Nobiletin Ameliorates Hepatic Lipid Deposition, Oxidative Stress, and Inflammation by Mechanisms That Involve the Nrf2/NF-κB Axis in Nonalcoholic Fatty Liver Disease.

Nobiletin (NOB), a flavonoid with significant antioxidant potential, holds promise for treating nonalcoholic fatty liver disease (NAFLD). In this work, we aim to assess the effects and investigate the molecular mechanisms of NOB on NAFLD. After using a methionine choline-deficient diet to induce C57BL/6J mice, as well as oleic acid to induce HepG2 and L02 cells, we administered NOB as an intervention. The results indicated that the NOB significantly ameliorated lipid deposition, oxidative stress, and inflammation in NAFLD in both models. Its mechanism may involve the Nrf2, SREBP-1c, and NF-κB signaling pathways. Furthermore, Nrf2 is not only a direct target for NOB to improve oxidative damage but also indirectly involved in lipid-lowering and anti-inflammatory processes in NAFLD. By inhibiting Nrf2, we found that the regulatory role of Nrf2 in lipid metabolism is not related to SREBP-1c but is closely associated with NF-κB in terms of inflammation. Our results suggest that Nrf2 is one of the most critical targets for NOB against NAFLD in multiple aspects.

Methane Saline Ameliorates Traumatic Brain Injury through Anti-Inflammatory, Antiapoptotic, and Antioxidative Effects by Activating the Wnt Signalling Pathway.

OBJECTIVE: Methane saline (MS) can be used to treat many diseases via its anti-inflammatory, antiapoptotic, and antioxidative activities. However, to date, there is no published evidence as to whether MS has any effect on traumatic brain injury (TBI). The Wnt signalling pathway regulates cell proliferation, differentiation, migration, and apoptosis; however, whether the Wnt signalling pathway regulates any effect of MS on TBI is unknown. This study was designed to explore the role of MS in the treatment of TBI and whether the Wnt pathway is involved. METHODS: Sprague-Dawley rats were randomly divided into five groups: sham, TBI, TBI+10 ml/kg MS, TBI+20 ml/kg MS, and TBI+30 ml/kg MS. After induction of TBI, MS was injected intraperitoneally once daily for seven consecutive days. Neurological function was evaluated by the Neurological Severity Score (NSS) at 1, 7, and 14 days after TBI. Haematoxylin-eosin (HE) staining, inflammatory factors, neuron-specific enolase (NSE) staining, oxidative stress, and cell apoptosis were measured and compared 14 d after TBI to identify the optimal dose of MS and to investigate the effect of MS on TBI. In the second experiment, Sprague-Dawley rats were randomly divided into four groups: sham, TBI, TBI+20 ml/kg MS, and TBI+20 ml/kg MS+Dickkopf-1 (DKK-1, a specific inhibitor of the Wnt pathway). NSE, caspase-3, superoxide dismutase (SOD), Wnt3a, and ß-catenin were detected by real-time PCR and Western blotting. The results from each group were compared 14 d after TBI to determine the regulatory role of the Wnt pathway. RESULTS: Methane saline significantly inhibited inflammation, oxidative stress, and cell apoptosis, thus protecting neurons within 14 days of TBI. The best treatment effect against TBI was obtained with 20 ml/kg MS. When the Wnt pathway was inhibited, the treatment effect of MS was impaired. CONCLUSION: Methane saline ameliorates TBI through its anti-inflammatory, antiapoptotic, and antioxidative effects via activation of the Wnt signalling pathway, which plays a part but is not the only mechanism underlying the effects of MS. Thus, MS may be a novel strategy for treating TBI.

Safety and efficacy of magnetic anchoring electrode-assisted irreversible electroporation for gastric tissue ablation.

BACKGROUND: Irreversible electroporation (IRE) is an emerging tissue ablation technique, which is safe for sites where thermal-basis techniques are not suitable. The aim of this study is to evaluate the safety and efficacy of magnetic anchoring electrode (MAE)-assisted IRE for normal gastric tissue ablation in a rabbit model. METHODS: IRE (500 V, 100 µs, 99 pulses, 1 Hz) of the gastric wall was performed in 24 adult New Zealand rabbits with a novel catheter-mounted MAE with fluoroscopy and a surgical approach. Procedure time, procedure-related bleeding, perforation, and other complications were recorded. Animals were sacrificed at 30 min, 1 day, 3 days, 7 days, 14 days, and 28 days post-IRE. The stomach was removed en bloc, and the diameter of each lesion was measured. Histopathological analyses by Hematoxylin-Eosin (H&E), masson trichrome, alpha-smooth muscle action (α-SMA), and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were performed. RESULTS: Gastric tissue ablation with MAE-assisted IRE was successfully performed without any interruption. No perforation or bleeding was observed during IRE or throughout the follow-up period. A demarcated hemorrhage was found in the ablated area upon gross examination. H&E staining showed complete cell death with inflammatory infiltration, edema, and hemorrhaging. TUNEL presented diffuse positive cells in the ablated area. The tissue scaffold was well preserved without damage as indicated by Masson trichrome staining. Ulceration was observed starting from 3 days post-IRE. The mucosal layer was gradually recovered and regenerated within 14-28 days. No other complication was observed post-IRE. CONCLUSIONS: MAE-assisted IRE is safe and effective for normal gastric tissue ablation and the gastric wall recovered in 14-28 days post-IRE.

Racial disparities in the survival time of patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma between Chinese patients and patients of other racial groups: A population-based study from 2004 to 2013.

The aim of the present study was to investigate the racial disparities in the presentation, treatment and survival time of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) between Chinese and other racial groups from the Surveillance, Epidemiology, and End Results (SEER) database between January 1st 2004, and December 31st 2013. Key covariates, including clinical presentation, treatment and survival time, were recorded and compared, demonstrating the racial differences. Kaplan-Meier analysis and Cox regression models were performed to identify these disparities in survival time. A total of 30,954 patients were identified in the SEER database. Among these, 27,767 (89.7%) had HCC and 3,187 (10.3%) had ICC. In the HCC cohort, Chinese patients had the highest survival time. Compared with the mortality risk of Chinese patients, the mortality risk of Other Asian, non-Hispanic white, Hispanic and African-American patients increased by 16.8, 35.1, 28.3 and 33.3%, respectively. Compared with other groups, Chinese patients were more likely to present with localized stage, and without vascular invasion, adjacent invasion and metastasis. In the ICC cohort, the Chinese group had improved survival time, compared with the other groups following univariate analysis, although no significant differences were observed between Chinese and Other Asian and Hispanic patients following adjusting for contributing factors. Furthermore, there was no significant differences in the presentation between the groups, which differed from the HCC analysis. In conclusion, race/ethnicity was a significant independent prognostic factor in the HCC cohort, whereas it was not significant in the ICC cohort. The synergistic effect of contributing factors, including demographic, socioeconomic, biological and treatment differences, caused the racial disparity observed in primary liver cancer survival time.

Intraoperative Blood Transfusion and Postoperative Morbidity Following Liver Resection.

BACKGROUND Blood transfusion is common during liver resection (LR). The objective of the present study was to investigate the effects of intraoperative transfusion of different blood components on post-LR morbidity. MATERIAL AND METHODS We included 610 patients undergoing LR and grouped them according to intraoperative transfusion of different blood components: packed red blood cells only (PRBC, n=81); frozen fresh plasma, platelets, and cryoprecipitate (FPC, n=38); transfusion only with PRBC + FPC transfusion (n=244); and no blood transfusion (n=247). Propensity score matching (PSM) analysis was used to mitigate selection bias in comparisons. RESULTS The overall blood transfusion rate was 59.5%. In comparison with the no blood transfusion group, PRBC-only and PRBC + FPC transfusion were more common in patients with lower preoperative hemoglobin, worse liver function, larger tumor size, and undergoing a major LR, and thus were associated with increased postoperative morbidity. In contrast, FPC-only transfusion was more frequent in patients with a liver function of Child-Pugh B and lower preoperative albumin vs. the no blood transfusion group. In the propensity model, transfusion of PRBC (PRBC-only and PRBC+FPC) and FPC (FPC-only and FPC+PRBC) were significantly associated with increased postoperative complications vs. the no blood transfusion group (OR and 95% CI, 1.9 [1.2-2.7], p=0.002; OR and 95% CI, 1.6 [1.0-2.4], p=0.029). In contrast, intraoperative PRBC-only or FPC-only transfusion showed no significant adverse effects on postoperative morbidity. CONCLUSIONS Allogenic transfusion of PRBC and FPC blood components was associated with increased postoperative morbidity after liver surgery. Different blood components should be used only when absolutely necessary.

Western diet feeding influences gut microbiota profiles in apoE knockout mice.

BACKGROUND: Gut microbiota plays an important role in many metabolic diseases such as diabetes and atherosclerosis. Apolipoprotein E (apoE) knock-out (KO) mice are frequently used for the study of hyperlipidemia and atherosclerosis. However, it is unknown whether apoE KO mice have altered gut microbiota when challenged with a Western diet. METHODS: In the current study, we assessed the gut microbiota profiling of apoE KO mice and compared with wild-type mice fed either a normal chow or Western diet for 12 weeks using 16S pyrosequencing. RESULTS: On a western diet, the gut microbiota diversity was significantly decreased in apoE KO mice compared with wild type (WT) mice. Firmicutes and Erysipelotrichaceae were significantly increased in WT mice but Erysipelotrichaceae was unchanged in apoE KO mice on a Western diet. The weighted UniFrac principal coordinate analysis exhibited clear separation between WT and apoE KO mice on the first vector (58.6%) with significant changes of two dominant phyla (Bacteroidetes and Firmicutes) and seven dominant families (Porphyromonadaceae, Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae, Helicobacteraceae, Erysipelotrichaceae and Veillonellaceae). Lachnospiraceae was significantly enriched in apoE KO mice on a Western diet. In addition, Lachnospiraceae and Ruminococcaceae were positively correlated with relative atherosclerosis lesion size in apoE KO. CONCLUSIONS: Collectively, our study showed that there are marked changes in the gut microbiota of apoE KO mice, particularly challenged with a Western diet and these alterations may be possibly associated with atherosclerosis.

Serotonin Exhibits Accelerated Bleomycin-Induced Pulmonary Fibrosis through TPH1 Knockout Mouse Experiments.

BACKGROUND: Pulmonary fibrosis is a chronic progressive fibrosis interstitial lung disease that is characterized by inflammatory infiltration and fibrotic changes. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation, immunomodulation, and fibrosis. The aim of this study was to investigate the role of 5-HT in bleomycin- (BLM-) induced pulmonary fibrosis through wild-type C57BL/6 (WT) and TPH1 knockout (KO) mouse experiments. METHODS: The mice were grouped as follows: WT control group, KO control group, WT BLM group, and KO BLM group. Mice were administrated bleomycin hydrochloride through intratracheal instillation to induce pulmonary fibrosis. Mice were sacrificed 0, 7, 14, and 21 days after modeling, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected to determine the severity of fibrotic changes. RESULTS: The results showed that the weight loss of mice in the WT BLM group was more severe than that in the KO BLM group. H&E and Sirius Red staining revealed that 5-HT markedly aggravated histological damage and fibrotic changes in the lung. Significantly lower levels of hydroxyproline, Ashcroft fibrosis score, total BALF protein and cells, BALF tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6, TNF-α and IL-6 mRNA, malondialdehyde (MDA), and myeloperoxidase- (MPO-) positive cells in the lung tissues, and fibrosis-associated proteins were discovered in the mice from the KO BLM group compared with the WT BLM group. CONCLUSION: 5-HT aggravated pulmonary fibrosis mainly by promoting the inflammation, exudation of proteins and cells, oxidative stress, and upregulation of fibrosis-associated genes in the lung tissues.