Inhibitory effect of fucoidan on TNF-α-induced inflammation in human retinal pigment epithelium cells

Sargassum horneri (S. horneri) is a brown seaweed that contains a fucose-rich sulfated polysaccharide called fucoidan and is known to possess beneficial bioactivities, such as anti-inflammatory, antiviral, antioxidative, and antitumoral effects. This study aimed to determine the anti-inflammatory effects of AB_SH (hydrothermal extracts from S. horneri) and its bioactive compound (fucoidan) against tumor necrosis factor alpha (TNF-α)-induced inflammation in human retinal pigment epithelial (RPE) cells. AB_SH did not exhibit any cytotoxicity, and it decreased the mRNA expression of interleukin (IL)-6 and IL-8 and the production of the cytokines IL-6 and TNF-α. It also suppressed the expression levels of phosphorylated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), including c-Jun amino-terminal kinases (JNK), p38 protein kinases (p38), and extracellular signal-regulated kinase (ERK) proteins, suggesting that AB_SH inhibits activation of the NF-kB/MAPK signaling pathway. Since fucoidan was identified in the composition analysis of AB_SH, it was additionally shown to be required for its anti-inflammatory effects in TNF-α-stimulated human RPE cells. In line with the AB_SH results, fucoidan reduced the mRNA levels of IL-6, IL-1ß, and IL-8 and production of the cytokines IL-6, TNF-α, and IL-8 through the downregulation of the NF-kB/MAPK signaling pathway in a dose-dependent manner. Collectively, the ability of AB_SH from S. horneri hydrothermal extracts to reduce inflammation indicates that it may be a good functional ingredient for managing ocular disorders

Anti-Melanogenic and Antioxidant Effects of Cell-Free Supernatant from Lactobacillus gasseri BNR17

In recent years, there has been considerable interest in the use of cell-free supernatant of probiotics culture for nutritional and functional applications. In this study, we investigated the effect of the cell-free supernatant from Lactobacillus gasseri BNR17 (CFS) on anti-melanogenesis and reducing oxidative stress in B16-F10 murine melanoma cells and HaCaT human keratinocytes. Treatment with CFS significantly inhibited the production of extracellular and intracellular melanin without cytotoxicity during melanogenesis induced by the α-MSH in B16-F10 cells. The CFS dramatically reduced tyrosinase activity and the melanogenesis-related gene expression. Further, it showed antioxidative effects in a dose-dependent manner in DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assays and significantly increased the mRNA levels of HO-1 and CAT in HaCaT cells. Furthermore, the CFS increased HO-1 and anti-oxidative-related gene expression during H2O2-induced oxidative stress in HaCaT cells. Together, this study suggests that the CFS reduces hyperpigmentation and inhibits oxidative stress, and thus can be used as a potential skincare product in the future

Table3_Comprehensive analysis on clinical significance and therapeutic targets of LDL receptor related protein 11 (LRP11) in liver hepatocellular carcinoma.DOCX

LDL lipoprotein receptor-related protein 11 (LRP11) plays a role in several tumors. However, their roles in hepatocellular carcinoma remain unclear. The present study aimed to explore the expression profile and prognostic value of LRP11 in liver hepatocellular carcinoma (LIHC) patients using various cancer databases and bioinformatic tools. In bioinformatics analysis, The Cancer Genome Atlas datasets showed increased LRP11 expression in tumor tissues compared to that in non-tumor tissues in various cancers. Moreover, patients with high expression LRP11 correlated with poor prognosis and clinical features. The LRP11 expression positively correlated with the infiltration of immune cells such as macrophages, neutrophils, and myeloid-derived suppressor cells and a combination of high LRP11 expression and high immune infiltrates was associated with the worst survival in LIHC tumors. Our results also indicated that LRP11 expression was closely associated with immune-modulate function, such as antigen presentation. In DNA methylation profiling, hypomethylation of LRP11 is widely observed in tumors and has prognostic value in LIHC patients. Functional enrichment analysis revealed that LIHC-specific LRP11 interacting genes are involved in protein binding, intracellular processing, and G-protein-related signaling pathways. Analyses of drug sensitivity and immune checkpoint inhibitor predict a number of drugs that could potentially be used to target LRP11. In addition, in vitro experiments verified the promoting effect of LRP11 on the migration, invasion, and colony formation capacity of hepatocellular carcinoma cells. Collectively, our results aided a better understanding of the clinical significance of LRP11 in gene expression, functional interactions, and epigenetic regulation in LIHC and suggested that it may be a useful prognostic biomarker for LIHC patients.</p

Table4_Comprehensive analysis on clinical significance and therapeutic targets of LDL receptor related protein 11 (LRP11) in liver hepatocellular carcinoma.DOCX

LDL lipoprotein receptor-related protein 11 (LRP11) plays a role in several tumors. However, their roles in hepatocellular carcinoma remain unclear. The present study aimed to explore the expression profile and prognostic value of LRP11 in liver hepatocellular carcinoma (LIHC) patients using various cancer databases and bioinformatic tools. In bioinformatics analysis, The Cancer Genome Atlas datasets showed increased LRP11 expression in tumor tissues compared to that in non-tumor tissues in various cancers. Moreover, patients with high expression LRP11 correlated with poor prognosis and clinical features. The LRP11 expression positively correlated with the infiltration of immune cells such as macrophages, neutrophils, and myeloid-derived suppressor cells and a combination of high LRP11 expression and high immune infiltrates was associated with the worst survival in LIHC tumors. Our results also indicated that LRP11 expression was closely associated with immune-modulate function, such as antigen presentation. In DNA methylation profiling, hypomethylation of LRP11 is widely observed in tumors and has prognostic value in LIHC patients. Functional enrichment analysis revealed that LIHC-specific LRP11 interacting genes are involved in protein binding, intracellular processing, and G-protein-related signaling pathways. Analyses of drug sensitivity and immune checkpoint inhibitor predict a number of drugs that could potentially be used to target LRP11. In addition, in vitro experiments verified the promoting effect of LRP11 on the migration, invasion, and colony formation capacity of hepatocellular carcinoma cells. Collectively, our results aided a better understanding of the clinical significance of LRP11 in gene expression, functional interactions, and epigenetic regulation in LIHC and suggested that it may be a useful prognostic biomarker for LIHC patients.</p

Table2_Comprehensive analysis on clinical significance and therapeutic targets of LDL receptor related protein 11 (LRP11) in liver hepatocellular carcinoma.DOCX

LDL lipoprotein receptor-related protein 11 (LRP11) plays a role in several tumors. However, their roles in hepatocellular carcinoma remain unclear. The present study aimed to explore the expression profile and prognostic value of LRP11 in liver hepatocellular carcinoma (LIHC) patients using various cancer databases and bioinformatic tools. In bioinformatics analysis, The Cancer Genome Atlas datasets showed increased LRP11 expression in tumor tissues compared to that in non-tumor tissues in various cancers. Moreover, patients with high expression LRP11 correlated with poor prognosis and clinical features. The LRP11 expression positively correlated with the infiltration of immune cells such as macrophages, neutrophils, and myeloid-derived suppressor cells and a combination of high LRP11 expression and high immune infiltrates was associated with the worst survival in LIHC tumors. Our results also indicated that LRP11 expression was closely associated with immune-modulate function, such as antigen presentation. In DNA methylation profiling, hypomethylation of LRP11 is widely observed in tumors and has prognostic value in LIHC patients. Functional enrichment analysis revealed that LIHC-specific LRP11 interacting genes are involved in protein binding, intracellular processing, and G-protein-related signaling pathways. Analyses of drug sensitivity and immune checkpoint inhibitor predict a number of drugs that could potentially be used to target LRP11. In addition, in vitro experiments verified the promoting effect of LRP11 on the migration, invasion, and colony formation capacity of hepatocellular carcinoma cells. Collectively, our results aided a better understanding of the clinical significance of LRP11 in gene expression, functional interactions, and epigenetic regulation in LIHC and suggested that it may be a useful prognostic biomarker for LIHC patients.</p

Table_1_Inhibitory effect of fucoidan on TNF-α-induced inflammation in human retinal pigment epithelium cells.docx

Sargassum horneri (S. horneri) is a brown seaweed that contains a fucose-rich sulfated polysaccharide called fucoidan and is known to possess beneficial bioactivities, such as anti-inflammatory, antiviral, antioxidative, and antitumoral effects. This study aimed to determine the anti-inflammatory effects of AB_SH (hydrothermal extracts from S. horneri) and its bioactive compound (fucoidan) against tumor necrosis factor alpha (TNF-α)-induced inflammation in human retinal pigment epithelial (RPE) cells. AB_SH did not exhibit any cytotoxicity, and it decreased the mRNA expression of interleukin (IL)-6 and IL-8 and the production of the cytokines IL-6 and TNF-α. It also suppressed the expression levels of phosphorylated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs), including c-Jun amino-terminal kinases (JNK), p38 protein kinases (p38), and extracellular signal-regulated kinase (ERK) proteins, suggesting that AB_SH inhibits activation of the NF-kB/MAPK signaling pathway. Since fucoidan was identified in the composition analysis of AB_SH, it was additionally shown to be required for its anti-inflammatory effects in TNF-α-stimulated human RPE cells. In line with the AB_SH results, fucoidan reduced the mRNA levels of IL-6, IL-1ß, and IL-8 and production of the cytokines IL-6, TNF-α, and IL-8 through the downregulation of the NF-kB/MAPK signaling pathway in a dose-dependent manner. Collectively, the ability of AB_SH from S. horneri hydrothermal extracts to reduce inflammation indicates that it may be a good functional ingredient for managing ocular disorders.</p

Arazyme Suppresses Hepatic Steatosis and Steatohepatitis in Diet-Induced Non-Alcoholic Fatty Liver Disease-Like Mouse Model

Arazyme, a metalloprotease from the spider Nephila clavata, exerts hepatoprotective activity in CCL4-induced acute hepatic injury. This study investigated the hepatoprotective effects in high-fat diet (HFD)-induced non-alcoholic fatty liver disease-like C57BL/6J mice. The mice were randomly divided into four groups (n = 10/group): the normal diet group, the HFD group, the arazyme group (HFD with 0.025% arazyme), and the milk thistle (MT) group (HFD with 0.1% MT). Dietary supplementation of arazyme for 13 weeks significantly lowered plasma triglyceride (TG) and non-esterified fatty acid levels. Suppression of HFD-induced hepatic steatosis in the arazyme group was caused by the reduced hepatic TG and total cholesterol (TC) contents. Arazyme supplementation decreased hepatic lipogenesis-related gene expression, sterol regulatory element-binding transcription protein 1 (Srebf1), fatty acid synthase (Fas), acetyl-CoA carboxylase 1 (Acc1), stearoyl-CoA desaturase-1 (Scd1), Scd2, glycerol-3-phosphate acyltransferase (Gpam), diacylglycerol O-acyltransferase 1 (Dgat1), and Dgat2. Arazyme directly reduced palmitic acid (PA)-induced TG accumulation in HepG2 cells. Arazyme suppressed macrophage infiltration and tumor necrosis factor &#945; (Tnfa), interleukin-1&#946; (Il1b), and chemokine-ligand-2 (Ccl2) expression in the liver, and inhibited secretion of TNF&#945; and expression of inflammatory mediators, Tnfa, Il1b, Ccl2, Ccl3, Ccl4, and Ccl5, in PA-induced RAW264.7 cells. Arazyme effectively protected hepatic steatosis and steatohepatitis by inhibiting SREBP-1-mediated lipid accumulation and macrophage-mediated inflammation

Diversity in the Extracellular Vesicle-Derived Microbiome of Tissues According to Tumor Progression in Pancreatic Cancer

This study was conducted to identify the composition and diversity of the microbiome in tissues of pancreatic cancer and to determine its role. First, extracellular vesicles (EVs) were obtained from the paired tumor and normal tissues, and 16s rRNA gene sequencing was performed. We identified the microbiomes, compared the diversity between groups, and found that Tepidimonas was more abundant in tumors. Second, larger tumors resulted in lower levels of Leuconostoc and Sutterella, and increased lymph node metastasis resulted in higher levels of Comamonas and Turicibacter in tumor tissues. Moreover, in the case of tumor recurrence, the levels of Streptococcus and Akkermansia were decreased in tumor tissues. Finally, with the supernatant of Tepidimonasfonticaldi, proliferation and migration of cells increased, and epithelial-mesenchymal transition and the Tricarboxylic Acid (TCA) cycle-related metabolites were enhanced. The composition and diversity of EV-derived microbiomes are important for providing novel insights into theragnostic approaches in pancreatic cancer

Anti-Itching and Anti-Inflammatory Effects of Kushenol F via the Inhibition of TSLP Production

Atopic dermatitis (AD) is a chronic inflammatory skin disease that results from eczema, itching, disrupted barrier function and aberrant cutaneous immune responses. The aim of the present study was to assess the efficacy of kushenol F as an effective treatment for AD via the suppression of thymic stromal lymphopoietin (TSLP) production. The results of the present study demonstrated that the clinical symptoms of AD were less severe and there was reduced ear thickening and scratching behavior in kushenol F-treated Dermatophagoides farinae extract (DFE)/1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD mice. Histopathological analysis demonstrated that kushenol F decreased the DFE/DNCB-induced infiltration of eosinophil and mast cells and TSLP protein expression levels. Furthermore, kushenol F-treated mice exhibited significantly lower concentrations of serum histamine, IgE and IgG2a compared with the DFE/DNCB-induced control mice. Kushenol F also significantly decreased phosphorylated NF-&kappa;B and IKK levels and the mRNA expression levels of IL-1&beta; and IL-6 in cytokine combination-induced human keratinocytes. The results of the present study suggested that kushenol F may be a potential therapeutic candidate for the treatment of AD via reducing TSLP levels