scholarly journals Antitumor Potential and Phytochemical Profile of Plants from Sardinia (Italy), a Hotspot for Biodiversity in the Mediterranean Basin

Plants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 26 ◽  
Author(s):  
Concettina Cappadone ◽  
Manuela Mandrone ◽  
Ilaria Chiocchio ◽  
Cinzia Sanna ◽  
Emil Malucelli ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Umbilical Vein ◽  
Sesquiterpene Lactones ◽  
Induce Cell Cycle Arrest ◽  
P53 Expression ◽  
Human Osteosarcoma Cells ◽  
Wide Range ◽  
M Phase ◽  
Centaurea Calcitrapa ◽  
Umbilical Vein Endothelial Cells

Sardinia (Italy), with its wide range of habitats and high degree of endemism, is an important area for plant-based drug discovery studies. In this work, the antitumor activity of 35 samples from Sardinian plants was evaluated on human osteosarcoma cells U2OS. The results showed that five plants were strongly antiproliferative: Arbutus unedo (AuL), Cynara cardunculus (CyaA), Centaurea calcitrapa (CcA), Smilax aspera (SaA), and Tanacetum audibertii (TaA), the latter endemic to Sardinia and Corsica. Thus, their ability to induce cell cycle arrest and apoptosis was tested. All extracts determined cell cycle block in G2/M phase. Nevertheless, the p53 expression levels were increased only by TaA. The effector caspases were activated mainly by CycA, TaA, and CcA, while AuL and SaA did not induce apoptosis. The antiproliferative effects were also tested on human umbilical vein endothelial cells (HUVEC). Except for AuL, all the extracts were able to reduce significantly cell population, suggesting a potential antiangiogenic activity. The phytochemical composition was first explored by 1H NMR profiling, followed by further purifications to confirm the structure of the most abundant metabolites, such as phenolic compounds and sesquiterpene lactones, which might play a role in the measured bioactivity.

A combination of NaCl and urea enhances survival of IMCD cells to hyperosmolality

1998 ◽  
Vol 274 (6) ◽  
pp. F1167-F1173 ◽  
Author(s):  
Bento C. Santos ◽  
Alejandro Chevaile ◽  
Marie-Josée Hébert ◽  
Jane Zagajeski ◽  
Steven R. Gullans
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Umbilical Vein ◽  
Collecting Duct ◽  
Renal Medulla ◽  
Physiological Adaptation ◽  
Hsp70 Expression ◽  
Cellular Processes ◽  
M Phase ◽  
Umbilical Vein Endothelial Cells

Physiological adaptation to the hyperosmolar milieu of the renal medulla involves a complex series of signaling and gene expression events in which NaCl and urea activate different cellular processes. In the present study, we evaluated the effects of NaCl and urea, individually and in combination, on the viability of murine inner medullary collecting duct (mIMCD3) cells. Exposure to hyperosmolar NaCl or urea caused comparable dose- and time-dependent decreases in cell viability, such that 700 mosmol/kgH2O killed >90% of the cells within 24 h. In both cases, cell death was an apoptotic event. For NaCl, loss of viability at 24 h paralleled decreases in RNA and protein synthesis at 4 h, whereas lethal doses of urea had little or no effect on these biosynthetic processes. Cell cycle analysis showed both solutes caused a slowing of the G2/M phase. Surprisingly, cells exposed to a combination of NaCl + urea were significantly more osmotolerant such that 40% survived 900 mosmol/kgH2O. Madin-Darby canine kidney cells but not human umbilical vein endothelial cells also exhibited a similar osmotolerance response. Enhanced survival was not associated with a restoration of normal biosynthetic rates or cell cycle progression. However, the combination of NaCl + urea resulted in a shift in Hsp70 expression that appeared to correlate with survival. In conclusion, hyperosmolar NaCl and urea activate independent and complementary cellular programs that confer enhanced osmotolerance to renal medullary epithelial cells.

Polyphyllin I Induces Cell Cycle Arrest and Cell Apoptosis in Human Retinoblastoma Y-79 Cells through Targeting p53

2018 ◽  
Vol 18 (6) ◽  
pp. 875-881 ◽  
Author(s):  
Xue Zhu ◽  
Ke Wang ◽  
Kai Zhang ◽  
Yi Pan ◽  
Fanfan Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Potential Effect ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
P53 Expression ◽  
Cycle Arrest ◽  
Wide Range ◽  
Human Retinoblastoma

Background: Retinoblastoma is the most common intraocular malignant tumor in childhood. Although external beam radiation and enucleation are effective to control retinoblastoma, eye salvage and vision preservation are still significant challenges. Polyphyllin I (PPI), a natural compound extracted from Paris polyphylla rhizomes, has a wide range of activities against many types of cancers. However, the potential effect of this herbal compound on retinoblastoma has not yet been investigated. Method: In the present study, we evaluated the cytotoxic effect of PPI on human retinoblastoma Y-79 cells as well as its underlying molecular mechanism. Our results indicated that PPI treatment significantly inhibited cell proliferation, arrested the cell cycle at G2/M phase and induced cell apoptosis of Y79 cells through the mitochondrial- dependent intrinsic pathway. Moreover, p53 is involved in PPI-induced cytotoxicity in human retinoblastoma Y-79 cells. Exposure to 10 μM PPI for 48 h dramatically induced the expression levels of p53, phosphorylated- p53 and acetylated-p53. Furthermore, blockade of p53 expression effectively attenuated PPI-induced cell cycle arrest and cell apoptosis in Y-79 cells. Result: These results demonstrated that PPI exhibits anti-proliferation effect on human retinoblastoma Y-79 cells through modulating p53 expression, stabilization and activation. This information shed light on the potential application of PPI in retinoblastoma therapy.

scholarly journals RNA-Seq Data-Mining Allows the Discovery of Two Long Non-Coding RNA Biomarkers of Viral Infection in Humans

2020 ◽  
Vol 21 (8) ◽  
pp. 2748 ◽  
Author(s):  
Ruth Barral-Arca ◽  
Alberto Gómez-Carballa ◽  
Miriam Cebey-López ◽  
María José Currás-Tuala ◽  
Sara Pischedda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Infections ◽  
Umbilical Vein ◽  
Cell Types ◽  
Dermal Fibroblasts ◽  
Learning Approaches ◽  
Rna Seq ◽  
Wide Range ◽  
Healthy Control ◽  
Umbilical Vein Endothelial Cells

There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by influencing gene expression through a wide range of mechanisms. By mining whole-transcriptome shotgun sequencing (RNA-seq) data using machine learning approaches, we detected two lncRNAs (ENSG00000254680 and ENSG00000273149) that are downregulated in a wide range of viral infections and different cell types, including blood monocluclear cells, umbilical vein endothelial cells, and dermal fibroblasts. The efficiency of these two lncRNAs was positively validated in different viral phenotypic scenarios. These two lncRNAs showed a strong downregulation in virus-infected patients when compared to healthy control transcriptomes, indicating that these biomarkers are promising targets for infection diagnosis. To the best of our knowledge, this is the very first study using host lncRNAs biomarkers for the diagnosis of human viral infections.

scholarly journals Polymer-Salt Aqueous Two-Phase System (ATPS) Micro-Droplets for Cell Encapsulation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mohammad Mastiani ◽  
Negar Firoozi ◽  
Nicholas Petrozzi ◽  
Seokju Seo ◽  
Myeongsub Kim
Keyword(s):  
Umbilical Vein ◽  
Cell Encapsulation ◽  
Salt System ◽  
Great Promise ◽  
Phase System ◽  
Two Phase ◽  
Aqueous Two Phase System ◽  
Wide Range ◽  
A Cell ◽  
Umbilical Vein Endothelial Cells

Abstract Biosample encapsulation is a critical step in a wide range of biomedical and bioengineering applications. Aqueous two-phase system (ATPS) droplets have been recently introduced and showed a great promise to the biological separation and encapsulation due to their excellent biocompatibility. This study shows for the first time the passive generation of salt-based ATPS microdroplets and their biocompatibility test. We used two ATPS including polymer/polymer (polyethylene glycol (PEG)/dextran (DEX)) and polymer/salt (PEG/Magnesium sulfate) for droplet generation in a flow-focusing geometry. Droplet morphologies and monodispersity in both systems are studied. The PEG/salt system showed an excellent capability of uniform droplet formation with a wide range of sizes (20–60 μm) which makes it a suitable candidate for encapsulation of biological samples. Therefore, we examined the potential application of the PEG/salt system for encapsulating human umbilical vein endothelial cells (HUVECs). A cell viability test was conducted on MgSO4 solutions at various concentrations and our results showed an adequate cell survival. The findings of this research suggest that the polymer/salt ATPS could be a biocompatible all-aqueous platform for cell encapsulation.

EFFECTS OF SUBSTRATE DEFORMABILITY ON CELL BEHAVIORS: ELASTIC MODULUS VERSUS THICKNESS

2017 ◽  
Vol 17 (05) ◽  
pp. 1750088 ◽  
Author(s):  
ZAHRA GOLI-MALEKABADI ◽  
MOHAMMAD TAFAZZOLI-SHADPOUR ◽  
EHSAN SEYEDJAFARI
Keyword(s):  
Cell Proliferation ◽  
Elastic Modulus ◽  
Umbilical Vein ◽  
Cell Behavior ◽  
Substrate Thickness ◽  
Microfluidic Chips ◽  
Cell Behaviors ◽  
Varying Thickness ◽  
Wide Range ◽  
Umbilical Vein Endothelial Cells

The deformability of the substrate stimulating cell mechanotransduction depends not only on elastic modulus but also on the thickness. Polydimethylsiloxane (PDMS) which is widely used in microfluidic chips and platforms can be fabricated in a wide range of elastic modulus and thickness. In this study, we cultured human umbilical vein endothelial cells (HUVECs) on four groups of PDMS substrates of varying thickness and elastic modulus to examine effects of these parameters on morphology, viability and proliferation of cells. Both elastic modulus and thickness affected cell behavior. In general, the thickness of substrates had relatively higher impact on endothelial morphology than elastic modulus. Elongation of HUVECs on thick substrates was more intense compared to those on thin substrates. Both lowering thickness and reducing elastic modulus of PDMS decreased the viability of HUVECs, although thickness was more influential. Decrease in substrate thickness reduced cell proliferation regardless of substrate elastic modulus. In conclusion, our results suggest that endothelial behavior depends on substrate deformability, but cells react differently to the elastic modulus and thickness of PDMS by morphology, viability and growth. Results can improve the comprehension of cell mechanotransduction.

scholarly journals Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Rende Ning ◽  
Guang Chen ◽  
Run Fang ◽  
Yanhui Zhang ◽  
Wenjuan Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Osteosarcoma Cells ◽  
Antitumor Property ◽  
Human Osteosarcoma ◽  
Cycle Arrest ◽  
Stat3 Phosphorylation ◽  
Human Osteosarcoma Cells ◽  
M Phase

Abstract Background Diosmetin is a bioflavonoid compound naturally abundant in citrus fruits. It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown. Methods Colony formation assay, cell cycle analysis and apoptosis analysis were conducted respectively to observe the effect of diosmetin on cell proliferation and apoptosis in human osteosarcoma cells. Western blot and immunoprecipitation were used to detect the expression of apoptotic molecules and activation of STAT3/c-Myc pathway in Saos-2 and U2SO cells. Results Diosmetin significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and promoted cell apoptosis in both Saos-2 and U2SO cells. Moreover, Diosmetin downregulated the expression of anti-apoptotic protein Bcl-xL while upregulated the levels of pro-apoptotic proteins including cleaved Caspase-3, cleaved-PARP and Bax. Furthermore, diosmetin dose-dependently inhibited STAT3 phosphorylation, reduced the expression of its downstream protein c-Myc and impeded the interaction between STAT3 molecules. Conclusions These results suggest that diosmetin exerts anti-osteosarcoma effects by suppressing cell proliferation and inducing apoptosis via inhibiting the activation of STAT3/c-Myc signaling pathway, which provide the possibility for diosmetin to be a chemotherapeutic candidate for osteosarcoma.

Abstract 17122: Cardioprotection With Proangiogenic Nanomaterials Formulated With CHIR99021 and FGF1

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Chengming Fan ◽  
Yasin Oduk ◽  
Meng Zhao ◽  
Yawen Tang ◽  
Gregory P. Walcott ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Treatment Group ◽  
Cardiac Fibrosis ◽  
Sham Group ◽  
Contractile Function ◽  
Umbilical Vein ◽  
Tunel Staining ◽  
Aurora B ◽  
Lv Remodeling ◽  
Umbilical Vein Endothelial Cells

Introduction: We aimed at to investigate whether activation of both FGF1 and Wnt1 synergistically enhances angiogenesis and render the cardioprotection in hearts with post infarction LV remodeling. Materials and methods: CHIR99021 (a Wnt1 activator) and FGF1 were encapsulated into poly lactic-co-glycolic acid nanoparticles (CHIR99021/FGF1-NPs). Ischemic heart models were generated in C57BL/6 mice or Yorkshire swine by ligation of the left anterior descending coronary. The mice were randomly divided into 6 groups: Myocardial infarction (MI) Only (n=11), MI with nanoparticles (CHIR99021 or/and FGF1 loaded) injection (n=12, each), MI with non-loaded nanoparticles injection (n=11) and Sham group (n=10). The swine were divided into 3 groups: ischemic reperfusion injury (IRI) (n=4), IRI with CHIR99021/FGF-NPs injection (n=4) and Sham group (n=4). Left ventricle function 4 week after surgery were evaluated by Echocardiography. Cell proliferation was assessed via immunostaining in ischemic hearts and in cultivated human umbilical vein endothelial cells (HUVECs) and Human vascular smooth muscle cells (HVSMCs) using the following markers: Ki67, Brdu, PH3, and Aurora B. Apoptosis was determined with TUNEL staining. Cardiac fibrosis was evaluated via Sirius red and Fast green staining (mice) and magnetic resonance imaging (swine). Results: CHIR99021/FGF1-NPs treatment attenuated fibrosis and preserved heart contractile function in mice and swine models of postinfarction LV remodeling. The proportion of cells that expressed cell cycle markers (Ki67; BrdU; Aurora B and PH3) was significantly greater in CHIR99021+FGF1 treatment group than CHIR99021, FGF1 and PBS treatment group. The proportion of apoptotic cells was significantly smaller in CHIR99021+FGF1 treatment group than in groups of control, VEGF, CHIR99021, or FGF1 treatment alone. Conclusions: CHIR99021 and FGF synergistically activate cell cycle and reduce apoptosis, which accompanied by a significant improvement of cardiac function.

Tanshinone IIA Attenuates H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells

2012 ◽  
Vol 40 (06) ◽  
pp. 1307-1319 ◽  
Author(s):  
Paul Chan ◽  
Yen-Cheng Chen ◽  
Li-Jen Lin ◽  
Tzu-Hurng Cheng ◽  
Kazunori Anzai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Protective Effect ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Umbilical Vein ◽  
Tanshinone Iia ◽  
Cardiovascular Disorders ◽  
P53 Expression ◽  
Umbilical Vein Endothelial Cells

The injury of endothelial cell is the critical event of vascular disease. In endothelial cell, oxidative stress is regarded as critical to pathogenic factors in endothelial cell injury and apoptosis. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as "Danshen" in traditional Chinese medicine for treating cardiovascular disorders, but the mechanism by which it exerts the protective effect is not well established. The present study was designed to test the hypothesis that tanshinone IIA can inhibit hydrogen peroxide ( H2O2 )-induced injury and unravel its intracellular mechanism in human umbilical vein endothelial cells (HUVECs). In this study, HUVECs were treated with tanshinone IIA in the presence/absence of H2O2 . The protective effects of tanshinone IIA against H2O2 were evaluated. Our results show that HUVECs incubated with 200 μM H2O2 had significantly decreased the viability of endothelial cells, which was accompanied with apparent cell apoptosis, the activation of caspase-3 and the upregulation of p53 expression, which was known to play a key role in H2O2 -induced cell apoptosis. However, pretreatment with tanshinone IIA (3–10 μM) resulted in a significant resistance to H2O2 -induced apoptosis. In addition, pretreatment with tanshinone IIA decreased the activity of caspase-3 and p53 expression. Tanshinone IIA also induced activating transcription factor (ATF) 3 expression; while knockdown of ATF-3 with ATF-3 siRNAsignificantly reduced tanshinone IIA's protective effect. In conclusion, the present study shows that tanshinone IIA can protect endothelial cells against oxidative injury induced by H2O2 , suggesting that this compound may constitute a promising intervention against cardiovascular disorders and ATF-3 may play an important role in this process.

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