scholarly journals NPM1 is a Novel Therapeutic Target and Prognostic Biomarker for Ewing Sarcoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Yangfan Zhou ◽  
Yuan Fang ◽  
Junjie Zhou ◽  
Yulian Liu ◽  
Shusheng Wu ◽  
...  
Keyword(s):  
Ewing Sarcoma ◽  
Es Cells ◽  
Differentially Expressed Gene ◽  
Bioinformatic Analysis ◽  
Dependent Manner ◽  
Hub Gene ◽  
Immune Infiltration ◽  
Proliferation And Apoptosis ◽  
Immune Related Genes ◽  
Dose Dependent

Ewing sarcoma (ES) is a cancer that may originate from stem mesenchymal or neural crest cells and is highly prevalent in children and adolescents. In recent years, targeted therapies against immune-related genes have shown good efficacy in a variety of cancers. However, effective targets for immunotherapy in ES are yet to be developed. In our study, we first identified the immune-associated differential hub gene NPM1 by bioinformatics methods as a differentially expressed gene, and then validated it using real time-PCR and western blotting, and found that this gene is not only closely related to the immune infiltration in ES, but also can affect the proliferation and apoptosis of ES cells, and is closely related to the survival of patients. The results of our bioinformatic analysis showed that NPM1 can be a hub gene in ES and an immunotherapeutic target to reactivate immune infiltration in patients with ES. In addition, treatment with NPM1 promoted apoptosis and inhibited the proliferation of ES cells. The NPM1 inhibitor NSC348884 can induce apoptosis of ES cells in a dose-dependent manner and is expected to be a potential therapeutic agent for ES.

44 Exploring the use of silver and diamond nanoparticles on sperm cell invitro and chicken embryo in ovo

2021 ◽  
Vol 33 (2) ◽  
pp. 129
Author(s):  
M. P. Thavhana ◽  
T. L. Nedambale ◽  
L. J. Shai ◽  
M. L. Mphaphathi
Keyword(s):  
Cell Viability ◽  
Chicken Embryo ◽  
Sperm Cell ◽  
Control Group ◽  
Dependent Manner ◽  
Ag Nps ◽  
In Ovo ◽  
Diamond Nanoparticles ◽  
Immune Related Genes ◽  
Dose Dependent

In poultry industry, chick viability is a crucial factor determining profitability from fertilized egg to placement at the farm. However, decreases in fertility and hatchability have been observed. Recently, there has been renewed interest in the use of silver nanoparticles (Ag-NPs) due to their antimicrobial properties and growth-promoting ability, and diamond nanoparticles (D-NPs) due to their biocompatibility properties. The aim of the study was to evaluate the effect of silver and diamond nanoparticles on chicken embryo oxidative status, biochemical indices, and expression of immune-related genes and on sperm cell viability. The experiment was conducted in Ross 308 chicken embryos and Ross 308 cockerels. One hundred and fifty fertilized eggs were divided randomly into 5 groups (5×30). Fertilized eggs were injected with 50 mg/L Ag-NPs at volumes of 100μL (group 1), 200μL (group 2) or 50 mg/L D-NPs at volumes of 100μL (group 3) or 200μL (group 4), or received no nanoparticles (control; group 5) and incubated at 37°C and 55% humidity for 20 days. Then, chicken blood was collected and centrifuged to evaluate alkaline phosphatase (ALP), alanine transaminase (ALT), lactate dehydrogenase (LDH), glucose, urea, and free haemoglobin. Chicken embryo liver was used to evaluate antioxidant capacity (TAC) and chicken embryo spleen was used to evaluate expression of the immune-related genes interleukin-1β (IL-1β), toll-like receptor (TLR)4, TLR2, and TLR15. Semen was randomly divided into 1 control and 8 treatment groups and treated with 50 mg/L Ag-NPs: group A (0.1ppm), group B (1ppm), group C (5ppm), group D (10ppm) or 50 mg/L D-NPs: group E (1ppm), group F (5ppm), group G (10ppm), and group H (20ppm). Sperm viability was analysed using prestoblue metabolic assay. Data were analysed using PROC in GLM procedure of SAS 2014 (SAS Institute Inc.). Decrease in sperm cell viability was recorded in a dose-dependent manner. Sperm cell viability decreased (P<0.005) as the concentration of Ag-NP or D-NP increased. Addition of 100μL of Ag-NPs increased the growth rate of chicken embryo but not 200μL of Ag-NPs or addition of D-NPs. Increases in ALP, ALT, LDH, glucose and urea enzyme were observed in a dose-dependent manner in both Ag-NPs and D-NPs. Addition of 50 mg/L Ag-NPs or 50 mg/L D-NPs increased (P<0.001) TAC of chicken embryo as the volume increased. Additions of 200μL of Ag-NPs, 100μL of D-NPs, and 200μL of D-NPs were haemolytic (P<0.001) but addition of 100μL of Ag-NPs was not. Additions of 100 or 200μL of Ag-NPs or 100μL of D-NPs downregulated IL-1β and 200μL of D-NPs upregulated IL-1β compared with the untreated control group. Additions of 100 or 200μL of Ag-NPs or 200μL of D-NPs induced expression of TLR4 and TLR15. Furthermore, addition of Ag-NPs did not result in expression of TLR2. We concluded that administration of 50 mg/L Ag-NPs and 50 mg/L D-NPs in ovo improve immune status and administration of 100μL of Ag-NPs improved the growth rate of chicken embryo. However, toxicity associated with 50 mg/L Ag-NPs and 50 mg/L D-NPs remains a concern and need to be addressed before use.

scholarly journals Potential Mechanisms of an Antiadenomyosis Chinese Herbal Formula Shaoyao-Gancao Decoction in Primary Cell Culture Model

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yong-Ge Guan ◽  
Jin-Bin Liao ◽  
Kun-Yin Li ◽  
Yu-Cui Li ◽  
Yang Song ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Culture Model ◽  
Proliferation And Apoptosis ◽  
Medicine Prescription ◽  
Chinese Medicine Prescription ◽  
Induced Apoptosis ◽  
Dose Dependent

Background. Shaoyao-Gancao Decoction (SGD), a well-known traditional Chinese medicine prescription, has been widely used to treat adenomyosis, dysmenorrhea, abdominal pain, and inflammation in Asia. However, the mechanism underlying the effectiveness of SGD in the treatment of adenomyosis still remains elusive. The present study aimed to investigate the bioactivity of SGD and its underlying molecular mechanisms using cultured human adenomyosis-derived cells.Methods. Human adenomyosis-derived cells were treated with SGD and its major constituents (paeoniflorin and liquiritin)in vitro. Effects of SGD, paeoniflorin, and liquiritin on cell proliferation and apoptosis were examined by MTT assay and flow cytometry analyses. The effects of SGD, paeoniflorin, and liquiritin on the production of PGE2and PGF2αwere assayed using ELISA. ER-αand OTR mRNA expression levels were also evaluated by real-time qRT-PCR.Results. SGD, paeoniflorin, and liquiritin inhibited proliferation and induced apoptosis of human adenomyosis-derived cells in a dose-dependent manner. SGD and paeoniflorin significantly reduced the PGE2and PGF2αproduction. Furthermore, they remarkably decreased the mRNA levels of ER-αand OTR.Conclusions. The results of this study provide possible mechanisms for the bioactivity of SGD for treating adenomyosis and contribute to the ethnopharmacological knowledge about this prescription.

scholarly journals Chlorogenic Acid Ameliorates Damage Induced by Fluorene-9-Bisphenol in Porcine Sertoli Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Shaoxuan Zhang ◽  
Boxing Sun ◽  
Dali Wang ◽  
Ying Liu ◽  
Jing Li ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Sertoli Cells ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Dependent Manner ◽  
Real Time Quantitative Pcr ◽  
Proliferation And Apoptosis ◽  
Apoptosis Assay ◽  
Underlying Mechanisms ◽  
Dose Dependent

4,4′-(9-Fluorenylidene) diphenol (BPFL, also known as BHPF and fluorene-9-bisphenol) is a novel bisphenol A substitute that is used in the plastics industry as an organic synthesis intermediate and is a potential endocrine disruptor. However, the deleterious effects of BPFL on porcine Sertoli cells (SCs) and the possible underlying mechanisms are still unclear. Chlorogenic acid (CA) is a free radical scavenger in the cellular antioxidant system that prevents oxidative damage and apoptosis. In the present research, we found that BPFL induced impairments in porcine SCs in a dose-dependent manner and that CA protected porcine SCs against BPFL exposure-induced impairments. Cell viability, proliferation and apoptosis assay results revealed that BPFL exposure could inhibit porcine SC proliferation and induce apoptosis, while CA supplementation ameliorated the effects of BPFL. Further analysis revealed that BPFL exposure induced oxidative stress, mitochondrial membrane potential dysfunction and DNA damage accumulation. Transcriptome analysis and further real-time quantitative PCR and Western blot results showed that BPFL exposure induced endoplasmic reticulum stress and apoptosis. Supplementation with CA dramatically ameliorated these phenotypes in BPFL-exposed porcine SCs. Overall, the present research reveals the possible underlying mechanisms by which BPFL exposure induced impairments and CA supplementation protected against these impairments in porcine SCs.

Roles of vitamin D and its receptor in the proliferation and apoptosis of luteinised granulosa cells in the goat

2020 ◽  
Vol 32 (3) ◽  
pp. 335 ◽  
Author(s):  
Xiaolei Yao ◽  
Zhibo Wang ◽  
M. A. El-Samahy ◽  
Caifang Ren ◽  
Zifei Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Vitamin D ◽  
Granulosa Cells ◽  
Expression Patterns ◽  
Follicular Development ◽  
Proliferation Rate ◽  
Control Group ◽  
Dependent Manner ◽  
Proliferation And Apoptosis ◽  
Dose Dependent

The objective of this study was to investigate the dose-dependent effect of 1α,25-(OH)2VD3 (Vit D3) on invitro proliferation of goat luteinised granulosa cells (LGCs) and to determine the underlying mechanisms of its action by overexpressing and silencing vitamin D receptor (VDR) in LGCs. Results showed that VDR was prominently localised in GCs and theca cells (TCs) and its expression increased with follicle diameter, but was lower in atretic follicles than in healthy follicles. The proliferation rate of LGCs was significantly higher in the Vit D3-treated groups than in the control group, with the highest proliferation rate observed in the 10nM group; this was accompanied by changes in the expression of cell cycle-related genes. These data indicate that Vit D3 affects LGC proliferation in a dose-dependent manner. Contrary to the VDR knockdown effects, its overexpression upregulated and downregulated cell cycle- and apoptosis-related genes respectively; moreover, supplementation with 10nM of Vit D3 significantly enhanced these effects. These results suggest that changes in VDR expression patterns in LGCs may be associated with follicular development by regulation of cell proliferation and apoptosis. These findings will enhance the understanding of the roles of Vit D3 and VDR in goat ovarian follicular development.

Different Kinetics and Function of Vascular Endothelial Growth Factor Recepotor-1 and −2 during Hemangioblast Development from Primate Embryonic Stem Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3920-3920
Author(s):  
Katsutsugu Umeda ◽  
Toshio Heike ◽  
Gen Shinoda ◽  
Akira Niwa ◽  
Masato Arai ◽  
...  
Keyword(s):  
Es Cells ◽  
Embryonic Stem ◽  
Cell Development ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Blocking Antibody ◽  
Cd34 Cells ◽  
Low Levels ◽  
Endothelial Growth Factor ◽  
Dose Dependent

Abstract The close developmental association between hematopoietic and endothelial cells suggests that both lineage cells share a common precursor, the hemangioblast. The vascular endothelial growth factor (VEGF)-A system has been proven to have roles in the embryonic development of hemangioblast in mouse by the use of embryos or embryonic stem (ES) cells deprived of the genes encoding its ligand or receptors (VEGFR-1 and VEGFR-2). On the other hand, there have been only a few reports on the hemangioblast development during primate (human and monkey) embryogenesis. We have previously demonstrated that the hemangioblast is highly enriched in the VEGFR-2high CD34+ cell fraction, differentiated from cynomolgus monkey ES cells by 6-day coculture with OP9 stromal cells. In the current study, we examined whether the VEGF-A system was involved in the development of hemangioblast induced from primate ES cells by using the coculture system. VEGFR-1 and −2 were expressed by undifferentiated monkey ES cells at low levels. The VEGFR-2low cells gradually decreased while VEGFR-2high cells could be detected on day 6. On the other hand, VEGFR-1 was constantly expressed at low levels on day 6 and thereafter. Exogenous VEGF-A165, the action of which is mediated VEGFR-1 and VEGFR-2, increased the proportion of VEGFR-2high CD34+ cells in a dose-dependent manner. Addition of VEGF-E (VEGFR-2-specific agonist) and VEGFR-1 blocking antibody resulted in the increase of VEGFR-2high CD34+ cells in a dose-dependent manner, while VEGFR-2 blocking antibody suppressed their development. Thus, VEGF-A/VEGFR-2 interaction promoted the development of hemangioblast, while VEGF-A/VEGFR-1 interaction acted as a negative regulator. We then examined when VEGF-related signals work on VEGFR-2high cell development by changing factors on day 4. The proportion of VEGFR-2high CD34+ cells with the last 2-day VEGF-A165 and -E treatment were almost equivalent to that with continuous exposure to the VEGF. On the contrary, initial 4-day VEGF-A165 and -E treatment did not any stimulatory effects on VEGFR-2high CD34+ cell development. Our previous results show that during differentiation, Brachyury (early mesodermal marker) is first expressed on day 4, followed by the up-regulation of genes, such as SCL, LMO2, and MYB, representing hematopoietic and/or endothelial potentials on day 6. Collectively, VEGFR-2-mediated signals might contribute to the commitment and/or expansion of the hemangioblast rather than their development. This coculture system provides an opportunity to better understand the regulative mechanisms on early hematopoietic and endothelial cell development, which remains unresolved by experiments using human embryos.

scholarly journals Direct Effect of Chenodeoxycholic Acid on Differentiation of Mouse Embryonic Stem Cells Cultured under Feeder-Free Culture Conditions

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Soon-Jung Park ◽  
Seul-Bi Lee ◽  
Dong-Sup Lee ◽  
Young-Joon Ryu ◽  
Gene Lee ◽  
...  
Keyword(s):  
Direct Effect ◽  
Chenodeoxycholic Acid ◽  
Es Cells ◽  
Smooth Muscle Actin ◽  
Embryonic Stem ◽  
Farnesoid X Receptor ◽  
Stem Cell Markers ◽  
Dependent Manner ◽  
Dose Dependent ◽  
Mes Cells

Chenodeoxycholic acid (CDCA), a farnesoid X receptor (FXR) ligand, is a member of the nuclear receptor family and is probably involved in regulating the cellular activities of embryonic stem (ES) cells. Recently, although it was reported that the FXR ligand can mediate differentiation, apoptosis, and/or growth arrest in several cell types, it is still not well known how CDCA mediates effects in ES cells. Therefore, we investigated the direct effect of CDCA on mES cells. Feeder-free mES cells were treated in a dose-dependent manner with CDCA (50, 100, and 200 μM) for 72 h, and then a 100 μM CDCA treatment was performed for an additional 72 h. We analyzed the morphology, cell growth, cell characteristics, immunocytochemistry, and RT-PCR. In CDCA-treated cells, we observed the disappearance of pluripotent stem cell markers including alkaline phosphatase, Oct4, and Nanog and a time- and dose-dependent increase in expression of nestin, PAX6, andα-smooth muscle actin, but notα-fetoprotein. The 100 μM CDCA-treated cells in their second passage continued this differentiation pattern similar to those in the controls. In conclusion, these results suggest that CDCA can guide mES cells by an FXR-independent pathway to differentiate into ectoderm and/or mesoderm, but not endoderm.

Anthocyanins Extracted from Chinese Blueberry and its Anticancer Effects on HepG2 Cells

2014 ◽  
Vol 887-888 ◽  
pp. 592-595 ◽  
Author(s):  
Ya Wei Li ◽  
Dan Wang ◽  
Xiao Guang Li ◽  
Ying Jin
Keyword(s):  
Cell Proliferation ◽  
Treatment Group ◽  
Liver Cancer ◽  
Western Blotting ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Dependent Manner ◽  
Anticancer Effects ◽  
Proliferation And Apoptosis ◽  
Dose Dependent

Recently studies have demonstrated that anthocyanins from blueberry have anticancer effects. Here, HepG2 cells were treated with anthocyanins (200、400、600、800 and 1000 μg/ml) for 48h, the effects on cell proliferation and apoptosis were investigated. The results suggested that anthocyanins can inhibit the proliferation of HepG2 cells in a dose-dependent manner. The activity of caspase-3 was increased in the anthocyanins treatment group. Moreover, results of Western blotting shown that the expression of Caspase-3 protein increased significantly in the treatment group. Taken together, our data suggest that anthocyanins could be developed as an agent against liver cancer.

scholarly journals Flow perfusion effects on three-dimensional culture and drug sensitivity of Ewing sarcoma

2015 ◽  
Vol 112 (33) ◽  
pp. 10304-10309 ◽  
Author(s):  
Marco Santoro ◽  
Salah-Eddine Lamhamedi-Cherradi ◽  
Brian A. Menegaz ◽  
Joseph A. Ludwig ◽  
Antonios G. Mikos
Keyword(s):  
Shear Stress ◽  
Ewing Sarcoma ◽  
Es Cells ◽  
Tumor Biology ◽  
Three Dimensional ◽  
Dependent Manner ◽  
Flow Perfusion ◽  
Biomechanical Stimulation ◽  
Static Conditions ◽  
Stress Dependent

Three-dimensional tumor models accurately describe different aspects of the tumor microenvironment and are readily available for mechanistic studies of tumor biology and for drug screening. Nevertheless, these systems often overlook biomechanical stimulation, another fundamental driver of tumor progression. To address this issue, we cultured Ewing sarcoma (ES) cells on electrospun poly(ε-caprolactone) 3D scaffolds within a flow perfusion bioreactor. Flow-derived shear stress provided a physiologically relevant mechanical stimulation that significantly promoted insulin-like growth factor-1 (IGF1) production and elicited a superadditive release in the presence of exogenous IGF1. This finding is particularly relevant, given the central role of the IGF1/IGF-1 receptor (IGF-1R) pathway in ES tumorigenesis and as a promising clinical target. Additionally, flow perfusion enhanced in a rate-dependent manner the sensitivity of ES cells to IGF-1R inhibitor dalotuzumab (MK-0646) and showed shear stress-dependent resistance to the IGF-1R blockade. This study demonstrates shear stress-dependent ES cell sensitivity to dalotuzumab, highlighting the importance of biomechanical stimulation on ES-acquired drug resistance to IGF-1R inhibition. Furthermore, flow perfusion increased nutrient supply throughout the scaffold, enriching ES culture over static conditions. Our use of a tissue-engineered model, rather than human tumors or xenografts, enabled precise control of the forces experienced by ES cells, and therefore provided at least one explanation for the remarkable antineoplastic effects observed by some ES tumor patients from IGF-1R targeted therapies, in contrast to the lackluster effect observed in cells grown in conventional monolayer culture.

scholarly journals Study on the effects of the different polar group of EPA-enriched phospholipids on the proliferation and apoptosis in 95D cells

2021 ◽  
Author(s):  
Yao Guo ◽  
Qin Zhao ◽  
Yingying Tian ◽  
Yuanyuan Liu ◽  
Ziyi Yan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Polar Group ◽  
Dependent Manner ◽  
Apoptotic Gene ◽  
Polar Groups ◽  
Marine Phospholipids ◽  
Proliferation And Apoptosis ◽  
Dose Dependent

AbstractEPA-enriched phosphatidylcholine (EPA-PC) and EPA-enriched phosphatidylethanolamine (EPA-PE) are newly identified marine phospholipids. The polar group of phospholipids is known to influence EPA-phospholipid activity. However, the differences in anti-tumor effects between EPA-PC and EPA-PE have not been reported. In this study, we evaluated the effects of two forms of EPA on the proliferation and apoptosis in the lung-cancer cell line 95D as well as possible molecular mechanisms. Our results showed that EPA-PC effectively inhibited proliferative activity and promoted apoptosis of 95D cells in a dose-dependent manner, while EPA-PE had no effect on cell proliferation, although it slightly promoted apoptosis. Western blot results showed that EPA-PC and EPA-PE upregulated the expression of PPARγ, RXRα, and PTEN, and downregulated the PI3K/AKT signaling pathway. Furthermore, EPA-PC and EPA-PE induced the expression of the pro-apoptotic gene, Bax, and reduced the expression of the anti-apoptotic gene, Bcl-xl. Additionally, EPA-PC and EPA-PE promoted the release of cytochrome c and activated the apoptotic enzyme-cleaved caspase-3. These data suggest that the anti-tumor effect of EPA-phospholipids may be exerted via a PPARγ-related mechanism. EPA-PC was more efficacious as compared to EPA-PE, which might be due to the different polar groups of phospholipids.

scholarly journals SrfABC Toxin from Xenorhabdus stockiae Induces Cytotoxicity and Apoptosis in HeLa Cells

Toxins ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 685
Author(s):  
Yawei Sun ◽  
Guoyong Zhang ◽  
Xiaoqing Hou ◽  
Shuai Xiao ◽  
Xi Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Hela Cells ◽  
Cytotoxic Effect ◽  
Dependent Manner ◽  
Native Page ◽  
Inhibition Of Proliferation ◽  
Mammalian Cell Lines ◽  
Proliferation And Apoptosis ◽  
Intracellular Expression ◽  
Dose Dependent

Our previous study showed that the srfABC operon, which was originally identified in Salmonella enterica as an SsrB-regulated operon clustered with the flagellar class 2 operon, exhibited significant cytotoxicity against insect midgut CF-203 cells and injectable insecticidal activity against Helicoverpa armigera larvae. The srfABC operon was widely distributed among bacteria, which raises the question of their biological roles in different species. In this study, we investigated the cytotoxic effect of SrfABC toxin on mammalian cell lines. When simultaneously expressed in the Escherichia coli cytoplasm, SrfABC exhibited cytotoxicity against all tested mammalian cancer cell lines (B16, 4T-1, Hep-3B, and HeLa) in a dose-dependent manner. Intracellular expression of SrfA–FLAG, SrfB–FLAG, or SrfC–FLAG also resulted in inhibition of proliferation and apoptosis on HeLa cells. When incubated with HeLa cells separately, SrfA, SrfB, and SrfC proteins alone could enter HeLa cells, then induce apoptosis and cytotoxicity. SrfC protein shifts its localization from cytoplasm to nucleus with the aid of SrfA and/or SrfB protein. Although SrfA, SrfB, and SrfC proteins alone exhibited a cytotoxic effect against HeLa cells, all three components were essential for the full cytotoxicity. Native PAGE and co-immunoprecipitation assay demonstrated that SrfA, SrfB, and SrfC proteins could interact with each other and form a heteromeric complex.

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