Monounsaturated fatty acid-enriched olive oil exacerbates chronic alcohol-induced hepatic steatosis and liver injury in C57BL/6J mice.

Dietary oil composition determines the pathological processes of alcoholic fatty liver disease (AFLD). Oil rich in saturated fatty acids protects, whereas oil rich in polyunsaturated fatty acids aggravates the alcohol-induced liver injury. However, limited studies have been conducted to address how monounsaturated fatty acids (MUFAs) enriched oil controls the pathological development of AFLD. Therefore, this study was designed to evaluate the effect of MUFA-enriched extra virgin olive oil (OO) on AFLD. Twenty C57BL/6J mice were randomly allocated into four groups and fed modified Lieber-DeCarli liquid diets containing isocaloric maltose dextrin a non-alcohol or alcohol with corn oil and OO for four weeks. Dietary OO significantly exacerbated alcohol-induced liver dysfunction, evidenced by histological examinations and disturbed biochemical parameters. Dietary OO with alcohol decreased hormone-sensitive lipase (HSL), phosphorylated 5'-AMP-activated protein kinase (p-AMPK), and carnitine palmitoyltransferase-Iα (CPT1α) expression, and increased sterol regulatory element-binding protein-1c (SREBP-1c), diacylglycerol acyltransferase-2 (DGAT2), and very low-density lipoprotein receptor (VLDLR) expression in the liver. It also promoted the expression of hepatic interleukin-6 (IL-6) and hepatic tumour necrosis factor-alpha (TNF-α) at the transcriptional level. Additionally, adipose tissue lipolysis partially had an etiologic effect on alcohol-induced hepatic steatosis under OO pretreatment. In conclusion, MUFA-enriched OO exacerbated liver dysfunction in vivo. OO should be cautiously considered as a unique dietary oil source for individuals with AFLD.

TMT-Based Quantitative Proteomics Analyses Reveal the Antibacterial Mechanisms of Anthocyanins from Aronia melanocarpa against Escherichia coli O157:H7.

Aronia melanocarpa anthocyanins (AMAs), as natural plant extracts, can control pathogens and are attracting increasing attention. In this study, a tandem mass tag (TMT) quantitative proteomics method combined with multiple reaction monitoring (MRM) was used to explore the antibacterial mechanism of AMAs against Escherichia coli at the protein level. The results showed that 1739 proteins were identified in E. coli treated with AMAs, of which 628 were altered, including 262 downregulated proteins and 366 upregulated proteins. Bioinformatics analysis showed that these differentially expressed proteins have different molecular functions and participate in different molecular pathways. AMAs can affect E. coli protein biosynthesis, DNA replication and repair, oxidative stress response, peptidoglycan biosynthesis, and homeostasis. These pathways induce morphological changes and cell death. The results of this study help understand the molecular mechanism of the inhibitory effect of AMAs on food-borne pathogens and provide a reference for further development of plant-derived antimicrobial agents.

[Atractylenolide â improves acetaminophen-induced acute liver injury in mice by inhibiting MAPK/NF-κB signaling pathway].

This study explored the protective effect of atractylenolide Ⅰ(AO-Ⅰ) against acetaminophen(APAP)-induced acute liver injury(ALI) in mice and its underlying mechanism. C57 BL/6 J mice were randomly divided into a control group, an APAP group(500 mg·kg~(-1)), a low-dose combination group(500 mg·kg~(-1) APAP + 60 mg·kg~(-1) AO-Ⅰ), and a high-dose combination group(500 mg·kg~(-1) APAP + 120 mg·kg~(-1) AO-Ⅰ). ALI was induced by intraperitoneal injection of APAP(500 mg·kg~(-1)). AO-Ⅰ by intragastric administration was performed 2 hours before APAP treatment, and the control group received the same dose of solvent by intragastric administration or intraperitoneal injection. The protective effect of AO-Ⅰ against APAP-induced ALI was evaluated by detecting alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels in the plasma and H&E staining in liver tissues of mice. The malondialdehyde(MDA) and glutathione(GSH) content and catalase(CAT) activity in mouse liver tissues were detected to evaluate the effect of AO-Ⅰ on APAP-induced oxidative stress in the liver. The proteins in the liver p38 mitogen-activated protein kinase(p38 MAPK), c-jun N-terminal kinase(JNK), and nuclear factor kappa-B p65(NF-κB p65) signaling pathways were measured by Western blot, and the liver inflammatory cytokines interleukin-1ß(IL-1ß) and interleukin-6(IL-6) were detected by real-time PCR. Compared with the APAP group, the combination groups showed reduced APAP-induced ALT level and liver MDA content, potentiated liver CAT activity, and elevated GSH content. Mechanistically, AO-Ⅰ treatment significantly inhibited APAP-up-regulated MAPK phosphorylation and NF-κB p65, and significantly reduced the transcriptional activities of IL-1ß and IL-6, downstream targets of NF-κB p65. AO-Ⅰ can improve APAP-induced ALI and the underlying mechanism is related to the inhibition of the MAPK/NF-κB p65 signaling pathway in APAP-challenged mice.

Effects of intense pulsed light treatment on tear cytokines and clinical outcomes in meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) has become a prevalent ocular surface disorder. Its pathogenesis is regarded as a self-perpetuating inflammatory vicious circle. Intense Pulsed Light (IPL) treatment was recently applied to improve the meibomian gland function and reduce symptoms of MGD. However, studies investigating the change of specific inflammatory cytokines during IPL treatment remained sparse. To further figure out how IPL treatment modulates the inflammatory cytokines in tears of MGD, we therefore performed a cross-sectional study and enrolled 32 patients from March 2019 to December 2020. The patients received 3 sessions of IPL treatment (10 to 16 J/cm2) at 4-week interval. The signs and symptoms of MGD were evaluated by ocular surface disease index (OSDI), tear film breakup time (TBUT), and meibomian gland yield secretion score (MGYSS). The clinical evaluators and tear samples were analyzed at baseline and at each IPL treatment session. Concentrations of (chemokine ligand) CXCL1, (C-C motif chemokine) CCL11, (tumor necrosis factor) TNF-α, (interferon) IFN-γ, (interleukin) IL-2, IL-6 and (tissue inhibitor of metalloproteinase) TIMP-1were measured by Quantibody Human Dry Eye Disease Array1. OSDI significantly decreased after IPL treatment compared with baseline. TBUT and MGYSS increased consecutively during treatment. CXCL1, CCL11, TNF-α, IFN-γ, IL-2, IL-6 presented significantly decrease and TIMP-1 showed significantly increase from the pretreatment baseline. The changed concentrations of TNF-α, IFN-γ, IL-2, TIMP-1 correlated with TBUT, the changed values of CXCL1, TNF-α, IFN-γ, CCL11, IL-2, IL-6, TIMP-1 correlated with MGYSS, and the changed concentrations of CXCL1, IFN-γ, CCL11, IL-2, IL-6 correlated with TIMP-1. The data supported IPL treatment could significantly relieve both signs and symptoms of MGD. The therapeutic effect of IPL treatment may originate from regulation of inflammatory cytokines including CXCL1, TNF-α, IFN-γ, CCL11, IL-2, IL-6, and TIMP-1.

Chicory inulin ameliorates type 2 diabetes mellitus and suppresses JNK and MAPK pathways in vivo and in vitro.

SCOPE: Chicory inulin is a naturally occurring fructan that is conducive to glucose and lipid metabolism in patients with diabetes mellitus. This study aims to investigate the mechanism by which chicory inulin improves glucolipid metabolism in diabetic conditions. METHODS AND RESULTS: Rats were injected with streptozotocin and fed with high fat diet to induce diabetes, and then administrated with different doses of chicory inulin for 8 weeks. The glycometabolism and lipid metabolism parameters were determined, the activity of insulin receptor substrate (IRS) and mitogen-activated protein kinase (MAPK) pathways were examined by western blot. The effect of chicory inulin on glucose uptake of myoblast and hepatocyte were also measured in vitro. Data were analyzed by student's t-test or one-way analysis of variance followed by the Bonferroni post-hoc testing. The results showed that chicory inulin improved glucolipid metabolism, and it activated IRS but suppressed the MAPK pathways in vivo and in vitro. CONCLUSION: Our study demonstrates that chicory inulin, as a nutritional supplement, may be beneficial for the patients with type 2 diabetes mellitus, and the metabolism-modulatory effect seems to be related with the inhibition of JNK and P38 MAPK pathways.

Lonicera caerulea berry extract suppresses lipopolysaccharide-induced inflammation via Toll-like receptor and oxidative stress-associated mitogen-activated protein kinase signaling.

The protective effects of Lonicera caerulea berry extract (LCBE) against hepatic inflammation and the underlying mechanisms were investigated in a rat model of lipopolysaccharide (LPS)-induced chronic liver inflammation. Male Sprague-Dawley rats were injected with LPS (200 µg per kg bw) with or without LCBE co-administration (50, 100 and 200 mg per kg bw intragastrically once daily) for 4 weeks. We found that LCBE supplementation inhibited the increase in Toll-like receptor (TLR)2 and TLR4 expression induced by LPS, while preventing glutathione depletion and reactive oxidative species generation and abrogating increases in C-reactive protein and interleukin-6 levels, restoring alanine and aspartate aminotransferase activities, and blocking the phosphorylation of p38 and c-Jun N-terminal kinase mitogen-activated protein kinases (MAPKs). The protective effects of LCBE against liver damage caused by LPS were dose-dependent. These results demonstrate that LCBE suppresses liver inflammation caused by LPS via inhibition of TLR and MAPK signaling and oxidative stress pathways, and suggest that LCBE treatment can potentially prevent chronic liver injury.

Comparison of polyphenol, anthocyanin and antioxidant capacity in four varieties of Lonicera caerulea berry extracts.

Four varieties of Lonicera caerulea berries--'Wild', 'Beilei', 'No. 1', and 'No. 2'--were compared with respect to extraction yield, fruit weight, total soluble solids, polyphenol and anthocyanin contents, oxygen radical absorbance capacity (ORAC), and anthocyanin composition. Sixteen individual anthocyanins were identified in the selected varieties. Acylated anthocyanins, cyanidin 3-acetylhexoside and peonidin 3-acetylhexoside, were identified in L. caerulea berries for the first time. Cyanidin-3-glucoside was the most prominent anthocyanin in all four tested varieties. Wild type of L. caerulea fruit ('Wild'), with the highest polyphenol content, contained 14 anthocyanins and the highest ORAC value. Eleven anthocyanins were found in 'Beilei' berries, which had a higher ORAC value than 'No. 1' and 'No. 2'. The highest total soluble solid content and extraction yield were found in 'No. 2' and 'Wild' berries, respectively.