.To this end,we and others have demonstrated the important role of mitochondria in neuroprotection for stroke by demonstrating that the translocation of DJ-1 in the mitochondria could potentially mitigate mitochondrial injury.Here,we discuss our recent findings testing the hypothesis that DJ-1 not only functions as a form of intracellular protection from oxidative stress,but that it also utilizes paracrine and/or autocrine cues in order to accomplish extracellular signaling between neighboring neuronal cells,resulting in neuroprotection.This article highlights recent evidence supporting the status of DJ-1 as key anti-oxidative stress therapeutic target for stroke.