TLRs are pattern recognition receptors that detect invading microorganisms and nonmicrobial endogenous molecules to trigger immune and inflammatory responses during host defense and tissue repair. TLR activity is closely linked to the risk of many inflammatory diseases and immune disorders. Therefore, TLR signaling pathways can provide efficient therapeutic targets for chronic diseases. Sulforaphane (SFN), an isothiocyanate, has been well known for its anti-inflammatory activities. In this study, we investigated the modulation of TLR activity by SFN and the underlying mechanism. SFN suppressed ligand-induced and ligand-independent TLR4 activation because it prevented IL-1R–associated kinase-1 degradation, activation of NF-κB and IFN regulatory factor 3, and cyclooxygenase-2 expression induced by LPS or overexpression of TLR4. Receptor oligomerization, which is one of the initial and critical events of TLR4 activation, was suppressed by SFN, resulting in the downregulation of NF-κB activation. SFN formed adducts with cysteine residues in the extracellular domain of TLR4 as confirmed by liquid chromatography-tandem mass spectrometry analysis and the inhibitory effects of SFN on oligomerization and NF-κB activation were reversed by thiol donors (DTT and N-acetyl-l-cysteine). These suggest that the reactivity of SFN to sulfhydryl moiety contributes to its inhibitory activities. Blockade of TLR4 signaling by SFN resulted in the reduced production of inflammatory cytokines and the decreased dermal inflammation and edema in vivo in experimental inflammatory animal models. Collectively, our results demonstrated that SFN downregulated TLR4 signaling through the suppression of oligomerization process in a thiol-dependent manner. These present a novel mechanism for beneficial effects of SFN and a novel anti-inflammatory target in TLR4 signaling.

Low-dose CT is highly effective for the diagnosis of suspected appendicitis and can be considered a valid alternative first-line imaging test that reduces the potential risk of exposure to ionizing radiation.

In order to evaluate the genetic diversity and discrimination among five Korean native chicken lines, a total of 86 individuals were genotyped using 150 microsatellite (MS) markers, and 15 highly polymorphic MS markers were selected. Based on the highest value of the number of alleles, the expected heterozygosity (He) and polymorphic information content (PIC) for the selected markers ranged from 6 to 12, 0.466 to 0.852, 0.709 to 0.882 and 0.648 to 0.865, respectively. Using these markers, the calculated genetic distance (Fst), the heterozygote deficit among chicken lines (Fit) and the heterozygote deficit within chicken line (Fis) values ranged from 0.0309 to 0.2473, 0.0013 to 0.4513 and −0.1002 to 0.271, respectively. The expected probability of identity values in random individuals (PI), random half-sib (PIhalf-sibs) and random sibs (PIsibs) were estimated at 7.98×10−29, 2.88×10−20 and 1.25×10−08, respectively, indicating that these markers can be used for traceability systems in Korean native chickens. The unrooted phylogenetic neighbor-joining (NJ) tree was constructed using 15 MS markers that clearly differentiated among the five native chicken lines. Also, the structure was estimated by the individual clustering with the K value of 5. The selected 15 MS markers were found to be useful for the conservation, breeding plan, and traceability system in Korean native chickens.

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Recent advances in fluorescence imaging techniques and super-resolution microscopy have extended the applications of fluorescent probes in studying various cellular processes at the molecular level. Specifically, organelle-targeted probes have been commonly used to detect cellular metabolites and transient chemical messengers with high precision and have become invaluable tools to study biochemical pathways. Moreover, several recent studies reported various labeling strategies and novel chemical scaffolds to enhance target specificity and responsiveness. In this review, we will survey the most recent reports of organelle-targeted fluorescent probes and assess their general strategies and structural features on the basis of their target organelles. We will discuss the advantages of the currently used probes and the potential challenges in their application as well as future directions.