scholarly journals Study of the Possible Alleviated Role of Atorvastatin on Irinotecan-Induced Lingual Mucosal Damage: Histological and Molecular Study

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Eetmad A. Arafat ◽  
S. M. Abo El-khair ◽  
A. Z. Elsamanoudy ◽  
Dalia A. Shabaan
Keyword(s):  
Gene Expression ◽  
Oral Mucositis ◽  
Molecular Study ◽  
Treated Group ◽  
Mucosal Damage ◽  
Ki 67 ◽  
Lingual Papillae ◽  
Study Results ◽  
Mrna Gene

Background. Oral mucositis is the most debilitating and troublesome adverse effect of irinotecan (CPT-11) treatment. It adversely affects the patient quality of life. The aim of this work was to study the histological, immunohistochemical, and molecular changes in the oral mucosa by CPT-11 and the possible alleviated role of atorvastatin. Methods. Rats were randomly divided into control, CPT-11-treated group, and CPT-11+ atorvastatin-treated group. At the end of the experiment, the anterior two-thirds of the tongue was dissected out and divided into two parts: one part for light microscopic examination and the second for molecular study. Results. CPT-11-treated group revealed loss of normal mucosal organization, areas of ulceration and inflammation, and loss of architecture of lingual papillae. A significant decrease in immunohistochemical and molecular gene expression of Ki-67 and antiapoptotic Bcl-2 levels was observed. A significant increase in NF-κB immunohistochemical and mRNA gene expression level and a nonsignificant increase in Nrf2 gene expression were detected. Coadministration of atorvastatin showed remarkable improvement in the histopathological picture with a significant increase in Ki-67 and Bcl-2, a significant decrease in NF-κB protein and gene expression, and a significant increase in Nrf2 gene expression. Conclusion. Atorvastatin substantially attenuates CPT-11-induced oral mucositis through the initiation of the antiapoptotic gene, modulation of the inflammatory, and antioxidant gene expression.

scholarly journals Comparative Study on Effect of Mesenchymal Stem Cells and Endothelial Progenitor Cells on Treatment of Experimental CCL4 Induced Liver Fibrosis

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
D Sabry ◽  
W A Khalifa ◽  
M M Abdelgwad ◽  
M Alhelf ◽  
Z M Altaib
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Liver Function ◽  
Liver Regeneration ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Treated Group ◽  
Ki 67

Abstract Background Bone marrow mesenchymal stem cells (BM-MSCs) and human umbilical cord endothelial progenitor cells (UC-EPCs) have several benefits for liver regeneration. We speculate huge impacts of rat BM-MSCs and UC-EPCs on reversal of hepatic injury and improvement of liver function in liver fibrosis induced by carbon tetrachloride (CCl4). Methods Forty adult rats were divided into 4 groups; control group, CCl4 group, CCl4/BM-MSCs group and CCl4/UCEPCs group. Blood samples were driven from rats at 1, 2 and 3months to measure serum concentration of albumin and alanine aminotransferase (ALT). Quantitative expression of HGF,TGF-β, MMP-2, and VEGF were assessed by polymerase chain reaction. Histological examination of the liver tissue was performed. α-SMA immunohistochemistry to identify the myoepithelial cells (MECs) and Ki-67 to identify cell prolifration immunohistochemistry are detected in groups injected with cells to confirm cells regeneration. Results Regarding liver function, there was elevating albumin (P < 0.05) and reducing ALT (P < 0.05) concentrations in groups treated with BM-MSCs and UC-EPCs effect compared to untreated CCL4 group. Concerning gene expression, UC-EPCs treated group have significantly higher MMP-2 and VEGF (P < 0.01) genes expression than BM-MSCs treated group. Furthermore, UC-EPCs were more valuable than BM-MSCs in increasing gene expression of HGF (P < 0.05) and immunohistochemistry of α-SMA and Ki-67 (P < 0.01). BM-MSCs have significantly lower TGF- β (P < 0.00) compared to UC-EPCs. Conclusion This study highlighted on liver regeneration role of both human UC-EPCs and BM-MSCs in liver fibrosis by different signaling mechanistic.

scholarly journals Retinoblastoma 1 (RB1) modulates the proliferation of chicken preadipocytes

2018 ◽  
Author(s):  
Yu-Xiang Wang ◽  
Hai-Xia Wang ◽  
Wei Na ◽  
Fei-Yue Qin ◽  
Zhi-Wei Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Phase Transition ◽  
Cell Cycle ◽  
Gene Expression Analysis ◽  
Mammalian Species ◽  
S Phase ◽  
Pcr Analysis ◽  
Quantitative Real Time Pcr ◽  
Ki 67

AbstractRetinoblastoma 1 (RB1) has been extensively studied in mammalian species, but its function in avian species is unclear. The objective of this study was to reveal the role of chicken RB1 (Gallus gallus RB1, gRB1) in the proliferation of preadipocytes. In the current study, quantitative real-time PCR analysis showed that the expression levels of gRB1 transiently increased during the proliferation of preadipocytes. The MTT assay showed that gRB1 overexpression suppressed preadipocyte proliferation, and gRB1 interference promoted preadipocyte proliferation. Additionally, cell-cycle analysis indicated that gRB1 may play a crucial role in the G1/S transition. Consistently, gene expression analysis showed that gRB1 knockdown promoted marker of proliferation Ki-67 (MKi67) expression at 96 h (P < 0.05), and that overexpression of gRB1 reduced MKi67 expression at 72 h (P < 0.05). Together, our study demonstrated that gRB1 inhibited preadipocyte proliferation at least in part by inhibiting the G1 to S phase transition.

scholarly journals Immunohistochemical features of gastrointestinal stromal tumors and the role of expression of p16ink4A, Ki-67, VEGF and MMP-9 in their behavior

Pathologia ◽  
2021 ◽  
Vol 18 (2) ◽  
pp. 136-141
Author(s):  
I. I. Yakovtsova ◽  
Ya. M. Miroshnichenko ◽  
T. M. Chertenko
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Immunohistochemical Study ◽  
Combined Treatment ◽  
Vegf Expression ◽  
Ki 67 ◽  
Primary Tumors ◽  
Cytoplasmic Expression ◽  
Stromal Tumors ◽  
Study Results

Aim: to clarify the prognostic value of cytoplasmic p16ink4A, VEGF, MMP-9 and Ki-67 expressions in gastrointestinal stromal tumors (GISTs) and connection of different levels of these markers expression with aggressive transformation of GISTs. Materials and methods. Our study included 36 samples of primary tumors and 10 relapses of GIST and metastases in liver after primary combined treatment (surgery and chemotherapy with imatinib). The immunohistochemical study was performed with 4 primary antibodies: Ki-67, p16ink4A, VEGF and MMP-9. We used formalin fixed and paraffin embedded (FFPE) tissue samples for immunohistochemical study. Results. In our study we showed significant connection between levels of cytoplasmic expression of p16ink4A in primary GISTs and such markers of tumor aggressive behaviour as Ki-67, MMP-9 and VEGF (Fisher’s exact P-value = 0.000753; 0.000101 and 0.000048 respectively). Between cytoplasmic expression of p16ink4A and VEGF and also between p16ink4A and MMP-9 strong direct correlation was found (γ = 0.829, P < 0.05 and rs = 0.961, P < 0.05 respectively). The correlation between expression of Ki-67 and p16ink4A was also direct and strong (rs = 0.754, P < 0.05), but with some exclusions, that’s why this correlation needs further investigation in larger groups with preciser molecular analysis. Analysis of metastatic GISTs samples showed prominent levels of MMP-9 and VEGF expression. Conclusions. Our study has shown very important role of cytoplasmic expression of p16ink4A in GIST as one of the markers of aggressive behavior, which can be used in complex with other markers for more accurate prognosis of GISTs progression. Prominent levels of MMP-9 and VEGF expression in metastatic GISTs can be a marker of resistance to imatinib. So probably evaluation of MMP-9 and VEGF expression can be used as a tool for correct choice of chemotherapy for patients with GISTs.

scholarly journals MicroRNA Response Elements-Mediated miRNA-miRNA Interactions in Prostate Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Mohammed Alshalalfa
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Progression ◽  
Biological Networks ◽  
Functional Role ◽  
Systems Perspective ◽  
Mrna Gene ◽  
Mrna Gene Expression ◽  
Tumor Suppressor Mirnas

The cell is a highly organized system of interacting molecules including proteins, mRNAs, and miRNAs. Analyzing the cell from a systems perspective by integrating different types of data helps revealing the complexity of diseases. Although there is emerging evidence that microRNAs have a functional role in cancer, the role of microRNAs in mediating cancer progression and metastasis remains not fully explored. As the amount of available miRNA and mRNA gene expression data grows, more systematic methods combining gene expression and biological networks become necessary to explore miRNA function. In this work I integrated functional miRNA-target interactions with mRNA and miRNA expression to infer mRNA-mediated miRNA-miRNA interactions. The inferred network represents miRNA modulation through common targets. The network is used to characterize the functional role of microRNA response element (MRE) to mediate interactions between miRNAs targeting the MRE. Results revealed that miRNA-1 is a key player in regulating prostate cancer progression. 11 miRNAs were identified as diagnostic and prognostic biomarkers that act as tumor suppressor miRNAs. This work demonstrates the utility of a network analysis as opposed to differential expression to find important miRNAs that regulate prostate cancer.

scholarly journals Lactulose: effect on apoptotic- and immunological-markers in the gastro-intestinal tract of pre-ruminant calves

2008 ◽  
Vol 52 (No. 10) ◽  
pp. 437-444 ◽  
Author(s):  
S. Fleige ◽  
W. Preißnger ◽  
H.H.D. Meyer ◽  
M.W. Pfaffl
Keyword(s):  
Gene Expression ◽  
Intestinal Tract ◽  
Caspase 3 ◽  
Fold Increase ◽  
Probiotic Strain ◽  
Treated Group ◽  
Control Group ◽  
High Dose ◽  
Mrna Gene ◽  
Mrna Gene Expression

The study was conducted to elucidate the effects of orally administered lactulose in combination with <i>Enterococcus faecium</i> on immune response of the intestinal tract in pre-ruminant calves. The mRNA expression of pro- and anti-inflammatory cytokines and proliferation and apoptosis markers were investigated in jejunum, ileum, colon and caecum. Simmental calves were fed diets containing 1% (L1) or 3% (L3) lactulose and the probiotic strain of the genus <i>E. faecium</i>, and compared with a non treated control group. Primarily the high dose feeding with lactulose showed an effect on several mRNA gene expression parameters. In the jejunum a down-regulation of the anti-apoptotic marker Bcl-xl was determined and IL-10 mRNA gene expression was 2.6-fold up-regulated (<i>P</i> < 0.05). In the colon a 1.9-fold (<i>P</i> < 0.05) up-regulation of IL-10 and only in caecum an about 2-fold increase of TGF-β1 (<i>P</i> < 0.05) was found for both lactulose feedings. Caspase 3 was up-regulated in caecum only in the 3% lactulose treated group (<i>P</i> < 0.05). The enhanced apoptotic rate of caspase 3 seems to be associated with a decrease in crypth depth due to lactulose supplementation. The results indicated that mainly the high 3% lactulose dose in probiotic-fed calves has an affect on the intestinal immune function and on diverse apoptotic markers.

scholarly journals Anti-Inflammatory Effect of Recreational Exercise in TNBS-Induced Colitis in Rats: Role of NOS/HO/MPO System

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Zita Szalai ◽  
András Szász ◽  
István Nagy ◽  
László G. Puskás ◽  
Krisztina Kupai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Physical Exercise ◽  
Inflammatory Mediators ◽  
Wheel Running ◽  
Treated Group ◽  
Mucosal Damage ◽  
Proinflammatory Mediators ◽  
Male Wistar Rats ◽  
Anti Inflammatory ◽  
Oxide Synthase

There are opposite views in the available literature: Whether physical exercise has a protective effect or not on the onset of inflammatory bowel disease (IBD). Therefore, we investigated the effects of recreational physical exercise before the induction of colitis. After 6 weeks of voluntary physical activity (running wheel), male Wistar rats were treated with TNBS (10 mg). 72 hrs after trinitrobenzene sulphonic acid (TNBS) challenge we measured colonic gene (TNF-α, IL-1β, CXCL1 and IL-10) and protein (TNF-α) expressions of various inflammatory mediators and enzyme activities of heme oxygenase (HO), nitric oxide synthase (NOS), and myeloperoxidase (MPO) enzymes. Wheel running significantly increased the activities of HO, constitutive NOS (cNOS) isoform. Furthermore, 6 weeks of running significantly decreased TNBS-induced inflammatory markers, including extent of lesions, severity of mucosal damage, and gene expression of IL-1β, CXCL1, and MPO activity, while IL-10 gene expression and cNOS activity were increased. iNOS activity decreased and the activity of HO enzyme increased, but not significantly, compared to the sedentary TNBS-treated group. In conclusion, recreational physical exercise can play an anti-inflammatory role by downregulating the gene expression of proinflammatory mediators, inducing anti-inflammatory mediators, and modulating the activities of HO and NOS enzymes in a rat model of colitis.

scholarly journals E.coli JM83 Damages Mucosal Barrier Inducing Hirschsprung-Associated Enterocolitis via Activated TLR4 / NF-κB / P-p38 Signaling

2021 ◽  
Author(s):  
Zebing Zheng ◽  
Mingjuan Gao ◽  
Chengyan Tang ◽  
Lu Huang ◽  
Yuan Gong ◽  
...  
Keyword(s):  
Mucosal Damage ◽  
Mucosal Barrier ◽  
Endothelin Receptor ◽  
Oral Gavage ◽  
E Coli ◽  
Treatment And Prevention ◽  
Tnf Α ◽  
Study Results ◽  
Actin Protein

Abstract Purpose Hirschsprung-associated enterocolitis (HAEC) is characterized by intestinal mucosal damage and unbalance of intestinal microbiota. Recent studies have shown that the TLR4/NF-κB/p-p38 signaling in the intestine is of great importance to intestinal mucosal integrity. This study aimed to investigate the role of TLR4/NF-κB/p-p38 signaling in the pathogenesis of HAEC in Escherichia coli (E. coli) JM83 infected Endothelin receptor B (Ednrb)−/− mice. Methods Ednrb −/− mice were administered with E. coli JM83 by oral gavage to establish the HAEC model, mice were randomly divided into WT group, Ednrb−/− group and Ednrb−/−+ E. coli JM83 group. The role of TLR4/NF-κB/p-p38 signaling was evaluated by vivo study. Results The activation of the TLR4/NF-κB/p-p38 signaling induced by E. coli JM83 caused HAEC in Ednrb−/− mice, which was evidenced by a significantly increased expression of TNF-α, TGF-β and IL-10, decreased density of F-actin protein. While TLR4 knockdown improved the degree of enterocolitis and attenuated the expression of IL-10, TNF-α, TGF-β and increased the density of F-actin protein in Ednrb−/− mice after E. coli infection. Conclusions These results indicate that E. coli JM83 activates TLR4/NF-κB/p-p38 signaling to promote the development of HAEC. However, inhibition of this signaling may be benefit to the treatment and prevention of HAEC.

A critical role of Sp1 transcription factor in regulating the human Ki-67 gene expression

Tumor Biology ◽  
2010 ◽  
Vol 32 (2) ◽  
pp. 273-283 ◽  
Author(s):  
Hui Tian ◽  
Guo-Wei Qian ◽  
Wang Li ◽  
Fei-Fei Chen ◽  
Jie-Hui Di ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Critical Role ◽  
Ki 67 ◽  
Sp1 Transcription Factor

scholarly journals A hypothesis for the pathogenesis of radiation-induced oral mucositis: when biological challenges exceed physiologic protective mechanisms. Implications for pharmacological prevention and treatment

2021 ◽  
Author(s):  
Stephen T. Sonis
Keyword(s):  
Oral Mucositis ◽  
Damage Control ◽  
Unmet Need ◽  
Mucosal Damage ◽  
Control Mechanisms ◽  
Protective Mechanisms ◽  
Pharmacological Prevention ◽  
Concomitant Chemoradiation ◽  
Radiation Induced

AbstractOral mucositis (OM) remains a significant unmet need for patients being treated with standard concomitant chemoradiation (CRT) regimens for head and neck cancers (HNC). OM’s pathogenesis is complex and includes both direct and indirect damage pathways. In this paper, the field is reviewed with emphasis on the initiating and sustaining role of oxidative stress on OM’s pathobiology. A hypothesis is presented which suggests that based on OM’s clinical and biological trajectory, mucosal damage is largely the consequence of cumulative CRT-induced biological changes overwhelming physiologic self-protective mechanisms. Furthermore, an individual’s ability to mount and maintain a protective response is dependent on interacting pathways which are primarily determined by a multiplex consisting of genomics, epigenomics, and microbiomics. Effective biologic or pharmacologic OM interventions are likely to supplement or stimulate existing physiologic damage-control mechanisms.

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