Mitochondrial dysfunction induced by callyspongiolide promotes autophagy-dependent cell death.

Callyspongiolide is a marine macrolide known to induce caspaseindependent cancer cell death. While its toxic effects have been known, the mechanism leading to cell death is yet to be identified. We report that Callyspongiolide R form at C-21 (cally2R) causes mitochondrial dysfunction by inhibiting mitochondrial complex I or II, leading to a disruption of mitochondrial membrane potential and a deprivation of cellular energy.

MicroRNA-148a/b-3p regulates angiogenesis by targeting neuropilin-1 in endothelial cells.

MicroRNAs (miRs) are crucial regulators of vascular endothelial cell (EC) functions, including migration, proliferation, and survival. However, the role of most miRs in ECs remains unknown. Using RNA sequencing analysis, we found that miR-148a/b-3p expression was significantly downregulated during the differentiation of umbilical cord blood mononuclear cells into outgrowing ECs and that decreased miR-148a/b-3p levels were closely related to EC behavior.

Efficacy and tolerability of desensitization in the treatment of delayed drug hypersensitivities to anti-tuberculosis medications.

Background: Delayed drug hypersensitivity to first-line anti-tuberculosis medication is a major challenge in tuberculosis treatment.

Objective: This study was performed to investigate the efficacy/tolerability of desensitization therapy in treatment of first-line anti-tuberculosis medication hypersensitivity and the usefulness of immunologic evaluation therein.

Methods: This study was conducted as a prospective, observational cohort study.

Integrative analysis of DNA methylation and mRNA expression during differentiation of umbilical cord blood derived mononuclear cells to endothelial cells.

Differentiation of umbilical cord blood derived mononuclear cells to endothelial cells is accompanied by massive changes in gene expression. Although methylation and demethylation of DNA likely play crucial roles in regulating gene expression, their interplay during differentiation remains elusive. To address this question, we performed deep sequencing of DNA methylation and mRNA expression to profile global changes in promoter methylation and gene expression during differentiation from mononuclear cells to outgrowing cells.

Sac-1004, a vascular leakage blocker, reduces cerebral ischemia-reperfusion injury by suppressing blood-brain barrier disruption and inflammation.

Background: Blood-brain barrier (BBB) breakdown and inflammation are critical events in ischemic stroke, contributing to aggravated brain damage. The BBB mainly consists of microvascular endothelial cells sealed by tight junctions to protect the brain from blood-borne substances. Thus, the maintenance of BBB integrity may be a potential target for neuroprotection.

The endothelial E3 ligase HECW2 promotes endothelial cell junctions by increasing AMOTL1 protein stability via K63-linked ubiquitination.

Cell-to-cell junctions are critical for the formation of endothelial barriers, and its disorganization is required for sprouting angiogenesis. Members of the angiomotin (AMOT) family have emerged as key regulators in the control of endothelial cell (EC) junction stability and permeability. However, the underlying mechanism by which the AMOT family is regulated in ECs remains unclear.

BMP9 Induces Cord Blood-Derived Endothelial Progenitor Cell Differentiation and Ischemic Neovascularization via ALK1.

Objective: Modulating endothelial progenitor cells (EPCs) is essential for therapeutic angiogenesis, and thus various clinical trials involving EPCs are ongoing. However, the identification of environmental conditions and development of optimal methods are required to accelerate EPC-driven vasculogenesis.

Approach And Results: We evaluated gene expression profiles of cord blood-derived EPCs and endothelial cells to identify the key factors in EPC→endothelial cell differentiation and to show that transforming growth factor-β family members contribute to EPC differentiation.