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Article ; Online: L-Shaped Distributions of the Relative Substitution Rates (c/micro) in SARS-COV-2 with or without Molecular Clocks, Challenging Mainstream Evolutionary Theories

Wu, Chun / Paradis, Nicholas J.

bioRxiv

Abstract: ... mutation rate ratio c/micro test (c: substitution rate in Translated Region/TR or UnTranslated Region/UTR; micro ... of c/micro and molecular clock were observed for SARS-COV-29s genome. We found that the proportion ... as Near-Neutral Balanced Selectionist Theory (NNBST). In this study, the c/micro analysis was extended ...

Abstract	A definitive test to quantify fitness changes of mutations is required to end a continuing 50-year "neutralist-selectionist" debate in evolutionary biology. Our previous work introduced a substitution-mutation rate ratio c/micro test (c: substitution rate in Translated Region/TR or UnTranslated Region/UTR; micro mutation rate) to quantify the selection pressure and thus the proportions of strictly neutral, nearly neutral, beneficial, and deleterious mutations in a genome. Intriguingly, both a L-shaped probability distribution of c/micro and molecular clock were observed for SARS-COV-29s genome. We found that the proportion of the different mutation types from the distribution is not consistent with the hypotheses of the three existing evolution theories (Kimura9s Neutral Theory/KNT, Ohta9s Nearly Neutral Theory/ONNT and the Selectionist Theory/ST), and a balance condition explains the molecular clock, thus we proposed a new theory named as Near-Neutral Balanced Selectionist Theory (NNBST). In this study, the c/micro analysis was extended beyond the genome to 26 TRs, 12 UTRs, and 10 TRSs (Transcriptional Regulatory Sequences) of SARS-COV-2. While L-shaped probability distributions of c/micro were observed for all of 49 segments, molecular clocks were observed for only 24 segments, supporting NNBST and Near-Neutral Unbalanced Selectionist Theory (NNUST) to explain the molecular evolution of 24/25 segments with/without molecular clocks. Thus, the Near-Neutral Selectionist Theory (NNST) integrates traditional neutral and selectionist theories to deepen our understanding of how mutation, selection, and genetic drift influence genomic evolution.
Keywords	covid19
Language	English
Publishing date	2024-04-30
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.04.29.591599
Database	COVID19

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Article ; Online: Mitochondrial stress in advanced fibrosis and cirrhosis associated with chronic hepatitis B, chronic hepatitis C, or nonalcoholic steatohepatitis.

Loureiro, Dimitri / Tout, Issam / Narguet, Stéphanie / Bed, Cheikh Mohamed / Roinard, Morgane / Sleiman, Ahmad / Boyer, Nathalie / Pons-Kerjean, Nathalie / Castelnau, Corinne / Giuly, Nathalie / Tonui, Dorothy / Soumelis, Vassili / El Benna, Jamel / Soussan, Patrick / Moreau, Richard / Paradis, Valérie / Mansouri, Abdellah / Asselah, Tarik

Hepatology (Baltimore, Md.)

2022 Volume 77, Issue 4, Page(s) 1348–1365

Abstract: ... with chronic hepatitis C (CHC; n = 33), nonalcoholic steatohepatatis (NASH; n = 12), and healthy controls ( n ...

Abstract	Background and aims: Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters mitochondria in experimental models. Our goal was to investigate whether HBV might alter liver mitochondria also in humans, and the resulting mitochondrial stress might account for the progression of fibrosis in chronic hepatitis B (CHB). Approach and results: The study included 146 treatment-naïve CHB mono-infected patients. Patients with CHB and advanced fibrosis (AF) or cirrhosis (F3-F4) were compared to patients with no/mild-moderate fibrosis (F0-F2). Patients with CHB were further compared to patients with chronic hepatitis C (CHC; n = 33), nonalcoholic steatohepatatis (NASH; n = 12), and healthy controls ( n = 24). We detected oxidative damage to mitochondrial DNA (mtDNA), including mtDNA strand beaks, and identified multiple mtDNA deletions in patients with F3-F4 as compared to patients with F0-F2. Alterations in mitochondrial function, mitochondrial unfolded protein response, biogenesis, mitophagy, and liver inflammation were observed in patients with AF or cirrhosis associated with CHB, CHC, and NASH. In vitro , significant increases of the mitochondrial formation of superoxide and peroxynitrite as well as mtDNA damage, nitration of the mitochondrial respiratory chain complexes, and impairment of complex I occurred in HepG2 cells replicating HBV or transiently expressing hepatitits B virus X protein. mtDNA damage and complex I impairment were prevented with the superoxide-scavenging Mito-Tempo or with inducible nitric oxide synthase (iNOS)-specific inhibitor 1400 W. Conclusions: Our results emphasized the importance of mitochondrial OS, mtDNA damage, and associated alterations in mitochondrial function and dynamics in AF or cirrhosis in CHB and NASH. Mitochondria might be a target in drug development to stop fibrosis progression.
MeSH term(s)	Humans ; Hepatitis B, Chronic ; Non-alcoholic Fatty Liver Disease/complications ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/genetics ; Superoxides ; Liver Cirrhosis/complications ; Fibrosis ; Hepatitis B virus/genetics ; Hepatitis B/complications ; DNA, Mitochondrial ; Mitochondria
Chemical Substances	Superoxides (11062-77-4) ; DNA, Mitochondrial
Language	English
Publishing date	2022-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.32731
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Article ; Online: L-shaped distribution of the relative substitution rate (c/μ) observed for SARS-COV-2's genome, inconsistent with the selectionist theory, the neutral theory and the nearly neutral theory but a near-neutral balanced selection theory: Implication on "neutralist-selectionist" debate.

Wu, Chun / Paradis, Nicholas J / Lakernick, Phillip M / Hryb, Mariya

Computers in biology and medicine

2023 Volume 153, Page(s) 106522

Abstract: The genomic substitution rate (GSR) of SARS-CoV-2 exhibits a molecular clock feature and does not change under fluctuating environmental factors such as the infected human population (10°- ... ...

Abstract	The genomic substitution rate (GSR) of SARS-CoV-2 exhibits a molecular clock feature and does not change under fluctuating environmental factors such as the infected human population (10°-10
MeSH term(s)	Humans ; Mutation ; SARS-CoV-2/genetics ; COVID-19/genetics ; Genome ; Biological Evolution ; Evolution, Molecular
Language	English
Publishing date	2023-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	127557-4
ISSN	1879-0534 ; 0010-4825
ISSN (online)	1879-0534
ISSN	0010-4825
DOI	10.1016/j.compbiomed.2022.106522
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Article ; Online: Social support and C-reactive protein in a Québec population cohort of children and adolescents.

Fairbank, Eloïse J / McGrath, Jennifer J / Henderson, Mélanie / O'Loughlin, Jennifer / Paradis, Gilles

PloS one

2022 Volume 17, Issue 6, Page(s) e0268210

Abstract: ... 2186) completed a fasting blood draw that was assayed for C-reactive protein (CRP).: Findings ...

Abstract	Objective: Robust evidence exists for the health-enhancing benefits of social support in adults. Inflammatory processes are thought to be an important mechanism linking social support and health risk. Less is known about the relation between social support and chronic inflammation during childhood and adolescence, or when the association emerges during the lifespan. Method: Data from the population-representative 1999 Quebec Child and Adolescent Health and Social (QCAHS) survey were analyzed. Youth aged 9, 13, and 16 years (N = 3613) and their parents answered questions about social support. A subsample (n = 2186) completed a fasting blood draw that was assayed for C-reactive protein (CRP). Findings: Higher social support was significantly associated with lower hs-CRPlog, after controlling for age, sex, body mass index (BMI Z-score), medication use, puberty, ethnoracial status (French-Canadian), smoking, household income, and parental education (F = 25.88, p = < .001, Total R2adj = 10.2%). The association was largely similar for boys and girls, and strengthened with age. Conclusion: Greater social support was linked to lower chronic low-grade inflammation in a large sample of children and adolescents. Effect sizes were small and consistent with prior findings in the adult literature. Importantly, these findings provide evidence that the relation between social support and inflammation emerges early in the lifespan. Future work should consider broader, more encompassing conceptualizations of social support, the role of social media, and prospective trajectories of social support and inflammatory markers.
MeSH term(s)	Adolescent ; Adult ; Body Mass Index ; C-Reactive Protein/analysis ; Canada/epidemiology ; Child ; Female ; Humans ; Inflammation ; Male ; Prospective Studies ; Quebec ; Social Support
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2022-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0268210
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Article ; Online: Procollagen C-Proteinase Enhancer-1 (PCPE-1) deficiency in mice reduces liver fibrosis but not NASH progression.

Sansilvestri Morel, Patricia / Duvivier, Valerie / Bertin, Florence / Provost, Nicolas / Hammoutene, Adel / Hubert, Edwige-Ludiwyne / Gonzalez, Arantxa / Tupinon-Mathieu, Isabelle / Paradis, Valerie / Delerive, Philippe

PloS one

2022 Volume 17, Issue 2, Page(s) e0263828

Abstract: ... mortality. Fibrosis is the main driver of mortality in NASH. Procollagen C-Proteinase Enhancer-1 (PCPE-1 ... Finally, PCPE-1 protein expression was increased in cirrhotic liver samples from both NASH and Hepatitis C ...

Abstract	Background and aims: Nonalcoholic Steatohepatitis (NASH) is a major cause of end-stage liver diseases such as cirrhosis and hepatocellular carcinoma resulting ultimately in increased liver-related mortality. Fibrosis is the main driver of mortality in NASH. Procollagen C-Proteinase Enhancer-1 (PCPE-1) plays a key role in procollagen maturation and collagen fibril formation. To assess its role in liver fibrosis and NASH progression, knock-out mice were evaluated in a dietary NASH model. Methods: Global constitutive Pcolce-/- and WT male mice were fed with a Choline Deficient Amino acid defined High Fat Diet (CDA HFD) for 8 weeks. Liver triglycerides, steatosis, inflammation and fibrosis were assessed at histological, biochemical and gene expression levels. In addition, human liver samples from control and NASH patients were used to evaluate the expression of PCPE-1 at both mRNA and protein levels. Results: Pcolce gene deficiency prevented diet-induced liver enlargement but not liver dysfunction. Furthermore, liver triglycerides, steatosis and inflammation were not modified in Pcolce-/- male mice compared to WT under CDA HFD. However, a significant decrease in liver fibrosis was observed in Pcolce-/- mice compared to WT under NASH diet, associated with a decrease in total and insoluble collagen content without any significant modifications in the expression of genes involved in fibrosis and extracellular matrix remodeling. Finally, PCPE-1 protein expression was increased in cirrhotic liver samples from both NASH and Hepatitis C patients. Conclusions: Pcolce deficiency limits fibrosis but not NASH progression in CDA HFD fed mice.
MeSH term(s)	Animals ; Diet, High-Fat ; Disease Models, Animal ; Disease Progression ; Extracellular Matrix Proteins/genetics ; Extracellular Matrix Proteins/metabolism ; Female ; Gene Knockout Techniques ; Humans ; Liver/chemistry ; Liver/metabolism ; Liver/pathology ; Liver Cirrhosis/etiology ; Liver Cirrhosis/genetics ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/pathology ; Male ; Mice ; Non-alcoholic Fatty Liver Disease/etiology ; Non-alcoholic Fatty Liver Disease/genetics ; Non-alcoholic Fatty Liver Disease/metabolism ; Non-alcoholic Fatty Liver Disease/pathology ; Triglycerides/chemistry ; Up-Regulation
Chemical Substances	Extracellular Matrix Proteins ; PCOLCE protein, human ; Pcolce protein, mouse ; Triglycerides
Language	English
Publishing date	2022-02-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0263828
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Article ; Online: L-shape distribution of the relative substitution rate (c micro) observed for SARS-COV-2 genome, inconsistent with the selectionist theory, the neutral theory and the nearly neutral theory but a near-neutral balanced selection theory: implication on neutralist-selectionist debate

Wu, Chun / Paradis, Nicholas / Lakernick, Phillip / Hryb, Mariya

bioRxiv

Abstract	The genomic substitution rate (GSR) of SARS-CoV-2 exhibits a molecular clock feature and does not change under fluctuating environmental factors such as the infected human population (10^0-10^7), vaccination etc. The molecular clock feature is believed to be inconsistent with the selectionist theory (ST). The GSR shows lack of dependence on the effective population size, suggesting Ohta nearly neutral theory (ONNT) is not applicable to this virus. Big variation of the substitution rate within its genome is also inconsistent with Kimura neutral theory (KNT). Thus, all three existing evolution theories fail to explain the evolutionary nature of this virus. In this paper, we proposed a Segment Substitution Rate Model (SSRM) under non-neutral selections and pointed out that a balanced mechanism between negative and positive selection of some segments that could also lead to the molecular clock feature. We named this hybrid mechanism as near-neutral balanced selection theory (NNBST) and examined if it was followed by SARS-CoV-2 using the three independent sets of SARS-CoV-2 genomes selected by the Nextstrain team. Intriguingly, the relative substitution rate of this virus exhibited an L-shaped probability distribution consisting with NNBST rather than Poisson distribution predicted by KNT or an asymmetric distribution predicted by ONNT in which nearly neutral sites are believed to be slightly deleterious only, or the distribution that is lack of nearly neutral sites predicted by ST. The time-dependence of the substitution rates for some segments and their correlation with the vaccination were observed, supporting NNBST. Our relative substitution rate method provides a tool to resolve the long standing neutralist-selectionist controversy. Implications of NNBST in resolving Lewontin Paradox is also discussed.
Keywords	covid19
Language	English
Publishing date	2023-01-03
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2023.01.01.522435
Database	COVID19

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Article ; Online: To probe the binding pathway of a selective compound (D089-0563) to c-MYC Pu24 G-quadruplex using free ligand binding simulations and Markov state model analysis.

Chen, Brian / Fountain, Griffin / Sullivan, Holli-Joi / Paradis, Nicholas / Wu, Chun

Physical chemistry chemical physics : PCCP

2020 Volume 22, Issue 39, Page(s) 22567–22583

Abstract: ... silencing G-quadruplex element (Pu27) at the promoter region of the human c-MYC oncogene ...

Abstract	D089-0563 is a highly promising anti-cancer compound that selectively binds the transcription-silencing G-quadruplex element (Pu27) at the promoter region of the human c-MYC oncogene; however, its binding mechanism remains elusive. The structure of Pu27 is not available due to its polymorphism, but the G-quadruplex structures of its two shorter derivatives in complex with a ligand (Pu24/Phen-DC3 and Pu22/DC-34) are available and show significant structural variance as well as different ligand binding patterns in the 3' region. Because D089-0563 shares the same scaffold as DC34 while having a significantly different scaffold from Phen-DC3, we picked Pu24 instead of Pu22 for this study in order to gain additional ligand binding insight. Using free ligand molecular dynamics binding simulations (33 μs), we probed the binding of D089-0563 to Pu24. Our clustering analysis identified three binding modes (top, side, and bottom) and subsequent MMPBSA binding energy analysis identified the top mode as the most thermodynamically stable. Our Markov State Model (MSM) analysis revealed that there are three parallel pathways for D089-0563 to the top mode from unbound state and that the ligand binding follows the conformational selection mechanism. Combining our predicted complex structures with the two experimental structures, it is evident that structural differences in the 3' region between Pu24 and Pu22 lead to different binding behaviors despite having similar ligands; this also explains the different promoter activity caused by the two G-quadruplex sequences observed in a recent synthetic biology study. Based on interaction insights, 625 D089-0563 derivatives were designed and docked; 59 of these showed slightly improved docking scores.
MeSH term(s)	DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/metabolism ; G-Quadruplexes ; Humans ; Ligands ; Molecular Dynamics Simulation ; Protein Binding ; Transcription Factors/chemistry ; Transcription Factors/metabolism
Chemical Substances	DNA-Binding Proteins ; Ligands ; MYCBP protein, human ; Transcription Factors
Language	English
Publishing date	2020-10-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1476244-4
ISSN	1463-9084 ; 1463-9076
ISSN (online)	1463-9084
ISSN	1463-9076
DOI	10.1039/d0cp03863f
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Meta-analysis of the Diagnostic Accuracy of C-Reactive Protein for Infectious Complications in Laparoscopic Versus Open Colorectal Surgery.

Paradis, Tiffany / Zorigtbaatar, Anudari / Trepanier, Maude / Fiore, Julio F / Fried, Gerald M / Feldman, Liane S / Lee, Lawrence

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract

2020 Volume 24, Issue 6, Page(s) 1392–1401

Abstract: Introduction: C-reactive protein may predict anastomotic complications after colorectal surgery ... characteristics of C-reactive protein to detect anastomotic leaks and infectious complications after laparoscopic ... of serum C-reactive protein to diagnose anastomotic leak or infectious complications specifically ...

Abstract	Introduction: C-reactive protein may predict anastomotic complications after colorectal surgery, but its predictive ability may differ between laparoscopic and open resection due to differences in stress response. Therefore, the objective of this study was to perform a systematic review and meta-analysis on the diagnostic characteristics of C-reactive protein to detect anastomotic leaks and infectious complications after laparoscopic and open colorectal surgery. Methods: A systematic review was performed according to PRISMA. Studies were included if they reported on the diagnostic characteristics of postoperative day 3-5 values of serum C-reactive protein to diagnose anastomotic leak or infectious complications specifically in patients undergoing elective laparoscopic and open colorectal surgery. The main outcome was a composite of anastomotic leak and infectious complications. A random-effects model was used to perform a meta-analysis of diagnostic accuracy. Results: A total of 13 studies were included (9 for laparoscopic surgery, 8 for open surgery). The pooled incidence of the composite outcome was 14.8% (95% CI 10.2-19.3) in laparoscopic studies and 21.0% (95% CI 11.9-30.0) for open. The pooled diagnostic accuracy characteristics were similar for open and laparoscopic studies. However, the C-reactive protein threshold cutoffs were lower in laparoscopic studies for postoperative days 3 and 4, but similar on day 5. Conclusions: The diagnostic characteristics of C-reactive protein in the early postoperative period to detect infectious complications and leaks are similar after laparoscopic and open colorectal surgery. However, thresholds are lower for laparoscopic surgery, suggesting that the interpretation of serum CRP values needs to be tailored based on operative approach.
MeSH term(s)	Anastomotic Leak/diagnosis ; Anastomotic Leak/etiology ; C-Reactive Protein/analysis ; Colorectal Surgery/adverse effects ; Digestive System Surgical Procedures ; Humans ; Laparoscopy/adverse effects ; Postoperative Complications/diagnosis ; Postoperative Complications/etiology
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2020-04-20
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	2012365-6
ISSN	1873-4626 ; 1934-3213 ; 1091-255X
ISSN (online)	1873-4626 ; 1934-3213
ISSN	1091-255X
DOI	10.1007/s11605-020-04599-2
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Zs.A 5207: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Procollagen C-Proteinase Enhancer-1 (PCPE-1) deficiency in mice reduces liver fibrosis but not NASH progression.

Patricia Sansilvestri Morel / Valerie Duvivier / Florence Bertin / Nicolas Provost / Adel Hammoutene / Edwige-Ludiwyne Hubert / Arantxa Gonzalez / Isabelle Tupinon-Mathieu / Valerie Paradis / Philippe Delerive

PLoS ONE, Vol 17, Iss 2, p e

2022 Volume 0263828

Abstract: ... mortality. Fibrosis is the main driver of mortality in NASH. Procollagen C-Proteinase Enhancer-1 (PCPE-1 ... expression was increased in cirrhotic liver samples from both NASH and Hepatitis C patients. Conclusions ...

Abstract	Background and aims Nonalcoholic Steatohepatitis (NASH) is a major cause of end-stage liver diseases such as cirrhosis and hepatocellular carcinoma resulting ultimately in increased liver-related mortality. Fibrosis is the main driver of mortality in NASH. Procollagen C-Proteinase Enhancer-1 (PCPE-1) plays a key role in procollagen maturation and collagen fibril formation. To assess its role in liver fibrosis and NASH progression, knock-out mice were evaluated in a dietary NASH model. Methods Global constitutive Pcolce-/- and WT male mice were fed with a Choline Deficient Amino acid defined High Fat Diet (CDA HFD) for 8 weeks. Liver triglycerides, steatosis, inflammation and fibrosis were assessed at histological, biochemical and gene expression levels. In addition, human liver samples from control and NASH patients were used to evaluate the expression of PCPE-1 at both mRNA and protein levels. Results Pcolce gene deficiency prevented diet-induced liver enlargement but not liver dysfunction. Furthermore, liver triglycerides, steatosis and inflammation were not modified in Pcolce-/- male mice compared to WT under CDA HFD. However, a significant decrease in liver fibrosis was observed in Pcolce-/- mice compared to WT under NASH diet, associated with a decrease in total and insoluble collagen content without any significant modifications in the expression of genes involved in fibrosis and extracellular matrix remodeling. Finally, PCPE-1 protein expression was increased in cirrhotic liver samples from both NASH and Hepatitis C patients. Conclusions Pcolce deficiency limits fibrosis but not NASH progression in CDA HFD fed mice.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fibrosis in Chronic Hepatitis C

Maha Akl / Ali EL Hindawi / Maha Mosaad / Ahmed Montasser / Ahmed El Ray / Heba Khalil / Amgad Anas / Raffat Atta / Valerie Paradis / Ahmed Abdel Hadi / Olfat Hammam

Open Access Macedonian Journal of Medical Sciences, Vol 4, Iss 4, Pp 578-

Correlation between Immunohistochemically-Assessed Virus Load with Steatosis and Cellular Iron Content

2016 Volume 584

Abstract: ... in chronic hepatitis C and role of VEGF and VEGFR overexpression in cirrhotic cases in evolving HCC. MATERIAL ... AND METHODS: Total of 120 cases were included from TBRI and Beaujon Hospital as chronic hepatitis C ... CHC), post-hepatitis C cirrhosis, and HCC. Cases of CHC were stained for Sirius red, Prussian blue and ...

Abstract	AIM: We aimed study impact of hepatocytic viral load, steatosis, and iron load on fibrosis in chronic hepatitis C and role of VEGF and VEGFR overexpression in cirrhotic cases in evolving HCC. MATERIAL AND METHODS: Total of 120 cases were included from TBRI and Beaujon Hospital as chronic hepatitis C (CHC), post-hepatitis C cirrhosis, and HCC. Cases of CHC were stained for Sirius red, Prussian blue and immunohistochemically (IHC) for HCV-NS3/NS4. HCC were stained IHC for VEGF and by FISH. RESULTS: Stage of fibrosis was significantly correlated with inflammation in CHC (P < 0.01). Noticed iron load did not correlate with fibrosis. Steatosis was associated with higher inflammation and fibrosis. The cellular viral load did not correlate with inflammation, steatosis or fibrosis. VEGF by IHC was significantly higher in cases of HCC when compared to cirrhotic group (P < 0.001). Amplification of VEGFR2 was confirmed in 40% of cases of HCC. Scoring of VEGF by IHC was the good indicator of VEGFR2 amplification by FISH (P < 0.005). CONCLUSION: Grade of inflammation is the factor affecting fibrosis in CHC. The degree of liver damage is not related to cellular viral load or iron load. Steatosis is associated with higher inflammation and fibrosis. VEGF by IHC is correlated with overexpression of VEGFR2 by FISH.
Keywords	Fibrosis ; HCV ; HCC ; NS3/NS4 ; VEGF ; VEGFR2 ; FISH ; Medicine ; R
Subject code	616
Language	English
Publishing date	2016-11-01T00:00:00Z
Publisher	ID Design 2012/DOOEL Skopje
Document type	Article ; Online
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