cGMP signaling pathway that modulates NF-κB activation in innate immune responses.

The nuclear factor-kappa B (NF-κB) pathway is an evolutionarily conserved signaling pathway that plays a central role in immune responses and inflammation. Here, we show that NF-κB signaling is activated via a pathway in parallel with the Toll receptor by receptor-type guanylate cyclase, Gyc76C. Gyc76C produces cyclic guanosine monophosphate (cGMP) and modulates NF-κB signaling through the downstream Tollreceptor components dMyd88, Pelle, Tube, and Dif/Dorsal (NF-κB).

Evaluating the Knockdown Activity of MALAT1 ENA Gapmers In Vitro.

Antisense oligonucleotides (ASOs) are widely used for the identification of gene functions and regulation of genes involved in different diseases for therapeutic purposes. For in vitro evaluation of the knockdown activity of gapmer ASOs, we often use lipofection or electroporation to deliver gapmer ASOs into the cells. Here, we describe a method for evaluating the knockdown activity of gapmer ASOs by a cell-free uptake mechanism, termed as gymnosis, using MALAT1 gapmer ASOs modified with 2'-O-methoxyethyl RNA (2'-MOE) or 2'-O,4'-C-ethylene-bridged nucleic acid (ENA).

A Receptor Guanylate Cyclase, Gyc76C, Mediates Humoral, and Cellular Responses in Distinct Ways in Immunity.

Innate immunity is an evolutionarily conserved host defense system against infections. The fruit fly relies solely on innate immunity for infection defense, and the conservation of innate immunity makes an ideal model for understanding the principles of innate immunity, which comprises both humoral and cellular responses. The mechanisms underlying the coordination of humoral and cellular responses, however, has remained unclear.

Loss of the fragile X mental retardation protein causes aberrant differentiation in human neural progenitor cells.

Fragile X syndrome (FXS) is caused by transcriptional silencing of the FMR1 gene during embryonic development with the consequent loss of the encoded fragile X mental retardation protein (FMRP). The pathological mechanisms of FXS have been extensively studied using the Fmr1-knockout mouse, and the findings suggest important roles for FMRP in synaptic plasticity and proper functioning of neural networks. However, the function of FMRP during early development in the human nervous system remains to be confirmed.

Ecrg4 peptide is the ligand of multiple scavenger receptors.

Esophageal cancer-related gene 4 (Ecrg4) encodes a hormone-like peptide that is believed to be involved in a variety of physiological phenomena, including tumour suppression. Recent progress in the study of Ecrg4 has shown that Ecrg4 is a proinflammatory factor and induces the expression of several cytokines and chemokines in macrophages/microglia. However, the detailed molecular mechanisms of Ecrg4 signalling, especially the Ecrg4 receptors, remain poorly understood.

Structure-based design, synthesis, and binding mode analysis of novel and potent chymase inhibitors.

Based on insight from the X-ray crystal structure of human chymase in complex with compound 1, a lactam carbonyl of the diazepane core was exchanged with O-substituted oxyimino group, leading to amidoxime derivatives. This modification resulted in highly potent chymase inhibitors, such as O-phenylamidoxime 5f. X-ray crystal structure analysis indicated that compound 5f induced movement of the Leu99 and Tyr94 side chains at the S2 site, and the increase in inhibitory activity of O-phenyl amidoxime derivatives suggested that the O-phenyl moiety interacted with the Tyr94 residue.

Cooperative regulation of the induction of the novel antibacterial Listericin by peptidoglycan recognition protein LE and the JAK-STAT pathway.

Intracellular bacteria cause serious infectious diseases such as tuberculosis, shigellosis, and listeriosis. The Drosophila peptidoglycan recognition protein (PGRP)-LE functions as an important host pattern recognition receptor against intracellular bacteria such as Listeria monocytogenes. One PGRP-LE-mediated intracellular response against L.