Novel Activity of ODZ10117, a STAT3 Inhibitor, for Regulation of NLRP3 Inflammasome Activation.

The NLRP3 inflammasome serves as a host defense mechanism against various pathogens, but there is growing evidence linking its activation in sterile condition to diverse inflammatory diseases. Therefore, the identification of specific inhibitors that target NLRP3 inflammasome activation is meaningful and important for novel therapies for NLRP3 inflammasome-associated diseases. In this study, we identified a chemical compound, namely ODZ10117 (ODZ), that showed NLRP3 inflammasome-targeting anti-inflammatory effects during the screening of a chemical library for anti-inflammatory activity. Although ODZ was initially discovered as a STAT3 inhibitor, here we found it also has inhibitory activity on NLRP3 inflammasome activation. ODZ inhibited the cleavage of caspase-1 and IL-1ß-induced canonical NLRP3 inflammasome triggers, but had no effect on those induced by AIM2 or NLRC4 triggers. Mechanistically, ODZ impairs NLRP3 inflammasome activation through the inhibition of NLRP3-NEK7 interaction that is required for inflammasome formation. Moreover, the results obtained from the in silico docking experiment suggested that ODZ targets NLRP3 protein, which provides evidence for the specificity of ODZ to the NLRP3 inflammasome. Furthermore, ODZ administration significantly reduced MSU-induced IL-1ß release and the mortality rate of mice with LPS-induced sepsis. Collectively, these results demonstrate a novel effect of ODZ10117 in regulating NLRP3 inflammasome activation both in vitro and in vivo, making it a promising candidate for the treatment of NLRP3-inflammasome-associated immune disorders and cancer.

Cornus officinalis Seed Extract Inhibits AIM2-Inflammasome Activation and Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation.

The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 inflammasome activation. In this study, we aimed to investigate the inhibitory activity of ethanolic extracts of seeds of Cornus officinalis (CO), a herb and food plant used in traditional medicine, on AIM2-inflammasome activation. We found that CO inhibited the release of IL-1ß induced by dsDNA in both BMDMs and HaCaT cells, but that it showed no effect on the release of IL-1ß induced by NLRP3 inflammasome triggers, such as nigericin and silica, or the NLRC4 inflammasome trigger flagellin. Furthermore, we demonstrated that CO inhibited the cleavage of caspase-1, an inflammasome activation marker, and an upstream event, the translocation and speck formation of ASC. In addition, further experiments and mechanistic investigations revealed that CO can inhibit AIM2 speck formation induced by dsDNA in AIM2-overexpressing HEK293T cells. To verify the correlation in vivo, we investigated the efficacy of CO in an imiquimod (IMQ)-induced psoriasis model, which has reported associations with the AIM2 inflammasome. We found that topical application of CO alleviated psoriasis-like symptoms, such as erythema, scaling, and epidermal thickening, in a dose-dependent manner. Moreover, CO also significantly decreased IMQ-induced expression of AIM2 inflammasome components, including AIM2, ASC, and caspase-1, and led to the elevation of serum IL-17A. In conclusion, our results suggest that CO may be a valuable candidate for the discovery of AIM2 inhibitors and the regulation of AIM2-related diseases.

Lactobacillus gasseri MG4247 and Lacticaseibacillus paracasei MG4272 and MG4577 Modulate Allergic Inflammatory Response in RAW 264.7 and RBL-2H3 cells.

Allergic inflammation refers to a hyperimmune reaction that causes hypersensitivity responses such as hives, itchiness, runny nose, and cough due to specific allergens. Allergic diseases are known to be influenced by the diversity and distribution of intestinal microbiota, and Lactobacill is known to relieve allergic symptoms by modulating cytokines secreted by T helper type 1 (Th1)/Th2 cells. This study was designed to investigate the effects of Lactobacillus gasseri MG4247 and Lacticaseibacillus paracasei MG4272, MG4577, and MG4657 on levels of pro-inflammatory cytokines and proteins associated with allergic symptoms in RAW 264.7 macrophages, and RBL-2H3 mast cells, as well as their probiotic properties. MG4247, MG4272, and MG4577 significantly reduced tumor necrosis factor-α and interleukin (IL)-6 levels in LPS-induced RAW 264.7 macrophages, and markedly decreased IL-4, IL-5, and IL-13 levels and STAT6 phosphorylation in DNP-IgE/HSA sensitized RBL-2H3 mast cells. Furthermore, MG4247, MG4272, and MG4577 tolerated the acidic condition with pepsin and basic condition with bile salt, and showed a high adhesion rate (≥ 73.9%). In safety evaluation, MG4247, MG4272, and MG4577 showed no hemolytic or bile salt hydrolase activity and no cytotoxicity to HT-29 cells (≥ 96.7%). Hence, MG4272, MG4272, and MG4577 can be used as candidate probiotic strains to relieve cytokines associated with allergic inflammation.

Bio-Degradable Polyesters with Rigid Cyclic Diester from Camphor and Tartaric Acid.

Despite their excellent, useful, and stable properties, thermoplastics are constantly subject to environmental risks because of their low degradability under thermal, chemical, and mechanical stresses. To overcome the aforementioned issues, we hereby introduce an eco-friendly camphor (Ct) cyclic diester. The Ct diester is designed as a monomer, including a ketal group from the Ct, and shows high thermal stability via a rigid spiro-ring and a bridged bicyclic structure. A series of polyester was synthesized using the Ct diester, including various types of diols and dimethyl terephthalate. PETxCty copolyesters showed appropriate thermal stability up to 414 °C and a high glass transition temperature. This thermal behavior led to amorphous regions as the Ct diester content increased. Regarding the proportion of the Ct diester in the polyester, it was sensitive to hydrolysis and contributed to the degradation of the polyester in acid buffer conditions.

Down-regulation of pro-necroptotic molecules blunts necroptosis during myogenesis.

Cell death and differentiation are closely related at the molecular level. Differentiation of skeletal muscle cells attenuates susceptibility to apoptosis. Necroptosis has recently been recognized as a form of regulated cell death but its role in myogenesis has not been studied. This study aimed to compare the sensitivity to TNF-induced necroptosis in skeletal muscle at the undifferentiated (myoblasts) and differentiated (myotubes) stages. Surprisingly, our results showed that TNF-induced necroptosis was blunted during myoblast differentiation. Moreover, our data revealed that the key molecules involved in necroptosis, including receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL), were significantly down-regulated during myogenic differentiation, resulting in suppression of necroptosis signal transduction in differentiated myotubes. In addition, RIPK1, RIPK3, and MLKL expression levels were significantly lower in the skeletal muscle of adult mice than in newborn mice, suggesting that the susceptibility to necroptosis might be attenuated in differentiated muscle tissue. In conclusion, this study revealed that expression of key molecules involved in necroptosis is down-regulated during muscle differentiation, which results in the differentiation of muscles becoming insensitive to necroptotic cell death.

Immunostimulatory Activity of Polysaccharides Extracted from Celosia cristata Flowers.

Macrophages play a major role in innate immune responses by producing a variety of immune mediators and cytokines. The stimulation of macrophages by natural products may lead to an enhanced innate immune system. This study evaluated the immunostimulatory effects of a polysaccharide-rich crude fraction of Celosia cristata L. flowers (CCP) on murine macrophages. CCP treatment induced the production of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines by macrophages. Mechanistically, the activation of mitogen-activated protein kinases, NF-κB and toll-like receptor 4 were found to be associated with the stimulatory functions of CCP. CCP was found to be primarily composed of galacturonic acid and glucose in addition to small amounts of arabinose and galactose. This study demonstrated that CCP may enhance the innate immune responses and potentially improve the immune functions in the body.

Change of Characterization and Film Morphology Based on Acrylic Pressure Sensitive Adhesives by Hydrophilic Derivative Ratio.

Hydrophilic acrylic pressure-sensitive adhesives (PSAs) were synthesized by controlling the contents of 2-ethylhexyl acrylate (EHA), isobornyl acrylate (IBOA), and 2-hydroxyethyl acrylate (HEA); especially, the characteristic change of the HEA content was analyzed. Surface contact angle of acrylic PSA film decreased from 77.87° to 70.23° in the case of Acryl-2 to Acryl-8 (below HEA 10 wt %). However, the surface contact angle of Acryl-10 to Acryl-40 (HEA 10 wt % to 40 wt %) increased up to 92.29°, indicating hydrophobicity. All acrylic PSA films showed high adhesive force above 1800 gf/25 mm. According to X-ray diffraction (XRD) measurement, hydrophilic acrylic PSAs exhibited amorphous property and it was confirmed that the morphology of acrylic PSA film was significantly affected by the flexibility of the polymer chain and the strength of hydrogen bonding. The affinity with hydrophilic materials for acrylic PSA films was evaluated by T-type peel test, confirming that the affinity with hydrophilic materials is determined by the hydrophilicity of the acrylic PSA film. The synthesized acrylic PSA film is non-toxic regardless of the hydrophilicity.

Analytical features of microwave plasma-atomic emission spectrometry (MP-AES) for the quantitation of manganese (Mn) in wild grape (Vitis coignetiae) red wines: Comparison with inductively coupled plasma-optical emission spectrometry (ICP-OES).

The analytical features of MP-AES for the determination of Mn in wine were studied as compared with ICP-OES. The optimum spectral line (403.076 nm) of MP-AES was different from that (259.373 nm) of ICP-OES. Significant matrix effect was observed with MP-AES, but not with ICP-OES. A simple and cost-effective MP-AES for the quantitation of Mn in wild grape (Vitis coignetiae) red wines were developed and validated. A standard addition method was used to compensate the matrix effects. The sensitivity of MP-AES was comparable to that of ICP-OES. MP-AES was sensitive, precise, accurate and reliable. The Mn concentration in the wild grape wines was in the range of 502-3627 µg L-1. MP-AES had a distinct drawback of low matrix tolerance. However, MP-AES had a clear advantage of the low running cost due to the use of nitrogen gas generated from air with a nitrogen generator.

One step derivatization with British Anti-Lewsite in combination with gas chromatography coupled to triple-quadrupole tandem mass spectrometry for the fast and selective analysis of inorganic arsenic in rice.

We developed a new fast and selective analytical method for the determination of inorganic arsenic (iAs) in rice by a gas chromatography - tandem mass spectrometry (GC-MS/MS) in combination with one step derivatization of inorganic arsenic (iAs) with British Anti-Lewsite (BAL). Two step derivatization of iAs with BAL has been previously performed for the GC-MS analysis. In this paper, the quantitative one step derivatization condition was successfully established. The GC-MS/MS was carried out with a short nonpolar capillary column (0.25 mm × 10 m) under the conditions of fast oven temperature ramp rate (4 °C/s) and high linear velocity (108.8 cm/s) of the carrier gas. The established GC-MS/MS method showed an excellent linearity (r(2) > 0.999) in a tested range (0.2-100.0 µg L(-1)), ultra-low limit of detection (LOD, 0.08 pg), and high precision and accuracy. The GC-MS/MS technique showed far greater selectivity (22.5 fold higher signal to noise ratio in rice sample) on iAs than GC-MS method. The gas chromatographic running time was only 2.5 min with the iAs retention time of 1.98 min. The established method was successfully applied to quantify the iAs contents in polished rice. The mean iAs content in the Korean polished rice (n = 27) was 66.1 µg kg(-1) with the range of 37.5-125.0 µg kg(-1). This represents the first report on the GC-tandem mass spectrometry in combination with the one step derivatization with BAL for the iAs speciation in rice. This GC-MS/MS method would be a simple, useful and reliable measure for the iAs analysis in rice in the laboratories in which the expensive and element specific HPLC-ICP-MS is not available.