Showing papers on "Liver cell published in 2018"

Transforming Growth Factor-β-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis.

Abstract: The Transforming Growth Factor-beta (TGF-β) family plays relevant roles in the regulation of different cellular processes that are essential for tissue and organ homeostasis. In the case of the liver, TGF-β signaling participates in different stages of disease progression, from initial liver injury toward fibrosis, cirrhosis and cancer. When a chronic injury takes place, mobilization of lymphocytes and other inflammatory cells occur, thus setting the stage for persistence of an inflammatory response. Macrophages produce profibrotic mediators, among them, TGF-β, which is responsible for activation -transdifferentiation- of quiescent hepatic stellate cells (HSC) to a myofibroblast (MFB) phenotype. MFBs are the principal source of extracellular matrix protein (ECM) accumulation and prominent mediators of fibrogenesis. TGF-β also mediates an epithelial-mesenchymal transition (EMT) process in hepatocytes that may contribute, directly or indirectly, to increase the MFB population. In hepatocarcinogenesis, TGF-β plays a dual role, behaving as a suppressor factor at early stages, but contributing to later tumor progression, once cells escape from its cytostatic effects. As part of its potential pro-tumorigenic actions, TGF-β induces EMT in liver tumor cells, which increases its pro-migratory and invasive potential. In parallel, TGF-β also induces changes in tumor cell plasticity, conferring properties of a migratory tumor initiating cell (TIC). The main aim of this review is to shed light about the pleiotropic actions of TGF-β that explain its effects on the different liver cell populations. The cross-talk with other signaling pathways that contribute to TGF-β effects, in particular the Epidermal Growth Factor Receptor (EGFR), will be presented. Finally, we will discuss the rationale for targeting the TGF-β pathway in liver pathologies.

Mesenchymal Stem Cell/Red Blood Cell-Inspired Nanoparticle Therapy in Mice with Carbon Tetrachloride-Induced Acute Liver Failure

Abstract: Acute liver failure is a critical condition characterized by global hepatocyte death and often time needs a liver transplantation. Such treatment is largely limited by donor organ shortage. Stem cell therapy offers a promising option to patients with acute liver failure. Yet, therapeutic efficacy and feasibility are hindered by delivery route and storage instability of live cell products. We fabricated a nanoparticle that carries the beneficial regenerative factors from mesenchymal stem cells and further coated it with the membranes of red blood cells to increase blood stability. Unlike uncoated nanoparticles, these particles promote liver cell proliferation in vitro and have lower internalization by macrophage cells. After intravenous delivery, these artificial stem cell analogs are able to remain in the liver and mitigate carbon tetrachloride-induced liver failure in a mouse model, as gauged by histology and liver function test. Our technology provides an innovative and off-the-shelf strategy to treat l...

Monitoring liver damage using hepatocyte-specific methylation markers in cell-free circulating DNA

Abstract: Liver damage is typically inferred from serum measurements of cytoplasmic liver enzymes. DNA molecules released from dying hepatocytes are an alternative biomarker, unexplored so far, potentially allowing for quantitative assessment of liver cell death. Here we describe a method for detecting acute hepatocyte death, based on quantification of circulating, cell-free DNA (cfDNA) fragments carrying hepatocyte-specific methylation patterns. We identified 3 genomic loci that are unmethylated specifically in hepatocytes, and used bisulfite conversion, PCR, and massively parallel sequencing to quantify the concentration of hepatocyte-derived DNA in mixed samples. Healthy donors had, on average, 30 hepatocyte genomes/ml plasma, reflective of basal cell turnover in the liver. We identified elevations of hepatocyte cfDNA in patients shortly after liver transplantation, during acute rejection of an established liver transplant, and also in healthy individuals after partial hepatectomy. Furthermore, patients with sepsis had high levels of hepatocyte cfDNA, which correlated with levels of liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Duchenne muscular dystrophy patients, in which elevated AST and ALT derive from damaged muscle rather than liver, did not have elevated hepatocyte cfDNA. We conclude that measurements of hepatocyte-derived cfDNA can provide specific and sensitive information on hepatocyte death, for monitoring human liver dynamics, disease, and toxicity.

Pathogenesis of NASH: the Impact of Multiple Pathways

Abstract: Advancing our understanding of the mechanisms that underlie NASH pathogenesis. Recent findings on NASH pathogenesis have expanded our understanding of its complexity including (1) there are multiple parallel hits that lead to NASH; (2) the microbiota play an important role in pathogenesis, with bacterial species recently shown to accurately differentiate between NAFL and NASH patients; (3) the main drivers of liver cell injury are lipotoxicity caused by free fatty acids (FFAs) and their derivatives combined with mitochondrial dysfunction; (4) decreased endoplasmic reticulum (ER) efficiency with increased demand for protein synthesis/folding/repair results in ER stress, protracted unfolded protein response, and apoptosis; (5) upregulated proteins involved in multiple pathways including JNK, CHOP, PERK, BH3-only proteins, and caspases result in mitochondrial dysfunction and apoptosis; and (6) subtypes of NASH in which these pathophysiological pathways vary may require patient subtype identification to choose effective therapy. Recent pathogenesis studies may lead to important therapeutic advances, already seen in patients treated with ACC, ASK1 and SCD1 inhibitors, and FXR agonists. Further, advancing our understanding of mechanisms underlying NASH pathogenesis and the complex interplay between them will be crucial for developing effective therapies.

Gut–liver on a chip toward an in vitro model of hepatic steatosis

Abstract: Hepatic steatosis is a process of abnormal lipid deposition within the liver cells, often caused by excessive alcohol uptake or obesity A conventional in vitro model for hepatic steatosis uses a liver cell culture, treated with fatty acids and measures accumulation of lipids within the cells This model does not recapitulate the complex process of absorption and metabolism of digestive lipids Here, we introduce a gut-liver chip, which mimics the gut absorption and hepatic metabolism in a microfluidic chip Absorption of fatty acids through gut layer and subsequent deposition within liver cells was demonstrated Tumor necrosis factor-α, butyrate, and α-lipoic acid were chosen as model molecules that can affect hepatic steatosis via different mechanisms, and their effects were evaluated Our results suggest that the gut-liver chip can mimic the absorption and accumulation of fatty acids in the gut and the liver

A three-dimensional in vitro HepG2 cells liver spheroid model for genotoxicity studies.

Abstract: The liver’s role in metabolism of chemicals makes it an appropriate tissue for toxicity testing. Current testing protocols, such as animal testing and two-dimensional liver cell systems, offer limited resemblance to in vivo liver cell behaviour, in terms of gene expression profiles and metabolic competence; thus, they do not always accurately predict human toxicology. In vitro three-dimensional liver cell models offer an attractive alternative. This study reports on the development of a 3D liver model, using HepG2 cells, by a hanging-drop technique, with a focus on evaluating spheroid growth characteristics and suitability for genotoxicity testing. The cytokinesis-blocked micronucleus assay protocol was adapted to enable micronucleus (MN) detection in the 3D spheroid models. This involved evaluating the difference between hanging vs non-hanging drop positions for dosing of the test agents and comparison of automated Metafer scoring with manual scoring for MN detection in HepG2 spheroids. The initial seeding density, used for all experiments, was 5000 cells/20 μl drop hanging spheroids, harvested on day 4, with >75% cell viability. Albumin secretion (7.8 g/l) and both CYP1A1 and CYP1A2 gene expression were highest in the 3D environment at day 4. Exposure to metabolically activated genotoxicants for 24 h resulted in a 6-fold increase in CYP1A1 enzyme activity (3 μM B[a]P) and a 30-fold increase in CYP1A2 enzyme activity (5 μM PhIP) in 3D hanging spheroids. MN inductions in response to B[a]P or PhIP were 2-fold and 3-fold, respectively, and were greater in 3D hanging spheroids than in 2D format, showing that hanging spheroids are more sensitive to genotoxic agents. HepG2 hanging-drop spheroids are an exciting new alternative system for genotoxicity studies, due to their improved structural and physiological properties, relative to 2D cultures.

Progress in non-invasive detection of liver fibrosis.

Abstract: Liver fibrosis is an important pathological precondition for hepatocellular carcinoma. The degree of hepatic fibrosis is positively correlated with liver cancer. Liver fibrosis is a series of pathological and physiological process related to liver cell necrosis and degeneration after chronic liver injury, which finally leads to extracellular matrix and collagen deposition. The early detection and precise staging of fibrosis and cirrhosis are very important for early diagnosis and timely initiation of appropriate therapeutic regimens. The risk of severe liver fibrosis finally progressing to liver carcinoma is >50%. It is known that biopsy is the gold standard for the diagnosis and staging of liver fibrosis. However, this method has some limitations, such as the potential for pain, sampling variability, and low patient acceptance. Furthermore, the necessity of obtaining a tissue diagnosis of liver fibrosis still remains controversial. An increasing number of reliable non-invasive approaches are now available that are widely applied in clinical practice, mostly in cases of viral hepatitis, resulting in a significantly decreased need for liver biopsy. In fact, the non-invasive detection and evaluation of liver cirrhosis now has good accuracy due to current serum markers, ultrasound imaging, and magnetic resonance imaging quantification techniques. A prominent advantage of the non-invasive detection and assessment of liver fibrosis is that liver fibrosis can be monitored repeatedly and easily in the same patient. Serum biomarkers have the advantages of high applicability (>95%) and good reproducibility. However, their results can be influenced by different patient conditions because none of these markers are liver-specific. The most promising techniques appear to be transient elastography and magnetic resonance elastography because they provide reliable results for the detection of fibrosis in the advanced stages, and future developments promise to increase the reliability and accuracy of the staging of hepatic fibrosis. This article aims to describe the recent progress in the development of non-invasive assessment methods for the staging of liver fibrosis, with a special emphasize on computer-aided quantitative and deep learning methods.

β‐Caryophyllene, the major constituent of copaiba oil, reduces systemic inflammation and oxidative stress in arthritic rats

Abstract: The current study investigated the action of β-caryophyllene, the major constituent of copaiba oil, on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant-induced arthritis, a model for rheumatoid arthritis. This study also compared the actions of β-caryophyllene with those previously reported for copaiba oil on arthritic rats. For this purpose, Holtzman healthy and arthritic rats received 215 and 430 mg·kg-1 β-caryophyllene orally once a day during 18 days. Both doses of β-caryophyllene reduced the adjuvant-induced paw edema, swollen of lymph nodes, and number of circulating and articular leukocytes. β-Caryophyllene, at the dose of 430 mg·kg -1 , abolished the increases of protein carbonyl groups and myeloperoxidase activity in the liver and plasma of arthritic rats and, at both doses, it restored the increased levels of reactive oxygen species and reduced glutathione in the arthritic liver. These beneficial actions were of the same extension as those of copaiba oil ( Copaifera reticulata) and, therefore, β-caryophyllene is possibly responsible for the anti-inflammatory and antioxidant actions of the oil. Hepatic gluconeogenesis was 40% lower in arthritic rats, which also presented a reduced number of hepatocytes per liver area (-23%) associated with increased hepatocyte area (+18%) and liver weight (+50%). None of these hepatic alterations were improved by β-caryophyllene, but not even by ibuprofen. However, unlike copaiba oil, β-caryophyllene did not modify the hepatic morphology and metabolism of healthy rats. These results reveal that β-caryophyllene improves the systemic inflammation and oxidative status of arthritic rats and, in addition, it was not associated with hepatotoxicity.

miR‑498 inhibits the growth and metastasis of liver cancer by targeting ZEB2

Abstract: MicroRNAs (miRNAs) play critical roles in the growth, metastasis and therapeutic resistance of liver cancer. Accumulating evidence suggests that miR-498 is aberrantly expressed in several human malignancies. However, the role and underlying mechanism of miR-498 in liver cancer remain unclear. In the present study, we investigated the potential roles and clinical value of miR-498 in liver cancer. We found that the miR-498 expression level was significantly lower in liver cancer patient tissues than that in healthy control tissues. The expression of miR-498 was also decreased in liver cancer cell lines compared to that noted in a normal human normal liver cell line. miR-498 overexpression markedly inhibited liver cancer cell proliferation, migration and invasion. miR-498 overexpression induced cell cycle arrest and apoptosis while it suppressed epithelial-mesenchymal transition (EMT) in liver cancer cells. Bioinformatic analysis and luciferase reporter assay further identified zinc finger E-box binding homeobox 2 (ZEB2) as a novel target of miR-498. Furthermore, ZEB2 knockdown recapitulated the inhibitory effects of miR-498 overexpression in liver cancer cells. ZEB2 overexpression rescued the inhibition of liver cancer cell proliferation, migration, and invasion by miR-498, indicating that ZEB2 acts as a downstream effector of miR-498 in liver cancer cells. Thus, we demonstrated that miR-498 suppresses the growth and metastasis of liver cancer cells, partly at least, by directly targeting ZEB2, suggesting that miR-498 may serve as a potential biomarker for the diagnosis and therapy of liver cancer.

Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device.

Abstract: Liver cell culture models are attractive in both tissue engineering and for development of assays for drug toxicology research. To retain liver specific cell functions, the use of adequate cell typ ...

Liver cell therapy: is this the end of the beginning?

Abstract: The prevalence of liver diseases is increasing globally. Orthotopic liver transplantation is widely used to treat liver disease upon organ failure. The complexity of this procedure and finite numbers of healthy organ donors have prompted research into alternative therapeutic options to treat liver disease. This includes the transplantation of liver cells to promote regeneration. While successful, the routine supply of good quality human liver cells is limited. Therefore, renewable and scalable sources of these cells are sought. Liver progenitor and pluripotent stem cells offer potential cell sources that could be used clinically. This review discusses recent approaches in liver cell transplantation and requirements to improve the process, with the ultimate goal being efficient organ regeneration. We also discuss the potential off-target effects of cell-based therapies, and the advantages and drawbacks of current pre-clinical animal models used to study organ senescence, repopulation and regeneration.

CYP450-mediated mitochondrial ROS production involved in arecoline N -oxide-induced oxidative damage in liver cell lines

Abstract: Background IARC has classified the betel nut as a human environmental carcinogen. Previous studies have found that arecoline (AR) is the major alkaloid present in the saliva of betel quid chewers. Saliva contains a large content of AR which has been further shown to cause mutation of oral mucosa cells, resulting in oral cancer. Whereas, to date, there are only few studies reported the hepatotoxicity associated with arecoline and betel nut chewing. Therefore, the main purpose of this study was to determine the toxic effects of AR and its oxidative metabolite, arecoline N-oxide (ARNO), in normal liver cell lines. Methods The cytotoxic, genotoxic, and mutagenic effects were detected by crystal violet staining, alkaline comet assay, and Salmonella mutagenicity test, respectively. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2-DCFDA assay. Results Our results demonstrated that ARNO exerted higher cytotoxicity, DNA damage, and mutagenicity than its parent compound arecoline in liver cells. Antioxidants, such as N-acetylcysteine, Trolox, and penicillamine, strongly protected liver cells from ARNO-induced DNA damage and ROS production. Furthermore, co-treatment with Mito-TEMPO also effectively blocked ARNO-induced ROS production in liver cells. Besides antioxidants, co-treatment with 1-aminobenzotriazole and methimazole nearly completely suppressed ARNO-induced ROS production in liver cells. Conclusions Our data suggest that arecoline ingested from the habit of chewing betel quid can be primarily oxidized to ARNO, thereby enhancing its toxicity through increased ROS production. Considering the excellent protective effects of both mitochondria-targeted antioxidant and CYP450 inhibitor on ARNO-induced ROS production in liver cells, mitochondria CYP450-mediated metabolism of ARNO may be a key mechanism. Collectively, our results provide novel cellular evidence for the positive connection between habitual betel quid chewing and the risk for liver damage.

LncRNA HOXA11-AS promotes hepatocellular carcinoma progression by repressing miR-214-3p.

Abstract: Accumulating studies supported that lncRNAs played important roles in tumorigenesis. LncRNA HOXA11-AS was a novel lncRNA that has been proved to involved in several tumours. However, the role of HOXA11-AS in the development of hepatocellular carcinoma (HCC) remains to be explained. In our study, we showed that HOXA11-AS expression was up-regulated in the HCC tissues, and the higher expression of HOXA11-AS was associated with the advanced stage in the HCC samples. In addition, we indicated that the expression of HOXA11-AS was up-regulated in HCC cell lines (Hep3B, SMMC-7721, MHCC97-H and BEL-7402) compared with normal liver cell lines (HL-7702). Overexpression of HOXA11-AS promoted HCC proliferation and invasion and induced the epithelial-mesenchymal transition (EMT) and knockdown of HOXA11-AS suppressed the HCC cell proliferation and invasion. However, we showed that miR-214-3p expression was down-regulated in the HCC tissues and cell lines. Ectopic expression of miR-214-3p suppressed HCC cell proliferation and invasion. Furthermore, we indicated that overexpression of HOXA11-AS decreased the miR-214-3p expression and the expression of miR-214-3p was negatively related with the HOXA11-AS expression in HCC samples. Ectopic expression of HOXA11-AS increased HCC proliferation and invasion and induced EMT through inhibiting miR-214-3p expression. These data suggested that HOXA11-AS/miR-214-3p axis was responsible for development of HCC.

Involvement of epithelial-mesenchymal transition in liver fibrosis.

Abstract: Fibrosis of the liver is an inherent wound healing response to chronic liver injury. Regeneration of liver epithelium and restoration of normal liver structure were generally involved in this process. Although the liver has a striking capacity to adapt to damage through tissue repair, excessive accumulation of extracellular matrix during this process often leads to scar tissue formation and subsequent fibrosis. Epithelial to mesenchymal transition (EMT) enables a polarized epithelial cell to undergo multiple changes biochemically and to bear a mesenchymal cell phenotype. EMT plays a critical role in tissue and organ development and embryogenesis. In the liver, it is proposed that epithelial cells can acquire fibroblastic phonotype via EMT and contribute to fibrogenesis. This made EMT a potential target for antifibrotic strategies. Following an original passion, many investigators devote themselves to exploring this mechanism in liver fibrosis. However, as research continues, this hypothesis became highly controversial. The exact contribution of EMT to fibrogenesis was challenged due to the contradictory results from related studies. In this review, we summarized the recent advances regarding EMT in hepatic fibrosis and discussed the potentially involved liver cell types and pathways in order to reach rational and helpful conclusions.

Dynamic imaging of adaptive stress response pathway activation for prediction of drug induced liver injury.

Abstract: Drug-induced liver injury remains a concern during drug treatment and development. There is an urgent need for improved mechanistic understanding and prediction of DILI liabilities using in vitro approaches. We have established and characterized a panel of liver cell models containing mechanism-based fluorescent protein toxicity pathway reporters to quantitatively assess the dynamics of cellular stress response pathway activation at the single cell level using automated live cell imaging. We have systematically evaluated the application of four key adaptive stress pathway reporters for the prediction of DILI liability: SRXN1-GFP (oxidative stress), CHOP-GFP (ER stress/UPR response), p21 (p53-mediated DNA damage-related response) and ICAM1 (NF-κB-mediated inflammatory signaling). 118 FDA-labeled drugs in five human exposure relevant concentrations were evaluated for reporter activation using live cell confocal imaging. Quantitative data analysis revealed activation of single or multiple reporters by most drugs in a concentration and time dependent manner. Hierarchical clustering of time course dynamics and refined single cell analysis allowed the allusion of key events in DILI liability. Concentration response modeling was performed to calculate benchmark concentrations (BMCs). Extracted temporal dynamic parameters and BMCs were used to assess the predictive power of sub-lethal adaptive stress pathway activation. Although cellular adaptive responses were activated by non-DILI and severe-DILI compounds alike, dynamic behavior and lower BMCs of pathway activation were sufficiently distinct between these compound classes. The high-level detailed temporal- and concentration-dependent evaluation of the dynamics of adaptive stress pathway activation adds to the overall understanding and prediction of drug-induced liver liabilities.

MicroRNA expression profiling involved in MC-LR-induced hepatotoxicity using high-throughput sequencing analysis.

Abstract: Microcystin-LR (MC-LR), the most common microcystin (MC) present in water is known to pose a significant threat to human health especially hepatotoxicity. However, the specific molecular mechanisms underlying MC-LR-induced hepatic cellular damage still remain to be determined. MicroRNAs (miRNAs) are known to play key roles in cellular processes including development, cell proliferation and responsiveness to stress. Thus, this study aimed to examine, whether miRNAs were involved in the observed MC-LR-mediated liver damage using miRNA profiling of a human normal liver cell line HL7702 using high-throughput sequencing techniques. Protein phosphatase 2A (PP2A) activity, an established biomarker of microcystin toxicity, was determined 24 hr following treatment with the algal toxin to confirm responsiveness. Data demonstrated that MC-LR significantly inhibited PP2A activity in a concentration-dependent manner with inhibitory concentration (IC50) value of 4.6 μM. Compared with control cells, treatment wi...

GC-MS Analysis, Antioxidant, Antimicrobial and Anticancer Activities of Extracts from Ficus sycomorus Fruits and Leaves

Abstract: Higher plants have been utilized worldwide as characteristic drug a long time to cure human diseases. About 80% of individuals globally use plants as safe sources of medication to cure human diseases through completely different medicine system. One of the available indigenous medicinal plants, Ficus sycomorus belongs to the Moraceae family. The plant contains totally different teams of biologically active compounds that square measure chargeable for the biological activity. Ethanolic and ethyl acetate extracts of leaves of Ficus sycomorus contain higher concentrations of total phenols, flavonoids, tannins, alkaloids and steroids than the fruit extracts. Ethanolic extract in both fruits and leaves gave higher concentrations of phytochemical compounds than the ethyl acetate extracts. Therefore, fruit and leaves extract have antioxidant and antimicrobial activity against gram positive, negative bacteria and fungus. Also, the percentage of Liver cell line (HepG2), Colorectal adenocarcinoma (Caco-2) and Breast cell line (MCF-7) viability was decreased with increasing the concentrations of the ethanolic extract of fruits and leaves of Ficus sycomorus . The high concentrations of ethanolic extract of fruits caused high reduction in the viability of cancer cells, especially in Colorectal adenocarcinoma (Caco-2) cell line. In addition, phytochemical compound screened by GC-MS method. In GC-MS analysis, 12 bioactive phytochemical compounds were identified in fruits and 29 bioactive compounds were detected in leaves extract. These totally different active phytochemicals are found to possess a good vary of activities, which can facilitate within the protection against incurable diseases.

Nuclear miR-122 directly regulates the biogenesis of cell survival oncomiR miR-21 at the posttranscriptional level.

Abstract: Hepatic miR-122 can serve as a pro-apoptotic factor to suppress tumorigenesis. The underlying mechanism, however, remains incompletely understood. Here we present the first evidence that miR-122 promotes hepatocellular carcinoma cell apoptosis through directly silencing the biogenesis of cell survival oncomiR miR-21 at posttranscriptional level. We find that miR-122 is strongly expressed in primary liver cell nucleus but its nuclear localization is markedly decreased in transformed cells particularly in chemoresistant tumor cells. MiRNA profiling and RT-qPCR confirm an inverse correlation between miR-122 and miR-21 in hepatocellular carcinoma tissues/cells, and increasing or decreasing nuclear level of miR-122 respectively reduces or increases miR-21 expression. Mechanistically, nuclear miR-122 suppresses miR-21 maturation via binding to a 19-nt UG-containing recognition element in the basal region of pri-miR-21 and preventing the Drosha-DGCR8 microprocessor's conversion of pri-miR-21 into pre-miR-21. Furthermore, both in vitro and in vivo studies demonstrate that nuclear miR-122 participates in the regulation of HCC cell apoptosis through modulating the miR-21-targeted programmed cell death 4 (PDCD4) signal pathway.

Design and development of vitamin C-encapsulated proliposome with improved in-vitro and ex-vivo antioxidant efficacy.

Abstract: Vitamin C, as an antioxidant additive in pharmaceutical and food products, is susceptible to environmental conditions, and new design strategies are needed to enhance its stability. The aim of this study is to prepare vitamin C proliposome using film deposition on the carrier by applying different factors, and optimise the characteristics of the obtained powder using the design expert® software. The optimised formulation demonstrated acceptable flowability with 20% vitamin C loading. This formulation released about 90% vitamin C within 2 h and showed higher (1.7-fold) in-vitro antioxidant activity. Ex-vivo antioxidant activity was 1.9 and 1.6 times higher in brain and liver cells, respectively. A 27% reduction in malondialdehyde (MDA) level of liver cell was obtained comparing free vitamin C. Therefore, this study results suggest that the vitamin C-encapsulated proliposome powder might be an appropriate carrier for oral drug delivery of vitamin C with better antioxidant efficacy.

Chicken astrovirus as an aetiological agent of runting-stunting syndrome in broiler chickens.

Abstract: Despite descriptions of runting-stunting syndrome (RSS) in broiler chickens dating back over 40 years, the aetiology has not yet been described A novel chicken astrovirus (CkAstV) was isolated in an LMH liver cell line from the intestines of chickens affected with RSS Clinical RSS is characterized by retarded growth and cystic crypt lesions in the small intestine In 1-day-old broiler chickens infected with the CkAstV isolate, virus was only detected in the intestinal epithelial cells during the first few days after infection Notably, the preferred host cells are the crypt epithelial cells following initial replication in the villous epithelial cells, thus implying viral preference for immature intestinal cells Nevertheless, the CkAstV isolate did not induce remarkable pathological changes, despite the presence of the virus in situ Serial chicken-to-chicken passages of the virus induced increased virulence, as displayed by decreased weight gain and the presence of cystic lesions in the small intestine reproducing clinical RSS in chickens The analysis of the full-length genome sequences from the isolated CkAstV and the CkAstV from the bird-to-bird passages showed >99 % similarity The data obtained in this study suggest that the CkAstV isolate is capable of inducing RSS following serial bird-to-bird passages in broilers and is as an aetiological agent of the disease

The Liver Protection Effects of Maltol, a Flavoring Agent, on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Inflammatory Response

Abstract: The purpose of this research was to evaluate whether maltol could protect from hepatic injury induced by carbon tetrachloride (CCl₄) in vivo by inhibition of apoptosis and inflammatory responses. In this work, maltol was administered at a level of 100 mg/kg for 15 days prior to exposure to a single injection of CCl₄ (0.25%, i.p.). The results clearly indicated that the intrapulmonary injection of CCl₄ resulted in a sharp increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities, tumor necrosis factor-α (TNF-α), irreducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and interleukin-1β (IL-1β) levels. Histopathological examination demonstrated severe hepatocyte necrosis and the destruction of architecture in liver lesions. Immunohistochemical staining and western blot analysis suggested an accumulation of iNOS, NF-κB, IL-1β and TNF-α expression. Maltol, when administered to mice for 15 days, can significantly improve these deleterious changes. In addition, TUNEL and Hoechst 33258 staining showed that a liver cell nucleus of a model group diffused uniform fluorescence following CCl₄ injection. Maltol pretreatment groups did not show significant cell nuclear condensation and fragmentation, indicating that maltol inhibited CCl₄-induced cell apoptosis. By evaluating the liver catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) activity, and further using a single agent to evaluate the oxidative stress in CCl₄-induced hepatotoxicity by immunofluorescence staining, maltol dramatically attenuated the reduction levels of hepatic CAT, GSH and SOD, and the over-expression levels of CYP2E1 and HO-1. In the mouse model of CCl₄-induced liver injury, we have demonstrated that the inflammatory responses were inhibited, the serum levels of ALT and AST were reduced, cell apoptosis was suppressed, and liver injury caused by CCl₄ was alleviated by maltol, demonstrating that maltol may be an efficient hepatoprotective agent.

Iron(III)-Tannic Molecular Nanoparticles Enhance Autophagy effect and T 1 MRI Contrast in Liver Cell Lines

Abstract: Herein, a new molecular nanoparticle based on iron(III)-tannic complexes (Fe–TA NPs) is presented. The Fe–TA NPs were simply obtained by mixing the precursors in a buffered solution at room temperature, and they exhibited good physicochemical properties with capability of inducing autophagy in both hepatocellular carcinoma cells (HepG2.2.15) and normal rat hepatocytes (AML12). The Fe–TA NPs were found to induce HepG2.2.15 cell death via autophagic cell death but have no effect on cell viability in AML12 cells. This is possibly due to the much higher uptake of the Fe–TA NPs by the HepG2.2.15 cells via the receptor-mediated endocytosis pathway. As a consequence, enhancement of the T1 MRI contrast was clearly observed in the HepG2.2.15 cells. The results demonstrate that the Fe–TA NPs could provide a new strategy combining diagnostic and therapeutic functions for hepatocellular carcinoma. Additionally, because of their autophagy-inducing properties, they can be applied as autophagy enhancers for prevention and treatment of other diseases.