Bacillus-Derived Manganese Superoxide Dismutase Relieves Ocular-Surface Inflammation and Damage by Reducing Oxidative Stress and Apoptosis in Dry Eye.

Purpose: We hypothesized that antioxidative enzymes supplementation could be a treatment option for dry eye. We investigated the efficacy of oral administration of Bacillus-derived superoxide dismutase (Bd-SOD) in a murine experimental dry eye (EDE). Methods: In part I, mice were randomly assigned to normal control, EDE, and mice groups that were treated with oral Bd-SOD after induction of EDE (EDE + Bd-SOD group; four mice in each group). Expression of SOD2, a major antioxidant enzyme with manganese as a cofactor, was assessed by immunofluorescence staining. In part II, mice were divided into seven groups (six mice in each group): normal control, EDE, vehicle-treated, topical 0.05% cyclosporin A (CsA)-treated, and oral Bd-SOD-treated (2.5, 5.0, and 10.0 mg/kg Bd-SOD) groups. Tear volume, tear-film break-up time (TBUT), and corneal fluorescein-staining scores (CFS) were measured at zero, five, and 10 days after treatment. Ten days after treatment, 2',7'-dichlorodihydrofluorescein diacetate for reactive oxygen species (ROS), enzyme-linked immunosorbent for malondialdehyde, and TUNEL assays for corneal apoptosis, flow cytometry inflammatory T cells, and histological assessment were performed. Results: Compared to the normal control group in part I, the EDE group showed significantly decreased SOD2 expression by immunofluorescence staining. However, the EDE + Bd-SOD group recovered similar to the normal control group. In part II, ROS, malondialdehyde, and corneal apoptosis were decreased in CsA and all Bd-SOD-treated groups. Corneal and conjunctival inflammatory T cells decreased, and conjunctival goblet cell density increased in CsA-treated and Bd-SOD-treated groups. Compared to the CsA-treated group, the 2.5 mg/kg Bd-SOD-treated group showed increased TBUT and decreased inflammatory T cells, and the 5.0 mg/kg Bd-SOD-treated group showed decreased CFS and increased conjunctival goblet cells. Conclusions: Oral Bd-SOD administration might increase autogenous SOD2 expression in ocular surface tissue in EDE and could be developed as a complementary treatment for DE in the future.

Potential Anti-Allergy and Immunomodulatory Properties of Lactococcus lactis LB 1022 Observed In Vitro and in an Atopic Dermatitis Mouse Model.

Lactococcus lactis is a lactic acid bacterium and used in the dairy food industry. The ameliorating effects of Lactobacillus species on atopic dermatitis (AD) have been extensively studied, but the specific effect of L. lactis strains has not yet been investigated. In this study, the efficacy of L. lactis LB 1022, isolated from natural cheese, was evaluated using RAW 264.7, HMC-1 and HaCaT cell lines and an ovalbumin-sensitized AD mouse model. L. lactis LB 1022 exhibited nitric oxide suppression and anti-allergy and anti-inflammatory activity in vitro. Oral administration of L. lactis LB 1022 to AD mice significantly reduced the levels of IgE, mast cells, and eosinophils, and a range of T cell-mediated T helper Th1, Th2, and Th17-type cytokines under interleukin (IL)-10, transforming growth factor-ß (TGF-ß), thymus and activation-regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP). In addition, L. lactis LB 1022 treatment increased the concentration of short-chain fatty acids. Overall, L. lactis LB 1022 significantly modulated AD-like symptoms by altering metabolites and the immune response, illustrating its potential as candidate for use in functional food supplements to alleviate AD.

Characterization of a Potential Probiotic Lactiplantibacillus plantarum LRCC5310 by Comparative Genomic Analysis and its Vitamin B6 Production Ability.

Safety assessment and functional analysis of probiotic candidates are important for their industrial applications. Lactiplantibacillus plantarum is one of the most widely recognized probiotic strains. In this study we aimed to determine the functional genes of L. plantarum LRCC5310, isolated from kimchi, using next-generation, whole-genome sequencing analysis. Genes were annotated using the Rapid Annotations using Subsystems Technology (RAST) server and the National Center for Biotechnology Information (NCBI) pipelines to establish the strain's probiotic potential. Phylogenetic analysis of L. plantarum LRCC5310 and related strains showed that LRCC5310 belonged to L. plantarum. However, comparative analysis revealed genetic differences between L. plantarum strains. Carbon metabolic pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database showed that L. plantarum LRCC5310 is a homofermentative bacterium. Furthermore, gene annotation results indicated that the L. plantarum LRCC5310 genome encodes an almost complete vitamin B6 biosynthetic pathway. Among five L. plantarum strains, including L. plantarum ATCC 14917T, L. plantarum LRCC5310 detected the highest concentration of pyridoxal 5'-phosphate with 88.08 ± 0.67 nM in MRS broth. These results indicated that L. plantarum LRCC5310 could be used as a functional probiotic for vitamin B6 supplementation.

Alleviation effects of Rubus coreanus Miquel root extract on skin symptoms and inflammation in chronic atopic dermatitis.

Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic inflammatory dermatitis with immunological manifestations. The aim of this study was to investigate the effects of polyphenol-containing Rubus coreanus Miquel root extract on skin allergy and AD. The protective effects of R. coreanus root ethanol extract against AD were investigated using the human keratinocyte cell line HaCaT, human mast cell line HMC-1, and the 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin NC/Nga mouse model. Treatment with R. coreanus root ethanol extracts reduced ß-hexosaminidase and histamine release from HMC-1 cells stimulated with compound 48/80 compared to treatment with R. coreanus fruit ethanol extract. Furthermore, topical application of R. coreanus root ethanol extract dramatically reduced the severity of skin symptoms and the thickening and swelling of the dorsal skin and ear in DNCB-treated NC/Nga mice. The protein and mRNA expression of several cytokines (IL-4, IL-5, IL-12, IFN-γ, TNF-α, and TARC) and IgE was significantly lowered upon application of the R. coreanus root ethanol extract. The promising candidate for the active ingredient of R. coreanus root polyphenols was revealed to be ellagic acid. These findings clearly indicate that the R. coreanus root polyphenols show strong anti-allergic effects and suppress the symptoms of AD. Therefore, polyphenol-containing R. coreanus root ethanol extract could be a novel therapeutic candidate for the treatment of allergy and AD.

Hepatoprotective effects of Lactococcus chungangensis CAU 1447 in alcoholic liver disease.

Alcoholic liver disease (ALD) is correlated with alcohol consumption, and ALD progression depends on various factors. Some lactic acid bacteria (LAB) are beneficial for mitigating ALD. However, the valuable effects of LAB-derived dairy products remain unclear. Here, we evaluated the effects of Lactococcus chungangensis CAU 1447 dry cells (CAU 1447) and cream cheese derived from CAU 1447 on ALD progression following long-term alcohol consumption in rats. Oral administration of CAU 1447 and CAU 1447 cream cheese significantly reduced alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and triglyceride levels. We found that CAU 1447 and CAU 1447 cream cheese downregulated mRNA encoding various cytokines and antioxidative factors in the liver. Oral CAU 1447 cream cheese administration increased short-chain fatty acid, butyrate, and acetate levels in feces. Thus, administration of CAU 1447 and CAU 1447 cream cheese induced hepatoprotective effects, indicating potential applications as a supplement for ALD mitigation.

Cream Cheese-Derived Lactococcus chungangensis CAU 28 Modulates the Gut Microbiota and Alleviates Atopic Dermatitis in BALB/c Mice.

Atopic dermatitis (AD) has a drastic impact on human health owing to complex skin, gut microbiota, and immune responses. Some lactic acid bacteria (LAB) are effective in ameliorating AD; however, the alleviative effects of dairy products derived from these LAB remain unclear. In this study, the efficacies of Lactococcus chungangensis CAU 28 (CAU 28) cream cheese and L. chungangensis CAU 28 dry cells were evaluated for treating AD in an AD mouse model. Overall, CAU 28 cream cheese administration was more effective against AD than L. chungangensis CAU 28 dry cells. Faeces from CAU 28 cream cheese-administered mice had increased short chain fatty acid, butyrate, acetate, and lactic acid levels, as well as butyrate-producing bacteria, including Akkermansia, Bacteroides, Lactobacillus, and Ruminococcus. Furthermore, oral CAU 28 cream cheese administration resulted in regulatory T cell (Treg)-mediated suppression of T helper type 2 (Th2) immune responses in serum and mRNA expression levels in the ileum. Oral CAU 28 cream cheese further reduced IgE levels, in addition to eosinophil and mast cell numbers. Therefore, CAU 28 cream cheese administration induced a coordinated immune response involving short-chain fatty acids and gut microbiota, indicating its potential for use as a supplement for AD mitigation.

Agouti Related Peptide Secreted Via Human Mesenchymal Stem Cells Upregulates Proteasome Activity in an Alzheimer's Disease Model.

The activity of the ubiquitin proteasome system (UPS) is downregulated in aggregation diseases such as Alzheimer's disease (AD). In this study, we investigated the therapeutic potential of the Agouti-related peptide (AgRP), which is secreted by human mesenchymal stem cells (MSCs), in terms of its effect on the regulation of proteasome activity in AD. When SH-SY5Y human neuroblastoma cells were co-cultured with MSCs isolated from human Wharton's Jelly (WJ-MSC), their proteasome activity was significantly upregulated. Further analysis of the conditioned media after co-culture allowed us to identify significant concentrations of a neuropeptide, called AgRP. The stereotactic delivery of either WJ-MSCs or AgRP into the hippocampi of C57BL6/J and 5XFAD mice induced a significant increase of proteasome activity and suppressed the accumulation of ubiquitin-conjugated proteins. Collectively, these findings suggest strong therapeutic potential for WJ-MSCs and AgRP to enhance proteasome activity, thereby potentially reducing abnormal protein aggregation and delaying the clinical progression of various neurodegenerative diseases.

Evaluation of soil flushing of complex contaminated soil: an experimental and modeling simulation study.

The removal of heavy metals (Zn and Pb) and heavy petroleum oils (HPOs) from a soil with complex contamination was examined by soil flushing. Desorption and transport behaviors of the complex contaminants were assessed by batch and continuous flow reactor experiments and through modeling simulations. Flushing a one-dimensional flow column packed with complex contaminated soil sequentially with citric acid then a surfactant resulted in the removal of 85.6% of Zn, 62% of Pb, and 31.6% of HPO. The desorption distribution coefficients, KUbatch and KLbatch, converged to constant values as Ce increased. An equilibrium model (ADR) and nonequilibrium models (TSNE and TRNE) were used to predict the desorption and transport of complex contaminants. The nonequilibrium models demonstrated better fits with the experimental values obtained from the column test than the equilibrium model. The ranges of KUbatch and KLbatch were very close to those of KUfit and KLfit determined from model simulations. The parameters (R, ß, ω, α, and f) determined from model simulations were useful for characterizing the transport of contaminants within the soil matrix. The results of this study provide useful information for the operational parameters of the flushing process for soils with complex contamination.

Amniopatch treatment for spontaneous previable, preterm premature rupture of membranes associated or not with incompetent cervix.

OBJECTIVE: We reviewed women with previable spontaneous premature rupture of membranes (sPPROM) in whom an amniopatch was performed and compared their pregnancy outcomes with a conservative management group. METHODS: Amniopatch, an amnioinfusion of autologous platelet concentrate followed by cryoprecipitate, was performed in 7 women with sPPROM diagnosed at 17-23 weeks' gestation, including one twin pregnancy. Three patients had incompetent cervices and the other 4 patients had sPPROM without incompetent cervices. Pregnancy outcomes of the cases were compared with the controls who were managed conservatively (n = 22). RESULTS: Amniopatch treatment was successful in 1 of 7 cases (14.3%), in which the ruptured membranes were completely sealed and the patient delivered a healthy baby at 39 weeks' gestation. No procedure-related complications were observed. Overall, neonatal outcome was similar in the amniopatch and conservatively managed groups, although the incidences of early neonatal sepsis and respiratory distress syndrome were lower in the amniopatch group. CONCLUSION: The overall success rate of amniopatch among our small number of cases was low. However, if successful, amniopatch may prolong a pregnancy with previable sPPROM to term.