2017

Permanent URI for this collectionhttps://hdl.handle.net/1807/75478

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Evaluation of Therapeutic Effect of Rice Husk Silica Combined with Platelets Derived Growth Factor in Hepatic Veno- Occlusive Disease
(Canadian Science Publishing, 2017-12-04) AL Adham, Eithar K; Hassan, Amal I; Hazem, M. M.; Shebl, Ahmed
Veno- occlusive disease is an important pattern of hepatotoxicity associated with antineoplastic drugs. The study aimed to investigate the possible therapeutic impact of rice husk silica (RHS) nanoparticles combined with a platelet-derived growth factor (PDGF) on the Veno-occlusive disease in liver (VOD) elicited by dactinomycin (DAC) in rats. Forty-eight male Sprague-Dawely rats were classified into six groups, 8 rats each. The first group served as control, the second, animals were infused by intraperitoneal injection with DAC (0.015 mg/kg; 1-3 days IP). The third group, rats were injected IP with DAC and then at 24 h followed the last dose of DAC received nano RHS incorporated with PDGF twice a week for four weeks. The fourth group, normal animals were injected with RHS. The fifth group normal rats were received with PDGF, and the sixth group normal rats were received nano RHS incorporated with PDGF. The results of this work showed that administration of nano RHS joined with PDGF significantly reversed the oxidative stress effects of DAC that was evidenced by decreasing in liver function. It could be concluded that the nano RHS combined with PDGF is useful in preventing of oxidative stress and hepatic Veno-occlusive induced by receiving chemotherapy (DAC).
The devastating effect of exposure to high irradiation dose on liver and the performance of synthesized nano-HAp in relieve the associated symptoms in rats
(Canadian Science Publishing, 2017-10-31) Gheriany, Eman Ismail; Awwad, Sameh A.
Ionizing radiation is one of the environmental factors that may contribute to liver dysfunction by a mechanism involving oxidative stress. The present investigation was undertaken to study the possible therapeutic effect of nano-HAp on whole body gamma irradiation induced hepatotoxicity in rats. The study consisted of three groups of 10 rats each. Group 1 (control), whereas group 2 received a single dose of γ-radiation (10Gy). The animals in groups 3 was treated with nano-HAp (100 mg/kg b.w.) once / week for three weeks starting in the next day of γ radiation. Gamma-irradiation of rats caused DNA fragmentation. It also resulted in a significant decrease in hepatic function (paraoxonase 1, gamma glutamyl, ALT AST. Pro-inflammatory factors such as IL-2, IL-6, TNF-α, IFN-γ in tissue showed a significant increase as compared to control. Also, gamma irradiation of animals significantly decreased the activity of superoxide dismutase and glutathione oxidase as well as elevated the lipid peroxidation in liver. These effects were accompanied by a severe histopathological alteration in hepatocytes. The present results revealed that nano- HAp may have a therapeutic effect against gamma irradiation-induced liver dysfunction by antagonizing the free radicals generation and enhancement of the antioxidant defense mechanisms.
Drosophila hep pathway mediates Lrrk2-induced neurodegeneration.
(Canadian Science Publishing, 2017-12-12) Yang, Dejun; Thomas, Joseph M; Li, Tianxia; Lee, Youngseok; Liu, Zhaohui; Smith, Wanli
Although the pathogenesis of Parkinsonâ s disease (PD) remains unclear, mutations in leucine-rich repeat kinase 2 (Lrrk2) are among the major causes of familial PD. Most of these mutations disrupt Lrrk2 kinase and/or GTPase domain function, resulting in neuronal degeneration. However, the signal pathways underlying Lrrk2-induced neuronal degeneration are not fully understood. There is an expanding body of evidence that suggests a link between Lrrk2 function and MAP kinase (MAPK) cascades. To further investigate this link in vivo, genetic RNAi screens of the MAPK pathways were performed in a Drosophila model to identify genetic modifier(s) that can suppress G2019S-Lrrk2-induced PD-like phenotypes. The results revealed that the knockdown of hemipterous (hep, or JNKK) increased fly survival time, improved locomotor function and reduced loss of dopaminergic neurons in G2019S-Lrrk2 transgenic flies. Expression of the dominant-negative allele of JNK (JNK-DN), a kinase that is downstream of hep in G2019S-Lrrk2 transgenic flies, elicited a similar effect. Moreover, treatment with the JNK inhibitor SP600125 partially reversed the G2019S-Lrrk2-induced loss of dopaminergic neurons. These results indicate that the hep pathway plays an important role in Lrrk2-linked Parkinsonism in flies. These studies provide new insights into the molecular mechanisms underlying Lrrk2-linked PD pathogenesis and aid in identifying potential therapeutic targets.
Identification of Nuclear Localization Signals in the Human Homeoprotein, MSX1
(Canadian Science Publishing, 2017-11-06) Shibata, Akio; Machida, Junichiro; Yamaguchi, Seishi; Kimura, Masashi; Tatematsu, Tadashi; Miyachi, Hitoshi; Nakayama, Atsuo; Shimozato, Kazuo; Tokita, Yoshihito
MSX1 is one of the homeoproteins with the homeodomain (HD) sequence, which regulates proliferation and differentiation of mesenchymal cells. In this study, we investigated the nuclear localization signal (NLS) in the MSX1 HD by deletion and amino acid substitution analyses. The web-based tool NLStradamus predicted two putative basic motifs in the N- and C-termini of the MSX1 HD. Green fluorescent protein (GFP) chimera studies revealed that NLS1 (161RKHKTNRKPR170) and NLS2 (216NRRAKAKR223) were independently insufficient for robust nuclear localization. However, they can work cooperatively to promote nuclear localization of MSX1, as was shown by the two tandem NLS motifs partially restoring functional NLS, leading to a significant nuclear accumulation of the GFP chimera. These results demonstrate a unique NLS motif in MSX1, which consists of an essential single core motif in helix-I, with weak potency, and an auxiliary subdomain in helix-III, which alone does not have nuclear localization potency. Additionally, other peptide sequences, other than predicted two motifs in the spacer, may be necessary for complete nuclear localization in MSX1 HD.
Camel whey protein protects lymphocytes from apoptosis via the PI3K/AKT, NF-κB, ATF-3 and HSP-70 signaling pathways in heat-stressed male mice
(Canadian Science Publishing, 2017-11-15) Badr, Gamal; Ramadan, Nancy K; Abdel-Tawab, Hanem S; Ahmed, Samia F; Mahmoud, Mohamed H
Heat stress (HS) is an environmental factor that depresses the immune systems mediating dysfunctional immune cells. Camel whey protein (CWP) can scavenge free radicals and enhance immunity. The present study investigated the impact of dietary supplementation with CWP on immune dysfunction induced by exposure to HS. Male mice (n = 45) were divided into three groups: control group; HS group; and HS mice that were orally administered CWP (HS+CWP group). The HS group exhibited elevated levels of reactive oxygen species (ROS) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) as well as a significant reduction in the IL-2 and IL-4 levels. Exposure to HS resulted in impaired AKT and IκB-α phosphorylation; increased ATF-3 and HSP70 expression; and aberrant distribution of CD3+ T cells and CD20+ B cells in the thymus and spleen. Interestingly, HS mice treated with CWP presented significantly restored levels of ROS and pro-inflammatory cytokines near the levels observed in control mice. Furthermore, supplementation of HS mice with CWP enhanced the phosphorylation of AKT and IκB-α; attenuated the expression of ATF-3, HSP70 and HSP90; and improved T and B cell distributions in the thymus and spleen. Our findings reveal a potential immunomodulatory effect of CWP in attenuating immune dysfunction induced by exposure to thermal stress.
The Avian Embryo as a Model for Fetal Alcohol Spectrum Disorders
(Canadian Science Publishing, 2017-09-25) Smith, Susan M.; Flentke, George R.
Prenatal alcohol exposure (PAE) remains a leading preventable cause of structural birth defects and permanent neurodevelopmental disability. The chick (Gallus gallus domesticus) is a powerful embryological research model and was possibly the first (Fere, 1895) in which alcohol’s teratogenicity was demonstrated. Pharmacologically relevant alcohol exposures in the range of 20-70 mM (20-80 mg/egg) disrupt chick embryo growth, morphogenesis, and behavior, and the resulting phenotypes strongly parallel those of mammalian models. The avian embryo’s direct accessibility has enabled novel insights into alcohol’s teratogenic mechanisms. These include the contribution of IGF1 signaling to growth suppression, the altered flow dynamics that reshape valvuloseptal morphogenesis and mediate its cardiac teratogenicity, and the suppression of Wnt and Shh signals to disrupt neural crest migration, expansion, and survival and underlie its characteristic craniofacial deficits. The genetic diversity within commercial avian strains enabled identification of unique loci, such as ribosome biogenesis, that modify vulnerability to alcohol. This venerable research model is equally relevant for the future, as the application of technological advances including CRISPR, optogenetics, and biophotonics to the embryo’s ready accessibility creates a unique model in which investigators can manipulate and monitor the embryo in real-time to investigate alcohol’s actions upon cell fate.
Thiamin deficiency on fetal brain development with and without prenatal alcohol exposure
(Canadian Science Publishing, 2017-08-29) Kloss, Olena; Eskin, Michael; Suh, Miyoung
Adequate thiamin levels are crucial for optimal health, through maintenance of homeostasis and viability of metabolic enzymes, which require thiamine as a co-factor. Thiamin deficiency occurs during pregnancy when dietary intake is inadequate or excessive alcohol is consumed. Thiamin deficiency leads to brain dysfunction due to its involvement in synthesis of myelin and neurotransmitters (eg. acetylcholine, Îł-aminobutyric acid, glutamate), and increases oxidative stress by decreasing the production of reducing agents. The deficiency also leads to neural membrane dysfunction since thiamin is the structural of component of mitochondrial and synaptosomal membranes. Similarly, alcohol exposure in-utero leads to fetal brain dysfunction, resulting in negative effects such as Fetal Alcohol Spectrum Disorders (FASD). The outcomes of thiamin deficiency and prenatal alcohol exposure could generate negative effects synergistically on fetal development, however this area of research is understudied. This review summarizes the evidence of the potential role of thiamin deficiency in fetal brain development with and without prenatal alcohol exposure. Such evidence may influence the development of new nutrition strategies for preventing or mitigating the symptoms of FASD.
Global Prevalence of Alcohol Use and Binge Drinking During Pregnancy and Fetal Alcohol Spectrum Disorder
(Canadian Science Publishing, 2017-08-18) Popova, Svetlana; Lange, Shannon; Probst, Charlotte; Gmel, Gerrit; Rehm, Jürgen
Alcohol use during pregnancy is an established cause of Fetal Alcohol Spectrum Disorder (FASD), with heavy drinking during pregnancy being explicitly linked to Fetal Alcohol Syndrome (FAS). The current paper presents recent estimates of the prevalence of: i) any amount of alcohol use during pregnancy, ii) one or more binge drinking episode(s) (four or more standard drinks on a single occasion) during pregnancy, iii) FAS, and iv) FASD among the general population globally and by World Health Organization region. It is apparent, based on the presented estimates, that alcohol use and binge drinking occur frequently among pregnant women in many countries and as a result, FASD is a prevalent alcohol-related developmental disability. Urgent action is required around the globe to eliminate prenatal alcohol exposure and prevent future children, adolescents and adults from having FASD.
Age-Related Differences in Neuropsychological Assessment of Fetal Alcohol Spectrum Disorder: A Cross-sectional Study
(Canadian Science Publishing, 2017-08-03) Taylor, Nicole; Enns, Leah
This cross-sectional study examined six key areas of neuropsychological functioning (cognitive, academic, attention, executive function, adaptive skills) comparing adolescents and school-age children with prenatal alcohol exposure (PAE). The aims were: (1) to examine which neuropsychological measures were predictive of an FASD diagnosis in adolescents and school-age children with PAE, and (2) to compare the neuropsychological performance of adolescents and children diagnosed with FASD. Hierarchical logistic regressions determined that the Full-Scale IQ, Verbal Comprehension and Perceptual Reasoning indices, basic reading and math skills, adaptive functioning at school, and components of executive functioning (dependent on age) improved the probability of an accurate FASD diagnosis in both groups: 9.1% to 19.2% for adolescence and 10.9% to 19.4% for school-age (61.5%-80.9% correct classifications overall). For the age comparison analyses (ANOVAs/MANOVAs), a significant difference was observed in the cognitive domain, as well as with basic math skills (trend) in the FASD diagnosed sample, with lower scores observed for adolescents across these measures. These findings provide further evidence for age differences in neuropsychological assessment as well as increased neuropsychological difficulties in adolescence compared to childhood with FASD. Longitudinal studies will be needed in order to make further inferences about developmental changes in neuropsychological functioning in FASD.
FASD: Folic acid and Formic Acid - An unholy alliance in the alcohol abusing mother
(Canadian Science Publishing, 2017-08-03) Kapur, Bhushan M; Baber, Marta
Alcohol consumption during pregnancy remains a significant cause of preventable birth defects and developmental disabilities, however, the mechanism of toxicity remains unclear. Methanol is present as a congener in many alcoholic beverages and is formed endogenously. Since ethanol is preferentially metabolized over methanol, it has been found in the sera and CSF of alcoholics. Toxicity resulting from methanol has been attributed to formic acid. Formic acid is present in significantly higher quantities in biofluids of alcoholic patients. These higher levels can be cytotoxic and cause neuronal cell death. However, the adverse effects can be mitigated by adequate levels of hepatic folic acid, since formic acid elimination depends on folic acid. During pregnancy, folate concentrations are at least two-fold higher in cord blood then in maternal blood due to increased folate requirements. The reverse has been demonstrated in alcohol abusing pregnancies, suggesting downregulation of folate transporters and low fetal folate levels. Moreover, formic acid can cross the placenta and its adverse effects can be mitigated by folic acid. Thus, the combination of low fetal folate levels and presence of formic acid form a potent cytotoxic combination that may play a significant role in the etiology of fetal alcohol spectrum disorder.
Preimplantation alcohol exposure and developmental programming of FASD: An epigenetic perspective.
(Canadian Science Publishing, 2017-10-26) Legault, Lisa-Marie; Bertrand-Lehouillier, Virginie; McGraw, Serge
Alcohol exposure during in utero development can permanently change the developmental programming of physiological responses, thereby increasing the risk of childhood neurological illnesses and later adverse health outcomes associated with fetal alcohol spectrum disorders (FASD). There is an increasing body of evidence indicating that alcohol exposure during gestation triggers lasting epigenetic alterations in offspring long after the initial insult; together, these studies support the role of epigenetics in FASD etiology. However, we still have little information about how ethanol interferes with the fundamental epigenetic reprogramming wave (e.g., erasure and re-establishment of DNA methylation marks) that characterizes preimplantation embryo development. This article will review key epigenetic processes occurring during preimplantation development and especially focus on the current knowledge regarding how a prenatal alcohol exposure during this period could affect the developmental programming of the early stage preimplantation embryo. We will also outline current limitations of studies examining the in vivo and in vitro effects of alcohol exposure on embryos as well as underline the next critical steps to be taken if we want to better understand the implicated mechanisms in order to strengthen the translational potential for non-invasive epigenetic diagnosis markers and the treatment of newborns that have higher risks of developing FASD.
Diving into the world of alcohol teratogenesis: A review of zebrafish models of fetal alcohol spectrum disorders
(Canadian Science Publishing, 2017-07-26) Fernandes, Yohaan; Buckley, Desirè M.; Eberhart, Johann K.
Fetal alcohol spectrum disorders (FASD) refer to the entire suite of deleterious outcomes resulting from embryonic alcohol exposure. Along with other reviews in this edition, we provide insight into how animal models, specifically the zebrafish; have informed our understanding of FASD. We first provide a brief introduction to FASD. We discuss the zebrafish as a model organism and its strengths for alcohol research. We detail how zebrafish has been used to model some of the major defects present in FASD. These include behavioral defects, such as social behavior as well as learning and memory, and structural defects, disrupting organs such as the brain, sensory organs, heart and craniofacial skeleton. We provide insights into how zebrafish research has aided in our understanding of the mechanisms of ethanol teratogenesis. We end by providing some relatively recent advances that zebrafish has provided in characterizing gene-ethanol interactions that may underlie FASD.
Prevalence of Externalizing Disorders and Autism Spectrum Disorder among Children with Fetal Alcohol Spectrum Disorder: Systematic Review and Meta-analysis
(Canadian Science Publishing, 2017-04-25) Lange, Shannon; Rehm, Jürgen; Anagnostou, Evdokia; Popova, Svetlana
Due to their central nervous system impairments, children with Fetal Alcohol Spectrum Disorder (FASD) commonly exhibit externalizing behaviours such as hyperactivity, impulsivity, and/or delinquency. The purpose of the current study was to estimate the prevalence of neurodevelopmental disorders with prominent externalizing behaviours, namely Attention-Deficit Hyperactivity Disorder (ADHD), Conduct Disorder (CD), Oppositional Defiant Disorder (ODD), as well as Autism Spectrum Disorder (ASD) among children with FASD. A comprehensive systematic literature search was performed, followed by disorder-specific random-effects meta-analyses. Of the disorders investigated, ADHD was found to be the most common co-morbid disorder among children with FASD (52.9%), followed by ODD (12.9%), CD (7.0%), and ASD (2.6%). When compared to the general population of the United States, these rates are notably higher: 15-times higher for ADHD, two-times higher for ASD, three-times higher for CD, and five-times higher for ODD. The results call attention to the need for identifying a distinct neurodevelopmental profile to aid in the accurate identification of children with FASD and the discrimination of FASD from certain idiopathic neurodevelopmental disorders.
The role of Folic acid and Selenium against oxidative ethanol damage in early life programming: a review
(Canadian Science Publishing, 2017-08-03) Ojeda Murillo, Mª Luisa; Nogales Bueno, Fatima; Murillo Taravillo, Mª Luisa; Carreras Sánchez, Olimpia
Several disorders in children, called Fetal Alcohol Spectrum Disorders (FASD), occur as result of alcohol consumption during pregnancy and lactation. They appear, at least in part, to be related to the oxidative stress that this drug generates. Ethanol metabolism generates reactive oxygen species and causes a depletion of the antioxidant molecule glutathione (GSH) leading to oxidative stress and lipid and protein damage which are related to growth retardation and neurotoxicity, increasing the incidence of FASD. Furthermore, prenatal and postnatal ethanol exposure in dams, as well as increasing oxidation in offspring, causes malnutrition of several micronutrients such as the antioxidant Folic acid and Selenium (Se), affecting their metabolism and body distribution. Despite alcohol abstinence being the only way to prevent FASD, it is possible to reduce its harmful effects with a maternal dietary antioxidant therapy. In this review Folic acid and Se have been chosen to be analyzed as antioxidant intervention systems related to FASD since, like ethanol, they act on the methionine metabolism cycle, being related to the endogenous antioxidants glutathione (GSH) and glutathione peroxidase. Moreover, several birth defects are related with a poor folate and Se status.
Lamin A/C mutation associated with lipodystrophy influences adipogenic differentiation of stem cells through interaction with Notch signaling
(Canadian Science Publishing, 2017-10-10) Perepelina, Ksenia; Dmitrieva, Renata I; Ignatieva, Elena; Borodkina, Aleksandra; Kostareva, Anna; Malashicheva, Anna
Lamin A/C is involved in many cellular functions due to its ability to bind chromatin and transcription factors and affect their properties. Mutations of LMNA gene encoding lamin A/C affect differentiation capacity of stem cells. However, signaling pathways involved in interaction with lamins in cellular differentiation remain unclear. Lipodystrophy associated with LMNA mutation R482L causes loss of fat tissue. In this study we investigated the role of LMNA mutation R482L in modulating Notch signaling activity in adipogenic differentiation of mesenchymal stem cells. Notch was activated using lentiviral Notch intracellular domain. Activation of Notch was estimated by expression of Notch-responsive genes by qPCR and by activation of luciferase CSL-reporter construct. Effect of LMNA mutation on Notch activation and adipogenic differentiation was analyzed in cells bearing lentiviral LMNA WT or LMNA R482L. We show that LMNA R482L contributes to down regulation of Notch activation in undifferentiated and differentiated cells and decreases adipogenic differentiation, when Notch is activated. Thus, lamin A/C interacts with Notch signaling thereby influencing cellular differentiation and point mutation in LMNA could halt this interaction.
MMS19 localizes to mitochondria and protects the mitochondrial genome from oxidative damage
(Canadian Science Publishing, 2017-08-14) Wu, Rui; Tan, Qunsong; Niu, Kaifeng; Zhu, Yuqi; Wei, Di; Zhao, Yongliang; Fang, Hongbo
MMS19 localizes to cytoplasmic and nuclear compartments involving in transcription and nucleotide excision repair (NER). However, whether or not MMS19 localizes to mitochondria where it plays a role in maintaining mitochondrial genome stability remains elusive. In this study, we provide the first evidence that MMS19 is localized in the inner membrane of mitochondria and participates in mtDNA oxidative damage repair. MMS19 knockdown led to mitochondrial dysfunctions including decreased mtDNA copy number, diminished mtDNA repair capacity and elevated level of mtDNA common deletion after oxidative stress. Immunoprecipitation-mass spectrometry analysis identified that MMS19 interacts with ANT2, a mitochondrial ATP metabolism-associated protein. ANT2 knockdown also resulted in a decreased mtDNA repair capacity post oxidative damage. Our findings suggest that MMS19 plays an essential role in maintaining mitochondrial genome stability.
Cardiac actin changes in the actomyosin interface have different effects on myosin duty ratio
(Canadian Science Publishing, 2017-09-25) Liu, Haidun; Henein, Mary Evelyn; Anillo, Maria; Dawson, John F.
Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disease (CD) that commonly causes an increased size of cardiomyocytes in the left ventricle. The proteins myosin and actin interact in the myocardium to produce contraction through the actomyosin ATPase cycle. The duty ratio (r) of myosin is the proportion of the actomyosin ATPase cycle that myosin is bound to actin and does work. A common hypothesis is that HCM mutations increase contraction in cardiac sarcomeres; however, the available data is not clear on this connection. Based on previous work with human Îą-cardiac actin (ACTC), we hypothesize that HCM-linked ACTC variants with alterations near the myosin binding site have an increased r, producing more force. Myosin duty ratios using human ACTC variant proteins were calculated with myosin ATPase activity and in vitro motility data. We found no consistent changes in the duty ratio of the ACTC variants, suggesting that other factors are involved in the development of HCM when ACTC variants are present.
Improved efficacy of hyperthermia by auraptene in human colon adenocarcinoma cells
(Canadian Science Publishing, 2017-08-29) Moussavi, Mahdi; Haddad, Farhang; Matin, Matin; Iranshahi, Mehrdad; Rassouli, Fatemeh
Colon adenocarcinoma is one of the most common cancers worldwide, and resistance to current therapeutic modalities is a serious drawback in its treatment. Auraptene is a natural coumarin with considerable anticancer effects. The goal of present study was to introduce a novel combinatorial approach against colon adenocarcinoma cells. To do so, HT29 cells were pretreated with non-toxic auraptene and then hyperthermia was applied. Afterwards, viability of cells was assessed, changes induced in the cell cycle were analyzed, and expression pattern of candidate genes was studied. Results of MTT assay demonstrated significant (p
Developmental neurotoxic effects of a low dose of TCE on 3D neurosphere system
(Canadian Science Publishing, 2017-09-14) Abdraboh, Mohamed Elsaid; Abdeen, Sherif H.; Salama, Mohamed; Elhussiny, Mahmoud; El-Sherbini, Yasser M.; Eldeen, Nada M.
Trichloroethylene (TCE) is one of the industrial toxic products that ever-present in air, soil and water. Several studies illustrated the toxicity of high doses of TCE on several organs. This study aims to determine the toxic effect of a low dose of TCE on development of rat neural stem cells (NSCs). Rat pups brains were collected, minced and harvested cells were cultured in the presence of neural growth factors B27/N8 to develop neurospheres. Afterwards, cells were subjected to a dose of 1ÂľM TCE for 1 and 2 weeks. The data indicated a significant effect of TCE on inhibiting the NSCs differentiation which was confirmed by cell immunolabelling with astrocytes marker GFAP. TCE inhibitory effect on NSCs proliferation was estimated by the decrease at neurospheres diameter, ki67 downregulation and cell cycle arrest at G1/S phase. Immunolabelling of TCE treated cells with annexin V indicated the effect of TCE on induction of NSCs apoptosis. The mechanism of these actions was illustrated via TCE dependent reduction at transcription of SOD enzyme. In conclusion, this study illustrated for the first time the neurotoxic effects of such low dose of TCE on NSCs ability to differentiate, proliferate and induction of cell apoptosis.
Portal vein ligation alters coding and non-coding gene expression in rat livers
(Canadian Science Publishing, 2017-08-22) Li, Bin; Zhu, Yan; Xie, Lei; Hu, Shuyang; Liu, Shupeng; Jiang, Xiaoqing
Portal vein occlusion increases the resectability of initially unresectable HCC by inducing the hypertrophy of non-occluded liver lobes. However, the mechanisms of how portal vein occlusion induces hepatic hypertrophy remains unclear. cDNA microarray was used to identify gene expression signatures of ligated and non-ligated lobes at different time after PVL. Bioinformatics analysis found that ligated liver lobes (LLL) and non-ligated liver lobes (NLLL) displayed different gene expression profiles. And expression of both coding and non-coding RNA were also different at the different time in LLL or NLLL after PVL. Series Test of Cluster analysis found that No.22 and No.5 expression patterns, which showed altered expression at 24h and maintained expression in the following 14d, had the lowest P value and the largest number of differentially expressed genes in both LLL and NLLL. GO analysis showed activation of Hypoxia in LLL and activation of cell proliferation and cell cycle pathways in NLLL, suggesting involvement of these pathways in PVL induced hepatic hypertrophy and regeneration. These results shed light on the molecular mechanisms underlying hepatic hypertrophy and regeneration induced by portal vein occlusion and identified the potential targeting pathways which can promote the clinic application of PVL in liver cancer therapy.

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