scholarly journals Sequential testicular atrophy involves changes in cellular proliferation and apoptosis associated with variations in aromatase P450 expression levels in Irs-2-deficient mice

2018 ◽  
Vol 234 (2) ◽  
pp. 227-243
Author(s):  
Leonardo Catalano-Iniesta ◽  
Virginia Sánchez-Robledo ◽  
Maria Carmen Iglesias-Osma ◽  
Maria José García-Barrado ◽  
Marta Carretero-Hernández ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Testicular Atrophy ◽  
Expression Levels ◽  
Proliferation And Apoptosis ◽  
P450 Expression ◽  
Deficient Mice

scholarly journals Scutellarein inhibits BLM-mediated pulmonary fibrosis by affecting fibroblast differentiation, proliferation, and apoptosis

2020 ◽  
Vol 11 ◽  
pp. 204062232094018 ◽  
Author(s):  
Kang Miao ◽  
Ting Pan ◽  
Yong Mou ◽  
Lei Zhang ◽  
Weining Xiong ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Cellular Proliferation ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Mice Model ◽  
Expression Levels ◽  
Proliferation And Apoptosis ◽  
Underlying Mechanisms ◽  
Interstitial Pulmonary Disease

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible interstitial pulmonary disease that has a poor prognosis. Scutellarein, which is extracted from the traditional Chinese medicine Erigeron breviscapus, is used to treat a variety of diseases; however, the use of scutellarein for the treatment of pulmonary fibrosis and the related mechanisms of action have not been fully explored. Methods: This study was conducted using a well-established mouse model of pulmonary fibrosis induced by bleomycin (BLM). The antifibrotic effects of scutellarein on histopathologic manifestations and fibrotic marker expression levels were examined. The effects of scutellarein on fibroblast differentiation, proliferation, and apoptosis and on related signaling pathways were next investigated to demonstrate the underlying mechanisms. Results: In the present study, we found that scutellarein alleviated BLM-induced pulmonary fibrosis, as indicated by histopathologic manifestations and the expression levels of fibrotic markers. Further data demonstrated that the ability of fibroblasts to differentiate into myofibroblasts was attenuated in scutellarein-treated mice model. In addition, we obtained in vitro evidence that scutellarein inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-β/Smad signaling, inhibited cellular proliferation by repressing PI3K/Akt signaling, and increased apoptosis of fibroblasts by affecting Bax/Bcl2 signaling. Discussion: In general, scutellarein might exert therapeutic effects on pulmonary fibrosis by altering the differentiation, proliferation, and apoptosis of fibroblasts. Although scutellarein has been demonstrated to be safe in mice, further studies are required to investigate the efficacy of scutellarein in patients with IPF.

scholarly journals Icaritin promotes apoptosis and inhibits proliferation by down-regulating AFP gene expression in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hui Li ◽  
Yujuan Liu ◽  
Wei Jiang ◽  
Junhui Xue ◽  
Yuning Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cellular Proliferation ◽  
Chinese Herb ◽  
New Drugs ◽  
Phase Iii ◽  
P53 Expression ◽  
Expression Levels ◽  
Cellular Apoptosis ◽  
Afp Promoter

Abstract Background Icaritin, an active ingredient of the Chinese herb Epimedium, plays an anti-tumor role in liver cancer by inhibiting the proliferation of hepatocellular cells and promoting their apoptosis. In China, phase II and a large phase III clinical trial of icaritin reagent for the treatment of hepatocellular cancer is under-going, but the specific mechanism of icaritin action was unclear. Alpha-fetoprotein (AFP), an oncofetal protein, produced in the healthy fetal liver and yolk sac. Intracellular AFP promoted cellular proliferation and inhibited cellular apoptosis in hepatocellular carcinoma (HCC). The study was aimed to investigate the effect of icaritin on HCC through p53/AFP pathway. Methods Real-time RT PCR and western blot were used to detect p53 and AFP expression levels in HCC cells treated with icaritin. The mechanism of icaritin affecting p53 expression was verified by ubiquitination experiment, and the binding activity of icaritin on p53 in AFP promoter region was verified by luciferase experiment. EdU, MTT and flow cytometry were used to determine whether icaritin affected HCC cellular proliferation and apoptosis through p53/ AFP pathway. Expression levels of p53 and AFP in xenograft mouse model were determined by western blotting. Results Our results showed icaritin inhibited AFP expression at mRNA and protein level. AFP was also identified as the target gene of the p53 transcription factor. Icaritin abrogated murine double minute (Mdm) 2-mediated p53 ubiquitination degradation to improve the stability of p53. Up-regulated p53 protein levels then transcriptionally inhibited the AFP promoter. Icaritin-mediated decrease of AFP through Mdm2/p53 pathways inhibited HCC cellular proliferation and promoted HCC cellular apoptosis. Conclusion Our findings revealed the mechanism of icaritin in promoting apoptosis and inhibiting proliferation in liver cancer cells. The regulatory mechanism of icaritin in AFP protein down-regulation provides a theoretical and experimental basis for further research into new drugs for the treatment of liver cancer.

scholarly journals Decitabine shows anti-acute myeloid leukemia potential via regulating the miR-212-5p/CCNT2 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 1013-1023
Author(s):  
Lina Xing ◽  
Jinhai Ren ◽  
Xiaonan Guo ◽  
Shukai Qiao ◽  
Tian Tian
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Myeloid Leukemia ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Proliferation And Apoptosis ◽  
Polymerase Chain ◽  
The Relationship ◽  
Acute Myeloid

AbstractPrevious research has revealed the involvement of microRNA-212-5p (miR-212-5p) and cyclin T2 (CCNT2) in acute myeloid leukemia (AML). However, whether the miR-212-5p/CCNT2 axis is required for the function of decitabine in AML has not been well elucidated. Quantitative reverse transcription-polymerase chain reaction was used to examine enrichment of miR-212-5p. The relationship between CCNT2 and miR-212-5p was verified by the luciferase reporter assay. Cell apoptosis was evaluated by flow cytometry and western blot. CCK-8 assay was performed to determine cell viability. Decitabine significantly repressed cell viability, while promoted cell apoptosis. Meanwhile, the expression levels of cyclinD1, CDK4, and Bcl-2 were suppressed in cells with decitabine exposure, but Bax and caspase-3 expression levels were upregulated. Besides, miR-212-5p upregulation had the similar function with decitabine in AML cell proliferation and apoptosis. Subsequently, restoration of CCNT2 attenuated miR-212-5p overexpression-induced effects in Kasumi-1 and SKNO-1 cells. In addition, miR-212-5p depletion reversed decitabine-induced CCNT2 downregulation. The miR-212-5p/CCNT2 axis had an implication in the anti-leukemic effect of decitabine in AML.

scholarly journals Long Non-coding RNA GAS5 Worsens Coronary Atherosclerosis Through MicroRNA-194-3p/TXNIP Axis

2021 ◽  
Author(s):  
Yanbing Li ◽  
Yu Geng ◽  
Boda Zhou ◽  
Xuejiao Wu ◽  
Ou Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Coronary Atherosclerosis ◽  
Growth Arrest ◽  
Interacting Protein ◽  
Expression Levels ◽  
Thioredoxin Interacting Protein ◽  
Non Coding Rna ◽  
Proliferation And Apoptosis ◽  
Regulatory Effects ◽  
Long Non Coding Rna

AbstractIt is formerly conducted that long non-coding RNA growth arrest-specific 5 (GAS5) is involved in the process of coronary atherosclerosis (AS). The regulatory effects of GAS5 on the microRNA (miR)-194-3p/thioredoxin-interacting protein (TXNIP) axis in AS have been insufficiently explored yet. Thereafter, this work is started from GAS5/miR-194-3p/TXNIP axis in AS. AS rats were modeled to obtain their coronary vascular tissues and endothelial cells (ECs), in which GAS5, miR-194-3p, and TXNIP expression were tested. ECs were identified by immunohistochemistry. The mechanism among GAS5, miR-194-3p, and TXNIP was determined. ECs were transfected with inhibited GAS5 or overexpressed miR-194-3p to decipher their functions in proliferation and apoptosis of ECs in AS. Raised GAS5 and TXNIP and degraded miR-194-3p expression levels exhibited in AS. GAS5 bound to miR-194-3p while miR-194-3p targeted TXNIP. Depleting GAS5 or restoring miR-194-3p enhanced proliferation and depressed apoptosis of ECs in AS. This work clearly manifests that inhibited GAS5 facilitates the growth of ECs through miR-194-3p-targeted TXNIP in AS, consolidating the basal reference to the curing for AS.

scholarly journals SPACIA1/SAAL1 Deletion Results in a Moderate Delay in Collagen-Induced Arthritis Activity, along with mRNA Decay of Cyclin-dependent Kinase 6 Gene

2018 ◽  
Vol 19 (12) ◽  
pp. 3828
Author(s):  
Ryoji Fujii ◽  
Rie Komatsu ◽  
Tomoo Sato ◽  
Iwao Seki ◽  
Koji Konomi ◽  
...  
Keyword(s):  
Severe Disease ◽  
Critical Factor ◽  
Synovial Fibroblasts ◽  
Transcriptional Level ◽  
Cyclin Dependent Kinase ◽  
Collagen Induced Arthritis ◽  
Expression Levels ◽  
Amyloid A ◽  
Interfering Rna ◽  
Deficient Mice

This study was performed to elucidate the molecular function of the synoviocyte proliferation-associated in collagen-induced arthritis (CIA) 1/serum amyloid A-like 1 (SPACIA1/SAAL1) in mice CIA, an animal model of rheumatoid arthritis (RA), and human RA-synovial fibroblasts (RASFs). SPACIA1/SAAL1-deficient mice were generated and used to create mouse models of CIA in mild or severe disease conditions. Cell cycle-related genes, whose expression levels were affected by SPACIA1/SAAL1 small interfering RNA (siRNA), were screened. Transcriptional and post-transcriptional effects of SPACIA1/SAAL1 siRNA on cyclin-dependent kinase (cdk) 6 gene expression were investigated in human RASFs. SPACIA1/SAAL1-deficient mice showed later onset and slower progression of CIA than wild-type mice in severe disease conditions, but not in mild conditions. Expression levels of cdk6, but not cdk4, which are D-type cyclin partners, were downregulated by SPACIA1/SAAL1 siRNA at the post-transcriptional level. The exacerbation of CIA depends on SPACIA1/SAAL1 expression, although CIA also progresses slowly in the absence of SPACIA1/SAAL1. The CDK6, expression of which is up-regulated by the SPACIA1/SAAL1 expression, might be a critical factor in the exacerbation of CIA.

scholarly journals SPOP Could Play a Potential Inhibitory Role in Human Renal Cell Carcinoma

2021 ◽  
Author(s):  
zhi chen ◽  
Zuan Li ◽  
Deyong Nong ◽  
Ximing Li ◽  
Guihai Huang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Immunohistochemical Staining ◽  
Human Renal Cell Carcinoma ◽  
Expression Levels ◽  
Normal Tissues ◽  
Proliferation And Apoptosis

Abstract Background: SPOP, a substrate adaptor of Cul3 ubiquitin ligase, plays crucial roles in solid neoplasms by promoting the ubiquitination and degradation of substrates. Limited studies have shown that SPOP is overexpressed in human renal cell carcinoma (RCC) tissue. However, the exact role of SPOP in RCC remains unclear and needs to be further elucidated. The present study showed that SPOP was expressed at different levels in different RCC cell lines. The purpose of this study was to explore the roles of SPOP in the biological features of RCC cells and determine the expression levels of SPOP in human tissue microarrays (TMAs) and kidney tissues.Methods: Here, SPOP was overexpressed by lentiviral vector transfection in ACHN and Caki-1 cells, and SPOP was knocked down in Caki-2 cells with similar transfection methods. The transfection efficiency was evaluated by quantitative PCR and western blotting analyses. The role of SPOP in the proliferation, migration, invasion and apoptosis of cell lines was determined by the MTT, wound-healing, Transwell and flow cytometry assays. Moreover, the cells were treated with different drug concentrations in proliferation and apoptosis assays to investigate the effect of sunitinib and IFN-α2b on the proliferation and apoptosis of SPOP-overexpressing cells and SPOP-knockdown RCC cells. Finally, immunohistochemical staining of SPOP was performed in kidney tissues and TMAs, which included RCC tissues and corresponding adjacent normal tissues.Results: Overexpression of SPOP inhibited cell proliferation, migration and invasion and increased cell apoptosis. Interestingly, sunitinib and IFN-α2b at several concentrations increased the proliferation inhibitory rate and total apoptosis rate of cells overexpressing SPOP. The findings of the present study showed that the SPOP protein was significantly expressed at low levels in most clear cell RCC (ccRCC) tissues and at relatively high levels in the majority of adjacent normal tissues and kidney tissues. Kaplan-Meier survival analysis showed that there was no statistically significant difference in cumulative survival based on the data of different SPOP expression levels in TMA and patients.Conclusions: In contrast to previous studies, our findings demonstrated that overexpression of SPOP might suppress the progression of RCC cells, which was supported by cell experiments and immunohistochemical staining. SPOP could be a potential tumour inhibitor in RCC.

scholarly journals Studying the Role and Molecular Mechanisms of MAP4K3 in Sorafenib Resistance of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yi Shi ◽  
Xiaofei Mo ◽  
Simei Hong ◽  
Tianbao Li ◽  
Baozhen Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Flow Cytometry ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Resistant Cell ◽  
Therapeutic Drug ◽  
Specific Gene ◽  
Sorafenib Treatment ◽  
Proliferation And Apoptosis

Sorafenib is the first FDA-approved therapeutic drug for molecular target medication on advanced-stage hepatocellular carcinoma. It is reported that sorafenib could improve the survival of progression-free patients for 4 to 6 months; however, most of the patients developed drug resistance. Thus, it is critical to reveal the biological mechanisms behind sorafenib resistance. In this study, a sorafenib-resistant model was developed by exposing HepG2 cells to sorafenib with gradient increasing concentration, and the resistance-related genes were screened by microarray. Real-time qPCR was used to validate selected gene expression of the resistance model, and lentivirus vector-mediated RNA interference was applied for specific gene knockdown. In addition, high-throughput High Celigo Select (HCS) and flow cytometry were used to measure the effect on cellular proliferation and apoptosis. As a result, our study established a sorafenib-resistant model with IC50 of 9.988 μM. The Affymetrix expression profile of the sorafenib-resistant model showed 35 resistant-related genes, and 91.4% of the resistant genes showed upregulation in HepG2 resistance cells. In addition, 20 genes were knocked down to measure cell proliferation, and MAP4K3 with high proliferation inhibiting phenotype was chosen for further study. Meanwhile, the HCS results revealed that shMAP4K3 transfection could downregulate resistant cell proliferation, and the flow cytometry results showed that cell apoptosis was significantly increased in the MAP4K3 knockdown group. In summary, MAP4K3 is a novel molecular marker for improving the drug sensitivity of sorafenib treatment in hepatocellular carcinoma.

scholarly journals Effects of Watermelon Consumption on Cellular Proliferation, and Apoptosis in Rat Colon (P05-019-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Meseret Fesseha ◽  
Mee Young Hong
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Dietary Intervention ◽  
Citrullus Lanatus ◽  
Proliferation Index ◽  
Cancer Center ◽  
Rat Colon ◽  
Proliferative Zone ◽  
Proliferation And Apoptosis

Abstract Objectives Colon Cancer is the second deadliest cancerous disease worldwide among men and women. It has been estimated that more than half of colon cancers may be preventable by dietary intervention. A disturbance of the homeostasis between cellular proliferation and apoptosis is associated with colon cancer development. Watermelon (Citrullus lanatus) is rich in L-citrulline, a precursor of L-arginine. It has been shown that L-arginine may have anti-inflammatory roles and serves as a substrate for synthesis of nitric oxide, which in turn exerts wide-ranging physiological effects including tumoricidal effects via modification of cell kinetics. Our research examined if colon cancer can be prevented with the supplementation of watermelon powder by lowering cellular proliferation but enhancing apoptosis. Methods In order to test the hypothesis, 21-days old 32 Sprague Dawley rats were allocated to three groups; control, L- arginine (0.36% L-arginine) and watermelon powder (0.5%, w/w). Carcinogen azoxymethane was injected at week 4 and 5, and colon tissues were harvested at 5 week after the 2nd carcinogen injection. Cell proliferation and apoptosis were enumerated using a quantitative immunohistochemical analysis of Ki-67 antibody and TUNEL assay, respectively. Results Cell proliferation was mainly located bottom of colonic crypt (P < 0.05). Apoptotic cells were mostly located in the upper part of crypt (P < 0.05). L-arginine and watermelon fed rats lowered cell proliferation index and proliferative zone (P < 0.05). However, no difference was found on apoptosis among the three groups. Conclusions These results suggest that watermelon powder supplementation may reduce the risk of colon cancer by reducing cell proliferation rather than alteration of apoptosis. Further study will follow to determine the mechanism of anti-proliferative effect of watermelon supplementation. Funding Sources National Watermelon Promotion Board; SDSU/UCSD Cancer Center Partnership Scholars Program.

scholarly journals TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1α activity

2014 ◽  
Vol 112 (1) ◽  
pp. 220-225 ◽  
Author(s):  
Marina Stantic ◽  
Habib A. M. Sakil ◽  
Hanna Zirath ◽  
Trixy Fang ◽  
Gema Sanz ◽  
...  
Keyword(s):  
Tumor Angiogenesis ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Vascular Endothelial ◽  
Human Breast ◽  
P53 Family ◽  
Blood Vessel Formation ◽  
Angiogenic Switch ◽  
Vascular Endothelial Cadherin ◽  
Proliferation And Apoptosis

The p53-family member TAp73 is known to function as a tumor suppressor and regulates genomic integrity, cellular proliferation, and apoptosis; however, its role in tumor angiogenesis is poorly understood. Here we demonstrate that TAp73 regulates tumor angiogenesis through repression of proangiogenic and proinflammatory cytokines. Importantly, loss of TAp73 results in highly vascularized tumors, as well as an increase in vessel permeability resulting from disruption of vascular endothelial-cadherin junctions between endothelial cells. In contrast, loss of the oncogenic p73 isoform ΔNp73 leads to reduced blood vessel formation in tumors. Furthermore, we show that up-regulated ΔNp73 levels are associated with increased angiogenesis in human breast cancer and that inhibition of TAp73 results in an accumulation of HIF-1α and up-regulation of HIF-1α target genes. Taken together, our data demonstrate that loss of TAp73 or ΔNp73 up-regulation activates the angiogenic switch that stimulates tumor growth and progression.

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