Soluble Guanylate Cyclase (sGC) is the intracellular receptor of Nitric Oxide (NO). The activation
of sGC results in the conversion of Guanosine Triphosphate (GTP) to the secondary messenger
cyclic Guanosine Monophosphate (cGMP). cGMP modulates a series of downstream cascades through
activating a variety of effectors, such as Phosphodiesterase (PDE), Protein Kinase G (PKG) and Cyclic
Nucleotide-Gated Ion Channels (CNG). NO-sGC-cGMP pathway plays significant roles in various
physiological processes, including platelet aggregation, smooth muscle relaxation and neurotransmitter
delivery. With the approval of an sGC stimulator Riociguat for the treatment of Pulmonary Arterial
Hypertension (PAH), the enthusiasm in the discovery of sGC modulators continues for broad clinical
applications. Notably, through activating the NO-sGC-cGMP pathway, sGC stimulator and activator
potentiate for the treatment of various diseases, such as PAH, Heart Failure (HF), Diabetic Nephropathy
(DN), Systemic Sclerosis (SS), fibrosis as well as other diseases including Sickle Cell Disease
(SCD) and Central Nervous System (CNS) disease. Here, we review the preclinical and clinical studies
of sGC stimulator and activator in recent years and prospect for the development of sGC modulators in
the near future.
Fibrosis occurs in a variety of organs and frequently brings great harm to patients, even contributes to their death. Despite great efforts made in the field of fibrosis over the past decades and considerable understanding of the pathogenesis of fibrotic reactions attained, there is still lack of effective anti-fibrotic treatments. A growing body of evidence indicates a significant anti-fibrotic potential of activated soluble guanylate cyclase (sGC), which emphasizes the importance of sGC in fibrogenesis of diverse organs including skin, kidney, liver and lung. While sGC has been well known for its role in the regulation of vascular tone and vascular remodeling, its possible implication in fibrosis remains to be illustrated. Emerging evidence in recent years provides new insights into anti-fibrotic effect of sGC stimulation by blocking non-canonical TGF-β signaling. In this review we will discuss the key role of sGC and its mechanism of action in fibrosis. Herein, sGC signaling pathway may represent a promising target for treating tissue fibrosis.
Groups often face difficulty reaching consensus. For complex decisions with multiple criteria, verbal and written discourse alone may impede groups from pinpointing and moving past fundamental disagreements. To help support consensus building, we introduce ConsensUs, a novel visualization tool that highlights disagreement by asking group members to quantify their subjective opinions across multiple criteria. To evaluate this approach, we conducted a between-subjects experiment with 87 participants on a comparative hiring task. The study compared three modes of sensemaking on a group decision: written discourse only, visualization only, and written discourse plus visualization. We confirmed that the visualization helped participants identify disagreements within the group and then measured subsequent changes to their individual opinions. The results show that disagreement highlighting led participants to align their ratings more with the opinions of other group members. While disagreement highlighting led to better score alignment, participants reported a number of reasons for shifting their score, from genuine consensus to appeasement. We discuss further research angles to understand how disagreement highlighting affects social processes and whether it produces objectively better decisions.
We unveiled the mechanism of how HPV employs Aurora kinase A (AurA) of host cells to exert its oncogenic capability synergistically. We systematically characterized the mode of interaction between E6-encoded by cancer-causing HPV and AurA.
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