Photochemically Inert Broad-Spectrum Sunscreen by Metal-Phenolic Network Coatings of Titanium Oxide Nanoparticles.

Titanium dioxide (TiO2) nanoparticles are extensively used as a sunscreen filter due to their long-active ultraviolet (UV)-blocking performance. However, their practical use is being challenged by high photochemical activities and limited absorption spectrum. Current solutions include the coating of TiO2 with synthetic polymers and formulating a sunscreen product with additional organic UV filters. Unfortunately, these approaches are no longer considered effective because of recent environmental and public health issues. Herein, TiO2-metal-phenolic network hybrid nanoparticles (TiO2-MPN NPs) are developed as the sole active ingredient for sunscreen products through photochemical suppression and absorption spectrum widening. The MPNs are generated by the complexation of tannic acid with multivalent metal ions, forming a robust coating shell. The TiO2-MPN hybridization extends the absorption region to the high-energy-visible (HEV) light range via a new ligand-to-metal charge transfer photoexcitation pathway, boosting both the sun protection factor and ultraviolet-A protection factor about 4-fold. The TiO2-MPN NPs suppressed the photoinduced reactive oxygen species by 99.9% for 6 h under simulated solar irradiation. Accordingly, they substantially alleviated UV- and HEV-induced cytotoxicity of fibroblasts. This work outlines a new tactic for the eco-friendly and biocompatible design of sunscreen agents by selectively inhibiting the photocatalytic activities of semiconductor nanoparticles while broadening their optical spectrum.

Sustainable Strategies for Synthesizing Lignin-Incorporated Bio-Based Waterborne Polyurethane with Tunable Characteristics.

In this study, we introduce a novel approach for synthesizing lignin-incorporated castor-oil-based cationic waterborne polyurethane (CWPU-LX), diverging significantly from conventional waterborne polyurethane dispersion synthesis methods. Our innovative method efficiently reduces the required solvent quantity for CWPU-LX synthesis to approximately 50% of that employed in traditional WBPU experimental procedures. By incorporating lignin into the polyurethane matrix using this efficient and reduced-solvent method, CWPU-LX demonstrates enhanced properties, rendering it a promising material for diverse applications. Dynamic interactions between lignin and polyurethane molecules contribute to improved mechanical properties, enhanced thermal stability, and increased solvent resistance. Dynamic interactions between lignin and polyurethane molecules contribute to improved tensile strength, up to 250% compared to CWPU samples. Furthermore, the inclusion of lignin enhanced thermal stability, showcasing a 4.6% increase in thermal decomposition temperature compared to conventional samples and increased solvent resistance to ethanol. Moreover, CWPU-LX exhibits desirable characteristics such as protection against ultraviolet light and antibacterial properties. These unique properties can be attributed to the presence of the polyphenolic group and the three-dimensional structure of lignin, further highlighting the versatility and potential of this material in various application domains. The integration of lignin, a renewable and abundant resource, into CWPU-LX exemplifies the commitment to environmentally conscious practices and underscores the significance of greener materials in achieving a more sustainable future.

Gas6 Ameliorates Inflammatory Response and Apoptosis in Bleomycin-Induced Acute Lung Injury.

Acute lung injury (ALI) is characterized by alveolar damage, lung edema, and exacerbated inflammatory response. Growth arrest-specific protein 6 (Gas6) mediates many different functions, including cell survival, proliferation, inflammatory signaling, and apoptotic cell clearance (efferocytosis). The role of Gas6 in bleomycin (BLM)-induced ALI is unknown. We investigated whether exogenous administration of mouse recombinant Gas6 (rGas6) has anti-inflammatory and anti-apoptotic effects on BLM-induced ALI. Compared to mice treated with only BLM, the administration of rGas6 reduced the secretion of proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and macrophage inflammatory protein-2, and increased the secretion of hepatocyte growth factor in bronchoalveolar lavage (BAL) fluid. rGas6 administration also reduced BLM-induced inflammation and apoptosis as evidenced by reduced neutrophil recruitment into the lungs, total protein levels in BAL fluid, caspase-3 activity, and TUNEL-positive lung cells in lung tissue. Apoptotic cell clearance by alveolar macrophages was also enhanced in mice treated with both BLM and rGas6 compared with mice treated with only BLM. rGas6 also had pro-resolving and anti-apoptotic effects in mouse bone marrow-derived macrophages and alveolar epithelial cell lines stimulated with BLM in vitro. These findings indicate that rGas6 may play a protective role in BLM-induced ALI.

STAT6 Signaling Mediates PPARγ Activation and Resolution of Acute Sterile Inflammation in Mice.

The signal transducer and activator of transcription 6 (STAT6) transcription factor promotes activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway in macrophages. Little is known about the effect of proximal signal transduction leading to PPARγ activation for the resolution of acute inflammation. Here, we studied the role of STAT6 signaling in PPARγ activation and the resolution of acute sterile inflammation in a murine model of zymosan-induced peritonitis. First, we showed that STAT6 is aberrantly activated in peritoneal macrophages after zymosan injection. Utilizing STAT6-/- and wild-type (WT) mice, we found that STAT6 deficiency further enhanced zymosan-induced proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-6, and macrophage inflammatory protein-2 in peritoneal lavage fluid (PLF) and serum, neutrophil numbers and total protein amount in PLF, but reduced proresolving molecules, such as IL-10 and hepatocyte growth factor, in PLF. The peritoneal macrophages and spleens of STAT6-/- mice exhibited lower mRNA and protein levels of PPARγ and its target molecules over the course of inflammation than those of WT mice. The deficiency of STAT6 was shown to impair efferocytosis by peritoneal macrophages. Taken together, these results suggest that enhanced STAT6 signaling results in PPARγ-mediated macrophage programming, contributing to increased efferocytosis and inflammation resolution.

Coralmycin Derivatives with Potent Anti-Gram Negative Activity Produced by the Myxobacteria Corallococcus coralloides M23.

Seven new coralmycin derivatives, coralmycins C (1), D (2), E (3), F (4), G (5), H (6), and I (7), along with three known compounds, cystobactamids 891-2 (8), 905-2 (9), and 507 (10), were isolated from a large-scale culture of the myxobacteria Corallococcus coralloides M23. The structures of these compounds, including their relative stereochemistries, were elucidated by interpretation of their spectroscopic and CD data. The structure-activity relationships of their antibacterial and DNA gyrase inhibitory activities indicated that the para-nitrobenzoic acid unit is critical for the inhibition of DNA gyrase and bacterial growth, while the nitro moiety of the para-nitrobenzoic acid unit and the isopropyl chain at C-4 could be important for permeability into certain Gram-negative bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae, and the ß-methoxyasparagine moiety could affect cellular uptake into all tested bacteria. These results could facilitate the chemical optimization of coralmycins for the treatment of multidrug-resistant Gram-negative bacteria.

Characterization of the hypersensitive response-like cell death phenomenon induced by targeting antiviral lectin griffithsin to the secretory pathway.

Griffithsin (GRFT) is an antiviral lectin, originally derived from a red alga, which is currently being investigated as a topical microbicide to prevent transmission of human immunodeficiency virus (HIV). Targeting GRFT to the apoplast for production in Nicotiana benthamiana resulted in necrotic symptoms associated with a hypersensitive response (HR)-like cell death, accompanied by H2 O2 generation and increased PR1 expression. Mannose-binding lectins surfactant protein D (SP-D), cyanovirin-N (CV-N) and human mannose-binding lectin (hMBL) also induce salicylic acid (SA)-dependent HR-like cell death in N. benthamiana, and this effect is mediated by the lectin's glycan binding activity. We found that secreted GRFT interacts with an endogenous glycoprotein, α-xylosidase (XYL1), which is involved in cell wall organization. The necrotic effect could be mitigated by overexpression of Arabidopsis XYL1, and by co-expression of SA-degrading enzyme NahG, providing strategies for enhancing expression of oligomannose-binding lectins in plants.

Association between Genetic Variations of MERTK and Chronic Obstructive Pulmonary Disease in Koreans.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease. To date, a large number of clinical studies have been conducted to investigate the association between genetic variations and COPD. However, little is known regarding the genetic susceptibility of Koreans to this disease. MER receptor tyrosine kinase (MERTK) plays important roles in the inhibition of inflammation and in the clearance of apoptotic cells. Here, we investigated the association between genetic variations in MERTK and the development of COPD in Koreans. METHODS: We conducted genetic analysis of MERTK using genomic DNA samples from 87 patients with COPD and 88 healthy controls and compared the frequency of each variation or haplotype between the patient and control groups. Subsequently, the effect of each variation was evaluated using in vitro assays. RESULTS: Ten variations were identified in this study, four of them for the first time. In addition, we found that the frequency of each variation or haplotype was comparable between the patient and control groups. However, we observed that the frequency for the wild-type haplotype was higher in the control group, compared to that in the group of patients with COPD, in the subgroup analysis of current smokers, although the difference was not statistically significant (P = 0.080). In in vitro assays, we observed that none of the variations affected the activity of the promoter or the expression of MERTK. CONCLUSION: Our findings indicate that the susceptibility to COPD is not related to the genetic variations or haplotypes of MERTK in Koreans.

Ethanol extract from Cnidium monnieri (L.) Cusson induces cell cycle arrest and apoptosis via regulation of the p53­independent pathway in HepG2 and Hep3B hepatocellular carcinoma cells.

Cnidium monnieri (L.) Cusson is a frequently used traditional Chinese medicine that treats gynecological diseases and carbuncles. However, the mechanism of action of C. monnieri remains to be fully elucidated. The present study examined the cell cycle arrest and apoptotic effects resulting from ethanol extract of C. monnieri (CME) in HepG2 (wild­type p53) and Hep3B (p53­null) hepatocellular carcinoma cells. An MTT assay was used to confirm the anti­proliferative effect of CME. The cells were stained with Hoechst 33342 or propidium iodide. It was demonstrated that proliferation of HepG2 cells was suppressed by CME. Cell cycle arrest occurred in the G1 phase following treatment with CME and the number of apoptotic bodies was increased. The expression levels of cell cycle­associated proteins, including protein kinase B (Akt), glycogen synthase kinase­3ß (GSK­3ß), p53, cyclin E and cyclin­dependent kinase 2 (CDK2) were determined by western blot analysis. The protein levels of phosphorylated (p)­Akt, p­GSK­3ß, p­MDM2 and cyclin E were decreased, whereas the protein levels of p53, p21 and p­CDK2 (Thr14/Tyr15) were increased following treatment with CME. Furthermore, treatment or co­treatment with LY294002 (phosphoinositide­3­kinase/Akt inhibitor) or Pifithrin­α (p53 inhibitor) with CME resulted in CME­induced G1 arrest which occurred through the p53­independent signaling pathway in hepatocellular carcinoma cells. In conclusion, CME induces G1 arrest and apoptosis via the Akt/GSK­3ß signaling pathway which is regulated by MDM2­induced degradation of p21, rather than p53.

Functional variation of SHP-2 promoter is associated with preterm birth and delayed myelination and motor development in preterm infants.

Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally characterize genetic variations in SHP-2 in 72 preterm and 58 full-term infants and to evaluate the effect of the variations on neurodevelopment in preterm infants. Twelve genetic variations were identified. Among them, two variations in the SHP-2 promoter, g.-317C > T and g.-273G > A, were found to significantly increase promoter activity, and the frequency of g.-273G > A was higher in preterm infants than in full-term infants. Two transcription factors, NF-κB and GABPα, were found to be involved in the transcriptional regulation of SHP-2 by the two above-mentioned variations. In particular, we found that g.-273G > A was significantly associated with delayed myelination and poor motor development in preterm infants. Our results suggest that a functional promoter variation in SHP-2 is associated with spontaneous preterm birth itself as well as white matter myelination and neurodevelopment.

rgs-CaM Detects and Counteracts Viral RNA Silencing Suppressors in Plant Immune Priming.

Primary infection of a plant with a pathogen that causes high accumulation of salicylic acid in the plant typically via a hypersensitive response confers enhanced resistance against secondary infection with a broad spectrum of pathogens, including viruses. This phenomenon is called systemic acquired resistance (SAR), which is a plant priming for adaption to repeated biotic stress. However, the molecular mechanisms of SAR-mediated enhanced inhibition, especially of virus infection, remain unclear. Here, we show that SAR against cucumber mosaic virus (CMV) in tobacco plants (Nicotiana tabacum) involves a calmodulin-like protein, rgs-CaM. We previously reported the antiviral function of rgs-CaM, which binds to and directs degradation of viral RNA silencing suppressors (RSSs), including CMV 2b, via autophagy. We found that rgs-CaM-mediated immunity is ineffective against CMV infection in normally growing tobacco plants but is activated as a result of SAR induction via salicylic acid signaling. We then analyzed the effect of overexpression of rgs-CaM on salicylic acid signaling. Overexpressed and ectopically expressed rgs-CaM induced defense reactions, including cell death, generation of reactive oxygen species, and salicylic acid signaling. Further analysis using a combination of the salicylic acid analogue benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) and the Ca2+ ionophore A23187 revealed that rgs-CaM functions as an immune receptor that induces salicylic acid signaling by simultaneously perceiving both viral RSS and Ca2+ influx as infection cues, implying its autoactivation. Thus, secondary infection of SAR-induced tobacco plants with CMV seems to be effectively inhibited through 2b recognition and degradation by rgs-CaM, leading to reinforcement of antiviral RNA silencing and other salicylic acid-mediated antiviral responses.IMPORTANCE Even without an acquired immune system like that in vertebrates, plants show enhanced whole-plant resistance against secondary infection with pathogens; this so-called systemic acquired resistance (SAR) has been known for more than half a century and continues to be extensively studied. SAR-induced plants strongly and rapidly express a number of antibiotics and pathogenesis-related proteins targeted against secondary infection, which can account for enhanced resistance against bacterial and fungal pathogens but are not thought to control viral infection. This study showed that enhanced resistance against cucumber mosaic virus is caused by a tobacco calmodulin-like protein, rgs-CaM, which detects and counteracts the major viral virulence factor (RNA silencing suppressor) after SAR induction. rgs-CaM-mediated SAR illustrates the growth versus defense trade-off in plants, as it targets the major virulence factor only under specific biotic stress conditions, thus avoiding the cost of constitutive activation while reducing the damage from virus infection.

Apoptosis-induced effects of extract from Artemisia annua Linné by modulating PTEN/p53/PDK1/Akt/ signal pathways through PTEN/p53-independent manner in HCT116 colon cancer cells.

BACKGROUND: The extracts from Artemisia annua Linné (AAE) has been known to possess various functions including anti-bacterial, anti-virus and anti-oxidant effects. However, the mechanism of those effects of AAE is not well known. Pursuantly, we determined the apoptotic effects of extract of AAE in HCT116 cell. In this study, we suggested that AAE may exert cancer cell apoptosis through PTEN/PDK1/Akt/p53signal pathway and mitochondria-mediated apoptotic proteins. METHODS: We measured 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) assay, Hoechst 33342 staining, Annexin V-PI staining, Mitopotential assay, immunofluorescence (IF) and Western blotting. Accordingly, our study showed that AAE treatment to HCT116 cells resulted in inhibition of PDK1, Akt, MDM2, Bcl-2, and pro-caspase 3 as well as activation of PTEN, p53-upregulated modulator of apoptosis (PUMA), Bax and Bak expression. Also we measured in vivo assay that xenograft model, H&E assay, TUNEL assay and IHC. RESULTS: AAE induced apoptosis via PTEN/p53/PDK1/Akt signal pathways through PTEN/p53-independent manner. AAE inhibit cell viability and increase LDH release in HCT116 colon cancer cell. Also, AAE increase apoptotic bodies, caspase -3,7 activation and reduces mitochondria membrane potential. AAE regulates cytochrome c translocation to the cytoplasm and Bax translocation to the mitochondrial membrane in an Immunofluorescence staining and increase PTEN and p53 expression in an in vivo tumor xenograft model. To elucidate the role of the PTEN/p53/PDK1/Akt signal pathways in cancer control, we conditionally inactivated PTEN/p53/PDK1/Akt signal pathways. We used inhibitors of PTEN, p53, PDK1, Akt. In consequence, these results indicate that AAE induced apoptosis by means of a mitochondrial event through the regulation of proteins such as Bax, Bak and cytochrome c in PDK1/Akt signaling pathways via PTEM/p53-independent manner. CONCLUSIONS: We confirmed the apoptotic effect of extracts of AAE by Modulating PTEN/p53/PDK1/Akt/Signal Pathways through PTEN/p53-independent pathwaysin HCT116 colon cancer cell.

Mass-Based Metabolomic Analysis of Lactobacillus sakei and Its Growth Media at Different Growth Phases.

Changes in the metabolite profiles of Lactobacillus sakei and its growth media, based on different culture times (0, 6, 12, and 24 h), were investigated using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS with partial least squares discriminant analysis, in order to understand the growth characteristics of this organism. Cell and media samples of L. sakei were significantly separated on PLS-DA score plots. Cell and media metabolites, including sugars, amino acids, and organic acids, were identified as major metabolites contributing to the difference among samples. The alteration of cell and media metabolites during cell growth was strongly associated with energy production. Glucose, fructose, carnitine, tryptophan, and malic acid in the growth media were used as primary energy sources during the initial growth stage, but after the exhaustion of these energy sources, L. sakei could utilize other sources such as trehalose, citric acid, and lysine in the cell. The change in the levels of these energy sources was inversely similar to the energy production, especially ATP. Based on these identified metabolites, the metabolomic pathway associated with energy production through lactic acid fermentation was proposed. Although further studies are required, these results suggest that MS-based metabolomic analysis might be a useful tool for understanding the growth characteristics of L. sakei, the most important bacterium associated with meat and vegetable fermentation, during growth.

Ginsenoside Rg3 Inhibits Constitutive Activation of NF-κB Signaling in Human Breast Cancer (MDA-MB-231) Cells: ERK and Akt as Potential Upstream Targets.

Ginsenoside Rg3, one of the major ingredients of heat-processed ginseng, has been reported to inhibit the growth of various cancer cells. We previously reported that Rg3 inhibited the proliferation and induced apoptosis of breast cancer (MDA-MB-231) cells. In the present study, we have explored the mechanism underlying the anti-proliferative and proapoptotic effects of Rg3 in MDA-MB-231 cells, which have constitutively activated NF-κB and the mutant form of p53. Rg3 inhibited DNA binding and transcriptional activity of NF-κB and these effects were attributable to its suppression of IKKß activity, degradation of IκBα and subsequent nuclear translocation of the p65 subunit of NF-κB. Similarly, the constitutive activation of ERK and Akt through phosphorylation was gradually reduced in MDA-MB-231 cells treated with Rg3. The pharmacological inhibitors of these kinases both U0126 (MEK1/2 inhibitor) and LY294002 (PI3K inhibitor) abrogated the NF-κB DNA binding activity in MDA-MB-231 cells. In addition, Rg3 treatment lowered the levels of the mutant p53 in concentration- and time-dependent manners. Rg3 also increased the association between p53 and its negative regulator Mdm2 in MDA-MB-231 cells. These findings suggest that Rg3 induced apoptosis in MDA-MB-231 cells, which is mediated by blocking NF-κB signaling via inactivation of ERK and Akt as well as destabilization of mutant p53.

Effect of steaming, blanching, and high temperature/high pressure processing on the amino Acid contents of commonly consumed korean vegetables and pulses.

In the present report, the effects of blanching, steaming, and high temperature/high pressure processing (HTHP) on the amino acid contents of commonly consumed Korean root vegetables, leaf vegetables, and pulses were evaluated using an Automatic Amino Acid Analyzer. The total amino acid content of the samples tested was between 3.38 g/100 g dry weight (DW) and 21.32 g/100 g DW in raw vegetables and between 29.36 g/100 g DW and 30.55 g/100 g DW in raw pulses. With HTHP, we observed significant decreases in the lysine and arginine contents of vegetables and the lysine, arginine, and cysteine contents of pulses. Moreover, the amino acid contents of blanched vegetables and steamed pulses were more similar than the amino acid contents of the HTHP vegetables and HTHP pulses. Interestingly, lysine, arginine, and cysteine were more sensitive to HTHP than the other amino acids. Partial Least Squares-Discriminate Analyses were also performed to discriminate the clusters and patterns of amino acids.

Ginsenoside Rg3 Induces Apoptosis of Human Breast Cancer (MDA-MB-231) Cells.

BACKGROUND: Rg3, a major ginsenoside derived from heat-processed ginseng, has been reported to have anti-inflammatory and anti-proliferative activities. In our previous studies, Rg3 inhibited phorbol ester-induced cyclooxygenase-2 expression and NF-κB activation in cultured human mammary epithelial (MCF-10A) cells and in mouse skin in vivo. In this study, we investigated Rg3-induced apoptosis in human breast cancer (MDA-MB-231) cells and underlying molecular mechanisms. METHODS: After Rg3 treatment, apoptotic cell death of MDA-MB-231 cell was investigated by the MTT reduction assay and measurement of the mitochondrial membrane depolarization. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells as well as measurement of reactive oxygen species. Expression of apoptotic-related proteins was determined by immunoblot analysis. RESULTS: MDA-MB-231 cells treated with Rg3 (30µM) exhibited the increased proportion of hypodiploid or apoptotic cells. Rg3 treatment resulted in an increase in the ratio of proapoptotic Bax to antiapoptotic Bcl-2, depolarization of the mitochondria membrane potential and the release of cytochrome c from mitochondria. Rg3 also induced the proteolytic cleavage of caspase-3 and poly (ADP-ribose) polymerase, which was attenuated by a caspase-3 inhibitor, z-VAD-fmk. CONCLUSIONS: Based on these findings, it is likely that Rg3 induces apoptosis in MDA-MB-231 cells via classical mitochondria-dependent caspase activation. These data suggest that Rg3 might be a potential candidate as a breast cancer chemopreventive agent.

Silicosis caused by chronic inhalation of snail shell powder.

A 70-yr-old woman visited our hospital for shortness of breath. Chest CT showed ground glass opacity and traction bronchiectasis at right middle, lower lobe and left lingular division. Video-assisted thoracic surgical biopsy at right lower lobe and pathologic examination revealed mixed dust pneumoconiosis. Polarized optical microscopy showed lung lesions were consisted of silica and carbon materials. She was a housewife and never been exposed to silica dusts occupationally. She has taken freshwater snails as a health-promoting food for 40 yr and ground shell powder was piled up on her backyard where she spent day-time. Energy dispersive X-ray spectroscopy of snail shell and scanning electron microscopy with energy dispersive x-ray spectroscopy of lung lesion revealed that silica occupies important portion. Herein, we report the first known case of silicosis due to chronic inhalation of shell powder of freshwater snail.