Methyl CpG binding protein 2 (MeCP2) was initially isolated as an exclusive reader of DNA methylated at CpG. This recognition site, was subsequently extended to other DNA methylated residues and it has been the persisting dogma that binding to methylated DNA constitutes its physiologically relevant role. As we review here, two very recent papers fundamentally change our understanding of the interactions of this protein with chromatin, as well as its functional attributes. In the first one, the protein has been shown to bind to tri-methylated histone H3 (H3K27me3), providing a hint for what might turn out to be the first described chromodomain-containing protein reader in the animal kingdom, and unequivocally demonstrates the ability of MeCP2 to bind to nonmethylated CpG regions of the genome. The second paper reports how the protein dynamically participates in the formation of constitutive heterochromatin condensates. Histone H3K27me3 is a critical component of this form of chromatin.Differentiating between subcortical ischemic vascular disease (SIVD), Alzheimer’s disease (AD), and normal cognition (NC) remains a challenge, and reliable neuroimaging biomarkers are needed. The current study, therefore, investigated the discriminative ability of diffusion kurtosis imaging (DKI) metrics in segregated thalamic regions and compare with diffusion tensor imaging (DTI) metrics. Twenty-three SIVD patients, 30 AD patients, and 24 NC participants underwent brain magnetic resonance imaging. The DKI metrics including mean kurtosis (MK), axial kurtosis (Kaxial ) and radial kurtosis (Kradial ) and the DTI metrics including diffusivity and fractional anisotropy (FA) were measured within the whole thalamus and segregated thalamic subregions. Strategic correlations by group, thalamo-frontal connectivity, and canonical discriminant analysis (CDA) were used to demonstrate the discriminative ability of DKI for SIVD, AD, and NC. Whole and segregated thalamus analysis suggested that DKI metrics are less affected by white matter hyperintensities compared to DTI metrics. Segregated thalamic analysis showed that MK and Kradial were notably different between SIVD and AD/NC. The correlation analysis between Kaxial and MK showed a nonsignificant relationship in SIVD group, a trend of negative relationship in AD group, and a significant positive relationship in NC group. A wider spatial distribution of thalamo-frontal connectivity differences across groups was shown by MK compared to FA. CDA showed a discriminant power of 97.4% correct classification using all DKI metrics. Our findings support that DKI metrics could be more sensitive than DTI metrics to reflect microstructural changes within the gray matter, hence providing complementary information for currently outlined pathogenesis of SIVD and AD.Neonatal hypoxic-ischemic (H-I) injury, which mainly causes neuronal damage and white matter injury (WMI), is among the predominant causes of infant morbidity (cerebral palsy, cognitive and persistent motor disabilities) and mortality. Disruptions to the oxygen and blood supply in the perinatal brain affect the cerebral microenvironment and may affect microglial activation, excitotoxicity, and oxidative stress. Microglia are significantly associated with axonal damage and myelinating oligodendrocytes, which are major pathological components of WMI. However, the effects of H-I injury on microglial functions and underlying transformation mechanisms remain poorly understood. see more The historical perception that these cells are major risk factors for ischemic stroke has been questioned due to our improved understanding of the diversity of microglial phenotypes and their alterable functions, which exacerbate or attenuate injuries in different regions in response to environmental instability. Unfortunately, although therapeutic hypothermia is an efficient treatment, death and disability remain the prognosis for a large proportion of neonates with H-I injury. Hence, novel neuroprotective therapies to treat WMI following H-I injury are urgently needed. Here, we review microglial mechanisms that might occur in the developing brain due to neonatal H-I injury and discuss whether microglia function as a double-edged sword in WMI. Then, we emphasize microglial heterogeneity, notably at the single-cell level, and sex-specific effects on the etiology of neurological diseases. Finally, we discuss current knowledge of strategies aiming to improve microglia modulation and remyelination following neonatal H-I injury. Overall, microglia-targeted therapy might provide novel and valuable insights into the treatment of neonatal H-I insult.In this work, the design, synthesis, and structure-activity relationships of a novel array of geranyloxy and farnesyloxy 3-acetylcoumarins were reported as potent soybean 15-lipoxygenase inhibitors. Among the prepared coumarins, 7-farnesyloxy-3-acetylcoumarin (12b) was found to be the most potent inhibitor by IC50 = 0.68 μM while O-geranyl substituents at positions 5 and 6 of 3-acetylcoumarin (10a and 11a) were not inhibitors. Using docking studies, the binding affinity and the preferred pose of synthetic compounds were considered. It was found that lipoxygenase inhibitory activity and prenyl length chain were directly related. The hydrophobic cavity of the enzyme was more effectively occupied by the farnesyl moiety of the potent inhibitor 12b rather than other derivatives. Also, with this pose of farnesyl chain in 7-farnesyloxy-3-acetylcoumarins, the acetyl group could be directed to the hydrophilic pocket in the active site.Opioid use disorder is a devastating disorder with a high burden in terms of overdose mortality, with an urgent need for more personalized prevention or therapeutic interventions. For this purpose, the description and validation of biological measures of staging or treatment response is a highly active research field. We conducted a narrative review on the pathophysiology of opioid use disorder to propose staging of the disease and search for research studies proposing or demonstrating the predictive value of biomarkers. We propose a IV stage description of opioid use disorder, from (I) vulnerability stage to (II) disease progression, (III) constituted opioid dependence and were several type of treatments can be applied, to the reach a (IV) modified health state. We classified biomarkers studies according to the stage of the disorder they were intended to predict, and to the three categories of methods they used anatomical and functional aspects of the brain, genetic/transcriptomic/epigenetic studies, and lastly biomarkers of systemic modifications associated with opioid use disorder, especially regarding the immune system.