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1.
Clement Ibi Mboto Angela Davies-Russell Mark Fielder Andrew Paul Jewell 《International Seminars in Surgical Oncology : ISSO》2005,2(1):20
Objectives
Hepatocellular Carcinoma is the commonest form of cancer in The Gambia, and although Hepatitis B and Hepatitis C are known risk factors, accurate baseline data on Hepatitis B and Hepatitis C distribution in the region are limited. Similarly data including information on the involvement of the viruses in HCC remains unknown. The current study was undertaken to estimate the risk of HCC in relation to HCV and HBV in The Gambia.Methods
Thirteen patients with histological proven history of HCC and 39 healthy controls were enrolled in the study. Each subject blood was screened individually for anti-HCV using ORTHO HCV 3.0 ELISA test system (Ortho-Clinical Diagnostics, Inc, U.S.A) and for HBsAg using QUADRATECH CHECK 4-HBs one step generation hepatitis B surface antigen test kit (VEDALAB, France) following the manufacturers instructions.Results
HBsAg and anti-HCV was detected in 38.5 %(5/13) and 7.7% (1/39) of the persons with a history of HCC respectively. HBsAg but not anti-HCV was detected in 12.8% (5/39 of the case control subjects. HBsAg and HCV rates among the HCC patients were higher in men than women. Rates were highest in patients 48 years and above (37.5%; 3/8). No patient was found with anti-HCV and anti-HBV.Conclusion
These results indicate that the involvement of HBV and HCV in HCC in the country is in a ratio of 5:1 and that these two viruses might be independently involved in the pathogenesis of the disease. The study revealed a statistically significant association (p = 0.04) between HBsAg and HCC patients.The results also indicate that up to 50% of HCC cases in the country may be due to non viral factors and calls for further studies in this regard. These findings call for provision of diagnostic facilities for these viruses in hospitals and for their routine screening in blood banks while intervention programmes should be put in place.2.
Sara M. Ø. Solbak Eldar Abdurakhmanov Anni Vedeler U. Helena Danielson 《Virology journal》2017,14(1):236
Background
Direct acting antivirals (DAAs) provide efficient hepatitis C virus (HCV) therapy and clearance for a majority of patients, but are not available or effective for all patients. They risk developing HCV-induced hepatocellular carcinoma (HCC), for which the mechanism remains obscure and therapy is missing. Annexin A2 (AnxA2) has been reported to co-precipitate with the non-structural (NS) HCV proteins NS5B and NS3/NS4A, indicating a role in HCC tumorigenesis and effect on DAA therapy.Methods
Surface plasmon resonance biosensor technology was used to characterize direct interactions between AnxA2 and HCV NS5B, NS3/NS4 and RNA, and the subsequent effects on catalysis and inhibition.Results
No direct interaction between AnxA2 and NS3/NS4A was detected, while AnxA2 formed a slowly dissociating, high affinity (K D?=?30 nM), complex with NS5B, decreasing its catalytic activity and affinity for the allosteric inhibitor filibuvir. The RNA binding of the two proteins was independent and AnxA2 and NS5B interacted with different RNAs in ternary complexes of AnxA2:NS5B:RNA, indicating specific preferences.Conclusions
The complex interplay revealed between NS5B, AnxA2, RNA and filibuvir, suggests that AnxA2 may have an important role for the progression and treatment of HCV infections and the development of HCC, which should be considered also when designing new allosteric inhibitors.3.
Yonghai Lu Jinling Fang Choon Nam Ong Shengsen Chen Ning Li Liang Cui Chong Huang Qinxia Ling Sin Eng Chia Mingquan Chen 《Metabolomics : Official journal of the Metabolomic Society》2017,13(1):6
Introduction
Arachidonic acid (AA)-derived prostaglandins recently have been implicated in pathogenesis of hepatocellular carcinoma (HCC). However, current understanding of omega-6-derived oxylipins that promote this disease remains limited, particularly on oxylipins derived from linoleic acid (LA).Objective
Hepatitis B virus (HBV) infection is a major risk factor for HCC in Asia, we thus quantified AA- and LA-derived oxylipins and the two parent polyunsaturated fatty acids in HBV-related HCC patients to assist in understanding of the molecular pathogenesis of HCC.Methods
Serum samples from 40 HBV-related HCC patients and 23 age-sex matched healthy controls were analyzed using liquid chromatography tandem mass spectrometry.Results
LA, LA-derived oxylipins such as 9-hydroxyoctadecadienoic acid (9-HODE), 13-HODE, 9,10-dihydroxyoctadecenoic acid (9,10-DiHOME), and 12,13-DiHOME, as well as AA-derived oxylipins such as 5,6-dihydroxyeicosatrienoic acid (5,6-DiHETrE), 11,12-DiHETrE, and 14,15-DiHETrE, were significantly elevated in HCC patients compared to healthy controls. Of these, LA, 13-HODE, and 9-HODE showed good potential in differentiating HCC patients from healthy controls (AUC >0.8).Conclusion
The study demonstrated LA- and AA-derived oxylipins via the lipoxygenase and cytochrome P450 pathways appeared to be most involved in the pathogenesis of HBV-related HCC.4.
Objectives
To investigate whether miR-1260b can regulate migration and invasion of hepatocellular carcinoma (HCC) by targeting RGS22.Results
miR-1260b was up-regulated in HCC tissues compared with their corresponding non-cancerous tissues. Over-expression of miR-1260b increased migration and invasion of HepG2 and SMMC-7721 cells associated with HCC. Regulator of G-protein signaling 22 (RGS22) was identified as a directly target of miR-1260b and was inhibited by miR-1260b. Knockdown of RGS22 increased proliferation of HCC cells.Conclusions
The new identified miR-1260b/RGS22 axis provides useful therapeutic methods for treatment of HCC deepening on our understanding of underlying mechanisms of HCC tumorigenesis.5.
Yonghai Lu Jinling Fang Li Zou Liang Cui Xu Liang Seng Gee Lim Yock-Young Dan Choon Nam Ong 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):26
Introduction
Chronic hepatitis B virus (HBV) infection is the main etiologic risk factor for hepatocellular carcinoma (HCC). Early studies indicated that the increase of omega-6-derived oxylipins may be involved in the pathogenesis of HBV-related HCC, yet their changes during the distinct clinical phases of chronic HBV infection remain unclear. To fill this gap, in this study we investigated the omega-6-derived oxylipin profiles in patients with three major clinical stages of chronic HBV infection (chronic hepatitis B, liver cirrhosis, and HCC).Methods
Eighteen omega-6-derived oxylipins were quantified in serum samples of 34 patients with chronic hepatitis B, 46 patients with HBV-related liver cirrhosis, 38 patients with HBV-related HCC, and 50 healthy controls using liquid chromatography tandem mass spectrometry.Results
Seven oxylipins were found to be altered in patients with HBV-related liver diseases, including 9,10-dihydroxyoctadecenoic acid (9,10-DiHOME), 12,13-DiHOME, 14,15-dihydroxyeicosatrienoic acid (14,15-DiHETrE), 13-hydroxyoctadecadienoic acid (13-HODE), 12-hydroxyeicosatetraenoic acid (12-HETE), 11-HETE, and thromboxane B2 (TXB2). Of these, three oxylipins derived from the cytochrome P450 (CYP450) pathways including 9,10-DiHOME, 12,13-DiHOME, and 14,15-DiHETrE were found to be associated with the levels of α-fetoprotein (AFP), a tumor marker. In combination with AFP, age, and gender, a combination of these seven differential oxylipins could significantly enhance the prediction of HBV-related liver diseases, particularly for liver cirrhosis (p?<?0.05).Conclusion
This study for the first time shows the correlations between CYP450-derived oxylipins and the progression of chronic HBV infection, and sheds a new light on the surveillance of HBV-related live diseases using oxylipins.6.
Yong Keun Park Sung Kyu Song Bong-Wan Kim Seung-Keun Park Chul-Woon Chung Hee-Jung Wang 《World journal of surgical oncology》2017,15(1):225
Background
The presence of microvascular invasion (McVI) in hepatocellular carcinoma (HCC) has been proposed as a cause of recurrence and poor survival, although this has not been officially emphasized in staging systems. Thus, we conducted a retrospective study to investigate the prognostic importance of McVI in tumor staging in patients with HCC who underwent hepatic resection.Methods
A retrospective analysis was performed of patients who underwent hepatic resection for HCC at our center from 1994 to 2012. Patients with HCC were classified into four groups based on the presence of McVI and extent of gross vascular invasion (VI).Results
The 5-year overall and recurrence-free survival rates of 676 patients were 63.3 and 42.6%, respectively. There was no difference in tumor recurrence or survival rate between patients with HCC and McVI without gross VI and those with gross VI confined to segmental/sectional branches. Multivariate analysis revealed that the extent of VI based on the presence of McVI and gross VI was independently associated with tumor recurrence and overall survival.Conclusions
McVI was revealed to be an important risk factor similar to gross VI confined to a segmental/sectional branch in patients with HCC who underwent hepatic resection. This finding should be considered when estimating the stage for prognosis.7.
Objectives
To clarify the potential biological function of miR-93 and its related molecular mechanism underlying metastasis in human hepatocellular carcinoma (HCC).Results
miR-93 was significantly up-regulated in HCC tissues and was associated with poor 5-year overall survival in HCC patients. Transwell assays showed that over-expression of miR-93 increased HCC cell migration and invasion in vitro. Programmed cell death 4 (PDCD4) was a target gene of miR-93 and miR-93 could down-regulate the expression of PDCD4 by directly targeting its 3′-UTR. The re-expression of PDCD4 could attenuate the HCC cell invasion and migration induced by miR-93, while the knockdown of PDCD4 would promote HCC cell migration and invasion via the epithelial-mesenchymal transition (EMT) pathway.Conclusions
miR-93 provides new insight into the molecular mechanisms of pathogenesis and progression in HCC and offer a potential therapeutic target for the treatment of HCC patients.8.
Weiling Xu Fangchao Gong Ting Zhang Baorong Chi Jingyu Wang 《Biotechnology letters》2017,39(9):1359-1367
Objectives
To investigate the roles of Dead end 1 (Dnd1) in modulating cancer stem cell-related traits of hepatocellular carcinoma (HCC).Results
Dead end (Dnd1) inhibited spheroid formation, suppressed the expression of stemness-related genes, and increased sensitivity to sorafenib in HCC cells. Mechanistically, Dnd1 could bind to 3′-UTR of LATS2, the key kinase of Hippo pathway, thus elevating LATS2 mRNA stability and its expression, subsequently leading to phosphorylation of YAP and its cytoplasmic retention. As a result, epithelial–mesenchymal transition (EMT) was weakened and therefore the generation of HCC stem cell properties was suppressed.Conclusions
Dnd1 functions as a tumor suppressor by prohibiting CSC-like characteristics via activating Hippo pathway in HCC cells. Dnd1 could thus be a novel therapeutic target for HCC patients.9.
Weiping?Zhu Yiming?Zhao Jiamin?Zhou Xin?Wang Qi?Pan Ning?Zhang Longrong?Wang Miao?Wang Dihua?Zhan Zeyang?Liu Xigan?He Dening?Ma Shuang?Liu Lu?Wang
Background
Monoacylglycerol lipase (MAGL), a critical lipolytic enzyme, has emerged as a key regulator of tumor progression, yet its biological function and clinical significance in hepatocellular carcinoma (HCC) is still unknown.Methods
In this study, we used a tissue microarray containing samples from 170 HCC patients to evaluate the expression of MAGL and its correlation with other clinicopathologic characteristics. In addition, we investigated the regulating effects of MAGL on various HCC lines. Finally, we identified the NF-κB signaling pathway participated in MAGL-mediated epithelial-mesenchymal transition (EMT) using HCC cell lines with different metastatic potentials.Results
The expression of MAGL was significantly higher in HCC tumors than in matched peritumor tissues. Specifically, high MAGL expression was found in tumors with larger tumor size, microvascular invasion, poor differentiation, or advanced TNM stage. In addition, the clinical prognosis for the MAGLhigh group was markedly poorer than that for the MAGLlow group in the 1-, 3-, and 5-year overall survival times and recurrence rates of HCC patients. MAGL expression was an independent prognostic factor for both survival and recurrence after curative resection. Furthermore, the upregulation of MAGL in HCC cells promoted cell growth and invasiveness abilities, and accompanied by EMT. In contrast, downregulation of MAGL obviously inhibited these characteristics. Moreover, further investigations verified that MAGL facilitates HCC progression via NF-κB-mediated EMT process.Conclusions
Our findings demonstrate MAGL could promote HCC progression by the induction of EMT and suggest a potential therapeutic target, as well as a biomarker for prognosis, in patients with HCC.10.
Mengjun Wang Anand Mehta Timothy M Block Jorge Marrero Adrian M Di Bisceglie Karthik Devarajan 《BMC medical genomics》2013,6(Z3):S9
Background
Currently, a surgical approach is the best curative treatment for those with hepatocellular carcinoma (HCC). However, this requires HCC detection and removal of the lesion at an early stage. Unfortunately, most cases of HCC are detected at an advanced stage because of the lack of accurate biomarkers that can be used in the surveillance of those at risk. It is believed that biomarkers that could detect HCC early will play an important role in the successful treatment of HCC.Methods
In this study, we analyzed serum levels of alpha fetoprotein, Golgi protein, fucosylated alpha-1-anti-trypsin, and fucosylated kininogen from 113 patients with cirrhosis and 164 serum samples from patients with cirrhosis plus HCC. We utilized two different methods, namely, stepwise penalized logistic regression (stepPLR) and model-based classification and regression trees (mob), along with the inclusion of clinical and demographic factors such as age and gender, to determine if these improved algorithms could be used to increase the detection of cancer.Results and discussion
The performance of multiple biomarkers was found to be better than that of individual biomarkers. Using several statistical methods, we were able to detect HCC in the background of cirrhosis with an area under the receiver operating characteristic curve of at least 0.95. stepPLR and mob demonstrated better predictive performance relative to logistic regression (LR), penalized LR and classification and regression trees (CART) used in our prior study based on three-fold cross-validation and leave one out cross-validation. In addition, mob provided unparalleled intuitive interpretation of results and potential cut-points for biomarker levels. The inclusion of age and gender improved the overall performance of both methods among all models considered, while the stratified male-only subset provided the best overall performance among all methods and models considered.Conclusions
In addition to multiple biomarkers, the incorporation of age and gender into statistical models significantly improved their predictive performance in the detection of HCC.11.
Adiponectin,biomarkers of inflammation and changes in cardiac autonomic function: Whitehall II study
Background
Biomarkers of inflammation and adiponectin are associated with cardiovascular autonomic neuropathy (CAN) in cross-sectional studies, but prospective data are scarce. This study aimed to assess the associations of biomarkers of subclinical inflammation and adiponectin with subsequent changes in heart rate (HR) and heart rate variability (HRV) in non-diabetic and diabetic individuals.Methods
Data are based on up to 25,050 person-examinations for 8469 study participants of the Whitehall II cohort study. Measures of CAN included HR and several HRV indices. Associations between baseline serum levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-1 receptor antagonist (IL-1Ra) and adiponectin and 5-year changes in HR and six HRV indices were estimated using mixed-effects models adjusting for age, sex, ethnicity, body mass index (BMI), metabolic covariates and medication. A modifying effect of diabetes was tested.Results
Higher levels of IL-1Ra were associated with higher increases in HR. Additional associations with measures of HRV were observed for hsCRP, IL-6 and IL-1Ra, but these associations were explained by BMI and other confounders. Associations between adiponectin, HR and HRV differed depending on diabetes status. Higher adiponectin levels were associated with more pronounced decreases in HR and increases in three measures of HRV reflecting both sympathetic and vagal activity, but these findings were limited to individuals with type 2 diabetes.Conclusions
Higher IL-1Ra levels appeared as novel risk marker for increases in HR. Higher adiponectin levels were associated with a more favourable development of cardiovascular autonomic function in individuals with type 2 diabetes independently of multiple confounders.12.
Blockade of ARHGAP11A reverses malignant progress via inactivating Rac1B in hepatocellular carcinoma
Bin Dai Xuan Zhang Runze Shang Jianlin Wang Xisheng Yang Hong Zhang Qi Liu Desheng Wang Lin Wang Kefeng Dou 《Cell communication and signaling : CCS》2018,16(1):99
Background
The molecular signaling events involving in high malignancy and poor prognosis of hepatocellular carcinoma (HCC) are extremely complicated. Blockade of currently known targets has not yet led to successful clinical outcome. More understanding about the regulatory mechanisms in HCC is necessary for developing new effective therapeutic strategies for HCC patients.Methods
The expression of Rho GTPase-activating protein 11A (ARHGAP11A) was examined in human normal liver and HCC tissues. The correlations between ARHGAP11A expression and clinicopathological stage or prognosis in HCC patients were analyzed. ARHGAP11A was downregulated to determine its role in the proliferation, invasion, migration, epithelial-to-mesenchymal transition (EMT) development, and regulatory signaling of HCC cells in vitro and in vivo.Results
ARHGAP11A exhibited high expression in HCC, and was significantly correlated with clinicopathological stage and prognosis in HCC patients. Moreover, ARHGAP11A facilitated Hep3B and MHCC97-H cell proliferation, invasion, migration and EMT development in vitro. ARHGAP11A knockdown significantly inhibited the in vivo growth and metastasis of HCC cells. Furthermore, ARHGAP11A directly interacted with Rac1B independent of Rho GTPase- activating activity. Rac1B blockade effectively interrupted ARHGAP11A-elicited HCC malignant phenotype. Meanwhile, upregulation of Rac1B reversed ARHGAP11A knockdown mediated mesenchymal-to-epithelial transition (MET) development in HCC cells.Conclusion
ARHGAP11A facilitates malignant progression in HCC patients via ARHGAP11A-Rac1B interaction. The ARHGAP11A/Rac1B signaling could be a potential therapeutic target in the clinical treatment of HCC.13.
Background
The aim of this study was to investigate the effect of a lifestyle intervention in obesity on the soluble form of the activated leukocyte cell adhesion molecule (sALCAM) and its association with metabolic parameters.Methods
Twenty-nine obese subjects selected from the OPTIFAST®52 program. This program consisted into 2 crucial phases: an initial 12-week active weight reduction phase, followed by a 40-week weight maintenance phase. At baseline, after 12 weeks and at the end of the program, fasting glucose and insulin, total cholesterol, LDL-C, HDL-C, triglycerides, adiponectin, leptin, high sensitivity CRP, sALCAM, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and leptin-to-adiponectin-ratio were determined. Oral glucose tolerance test (OGTT) was performed when indicated.Results
At baseline, the serum concentration of sALCAM was increased and correlated positively with HOMA-IR and negatively with age. At the end of the program, sALCAM concentrations decreased significantly. Multivariate analysis showed that sALCAM significantly correlated with age, glucose concentration after 2 h OGTT and the HOMA-IR. A higher decrease of HOMA-IR during the study was observed in subjects with higher concentration of sALCAM at baseline.Conclusions
sALCAM might be a novel biomarker in obesity that correlates and predicts insulin sensitivity improvement and that can be affected by lifestyle intervention.14.
Ryoko Sawamoto Jun Nagano Eiji Kajiwara Junko Sonoda Tetsuya Hiramoto Nobuyuki Sudo 《BioPsychoSocial medicine》2016,10(1):24
Background
The role of psycosocial factors in the disease progression of chronic hepatitis C (CHC) patients remains unclear. The aim of the present study was to prospectively evaluate the prognostic value of behavioral patterns and the quality of life (QOL) of patients with CHC.Methods
Two hundred and forty Japanese CHC patients (mean age 62.4 years) were assessed for behavioral patterns (Stress Inventory), QOL (Functional Assessment of Chronic Illness Therapy-Spiritual), and known prognostic factors at baseline then followed for a maximum of 8 years for disease progression, defined as either the first diagnosis of hepatocellular carcinoma (HCC) or hepatitis-related death.Results
Forty-nine events occurred during the study period (46 newly diagnosed HCC cases, three hepatitis-related deaths). In a Cox proportional hazard model including known prognostic factors and treatment-related factors as time-dependent variables, behavioral patterns associated with inhibition of emotional needs (hazard ratio (HR): 1.35; 95 % confidence interval (CI): 1.02–1.77; p?=?0.036) and QOL, representing emotional wellbeing (HR 0.60; 95 % CI 0.37–0.98; p?=?0.041), were each associated with the risk of disease progression.Conclusion
Psychosocial factors such as behavioral patterns relevant to the inhibition of emotional needs and emotional wellbeing independently affect the clinical course of patients with CHC.15.
D. Jacob C. Deborde M. Lefebvre M. Maucourt A. Moing 《Metabolomics : Official journal of the Metabolomic Society》2017,13(4):36
Introduction
Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.Objectives
The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.Methods
NMRProcFlow was developed to be a graphical and interactive 1D NMR (1H & 13C) spectra processing tool.Results
NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.Conclusion
Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.16.
Background
Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma and infects about 3% world population. Response to interferon therapy depends upon the genotype of the virus and factors associated with the host. Despite a good response to interferon therapy, a considerable number of genotype 3a infected patients remains unalleviated.Results
In total forty-nine patients including twenty-five non-responders (non-SVR) and twenty-four responders (SVR) were recruited. Patients were tested for viral status at different intervals and the isolated RNA was sequenced for the NS5A region in both groups. The comparison of PKRBD of HCV between the SVR and non-SVR patients did not confirm any significant difference in the number of mutations. However, when the sequence downstream to the PKRBD of NS5A was compared, two important statistically significant mutations were observed; at positions 2309 (Ala to Ser) and 2326 (Gly to Ala). These mutations were then analysed for tertiary protein structure and important structural changes were observed. Statistically significant difference was also observed when age groups of patients were compared; younger patients showed better response than the older ones.Conclusions
The region between PKRBD and IRRDR may be important for prediction of response to IFN therapy for genotype 3a. ISDR and PKRBD have not shown any involvement in treatment response. Further functional analyses of these findings can help in understanding the involvement of the NS5A region in interferon treatment of HCV-3a infected patients.17.
Qin-Qin Zhang Xuan An Ying-Hong Liu Shi-Ying Li Qing Zhong Jing Wang Huai-Dong Hu Da-Zhi Zhang Hong Ren Peng Hu 《Virology journal》2011,8(1):72
Background
The effect of antiviral therapy in chronic hepatitis B (CHB) on reducing the risk of long-term complications (LTCs) remains unclear so far. To study whether long-term nucleos(t)ide analogues therapy can reduce the risk of long-term complications.Methods
We searched MEDLINE, EMBASE, OVID, the Cochrane Central Register of Controlled Trials. Relative risks (RRs) of long-term complications with or without treatment were studied. Also subgroup analyses including the status of drug-resistance, HBeAg and pre-existing compensated cirrhosis were done using relative risks of long-term complications either with or without treatment or among nucleos(t)ide analogues treatment groups.Results
Six eligible studies (3644 patients in all) were included. Data showed the incidence of long-term complications in treatment groups was induced by 74%(RR:0.26, 95% CI: 0.15-0.47) compared with no treatment. Whether drug-resistant happened or not during the long-term therapy, the incidence of long-term complications was still significantly induced respectively by 45%(RR: 0.55,95%CI:0.40-0.76) and 78% (RR:0.22, 95%CI: 0.13-0.36). For both different status of HBeAg and pre-existing compensated cirrhosis, there was significant lower incidence of long-term complications in treatment groups compared with no treatment, too. Moreover, among the NA treatment groups, patients with drug-resistance had 2.64 times (RR:2.64, 95%CI: 1.58-4.41) higher chance of developing to long-term complications, and patients with pre-existing compensated cirrhosis also had 3.07 times (RR:3.07, 95%CI: 1.04-9.11) higher chance of developing to long-term complications.Conclusions
Long-term nucleos(t)ide analogue therapy for adults with CHB prevents or delays the development of long-term complications including decompensated cirrhosis, CHB-related death or CHB-related HCC in patients with CHB. The patients who need take antiviral drugs should receive the antiviral therapy as soon as possible.18.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.19.
Maoyun Fei Jianming Guan Tao Xue Lianjin Qin Chengwu Tang Ge Cui Yao Wang Hui Gong Wenming Feng 《Cellular & molecular biology letters》2018,23(1):46
Background
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. The 5-year survival rate remains low despite considerable research into treatments of HCC, including surgery, radiotherapy and chemotherapy. Many mechanisms within HCC still require investigation, including the influence of hypoxia, which has a crucial role in many cancers and is associated with metastasis. Hypoxia inducible factor-1α (HIF-1α) is known to regulate the expression of many chemokines, including interleukin-8 (IL-8), which is associated with tumor metastasis. Although many studies have reported that HIF-1α is associated with HCC migration and invasion, the underlying mechanisms remain unknown.Methods
The expression level of HIF-1α was determined in HCC cells. The correlation of IL-8 and HIF-1α expressions was assessed via knockdown of HIF-1α. HCC cells were also used to assess the influence of HIF-1α on HCC cell migration and invasion. LY294002, an inhibitor of the Akt pathway, was used to confirm the associated signaling pathways.Results
We observed a significant attenuation of cell migration and invasion after silencing of HIF-1α. Exogenously expressing IL-8 restored migration and invasion. Akt was found to be involved in this process.Conclusion
Hypoxia promotes HCC cell migration and invasion through the HIF-1α–IL-8–Akt axis.20.
J. C. Martínez-Ávila A. García Bartolomé I. García I. Dapía Hoi Y. Tong L. Díaz P. Guerra J. Frías A. J. Carcás Sansuan A. M. Borobia 《Metabolomics : Official journal of the Metabolomic Society》2018,14(5):70