Effects of sn-2 Palmitic Triacylglycerols and the Ratio of OPL to OPO in Human Milk Fat Substitute on Metabolic Regulation in Sprague-Dawley Rats.

In this study, the influence of total sn-2 palmitic triacylglycerols (TAGs) and ratio of 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO) in human milk fat substitute (HMFS) on the metabolic changes were investigated in Sprague-Dawley rats. Metabolomics and lipidomics profiling analysis indicated that increasing the total sn-2 palmitic TAGs and OPL to OPO ratio in HMFS could significantly influence glycine, serine and threonine metabolism, glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid metabolism, bile acid biosynthesis, and taurine and hypotaurine metabolism pathways in rats after 4 weeks of feeding, which were mainly related to lipid, bile acid and energy metabolism. Meanwhile, the up-regulation of taurine, L-tryptophan, and L-cysteine, and down-regulations of lysoPC (18:0) and hypoxanthine would contribute to the reduction in inflammatory response and oxidative stress, and improvement of immunity function in rats. In addition, analysis of targeted biochemical factors also revealed that HMFS-fed rats had significantly increased levels of anti-inflammatory factor (IL-4), immunoglobulin A (IgA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px), and decreased levels of pro-inflammatory factors (IL-6 and TNF-α) and malondialdehyde (MDA), compared with those of the control fat-fed rats. Collectively, these observations present new in vivo nutritional evidence for the metabolic regulatory effects of the TAG structure and composition of human milk fat substitutes on the host.

Exploration of the structural mechanism of hydrogen (H2)-promoted horseradish peroxidase (HRP) activity via multiple spectroscopic and molecular dynamics simulation techniques.

Horseradish peroxidase (HRP) is an enzyme that is widely used in various fields. In this study, the effects of molecular hydrogen (H2) on the activity and structural characteristics of HRP were investigated by employing multiple spectroscopic techniques, atomic force microscopy (AFM) and molecular dynamics (MD) simulations. The results demonstrated that H2 could enhance HRP activity, especially in 1.5 mg/L hydrogen-rich water (HRW). The structural analysis results showed that H2 might alter HRP activity by affecting the active sites, secondary structure, hydrogen bonding network, CS groups, and morphological characteristics. The MD results also confirmed that H2 could increase the FeN bond distance in the active site, affect the secondary structure, and increase the number of hydrogen bonds. The MD results further suggested that H2 could increase the number of salt bridges, and lengthen the SS bonds in HRP. This study primarily revealed the mechanism by which H2 enhances the HRP activity, providing insight into the interactions between gas and macromolecular proteins. However, some of the results obtained via MD simulations still need to be verified experimentally. In addition, our study also provided a new convenient strategy to enhance enzyme activity.

Resveratrol inhibits proliferation, invasion and cell cycle of hepatobiliary carcinoma SMMC-7721 cells by downregulating the expression of PRMT5 / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探究白藜芦醇（Res）通过调控PRMT5表达对肝胆管癌SMMC-7721细胞增殖、侵袭、细胞周期的影响及其机制。方法：常规培养正常肝细胞LO2和SMMC-7721细胞，用0、20、40、80 μmol/L的Res进行处理，用qPCR法、MTT法、Transwell实验、流式细胞术和WB法分别检测Res处理后PRMT5 mRNA在LO2和SMMC-7721细胞中的表达，Res对SMMC-7721细胞增殖能力、侵袭能力、细胞周期和凋亡，以及PRMT5、cyclin D1和cyclin E1蛋白表达的影响。结果：PRMT5在SMMC-7721细胞中呈高表达（P<0.01）；20、40、80 μmol/L Res均能明显抑制PRMT5 mRNA和蛋白在SMMC-7721细胞中的表达（均P<0.01），抑制SMMC-7721细胞的增殖能力（P<0.01）和侵袭能力（P<0.05），阻滞SMMC-7721细胞周期于G0/G1期并促进其凋亡（P<0.01），明显抑制SMMC-7721细胞中周期蛋白cyclin D1、cyclin E1蛋白的表达（P<0.01）。结论：PRMT5在SMMC7721细胞中呈高表达，Res可有效抑制SMMC-7721细胞的增殖和侵袭能力并诱导其凋亡，其机制可能与抑制PRMT5表达相关。

Total Sn-2 Palmitic Triacylglycerols and the Ratio of OPL to OPO in Human Milk Fat Substitute Modulated Bile Acid Metabolism and Intestinal Microbiota Composition in Rats.

In this study, the impact of sn-2 palmitic triacyclglycerols (TAGs) in combination with their ratio of two major TAGs (1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL) to 1,3-dioleoyl-2-palmitoylglycerol (OPO)) in human milk fat substitute (HMFS) on bile acid (BA) metabolism and intestinal microbiota composition was investigated in newly-weaned Sprague-Dawley rats after four weeks of high-fat feeding. Compared to those of control group rats, HMFS-fed rats had significantly increased contents of six hepatic primary BAs (CDCA, αMCA, ßMCA, TCDCA, TαMCA and TßMCA), four ileal primary BAs (UDCA, TCA, TCDCA and TUDCA) and three secondary BAs (DCA, LCA and ωMCA), especially for the HMFS with the highest sn-2 palmitic acid TAGs of 57.9% and OPL to OPO ratio of 1.4. Meanwhile, the inhibition of ileal FXR-FGF15 and activation of TGR5-GLP-1 signaling pathways in HMFS-fed rats were accompanied by the increased levels of enzymes involved in BA synthesis (CYP7A1, CYP27A1 and CYP7B1) in the liver and two key thermogenic proteins (PGC1α and UCP1) in perirenal adipose tissue, respectively. Moreover, increasing sn-2 palmitic TAGs and OPL to OPO ratio in HMFS also altered the microbiota composition both on the phylum and genus level in rats, predominantly microbes associated with bile-salt hydrolase activity, short-chain fatty acid production and reduced obesity risk, which suggested a beneficial effect on host microbial ecosystem. These observations provided important nutritional evidence for developing new HMFS products for infants.

The phenolic profile of walnut meal protein isolate and interaction of phenolics with walnut protein.

The aim of this study was to interpret the interaction of phenolics with walnut protein and determine their effects on protein functional properties. The phenolic profiles of walnut meal (WM) and walnut meal protein isolate (WMPI) were established using UPLC-Q-TOF-MS. A total of 132 phenolic compounds were detected, including 104 phenolic acids and 28 flavonoids. Phenolic compounds bound to protein via hydrophobic interactions, hydrogen bonds, and ionic bonds were identified in WMPI. They were also present as free forms, but the hydrophobic interactions and hydrogen bonds were the main non-covalent binding forces between phenolics and walnut proteins. The interaction mechanisms were further supported by the fluorescence spectra of WMPI with ellagic acid and quercitrin. In addition, changes in the functional properties of WMPI after removal of phenolic compounds were evaluated. Dephenolization significantly increased water holding capacity, oil absorptive capacity, foaming capacity, foaming stability, emulsifying stability index, and the in vitro gastric digestibility. However, in vitro gastric-intestinal digestibility was not significantly affected. These results provide insights into the interactions between walnut protein and phenolics, which indicates potential strategies for removing phenolics from walnut protein.

Protective effects of salvianolic acid B on intestinal ischemia/reperfusion injury in rats by regulating the AhR/IL-22/STAT6 axis.

PURPOSE: Intestinal ischemia/reperfusion (I/R) injury (IIRI) is associated with high morbidity and mortality. Salvianolic acid B (Sal-B) could exert neuroprotective effects on reperfusion injury after cerebral vascular occlusion, but its effect on IIRI remains unclear. This study set out to investigate the protective effects of Sal-B on IIRI in rats. METHODS: The rat IIRI model was established by occluding the superior mesenteric artery and reperfusion, and they were pretreated with Sal-B and aryl hydrocarbon receptor (AhR) antagonist CH-223191 before surgery. Pathological changes in rat ileum, IIRI degree, and intestinal cell apoptosis were evaluated through hematoxylin-eosin staining, Chiu's score scale, and TUNEL staining, together with the determination of caspase-3, AhR protein level in the nucleus, and STAT6 phosphorylation by Western blotting. The levels of inflammatory cytokines (IL-1ß/IL-6/TNF-α) and IL-22 were determined by ELISA and RT-qPCR. The contents of superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in intestinal tissues were determined by spectrophotometry. RESULTS: Sal-B alleviated IIRI in rats, evidenced by slight villi shedding and villi edema, reduced Chiu's score, and diminished the number of TUNEL-positive cells and caspase-3 expression. SAL-B alleviated inflammation and oxidative stress (OS) responses induced by IIRI. Sal-B promoted IL-22 secretion by activating AhR in intestinal tissue after IIRI. Inhibition of AhR activation partially reversed the protective effect of Sal-B on IIRI. Sal-B promoted STAT6 phosphorylation by activating the AhR/IL-22 axis. CONCLUSION: Sal-B plays a protective role against IIRI in rats by activating the AhR/IL-22/STAT6 axis, which may be achieved by reducing the intestinal inflammatory response and OS responses.

Erratum: MicroRNA-423 enhances the invasiveness of hepatocellular carcinoma via regulation of BRMS1.

[This corrects the article on p. 5576 in vol. 9, PMID: 29312509.].

LncRNA SLC9A3-AS1 knockdown increases the sensitivity of liver cancer cell to triptolide by regulating miR-449b-5p-mediated glycolysis.

Triptolide (TP) is involved in the progression of liver cancer. However, the detailed molecular network regulated through TP is still unclear. Long non-coding RNA (LncRNA) SLC9A3 exerts roles in various pathological progresses. Nevertheless, whether SLC9A3 affects the sensitivity of liver cancer cells to TP have not been uncovered. The content of SLC9A3-AS1 and miR-449b-5p was estimated by utilizing quantitative real-time polymerase-chain reaction (qRT-PCR). Cell counting kit 8 (CCK-8) assay was introduced to assess cell viability. Additionally, cell viability as well as invasion was tested via transwell assay. The direct binding between miR-449b-5p and SLC9A3-AS1 or LDHA was confirmed through luciferase reporter gene assay. Moreover, glycolysis rate was tested by calculating the uptake of glucose in addition to the production of lactate in Huh7 cells. LncRNA SLC9A3-AS1 was up-regulated in liver cancer tissue samples and cells. Knockdown of SLC9A3-AS1 notably further inhibited viability, migration as well as invasion in Huh7 cells. MiR-449b-5p was the direct downstream miRNA of SLC9A3-AS1 and was down-regulated by SLC9A3-AS1 in Huh7 cells. In addition, miR-449b-5p was reduced in liver cancer tissues and cells. Overexpressed miR-449b-5p increased the sensitivity of Huh7 cells to TP remarkably. Moreover, miR-449b-5p negatively regulated LDHA expression in Huh7 cells. This work proved that SLC9A3-AS1 increased the sensitivity of liver cancer cells to TP by regulating glycolysis rate mediated via miR-449b-5p/LDHA axis. These findings implied that TP is likely to be a potent agent for treating patients diagnosed with liver cancer.

LncRNA MBNL1-AS1 knockdown increases the sensitivity of hepatocellular carcinoma to tripterine by regulating miR-708-5p-mediated glycolysis.

Hepatocellular carcinoma (HCC) is identified as a common cancer type across the world and needs novel and efficient treatment. Tripterine, a well-known compound, exerts suppressive role in HCC development. However, the related molecular mechanism of tripterine in HCC remains unclear. The expression of MBNL1-AS1in HCC tissues and cells was measured via qRT-PCR assay. MTT assay was employed to estimate cell viability. Besides, cell migration as well as invasion was determined through transwell assay. Additionally, the binding ability of miR-708-5p and MBNL1-AS1or HK2 was proved by starBase database and luciferase reporter gene assay. Moreover, the HK2 level was detected by immunoblotting. MBNL1-AS1 was reduced in HCC tissues and cells. Overexpression of MBNL1-AS1 decreased the sensitivity of HCC cells to tripterine while MBNL1-AS1 silence played opposite effect. In addition, miR-708-5p was the target of MBNL1-AS1 and was down-regulated through MBNL1-AS1 in HCC cells. Moreover, miR-708-5p suppressed glycolysis rate and reduced the expression of vital glycolytic enzyme (HK2, LDHA and PKM2) in HCC cells. Furthermore, miR-708-5p reduced HK2 expression by binding to it directly. In this investigation, we proved that LncRNA MBNL1-AS1 increased the tripterine resistance of HCC cells at least partly by mediating miR-708-5p-related glycolysis. These findings revealed a potent therapeutic target for the treatment of HCC.

Impact of COVID-19 on China's international liner shipping network based on AIS data.

As an essential sub-network of the global liner shipping network, China's international liner shipping network was the earliest to be affected by the COVID-19 and also had a significant impact on the global shipping network. This paper uses Automatic Identification System (AIS) data to analyze the impact of COVID-19 on the typical route networks and major ports of China's international liner shipping. On this basis, the changes in network efficiency and connectivity under the failure of important nodes is simulated. The research finds that, during the epidemic period, the scale of China's international liner shipping network increased, with more routes gathering at fewer hub ports. Still, the overall connectivity and connection strength declined. Meanwhile, the epidemic caused fluctuations in container volume and the mismatch of ship cargo capacity supply, in which China-U.S. routes was the most prominent. From the view of node, the competitiveness of China's mainland ports was significantly promoted during the epidemic. In addition, ports such as Busan, Singapore, and Hong Kong substantially impacted China's international liner shipping network. The current study might be helpful for the industry management departments and related companies to prepare contingency plans, thus enhancing the resilience of the logistics chain and ensuring the stability of the global supply chain.

Recent Studies on Protective Effects of Walnuts against Neuroinflammation.

Neuroinflammation plays a significant role in the aging process and the pathophysiology of neurodegenerative diseases, such as Alzheimer's disease. Accordingly, possible therapeutic strategies aimed at anti-inflammatory effects may be beneficial to brain health. Walnut kernels contain large quantities of unsaturated fatty acids, peptides, and phenolic compounds that have anti-inflammatory effects. The long-term intake of walnuts has been found to improve cognitive function and memory in rats and humans. However, the modulatory effect of walnuts on neuroinflammation has received much less attention. This review focuses on the potential influence and main regulating mechanisms of walnuts and their active ingredients on neuroinflammation, including the regulation of microglia activation induced by amyloid ß or lipopolysaccharides, inhibition of peripheral inflammation mediated by macrophages, reduction in oxidative stress by decreasing free radical levels and boosting antioxidant defenses, and control of gut microbes to maintain homeostasis. However, the majority of evidence of the beneficial effects of walnuts or their components on neuroinflammation and neurodegeneration comes from experimental work, whereas evidence from clinical studies on the beneficial effects is scarcer and less conclusive. This review aims to provide new insights into the neuroinflammation-regulating mechanisms and natural active ingredients of walnuts and the development of walnut-based functional foods for the alleviation of neurodegenerative diseases.

Effects of salvianolic acid A on intestinal microbiota and lipid metabolism disorders in Zucker diabetic fatty rats.

Salvianolic acid A (SalA) is the main water-soluble component isolated from Salvia miltiorrhiza. This study explored the influences of SalA on intestinal microbiota composition and lipid metabolism in Zucker diabetic fatty (ZDF) rats. The 6-week-old male ZDF rats were treated with distilled water (N = 10) and low dose (SalA 0.5 mg/kg/d, N = 10), medium dose (SalA 1 mg/kg/d, N = 10), and high dose (SalA 2 mg/kg/d, N = 10) of SalA, with the male Zucker lean normoglycemic rats of the same week age as controls (given distilled water, N = 10). The blood glucose, body weight, and food intake of rats were examined. After 7 and 8 weeks of continuous administration, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed, respectively. Serum fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) were determined. Liver tissues were stained using hematoxylin-eosin (HE) and oil red O staining. Fecal samples were analyzed by 16S rRNA gene sequencing. Small intestinal tissues were stained using HE and immunohistochemistry. The tight junction proteins (ZO-1/Occludin/Claudin-1) and serum levels of LPS/TNF-α/IL-6 were evaluated. SalA reduced insulin resistance, liver injury, serum FFA, liver TC and TG levels in ZDF rats, and improved lipid metabolism. After SalA treatment, intestinal microbiota richness and diversity of ZDF rats were promoted. SalA retained the homeostasis of intestinal core microbiota. SalA reduced intestinal epithelial barrier damage, LPS, and inflammatory cytokines in ZDF rats. Overall, SalA can sustain intestinal microbiota balance and improve the lipid metabolism of ZDF rats.

Elucidation of Interaction between Whey Proteins and Proanthocyanidins and Its Protective Effects on Proanthocyanidins during In-Vitro Digestion and Storage.

Whey proteins and oligomeric proanthocyanidins have nutritional value and are widely used in combination as food supplements. However, the effect of the interactions between proanthocyanidins and whey proteins on their stability has not been studied in depth. In this work, we aimed to characterize the interactions between ß-Lactoglobulin (ß-LG) and α-lactalbumin (α-LA) and oligomeric proanthocyanidins, including A1, A2, B1, B2, B3, and C1, using multi-spectroscopic and molecular docking methods. Fluorescence spectroscopic data revealed that all of the oligomeric proanthocyanidins quenched the intrinsic fluorescence of ß-LG or α-LA by binding-related fluorescence quenching. Among the six oligomeric proanthocyanidins, A1 showed the strongest affinity for ß-LG (Ka = 2.951 (±0.447) × 104 L∙mol-1) and α-LA (Ka = 1.472 (±0.236) × 105 L∙mol-1) at 297 K. ß-LG/α-LA and proanthocyanidins can spontaneously form complexes, which are mainly induced by hydrophobic interactions, hydrogen bonds, and van der Waals forces. Fourier-transform infrared spectroscopy (FTIR) and circular dichroism spectroscopy showed that the secondary structures of the proteins were rearranged after binding to oligomeric proanthocyanidins. During in vitro gastrointestinal digestion, the recovery rate of A1 and A2 increased with the addition of WPI by 11.90% and 38.43%, respectively. The addition of WPI (molar ratio of 1:1) increased the retention rate of proanthocyanidins A1, A2, B1, B2, B3, and C1 during storage at room temperature by 14.01%, 23.14%, 30.09%, 62.67%, 47.92%, and 60.56%, respectively. These results are helpful for the promotion of protein-proanthocyanidin complexes as functional food ingredients in the food industry.

Cancer-associated fibroblast-derived CCL5 contributes to cisplatin resistance in A549 NSCLC cells partially through upregulation of lncRNA HOTAIR expression.

Aberrant C-C motif chemokine ligand 5 (CCL5) is associated with disease progression, poor prognosis and chemotherapy resistance in human malignancy. The tumor microenvironment (TME) contributes to chemotherapy resistance. However, the role of cancer-associated fibroblasts (CAFs)-derived CCL5 is not well documented. Hence, the present study aimed to investigate the effects of CAFs on chemotherapy resistance in A549 non-small cell lung cancer (NSCLC) cells and the underlying mechanism. Primary CAFs isolated from patients with NSCLC were found to express and secrete elevated levels of CCL5, which attenuated cisplatin (DDP)-induced apoptosis, as indicated by flow cytometry analysis. In addition, CCL5 upregulated the expression levels of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in the tumor cells, and silencing HOTAIR in tumor cells enhanced the cytotoxic effect of cisplatin, characterized by decreased cell viability and increased apoptotic rate. Mechanistically, HOTAIR was found to inactivate the caspase-3/BCL-2 signaling pathway in A549 NSCLC cells. Collectively, the current study demonstrated that CAFs in the TME may serve a crucial role in the higher expression levels of CCL5 in tumors and that CAF-derived CCL5 may promote cisplatin resistance via upregulating lncRNA HOTAIR expression.

Cross-linked arabinoxylan in a Ca2+-alginate matrix reversed the body weight gain of HFD-fed C57BL/6J mice through modulation of the gut microbiome.

Here, we compared the effects of different physical forms of arabinoxylan (AX) - a microsphere of cross-linked arabinoxylan (CAX) in a Ca2+-alginate matrix (MC) and physical mixture of AX and alginate (PM) on gut microbiota and development of obesity in C57BL/6J mice. Supplementation of MC in high fat (HF) diet to mice for 10 weeks significantly reversed the body weight gain induced by the HF diet, along with less fat accumulation in both livers and the epididymal adipose than the PM group. Microbiome analysis showed that MC significantly altered the gut microbiota composition with a noticeable increase of butyrogenic bacteria of Lachnospiraceae. The butyrate produced by MC fermentation and the increased abundance of Lachnospiraceae might be the underlying mechanism of the anti-obesity effect of MC. The results indicated that the physical forms of dietary fiber are closely associated with its health benefits, and MC might be served as a new functional food ingredient to prevent obesity.

Triacylglycerols compositions, soluble and bound phenolics of red sorghums, and their radical scavenging and anti-inflammatory activities.

Six commercial red sorghum varieties (Tong Za 117, 141, 142 and 143, Chi Za 109 and 101) were investigated for their triacylglycerol (TAG) profiles, soluble and bound phenolics, and radical scavenging and anti-inflammatory activities. A total of 21 TAGs were identified in red sorghum oils for the first time. Total phenolic (TPC) and flavonoid contents (TFC) in the soluble or bound phenolic fractions differed among red sorghums. Significant correlation among TPC, TFC and DPPH radical scavenging activities was observed in both fractions. Except for caffeic acid, most of phenolic acids in red sorghums are in the bound form. Soluble 3-deoxyanthocyanidins contents (2.12-57.14 µg/g) were significantly higher than those of bound forms (0.01-0.18 µg/g) regardless of sorghum varieties and types of 3-deoxyanthocyanidins. Moreover, the stronger anti-inflammatory capacity of soluble phenolic fraction in Tong Za 117 correlated with its higher TPC, TFC and radical scavenging activity than those of its bound counterpart.

Potential Biomarkers for Early Detection of 3-MCPD Dipalmitate Exposure in Sprague-Dawley Rats.

3-Chloro-1,2-propandiol (3-MCPD) dipalmitate is one of the major 3-MCPD esters formed during food processing. In this single-dose study, the metabonomic profile changes in the 48 h after orally administrated 3-MCPD dipalmitate at 1600 mg/kg BW to Sprague-Dawley (SD) rats were determined with liquid chromatography (LC) coupled with mass spectrometry (MS) system. The chemical structures of 12 potential biomarkers for 3-MCPD dipalmitate exposures early detection were detected and tentatively identified from the plasma of SD rats, including indoxyl sulfate, phenol sulfate, p-cresol sulfate, 2-phenylethanol glucuronide, p-cresol glucuronide, p-cresol, allantoin, phenylacetylglycine, pyrocatechol sulfate, phenyllactic acid, 5-hydroxyindoleacetic acid, and creatinine. Taking into account the metabolites identified from SD rats' kidney, liver, testes, and spleen samples, 3-MCPD dipalmitate might potentially disturb the phenylalanine, tryptophan, tyrosine, glycine, fatty acid, and purine metabolisms. The results suggested that the 12 plasma metabolites could be potentially applied in detecting the early exposures of 3-MCPD esters.

Chemical composition of tetraploid Gynostemma pentaphyllum gypenosides and their suppression on inflammatory response by NF-κB/MAPKs/AP-1 signaling pathways.

The chemical composition and anti-inflammatory activity of gypenosides isolated from tetraploid Gynostemma pentaphyllum (GP) leaves were investigated. The gypenosides accounted for 7.43 mg/g of the tested GP sample, which were composed of four major saponins including isomers of gypenoside 1 and 2 (C47H76O18), 3 (C47H76O17), and 4 (C46H74O17). Pretreatment of gypenosides reduced mRNA expressions of the proinflammatory mediators in LPS-stimulated RAW264.7 macrophage cells, such as IL-6, IL-1ß, COX-2, and TNF-α in a dose-dependent manner. The secreted protein levels of IL-6 and TNF-α, and NO production were also decreased by gypenosides within the concentration range of 50-200 µg/ml. Moreover, the mechanism studies demonstrated that gypenosides (200 µg/ml) treatment significantly inhibited the nuclear translocation of nuclear factor-κB and activator protein 1 (c-Fos and c-Jun) through down-regulating the phosphorylation of their upstream IκB kinase and mitogen-activated protein kinases (MAPKs), especially that of c-Jun N-terminal kinase and extracellular regulated protein kinase(JNK and ERK), but not that of the p38 MAPK. These results suggested that the gypenosides might have potential anti-inflammatory effect and use for improving human health.

Grape Seed Extracts Inhibit the Overexpression of Inflammatory Cytokines in Mouse Retinas and ARPE-19 Cells: Potentially Useful Dietary Supplement for Age-Related Eye Dysfunction.

Aging can cause retinal degeneration, which leads to visual impairment among the elderly population. Age-dependent increases in amyloid beta (Aß) inducesinflammatory cytokine overexpression in the retinal pigment epithelium (RPE), which promotes the progression of age-related retinal degeneration. However, whether dietary antioxidants are useful for the treatment of RPE degeneration remains to be clarified. This study exposited the protective activities and underlying mechanisms of grape seed extracts (GSEs) against Aß-induced proinflammatory events in mouse retinas and ARPE-19 cells. The experimental data demonstrated that GSEs attenuated the increases in messenger RNA (mRNA) levels of interleukin 12 (IL-12), interleukin 6 (IL-6), interleukin 1ß (IL-1ß), and interleukin 18 (IL-18) in the retinal tissues of Aß-treated mice. The experimental results in mice were confirmed by findings in ARPE-19 cells with or without treatment with GSEs. GSEs affected the protein expression levels of endoplasmic reticulum stress markers in ARPE-19 cells exposed to Aß. Knockdown of Bip blocked the inhibitory activities of GSEs on mRNA levels of IL-6, IL-1ß, IL-18, and IL-8. We conclude that GSEs may suppress proinflammatory cytokines partly by increasing the expression of Bip.

Identification of circular RNA-microRNA-messenger RNA regulatory network in hepatocellular carcinoma by integrated analysis.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is the most common types of hepatic malignancies. This study aimed to better understand the pathogenesis of HCC and may help facilitate the improvement of the diagnostic of HCC. METHODS: The mRNA and miRNA expression profiles of HCC, which was retrieved from The Cancer Genome Atlas database, and the circRNA expression profiles of HCC, which was retrieved from Gene Expression Omnibus database, were included in this study to perform an integrated analysis. The differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were identified, and competing endogenous RNA (ceRNA) (DEcircRNA-DEmiRNA-DEmRNA) regulatory network was conducted. Functional annotation of host gene of DEcircRNAs and DEmRNAs in ceRNA regulatory network was performed. Quantitative real-time polymerase chain reaction validation of the expression of the selected DEmRNAs, DEmiRNAs, and DEcircRNAs was performed. RESULTS: A total of 2982 DEmRNAs, 144 DEmiRNAs, and 264 DEcircRNAs were obtained. The ceRNA network contained 61 circRNA-miRNA pairs and 1149 miRNA-mRNA pairs, including 48 circRNAs, 30 miRNAs, and 1149 mRNAs. Functional annotation of DEmRNAs in ceRNA regulatory network revealed that these DEmRNAs were significantly enriched in tryptophan metabolism, fatty acid metabolism, and pathways in cancer. Except for ARNT2 and hsa-miR-214-3p, expression of the others in the quantitative real-time polymerase chain reaction results was consistent with that in our integrated analysis, generally. CONCLUSION: We speculate that hsa_circRNA_104268/hsa-miR-214-3p/E2F2, hsa_circRNA_104168/hsa-miR-139-5p/HRAS, and hsa_circRNA_104769/hsa-miR-93-5p/JUN interaction pairs may play a vital role in HCC. This study expected to provide a novel insight into the pathogenesis and therapy of HCC from the circRNA-miRNA-mRNA network view.