Changes in the Proliferation/Apoptosis Balance in the Bovine Ovary: A Key Early Event in Follicular Persistence

2017 ◽  
Vol 204 (5-6) ◽  
pp. 314-325 ◽  
Author(s):  
E. Matías Belotti ◽  
Antonela F. Stassi ◽  
Melisa M.L. Velázquez ◽  
Pablo U. Díaz ◽  
Belkis E. Marelli ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Caspase 3 ◽  
Control Group ◽  
Early Event ◽  
Ki 67 ◽  
Antral Follicles ◽  
Theca Cells ◽  
Bovine Ovary ◽  
Bcl2 Expression

The objective of this work was to evaluate proliferation and apoptosis in the bovine ovary in a model of follicular persistence induced by low levels of progesterone to detect incipient changes during cystic ovarian disease development on the expected day of ovulation (day 0) and after 5, 10, and 15 days of follicular persistence. We analyzed cell proliferation by evaluating the expression of Ki-67 and apoptosis by evaluating caspase-3, BAX, and BCL2 expression. Proliferation was similar in the granulosa and theca cells of antral follicles in the P0 group (treated with progesterone up to the expected day of ovulation) and in the control group. A decrease in cell proliferation was detected after 5 days of persistence (P5) in relation to P0 (p < 0.05). Similar changes were found in the granulosa cells of the persistent follicles in relation to the control group (p < 0.05). Caspase-3 expression was similar in granulosa cells of antral follicles at early stages of persistence, with an increase after 15 days of persistence (p < 0.05). In the granulosa cells of group P10 (10 days of persistence), caspase-3 expression was reduced relative to that of antral follicles from the control group (p < 0.05). BCL2 expression was higher in granulosa cells of the persistent follicles of group P0 relative to the control follicles, with no changes in BAX expression, which was increased in persistent follicles of group P15 (p < 0.05). Similar results were observed in theca cells at initial stages of persistence. The results show that, initially, proliferation is maintained with low apoptosis and an increase in cell survival.

Effects of Papaya Leaf Extract (Carica papaya L.) on Cellular Proliferation and Apoptosis in Cervical Cancer Mice Model

2019 ◽  
Vol 17 (5) ◽  
pp. 265-275
Author(s):  
Y. Peristiowati ◽  
Y. Puspitasari ◽  
Indasah
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Hela Cells ◽  
Leaf Extract ◽  
Caspase 3 ◽  
Methanol Extract ◽  
Negative Control ◽  
Proliferation Index ◽  
Control Group ◽  
P53 Expression

This study is aimed at analyzing the anticancer properties of papaya leaf extract, specifically the inhibition of cell proliferation and apoptotic induction through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p53 pathways. Twenty-five mice (Mus musculus), aged 2 months and weighing 20–30 g, was injected with 0.5 mg dexamethasone for 7 days. The mice were then injected intracutaneously with 1 ml of HeLa cells (8 × 106 HeLa cells/microliter). The mice were divided into five groups (5 each): negative control (P1) (5% CMC-Na, sodium carboxymethyl cellulose), treatment II (225 mg/kg BW (body weight) papaya leaves methanol extract), treatment III (450 mg/kg BW), treatment IV (750 mg/kg BW), and treatment PV (2 mg alcohol anticancer drug). Papaya leaf extract treatments were applied for 2 weeks. Then, the tumor tissue was isolated for hematoxylin and eosin staining. Immunohistochemical imaging was used to detect Ki-67, caspase-3, NF-κB, and p53 expression. Further analysis was undertaken using the ImmunoRatio software program. The results indicated that administration of papaya leaf methanol extract significantly increased the expression of NF-κB and p53 at a dose of 450 mg/kg BW. Our results also showed that the mice treated with 450 mg of papaya leaf extract per kg of BW (P3) had the largest increase of caspase-3 expression compared to the negative control group. Papaya leaf ethanol extract decreased the cancer cell proliferation index and increased apoptosis of cancer cells in animal models of cervical cancer; it may also work to increase NF-kB expression and expression of the p53 gene.

scholarly journals Sirtuin 1 and Sirtuin 3 in Granulosa Cell Tumors

2021 ◽  
Vol 22 (4) ◽  
pp. 2047
Author(s):  
Nina Schmid ◽  
Kim-Gwendolyn Dietrich ◽  
Ignasi Forne ◽  
Alexander Burges ◽  
Magdalena Szymanska ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Drug Targets ◽  
Growth Regulation ◽  
Sirtuin 1 ◽  
Ki 67 ◽  
Granulosa Cell Tumors ◽  
Novel Drug

Sirtuins (SIRTs) are NAD+-dependent deacetylases that regulate proliferation and cell death. In the human ovary, granulosa cells express sirtuin 1 (SIRT1), which has also been detected in human tumors derived from granulosa cells, i.e., granulosa cell tumors (GCTs), and in KGN cells. KGN cells are an established cellular model for the majority of GCTs and were used to explore the role of SIRT1. The SIRT1 activator SRT2104 increased cell proliferation. By contrast, the inhibitor EX527 reduced cell numbers, without inducing apoptosis. These results were supported by the outcome of siRNA-mediated silencing studies. A tissue microarray containing 92 GCTs revealed nuclear and/or cytoplasmic SIRT1 staining in the majority of the samples, and also, SIRT2-7 were detected in most samples. The expression of SIRT1–7 was not correlated with the survival of the patients; however, SIRT3 and SIRT7 expression was significantly correlated with the proliferation marker Ki-67, implying roles in tumor cell proliferation. SIRT3 was identified by a proteomic analysis as the most abundant SIRT in KGN. The results of the siRNA-silencing experiments indicate involvement of SIRT3 in proliferation. Thus, several SIRTs are expressed by GCTs, and SIRT1 and SIRT3 are involved in the growth regulation of KGN. If transferable to GCTs, these SIRTs may represent novel drug targets.

scholarly journals Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer

2018 ◽  
Vol 40 (02) ◽  
pp. 079-085 ◽  
Author(s):  
Mariana Seabra ◽  
Eduardo Cândido ◽  
Paula Vidigal ◽  
Rivia Lamaita ◽  
Angélica Rodrigues ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cervical Squamous Cell Carcinoma ◽  
Pelvic Lymphadenectomy ◽  
Histological Evaluation ◽  
Clinicopathological Parameters ◽  
Control Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
P53 Expression ◽  
Hematoxylin And Eosin

Objective The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association. Methods Women with IB stage-ICSCC (n = 20) and women with uterine leiomyoma (n = 20) were prospectively evaluated. Patients with ICSCC were submitted to type B-C1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies. Results The WWOX expression was significantly lower in the tumor compared with the expression in the benign cervix (p = 0.019). The WWOX expression was inversely associated with the CD31 expression in the tumor samples (p = 0.018). There was no association between the WWOX expression with the p53 expression (p = 0.464) or the Ki-67 expression (p = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p = 0.156), grade of differentiation (p = 0.914), presence of lymphatic vascular invasion (p = 0.155), parametrium involvement (p = 0.421) or pelvic lymph node metastasis (p = 0.310) in ICSCC tissue samples. Conclusion The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.

Effect of SRY-Related High Mobility Group Box 9 on Extracellular Signal-Regulated Kinase/p38 Signaling Pathway in Glioma

2021 ◽  
Vol 11 (1) ◽  
pp. 171-175
Author(s):  
Tianlong Quan ◽  
Chunhua Zhang ◽  
Xin Song ◽  
Lu Wang
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
High Mobility ◽  
Negative Control ◽  
Glioma Cell Line ◽  
High Mobility Group ◽  
Control Group

As a common malignant tumor in neurosurgery, glioma is characterized as high incidence rate, easy to invade, metastasize and recurrent. It is difficult to treat and has a poor prognosis. The gliomas pathogenesis is complex and has not been fully resolved. Therefore, finding effective molecular targets for glioma is beneficial to improve therapeutic effect. The SRY-related high mobility group box 9 (SOX9) gene involves in mammalian development and is significantly increased in glioma. However, SOX9’s role in gliomas is unclear. The glioma cell line U87 was assigned into control group, scramble group that was transfected with siRNA negative control, and SOX9 siRNA group that was transfected with SOX9 siRNA followed by analysis of SOX9 mRNA and protein level by qPCR and Western blot, cell proliferation by MTT assay, cell apoptosis by Caspase 3 activity assay, cell invasion by Transwell assay, and MMP-9 level by ELISA. SOX9 siRNA transfection significantly downregulated SOX9 mRNA and protein expressions, inhibited U87 cell proliferation, enhanced Caspase 3 activity, suppressed cell invasion of U87, decreased the secretion of MMP-9 in the supernatant, and reduced ERK1/2 and P38 phosphorylation levels (P < 0.05). SOX9 can regulate the progression of glioma by regulating ERK/P38 signaling pathway, promoting cell apoptosis, inhibiting cell proliferation, and restraining cell invasion.

scholarly journals Expression of Notch–Hif-1α signaling pathway in liver regeneration of rats

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094379
Author(s):  
Yanshan Li ◽  
Yunxiuxiu Xu ◽  
Ruomei Wang ◽  
Wenxin Li ◽  
Wenguang He ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Body Weight ◽  
Protein Expression ◽  
Liver Regeneration ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Saline Control ◽  
Control Group ◽  
Mrna Levels ◽  
Ki 67

Objective To investigate whether the Notch–Hif-1α signaling pathway is involved in liver regeneration. Methods Rats were divided into two groups and treated with daily intraperitoneal injections of saline (control) or the gamma-secretase inhibitor, Fli-06, for 2 days. Two-thirds of the rat livers were resected and rats were later euthanized at specific time points post-resection to analyze the remnant livers. Each group's liver/body weight ratio was calculated, and immunostaining and western blotting were used to determine the cell proliferation marker, PCNA and Ki-67 expression. Real-time PCR and western blotting were used to compare the mRNA expression of Notch homolog-1 ( Notch1), hairy and enhancer of split-1 ( Hes1), and vascular endothelial growth factor ( Vegf), and the protein expression of NICD and HIF-1α, respectively. Results The liver/body weight ratios and number of Ki-67- and PCNA-positive cells were significantly lower in the experimental group than the control group, indicating lower levels of liver regeneration following the disruption of Notch signaling by Fli-06. The Hes1 and Vegf mRNA levels and NICD and HIF-1α protein expression levels were all down-regulated by Fli-06 treatment. Conclusion Notch–Hif-α signaling pathway activation plays an important role in liver regeneration, where it may contribute toward liver cell proliferation.

Effect of Silent Information Regulator on the Survival and Osteogenic Differentiation of Inflammatory Bone Marrow Mesenchymal Stem Cells by Regulating NF-κB Signaling Pathway

2020 ◽  
Vol 10 (1) ◽  
pp. 121-126
Author(s):  
Wenkun Lu ◽  
Tao Wang ◽  
Xunjian Gao ◽  
Fuqiang Yang ◽  
Jianjian Ge
Keyword(s):  
Cell Proliferation ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Adipogenic Differentiation ◽  
Control Group ◽  
Promote Cell Proliferation ◽  
Alp Activity ◽  
Marrow Mesenchymal Stem Cells ◽  
Inflammation Group

Osteogenic differentiation of BMSCs is beneficial for osteoarthritis (OA) treatment. Silent information regulator (SIRT1) plays a role in endocrine diseases and aging-related diseases. However, the role of SIRT1 in OA has not yet been elucidated. Rat BMSCs were isolated and divided into control group, inflammation group (BMSCs were cultured with IL-6), SIRT1 group (SIRT1 agonist Resveratrol was added under the action of IL-6) followed by analysis of cell proliferation by MTT assay, Caspase 3 activity, ALP activity, expression of osteogenic genes Runx2 and OC and adipogenic differentiation gene PPARγ2 by Real time PCR, NF-κB expression by western blot and secretion of TNF-α and IL-6 by ELISA. In inflammation group, SIRT1 expression was significantly decreased, cell proliferation was significantly inhibited, and Caspase 3 activity was increased. Meanwhile, ALP activity, Runx2 and OC expression was decreased, PPARγ2 and NF-κB expression was increased, along with elevated TNF-α and IL-6 secretion compared to control (P < 0.05). Resveratrol can significantly promote the expression of SIRT1 in BMSCs of inflammation group, promote cell proliferation, decrease Caspase 3 activity, and increase Runx2 and OC expression. In addition, it decreased PPARγ2 and NF-κB expression and reduced the secretion of TNF-α and IL-6 (P < 0.05). The expression of SIRT1 was decreased in BMSCs under inflammation. SIRT1 overexpression in BMSCs under inflammation inhibits inflammation, promotes proliferation and osteogenic differentiation of BMSCs through regulating NF-κB signaling pathway.

scholarly journals Dysregulation of autophagy-associated microRNAs in condyloma acuminatum

2020 ◽  
Author(s):  
Shi Wu ◽  
Dan Lu ◽  
Xinkai Zheng ◽  
Jin Xu ◽  
Zhen Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Light Chain ◽  
Target Genes ◽  
Condyloma Acuminatum ◽  
Differentially Expressed ◽  
Control Group ◽  
Healthy Controls ◽  
Related Protein ◽  
Ki 67 ◽  
Differentially Expressed Mirnas

Abstract Objectives This study was designed to investigate the miRNAs that regulate the cell proliferation of condyloma acuminatum (CA) lesions and their targets.Methods The expression of Ki-67 in 26 CA patients compared with 10 healthy controls was assessed by immunohistochemistry. And the different miRNAs in 4 CA patients and 4 control cases were analyzed by bioinformatics. PCR was used to validate the expression of screened miRNA and its corresponding target genes.Results The expression of Ki-67 was abnormally increased in CA compared with healthy controls ( P <0.05). The comparison of the control group with the CA group revealed 81 differentially expressed miRNAs, of which 56 were downregulated and 25 were upregulated. Two of the differentially expressed miRNAs, miR-30a-5p and miR-514a-3p, are associated with cell proliferation and their target genes are autophagy-related protein (Atg) 5 and Atg12, and Atg3 and Atg12, respectively. PCR results showed that the expression levels of miR-30a-5p and miR-514a-3p were decreased in CA patients compared with healthy controls ( P <0.05), whereas the expression of Atg5, Atg12 and Atg3 was increased ( P <0.05). The expression of the autophagy proteins microtubule-associated protein 1 light chain 3 (LC3) and P62/SQSTM1 (P62) was abnormally increased in the local lesion tissue of the 26 patients with CA compared with the 10 healthy controls, as assessed by immunohistochemistry ( P <0.05).Conclusions Our results suggest that autophagy levels may be modulated by has-miRNA30a-5p and has-miRNA514a-3p in CA patients, leading to dysregulated cell proliferation.

Exploring molecular mechanism of novel liposomal nanoparticles application in glioma

2021 ◽  
Vol 11 (7) ◽  
pp. 1161-1167
Author(s):  
Guo-Shi Lin ◽  
Song-Jie Tu ◽  
Shui-Shun Zheng ◽  
Wei-Wen Wang ◽  
Rui-Sheng Lin
Keyword(s):  
Cell Proliferation ◽  
Caspase 3 ◽  
Mrna Level ◽  
Glioma Cells ◽  
Glioma Cell Line ◽  
Control Group ◽  
Targeted Nanoparticles ◽  
Reduce Cell Proliferation ◽  
Liposomal Nanoparticles ◽  
Tissue Specimens

This study investigated whether miR-509 plays a role in regulating autophagy and apoptosis-related caspase 3 genes, and analyzes targeted nanoparticles intervention in glioma cells. The surgically resected glioma tissue specimens were included as observation group, and control group used a 2-cm open tissue next to the glioma followed by analysis of miR-509 and caspase 3 level by qPCR. Glioma cell line U251 was divided into miRNC group, targeted nanoparticle group, siRNA-NC group, and siRNA-caspase 3 group, followed by analysis of caspase 3 expression, cell proliferation by flow cytometry, and cell invasion and metastasis by trans well. Caspase 3 mRNA expression was significantly higher in glioma tissues compared with controls. Lower miR-509 and higher caspase 3 expression were correlated with TNM stage. Caspase 3 mRNA level was significantly higher and miR-509 was lower in glioma cells or glioma ell line U251 than those in normal cells. Transfection of siRNA-caspase 3, targeted nanoparticles effectively reduced cell proliferation, metastasis, and invasion and down-regulated caspase 3 levels in U251 cells. Reduced miR-509 expression was associated with elevated caspase 3 expression and enhanced invasive metastatic capacity of glioma cells. Overexpression of miR-509 can effectively reduce cell proliferation, metastasis, and invasion by targeted nanoparticles inhibiting caspase 3 expression.

MiR-144-3p Regulates Lipopolysaccharide-Stimulated Chondrocyte Biological Behavior via Wingless-Related Integration Site/Beta-Catenin

2021 ◽  
Vol 11 (8) ◽  
pp. 1612-1617
Author(s):  
Nanxin Zhang ◽  
Kuangda Li ◽  
Qiong Han ◽  
Maohou Wu ◽  
Qiang Li
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Caspase 3 ◽  
Biological Behavior ◽  
Cartilage Tissue ◽  
Control Group ◽  
Beta Catenin ◽  
Activity Increase ◽  
Signaling Protein ◽  
Promote Cell Proliferation

Osteoarthritis (OA) gradually affects all joint tissues. Chondrocytes participate in osteoarthritis. However, the role and mechanism of MiR-144-3p on chondrocytes during the development of OA has not been elucidated. OA patients and normal bone and articular cartilage tissues were collected to measure MiR-144-3p level by Real-time PCR. Chondrocytes were divided into control group, LPS group (1 μg/ml lipopolysaccharide (LPS) was added to establish an osteoarthritis (OA) stimulation model, and MiR-144-3p inhibitor group which was transfected with MiR-144-3p inhibitor followed by analysis of cell proliferation by MTT, Caspase 3 activity, Wnt/β-catenin signaling protein expression by Western blot and TNF-α and IL-6 secretion by ELISA. MiR-144-3p was significantly upregulated in OA patients (P <0.05). In LPS group, MiR-144-3p was significantly upregulated, chondrocyte proliferation decreased, Caspase 3 activity increased, Wnt/β-catenin signaling protein decreased, and TNF-α and IL-6 secretion increased (P <0.05). MiR-144-3p inhibitor transfection can significantly down-regulate MiR-144-3p, promote cell proliferation, reduce Caspase 3 activity, increase Wnt/β-catenin signaling protein expression, and reduce TNF-α and IL-6 secretion (P <0.05). MiR-144-3p is upregulated in osteoarthritis cartilage tissue. Inhibition of MiR-144-3p can inhibit articular chondrocytes apoptosis under inflammatory condition, promote cell proliferation, and alleviate joint inflammation by regulating Wnt/β-catenin signaling pathway.

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