Cera-Glow, ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, improves skin barrier function in clinical study.

BACKGROUND: Ceramides are essential lipids in stratum corneum for skin permeability barrier function in that they retain the skin moisture and protect from the invasion of foreign pathogens. Previously, we demonstrated that ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201 enhanced ceramide production in human epidermal keratinocytes. Furthermore, for comprehensive knowledge of this effect, in vitro experiments and multi-omics analysis were conducted to explore the underlying mechanisms. AIMS: This study was designed to identify whether a cosmetic sample (i.e., Cera-Glow) containing the lysates improves the skin barrier function in clinical trials. PATIENTS/METHODS: Twenty-four female participants (45.46 ± 9.78 years) had been enrolled in the transepidermal water loss (TEWL) measurement for 5 days and 21 female participants (50.33 ± 5.74 years) had undergone a skin hydration evaluation for 4 weeks. TEWL and skin hydration were evaluated using a Tewameter and the Epsilon Permittivity Imaging System, respectively. After applying the Cera-Glow sample, all participants recorded a satisfaction survey questionnaire (e.g., satisfaction, efficacy, and adverse reactions). RESULTS: Application of Cera-Glow significantly improved transepidermal water loss induced by 1% (w/v) sodium lauryl sulfate (p < 0.05-0.01) and increased skin hydration (p < 0.01). Metabolic analysis suggested that Cera-Glow should contain beneficial gradients for skin barrier function. According to the questionnaire, most of participants were satisfied with the skin hydration improvement and efficacy of Cera-Glow. CONCLUSIONS: Cera-Glow, ferment lysates of Lacticaseibacillus rhamnosus IDCC 3201, can significantly improve skin barrier function.

Association of serum carotenoid, retinol, and tocopherol concentrations with the progression of Parkinson's Disease.

BACKGROUND/OBJECTIVES: A pivotal role of oxidative stress has been emphasized in the pathogenesis as well as in the disease progression of Parkinson's disease (PD). We aimed at investigating serum levels of antioxidant vitamins and elucidating whether they could be associated with the pathogenesis and progression of PD. MATERIALS/METHODS: Serum levels of retinol, α- and γ-tocopherols, α- and ß-carotenes, lutein, lycopene, zeaxanthin and ß-cryptoxanthin were measured and compared between 104 patients with idiopathic PD and 52 healthy controls matched for age and gender. In order to examine the relationship between antioxidant vitamins and the disease progression, multiple group comparisons were performed among the early PD (Hoehn and Yahr stage I and II, N = 47), advanced PD (stage III and IV, N = 57) and control groups. Separate correlation analyses were performed between the measured antioxidant vitamins and clinical variables, such as Hoehn and Yahr stage and Unified Parkinson's Disease Rating Scale (UPDRS) motor score. RESULTS: Compared to controls, PD patients had lower levels of α- and ß-carotenes and lycopene. α-carotene, ß-carotene and lycopene levels were significantly reduced in advanced PD patients relative to early PD patients and were negatively correlated with Hoehn and Yahr stage and UPDRS motor score in PD patients. No significant differences were found in serum levels of retinol, α- and γ-tocopherols, and other carotenoids between PD patients and controls. No significant correlations were found between these vitamin levels and clinical variables in PD patients. CONCLUSIONS: We found that serum levels of some carotenoids, α-carotene, ß-carotene and lycopene, were lower in PD patients, and that these carotenoids inversely correlated with clinical variables representing disease progression. Our findings suggest that decreases in serum α-carotene, ß-carotene and lycopene may be associated with the pathogenesis as well as progression of PD.

The phenyl-thiophenyl propenone RK-I-123 reduces the levels of reactive oxygen species and suppresses the activation of NF-κB and AP-1 and IL-8 expression in Helicobacter pylori-infected gastric epithelial AGS cells.

OBJECTIVE: To investigate whether the phenyl-thiophenyl propenone RK-I-123 suppresses interleukin-8 (IL-8) expression and activation of mitogen-activated protein kinases (MAPKs) and transcription factors (nuclear factor-κB [NF-κB] and activator protein-1 [AP-1]) by reducing reactive oxygen species (ROS) levels in Helicobacter pylori-infected gastric epithelial cells. MATERIAL: Helicobacter pylori in Korean isolates, human gastric epithelial AGS cells. TREATMENT: AGS cells pretreated with or without RK-I-123 were cultured in the presence of H. pylori at a bacterium/cell ratio of 300:1. METHODS: Reactive oxygen species and IL-8 levels were determined by dichlorofluorescein fluorescence and enzyme-linked immunosorbent assay. The IL-8 mRNA expression was analyzed by the real-time reverse transcription-polymerase chain reaction (RT-PCR). The MAPK and IκBα levels were determined by western blotting. The activation of NF-κB and AP-1 was determined by the electrophoretic mobility shift assay. RESULTS: Helicobacter pylori induced an increase in ROS and IL-8 expression and activation of MAPKs and transcription factors (NF-κB and AP-1) together with the degradation of IκBα in AGS cells, all of which were inhibited by RK-I-123. CONCLUSIONS: The RK-I-123 suppressed the H. pylori-induced IL-8 expression and activation of MAPKs, NF-κB, and AP-1 by reducing ROS levels in AGS cells. The RK-I-123 may be a potential candidate for the treatment of H. pylori-induced gastric inflammation.

PINK1 stimulates interleukin-1ß-mediated inflammatory signaling via the positive regulation of TRAF6 and TAK1.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of neuronal death in PD is largely unknown, but several genetic loci, including PTEN-induced putative kinase 1 (PINK1), have been linked to early onset autosomal recessive forms of familial PD. PINK1 encodes a serine/threonine kinase, which phosphorylates several substrates and consequently leads to cell protection against apoptosis induced by various stresses. In addition, research has shown that inflammation largely contributes to the pathogenesis of PD, but the functional link between PINK1 and PD-linked neuroinflammation remains poorly understood. Therefore, in the present study, we investigated the functional role of PINK1 in interleukin (IL)-1ß-mediated inflammatory signaling. We show that PINK1 specifically binds to TRAF6 and TAK1, and facilitates the autodimerization and autoubiquitination of TRAF6. PINK1 also enhances the association between TRAF6 and TAK1, phosphorylates TAK1, and stimulates polyubiquitination of TAK1. Furthermore, PINK1 leads to the potentiation of IL-1ß-mediated NF-κB activity and cytokine production. These findings suggest that PINK1 positively regulates two key molecules, TRAF6 and TAK1, in the IL-1ß-mediated signaling pathway, consequently up-regulating their downstream inflammatory events.

Lycopene inhibits Helicobacter pylori-induced ATM/ATR-dependent DNA damage response in gastric epithelial AGS cells.

Oxidative stress linked to DNA damage is involved in the pathogenesis of Helicobacter pylori-associated gastric diseases. The DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair, and apoptosis through the activation of ataxia-telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR) and their target proteins. However, neither H. pylori-induced DDR nor the effects of antioxidants on the DNA damage have been established. This study aimed to investigate the detailed process of H. pylori-induced DNA damage and to examine whether lycopene, a natural antioxidant, inhibits DNA damage and cellular response of gastric epithelial AGS cells infected with H. pylori. AGS cells were cultured with H. pylori in Korean isolates and treated with or without lycopene. Cell viability, DNA damage indices, levels of 8-OH-dG, and reactive oxygen species (ROS) as well as cell-cycle distributions were determined. The activation of ATM, ATR, Chk1, and Chk2; histone H2AX focus formation; activation and induction of p53; and levels of Bax and Bcl-2 and poly(ADP-ribose) polymerase-1 (PARP-1) were assessed. The results showed that H. pylori induced apoptosis in AGS cells with increased Bax and decreased Bcl-2 expression as well as PARP-1 cleavage. Culture with H. pylori led to increases in intracellular ROS, 8-OH-dG, double-strand DNA breaks (DSBs), and DNA fragmentation. H. pylori induced activation of the ATM/Chk2 and ATR/Chk1 pathways, phosphorylation of H2AX and p53, and a delay in the progression of the cells entering the S phase. Lycopene inhibited H. pylori-induced increases in ROS, apoptosis, alterations in cell-cycle distribution, DSBs, and ATM- and ATR-mediated DDR in AGS cells. In conclusion, lycopene may be beneficial for treatment of H. pylori-induced gastric diseases associated with oxidative DNA damage.

Serial changes of fatty acids in preterm breast milk of Korean women.

Samples of breast milk were collected at postpartum weeks 1, 2, 4, 6, 8, and 12 from 104 Korean mothers who had delivered infants at less than 34 weeks or weighing less than 1.8 kg to investigate changes in fatty acid (FAs). Full-term breast milk (FBM) collected at the end of first week postpartum from 26 Korean women delivering healthy, term infants was used for comparison. Stability in relative FA composition was maintained during the first 3 months of lactation in preterm breast milk (PBM), and the relative composition of polyunsaturated FAs (PUFA), monounsaturated FAs, and saturated FAs remained constant in PBM. However, the ω6/ω3 ratio was significantly higher as lactation progressed owing to lower ω3 PUFA in PBM. The proportions of docosahexaenoic acid (DHA) and arachidonic acid (AA) in PBM gradually decreased over time, but the DHA/AA ratio was kept constant at 1.13, higher than that of Western countries. At the end of the first week, relative proportions of FAs were similar in PBM and FBM, but absolute concentrations of FA were higher in PBM.

Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling.

BACKGROUND: The Down syndrome candidate region-1 gene (DSCR1, also known as RCAN1) is situated close to the Down Syndrome Critical Region (DSCR), which contains genes responsible for many features of Down syndrome. DSCR1 modulates calcineurin phosphatase activity, though its functional role is incompletely understood. METHODS: Here we investigated the role of DSCR1-1S isoform in IL-1 receptor (IL-1R)-mediated signaling by analyzing interaction between DSCR1-1S and the IL-1R pathway components Tollip, IRAK-1, and TRAF6. RESULTS: Co-immunoprecipitation analyses of HEK293 cells revealed that DSCR1-1S interacted with Tollip, an IRAK-1 inhibitor, leading to the dissociation of IRAK-1 from Tollip. Similarly, both DSCR1-1S and Tollip interacted with TRAF6, with DSCR1 reducing interaction between Tollip and TRAF6. DSCR1-1S also stimulated IL-1R-mediated signaling pathways, TAK1 activation, NF-kappaB transactivation, and IL-8 production, all downstream consequences of IL-1R activation. GENERAL SIGNIFICANCE: Together, these results suggest that DSCR1-1S isoform positively modulates IL-1R-mediated signaling pathways by regulating Tollip/IRAK-1/TRAF6 complex formation.

Mechanism of beta-carotene-induced apoptosis of gastric cancer cells: involvement of ataxia-telangiectasia-mutated.

Beta-carotene acts as an antioxidant or a pro-oxidant depending on the concentrations that cells are treated with. Oxidative DNA damage is related to apoptosis of various cells. Ataxia-telangiectasia-mutated (ATM), a sensor for DNA-damaging agents, activates a variety of effectors in multiple signaling pathways, such as DNA repair and apoptosis. In the present study, we investigated whether a high concentration of beta-carotene induces apoptosis of gastric adenocarcinoma (AGS) cells and whether ATM is involved in beta-carotene-induced apoptosis of AGS cells. We found that beta-carotene (100 micromol/L) induced apoptosis (determined by cell viability), DNA fragmentation, and the protein levels of p53 and Bcl-2 in AGS cells. ATM levels in the nucleus decreased from beta-carotene in AGS cells. beta-Carotene-induced alterations, including an increase in DNA fragmentation and p53 levels and a decrease in nuclear ATM and cellular Bcl-2 levels, were inhibited in the cells transfected with full-length ATM cDNA compared to wild-type cells or the cells transfected with control vector plasmid control DNA vector (pcDNA). In conclusion, beta-carotene induces apoptosis by increasing apoptotic protein p53 and decreasing anti-apoptotic Bcl-2 as well as nuclear ATM in AGS cells. Nuclear loss of ATM may be the underlying mechanism of beta-carotene-induced apoptosis of gastric cancer cells.