How does ethical leadership trickle down? Test of an integrative dual-process model

Although the trickle-down effect of ethical leadership has been documented in the literature, its underlying mechanism still remains largely unclear. To address this gap, we develop a cross-level dual-process model to explain how the effect occurs. Drawing on social learning theory, we hypothesize that the ethical leadership of high-level managers could cascade to middle-level supervisors via its impact on middle-level supervisors’ two ethical expectations. Using a sample of 69 middle-level supervisors and 381 subordinates across 69 sub-branches from a large banking firm in China, we found that middle-level supervisors’ ethical efficacy expectation and unethical behavior–punishment expectation (as one form of ethical outcome expectations) accounted for the trickle-down effect. The explanatory role of middle-level supervisors’ ethical behavior–reward expectation (as the other form of ethical outcome expectations), however, was not supported. The theoretical and practical implications are discussed

The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO3− by the Porcine Colon

A therapeutic potential of the TRPA1 channel agonist cinnamaldehyde for use in inflammatory bowel disease is emerging, but the mechanisms are unclear. Semi-quantitative qPCR of various parts of the porcine gastrointestinal tract showed that mRNA for TRPA1 was highest in the colonic mucosa. In Ussing chambers, 1 mmol·L−1 cinnamaldehyde induced increases in short circuit current (ΔIsc) and conductance (ΔGt) across the colon that were higher than those across the jejunum or after 1 mmol·L−1 thymol. Lidocaine, amiloride or bumetanide did not change the response. The application of 1 mmol·L−1 quinidine or the bilateral replacement of 120 Na+, 120 Cl− or 25 HCO3− reduced ΔGt, while the removal of Ca2+ enhanced ΔGt with ΔIsc numerically higher. ΔIsc decreased after 0.5 NPPB, 0.01 indometacin and the bilateral replacement of 120 Na+ or 25 HCO3−. The removal of 120 Cl− had no effect. Cinnamaldehyde also activates TRPV3, but comparative measurements involving patch clamp experiments on overexpressing cells demonstrated that much higher concentrations are required. We suggest that cinnamaldehyde stimulates the secretion of HCO3− via apical CFTR and basolateral Na+-HCO3− cotransport, preventing acidosis and damage to the epithelium and the colonic microbiome. Signaling may involve the opening of TRPA1, depolarization of the epithelium and a rise in PGE2 following a lower uptake of prostaglandins via OATP2A1

Junctional Adhesion Molecule-C expression specifies a {CD}138low/neg multiple myeloma cell population in mice and humans

Deregulation such as overexpression of adhesion molecules influences cancer progression and survival. Metastasis of malignant cells from their primary tumor site to distant organs is the most common reason for cancer-related deaths. Junctional adhesion molecule (JAM)-C, a member of the Ig-like JAM family, can homodimerize and aid cancer cell migration and metastasis. Here we show that this molecule is dynamically expressed on multiple myeloma (MM) cells in the marrow and co-localizes with blood vessels within the bone marrow of mice and humans. Additionally, JAM-C upregulation inversely correlates with the downregulation of the canonical plasma cell marker CD138 (syndecan-1), whose surface expression has recently been found to dynamically regulate a switch between MM growth in situ and MM dissemination. Moreover, targeting JAM-C in a syngeneic in vivo MM model ameliorates MM progression and improves outcome. Overall, our data demonstrate that JAM-C might serve not only as an additional novel diagnostic biomarker but also as a therapeutic target in MM disease

Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression

Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to disease relapse in patients. In the bone marrow, CD4$^{+}$FoxP3$^{+}$ regulatory T cells (Tregs) are highly abundant amongst CD4$^{+}$ T cells providing an immune protective niche for different long-living cell populations, e.g., hematopoietic stem cells. Here, we addressed the functional role of Tregs in multiple myeloma dissemination to bone marrow compartments and disease progression. To investigate the immune regulation of multiple myeloma, we utilized syngeneic immunocompetent murine multiple myeloma models in two different genetic backgrounds. Analyzing the spatial immune architecture of multiple myeloma revealed that the bone marrow Tregs accumulated in the vicinity of malignant plasma cells and displayed an activated phenotype. In vivo Treg depletion prevented multiple myeloma dissemination in both models. Importantly, short-term in vivo depletion of Tregs in mice with established multiple myeloma evoked a potent CD8 T cell- and NK cell-mediated immune response resulting in complete and stable remission. Conclusively, this preclinical in-vivo study suggests that Tregs are an attractive target for the treatment of multiple myeloma

Adhesion-Mediated Multiple Myeloma (MM) Disease Progression: Junctional Adhesion Molecule a Enhances Angiogenesis and Multiple Myeloma Dissemination and Predicts Poor Survival

Adhesion-Mediated Multiple Myeloma (MM) Disease Progression: Junctional Adhesion Molecule a Enhances Angiogenesis and Multiple Myeloma Dissemination and Predicts Poor Surviva