A comprehensive analysis of GAS2 family members identifies that GAS2L1 is a novel biomarker and promotes the proliferation of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common primary liver cancer with a high incidence and mortality. Members of the growth-arresting-specific 2 (GAS2) family are involved in various biological processes in human malignancies. To date, there is only a limited amount of information available about the expression profile and clinical importance of GAS2 family in HCC. In this study, we found that GAS2L1 and GAS2L3 were distinctly upregulated in HCC specimens compared to non-tumor specimens. Pan-cancer assays indicated that GAS2L1 and GAS2L3 were highly expressed in most cancers. The Pearson's correlation revealed that the expressions of GAS2, GAS2L1 and GAS2L2 were negatively associated with methylation levels. Survival assays indicated that GAS2L1 and GAS2L3 were independent prognostic factors for HCC patients. Immune cell infiltration analysis revealed that GAS2, GAS2L1 and GAS2L3 were associated with several immune cells. Finally, we confirmed that GAS2L1 was highly expressed in HCC cells and its knockdown suppressed the proliferation of HCC cells. Taken together, our findings suggested the expression patterns and prognostic values of GAS2 members in HCC, providing insights for further study of the GAS2 family as sensitive diagnostic and prognostic markers for HCC.

Chemodiversity and Bioactivity of the Essential Oils of Juniperus and Implication for Taxonomy.

The essential oils of Juniperus are highly beneficial medicinally. The present study aimed to assess the chemodiversity and bioactivity of Juniperus formosana, Juniperus przewalskii, Juniperus convallium, Juniperus tibetica, Juniperus komarovii, and Juniperus sabina essential oils from the Qinghai-Tibet Plateau. The results revealed 92 components in six essential oils: α-pinene (2.71-17.31%), sabinene (4.91-19.83%), and sylvestrene (1.84-8.58%) were the main components. Twelve components were firstly reported in Juniperus oils, indicating that the geographical location and climatic conditions of the Qinghai-Tibet Plateau produced the unique characteristics of Juniperus essential oils. The chemodiversity of Juniperus essential oils varied greatly, with J. sabina having the most recognized components (64) and the highest chemodiversity (Shannon-Wiener index of 3.07, Simpson's diversity index of 0.91, and Pielou evenness of 0.74). According to the chemodiversity of essential oils, the six plants were decided into the α-pinene chemotype (J. formosana), hedycaryol chemotype (J. przewalskii, J. komarovii, J. convallium, J. tibetica), and sabinene chemotype (J. sabina). PCA, HCA and OPLS-DA showed that J. formosana and J. sabina were distantly related to other plants, which provides a chemical basis for the classification of Juniperus plants. Furthermore, bioactivity tests exhibited certain antioxidant and antibacterial effects in six Juniperus oils. And the bioactivities of J. convallium, J. tibetica, and J. komarovvii were measured for the first time, broadening the range of applications of Juniperus. Correlation analysis of components and bioactivities showed that δ-amorphene, ß-udesmol, α-muurolol, and 2-nonanone performed well in the determination of antioxidant activity, and α-pinene, camphene, ß-myrcene, as well as (E)-thujone, had strong inhibitory effects on pathogenic bacteria, providing a theoretical basis for further research on these components.

Dynamic change of bacterial diversity, metabolic pathways, and flavor during ripening of the Chinese fermented sausage.

Chinese fermented sausage is a famous fermented meat product with a complex microbiota that has a potential impact on flavor and quality. In this study, Lactobacillus plantarum MSZ2 and Staphylococcus xylosus YCC3 were used as starter cultures to investigate the change in bacterial diversity, metabolic pathways, and flavor compounds during the ripening process of fermented sausages. High-throughput sequencing technology and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC/MS) were applied for characterizing the profiles of bacterial diversity, metabolic pathways, and flavor compounds in sausage samples on days 0, 6, and 12 during ripening. Results showed that Lactobacillus, Staphylococcus, Lactococcus, Leuconostoc, and Weissella were the most abundant bacterial genera found in the sausage samples during all stages of fermentation. Functional prediction reveals the abundance of 12 different metabolic pathways, the most important pathways are carbohydrate metabolism, nucleotide metabolism, lipid metabolism, and amino acid metabolism. A total of 63 volatile compounds were successfully identified in fermented sausage samples. Correlational analysis demonstrated that Staphylococcus and Leuconostoc were closely related to the formation of flavor compounds. Therefore, the present study may provide guidance for future use of microbiota to improve flavor, quality, and preservation of fermented sausages.

Baicalin confers hepatoprotective effect against alcohol-associated liver disease by upregulating microRNA-205.

Recently, baicalin refers to flavonoid compound extracted from Scutellaria baicalensis Georgi has been indicated to hold promising therapeutic effects in alcohol-associated liver disease (ALD). However, knowledge of the molecular mechanisms for its hepatoprotective effect is still very limited. Evidence exists suggesting potential association between miR-205 and baicalin's function. Bioinformatic analysis and dual luciferase reporter assay were conducted to determine the binding affinity between miR-205 and importinα5. Our findings revealed that baicalin could alleviate ALD by raising the expression of miR-205. Additionally, miR-205 repressed NF-κB signaling pathway activation by binding to importinα5 to relieve ALD. Baicalin inhibited importinα5-mediated NF-κB signaling pathway to protect the liver against alcohol-induced injury, inflammation, oxidative stress and hepatocyte apoptosis. Taken conjointly, baicalin confers hepatoprotective effect against ALD through miR-205-mediated importinα5 inhibition via the NF-κB signaling pathway, highlighting a promising therapeutic target for ALD treatment with the help of traditional Chinese medicine.

Subjective and objective quality assessment of gastrointestinal endoscopy images: From manual operation to artificial intelligence.

Gastrointestinal endoscopy has been identified as an important tool for cancer diagnosis and therapy, particularly for treating patients with early gastric cancer (EGC). It is well known that the quality of gastroscope images is a prerequisite for achieving a high detection rate of gastrointestinal lesions. Owing to manual operation of gastroscope detection, in practice, it possibly introduces motion blur and produces low-quality gastroscope images during the imaging process. Hence, the quality assessment of gastroscope images is the key process in the detection of gastrointestinal endoscopy. In this study, we first present a novel gastroscope image motion blur (GIMB) database that includes 1,050 images generated by imposing 15 distortion levels of motion blur on 70 lossless images and the associated subjective scores produced with the manual operation of 15 viewers. Then, we design a new artificial intelligence (AI)-based gastroscope image quality evaluator (GIQE) that leverages the newly proposed semi-full combination subspace to learn multiple kinds of human visual system (HVS) inspired features for providing objective quality scores. The results of experiments conducted on the GIMB database confirm that the proposed GIQE showed more effective performance compared with its state-of-the-art peers.

Overexpressed sFRP3 exerts an inhibitory effect on hepatocellular carcinoma via inactivation of the Wnt/ß-catenin signaling pathway.

Hepatocellular carcinoma (HCC) is recognized as the most common malignancy of the liver in adults. Many human cancers have been associated with the oncogenic activation of the Wnt/ß-catenin signaling pathway. The secreted frizzled-related proteins (sFRPs) function as negative regulators of the Wnt signaling and have important implications in carcinogenesis. This study aims to investigate the possible regulatory effects of sFRP3 on the Wnt/ß-catenin signaling pathway and their interactions in HCC occurrence. Firstly, sFRP3 expression was quantified in the collected cancer and adjacent normal tissue samples from HCC patients. The lowly expressed sFRP3 in HCC tissues was found to be correlated with HCC development. The expression of sFRP3 was regulated by a lentivirus-based packaging system, and the Wnt/ß-catenin signaling pathway was inactivated by DDK-1 in HepG2 cells. The expressions of Wnt1, ß-catenin and the nuclear translocation of ß-catenin were determined, both of which were down-regulated by sFRP3 overexpression. CCK8 assay, EdU staining, Colony formation assay, flow cytometry, scratch test and Transwell assay were employed to test cell viability, proliferation, cell cycle, apoptosis, migration and invasion, respectively. Overexpressed levels of sFRP3 were found to produce a reduction in MMP-2, MMP-7, MMP-9, PCNA, Ki67, and Bcl-2 expressions but an increase in the expressions of caspase-3 and Bax. In addition, overexpression of sFRP3 inhibited cell proliferation, migration, invasion, and colony formation, but promoted cell cycle arrest and cell apoptosis in HCC cells. The addition of the Wnt/ß-catenin signaling pathway inhibitor, DKK-1, reversed the contributory effect of sFRP3 silencing on HCC development. Lastly, in vivo tumor formation was inhibited by enforced sFRP3 expressions. The obtained results suggested that sFRP3 acts as an anti-oncogene in HCC by inhibiting the activation of the Wnt/ß-catenin signaling pathway.

Withdrawal Notice: Therapeutic Effect of Prdx1 on NAFLD Mice May be Related to the Activation of Nrf-2/HO-1 Pathway

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Repression of TXNIP-NLRP3 axis restores intestinal barrier function via inhibition of myeloperoxidase activity and oxidative stress in nonalcoholic steatohepatitis.

Dysfunction of the intestinal barrier function occurs in hepatic injury, but the specific mechanisms responsible are largely unknown. Recently, NOD-like receptor 3 (NLRP3) inflammasome functions in impairing endothelial barrier function. In this study, we test the hypothesis that TXNIP-NLRP3 axis repression prevents against intestinal barrier function disruption in nonalcoholic steatohepatitis (NASH). First, lipopolysaccharide (LPS)-induced alterations in expression of ZO-1 and occludin, myeloperoxidase (MPO) activity, reactive oxygen species (ROS) level, and transepithelial electric resistance (TEER) in intestinal epithelial cells (IECs) isolated from C57BL/6 wild-type (WT) and TXNIP-/- mice were evaluated. The underlying regulatory mechanisms of TXNIP knockout in vivo were investigated with the detection of expressions of TXNIP, NLRP3 and ZO-1, and occludin, the interaction of TXNIP-NLRP3, MPO activity, ROS level, permeability of intestinal mucosa, levels of inflammatory factors in serum, and LPS concentration. We identified that TXNIP knockout promoted ZO-1 and occludin expression, yet reduced MPO activity, ROS level, and cell permeability in IECs, indicating restored the intestinal barrier function. However, LPS upregulated TXNIP and NLRP3 expression, as well as contributed to the interaction between TXNIP and NLRP3 in vitro. Furthermore, TXNIP was significantly upregulated in the intestinal mucosa of NASH mice and its knockout repaired the intestinal barrier disrupt, inhibited expression of inflammatory factors, and reduced LPS concentration as well as hepatic injury in vivo. Taken together, our findings demonstrated that inhibited the activation of the TXNIP-NLRP3 axis reduced MPO activity and oxidative stress and thus restoring the intestinal barrier function in NASH. TXNIP-NLRP3 axis may be a promising therapeutic strategy for the NASH treatment.

Deep eutectic solvents from hemicellulose-derived acids for the cellulosic ethanol refining of Akebia' herbal residues.

Here, the potential use of herbal residues of Akebia as feedstock for ethanol production is evaluated. Additionally, five deep eutectic solvents from hemicellulose-derived acids were prepared to overcome biomass recalcitrance. Reaction temperatures had more significant influences on solid loss and chemical composition than the molar ratios of choline chloride (ChCl) to derived acids. Glycolic acid resulted in the maximum levels of lignin, xylan and glucan removal, which were 60.0%, 100% and 71.5%, respectively, at 120°C with a 1:6M ratio of ChCl-glycolic acid. In contrast, ChCl-formic acid resulted in the greatest level of glucan retention, at 97.8%, with a lignin removal rate of 40.7% under the same pretreatment conditions. Moreover, ChCl loading could significantly enhance the selectivity of carboxylic acid for lignin dissolution. A 98.0% level of subsequent enzymatic saccharification and a 100% ethanol yield were achieved after ChCl-formic acid pretreatments of Akebia' herbal residues.

Baicalin Attenuates Alcoholic Liver Injury through Modulation of Hepatic Oxidative Stress, Inflammation and Sonic Hedgehog Pathway in Rats.

BACKGROUND/AIMS: Lipid accumulation, inflammatory responses and oxidative stress have been implicated in the pathology of alcoholic liver disease (ALD). Targeting inhibition of these features may provide a promising therapeutic strategy for ALD. Baicalin, a flavonoid isolated from Scutellaria baicalensis Georgi, has been shown to exert a hepatoprotective effect. However, its effects on ALD remain obscure. This study was aimed to investigate the effects of baicalin on alcohol-induced liver injury and its related mechanisms. METHODS: For in vivo experiments, rats were supplied intragastrical administration of alcohol continuously for 4 or 8 weeks, and then received baicalin treatment in the latter 4 weeks in the presence / absence of alcohol intake. Liver histology and function, inflammatory cytokines, oxidative mediators, and the components of the Sonic hedgehog pathway were evaluated. For in vitro experiments, alcohol-stimulated human normal liver cells LO2 were used. RESULTS: Baicalin treatment significantly alleviated alcoholic liver injury, improved liver function impaired by alcohol, and inhibited hepatocytes apoptosis. In addition, baicalin decreased the expression levels of proinflammatory cytokines TNF-α, IL-1ß, IL-6) and malonyldialdehyde (MDA), and increased the activities of antioxidant enzymes SOD and GSH-Px. Furthermore, baicalin modulated the activation of Sonic hedgehog (Shh) pathway. Administration of baicalin upregulated the expression of sonic hedgehog (Shh), patched (Ptc), Smoothened (Smo), and Glioblastoma-1(Gli-1). Blockade of the Shh pathway in cyclopamine abolished the effects of baicalin in vitro. CONCLUSION: Both in vivo and in vitro experimental results indicate that baicalin exerts hepatoprotective roles in alcohol-induced liver injury through inhibiting oxidative stress, inflammatory response, and the regulation of the Shh pathway.

Lutein prevents alcohol-induced liver disease in rats by modulating oxidative stress and inflammation.

OBJECTIVE: Oxidative stress and inflammation play an important role in pathogenesis of alcohol-induced liver injury. The present study was designed to investigate the protective role of Lutein against alcohol-induced liver injury. TREATMENT: Wistar rats weighing 150-200 g were divided into 3 groups, control, EtOH treatment, Lutein followed by EtOH treatment. Ethanol-treated rats received EtOH [5 g/kg body weight] by gavage every 12 hours for a total of 3 doses. For Lutein pre-treatment, Lutein at a dose of 40 mg/kg was dissolved in the EtOH and gavaged 30 mins before EtOH treatment. METHODS: Oxidative stress markers-(reactive oxygen species, lipid peroxidation, protein carbonyls and sulfhydryls content), liver markers (ALT, AST, ALP and LDH) were determined. Antioxidant enzyme activities and its master regulator Nrf-2 expression were analyzed. Further, inflammatory proteins NF-κB, COX-2, iNOS and inflammatory cytokines (TNF-α, MCP-1, IL-1ß, IL-6) were analyzed. RESULTS: The results showed significant decrease in oxidative stress markers and liver markers in the lutein pre-treatment. Lutein treatment down regulated inflammatory proteins and cytokines with concomitant up regulation in Nrf-2 levels and antioxidant enzymic activities. CONCLUSION: The present study showed that Lutein treatment exerted potent antioxidant and anti-inflammatory property and offered significant cytoprotection against alcohol-induced liver injury.

Characterization of sonic hedgehog inhibition in gastric carcinoma cells.

Aberrant activation of the sonic hedgehog (Shh) signaling pathway plays an important role in gastric cancer. The exact mechanisms defining how the Shh pathway promotes tumorigenesis or regulates its downstream targets remains elusive. In the present study, the effects of inhibiting the Shh signaling pathway in gastric cancer AGS cells was examined. It was identified that the Shh antagonist, cyclopamine, inhibited cancer proliferation, migration and invasion in a dose- and time-dependent manner. Additionally, it was revealed that several key targets that are activated by the Shh signaling pathway, Gli1 and CXCR4, were downregulated at an RNA and protein level by cyclopamine. The results from the present study may be of benefit in facilitating the development of novel therapeutic strategies to treat gastric cancer in human patients.