scholarly journals Palladium Nanoparticles Induce Disturbances in Cell Cycle Entry and Progression of Peripheral Blood Mononuclear Cells: Paramount Role of Ions

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Claudia Petrarca ◽  
Emanuela Clemente ◽  
Luca Di Giampaolo ◽  
Renato Mariani-Costantini ◽  
Kerstin Leopold ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Palladium Nanoparticles ◽  
Cell Cycle Progression ◽  
Mononuclear Cells ◽  
Mitotic Division ◽  
Ros Generation ◽  
Peripheral Blood Mononuclear ◽  
Temporary Response ◽  
High Concentrations

There is concern about the possible toxicity of palladium nanoparticles (Pd-NP), as they are released in the environment through many applications. We previously studied the toxicity of Pd-NP at high concentrations; here we address the possible toxicity of Pd-NP at low, subtoxic doses. In particular, we have exposed normal human PBMC entering into the first in vitro mitotic division to Pd-NP and to Pd(IV) ions to evaluate ROS generation and cell cycle progression. We have measured a statistically significant increase of intracellular ROS in Pd(IV) exposed cells, but not in Pd-NP exposed cells. TEM revealed accumulation of lipid droplets and autophagic and mitophagic vacuoles, which appeared more conspicuous in cells exposed to Pd(IV) ions than to Pd-NP. Pd-NP were visible in the cytoplasm of Pd-NP exposed cells. Pd-NP addition was associated with a significant increase of cells within the G0/G1-phase and a significant reduction in GS- and G2/M-phases. Cells exposed to Pd(IV) ions showed a significant amplification of these cell cycle alterations. These results suggest that ions, per se or released by NPs, are the true inducers of Pd toxicity. It will be essential to verify whether the observed disturbance represents a temporary response or might result in permanent alterations.

G1 Arrest and Caspase-Mediated Apoptosis in HL-60 Cells by Dichloromethane Extract of Centrosema pubescens

2010 ◽  
Vol 38 (06) ◽  
pp. 1143-1159 ◽  
Author(s):  
Subramanireddy Ramadevi Mani ◽  
Baddireddi Subhadra Lakshmi
Keyword(s):  
Cell Cycle ◽  
Mononuclear Cells ◽  
Tumor Biology ◽  
G1 Phase ◽  
G1 Arrest ◽  
Synergistic Activity ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Vitro Model

Cell division and apoptosis are two crucial components of tumor biology and the importance of increased cell proliferation and reduced cell death have made them valid therapeutic targets. The plant kingdom is a relatively underexploited cache of novel drugs, and crude extracts of plants are known for their synergistic activity. The present study assessed the anti-proliferative activity of the medicinal plant Centrosema pubescens Benth. Centrosema pubescens dichloromethane extract (CPDE) inhibited the proliferation of HL-60 (promyelocytic acute leukaemia) cells with an IC 50 value of 5 μg/ml. Further studies also showed that CPDE induces growth arrest at the G1 phase and specifically down-regulates the expressions of cyclin E and CDK2 and up-regulates p27(CKI) levels. These events apparently lead to the induction of apoptosis, which was demonstrated qualitatively by a DNA fragmentation assay and propidium iodide staining. Quantitative assessment of the effective arrest of the cell cycle and of apoptosis was confirmed by flow cytometry. CPDE exhibited negligible cytotoxicity even at the highest dose tested (100 μg/ml) in both normal peripheral blood mononuclear cells and in an in vitro model (HL-60). Our results strongly suggest that CPDE arrests the cell cycle at the G1 phase and triggers apoptosis by caspase activation.

scholarly journals Activation signals leading to proliferation of normal and leukemic CD3+ large granular lymphocytes

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1282-1285 ◽  
Author(s):  
JA Aprile ◽  
M Russo ◽  
MS Pepe ◽  
TP Jr Loughran
Keyword(s):  
Cell Cycle ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
Large Granular Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Incorporation Assay ◽  
Granular Lymphocytes

Abstract The activation signals leading to proliferation of normal and leukemic CD3+ large granular lymphocytes (LGL) were studied in vitro. Anti-CD3 monoclonal antibody (MoAb) alone (P less than .01) and recombinant interleukin-2 (IL-2) alone (P less than .01) caused significant stimulation of peripheral blood mononuclear cells (PBMC) from four CD3+ LGL leukemia patients, as measured in a 3H-thymidine incorporation assay. Recombinant interleukin-4 (IL-4) alone had no effect (P = .11). The combination signals of anti-CD3 MoAb and either IL-2 or IL-4 produced a proliferative response greater than anti-CD3 MoAb alone (P less than .01) or lymphokine alone (P less than .01). Leukemic LGL, purified by two-color sorting, were subsequently activated by anti-CD3 MoAb and IL-2 and assessed for DNA content by viable Hoechst No. 33342 (HO) staining. Results of these studies demonstrated that leukemic LGL were stimulated directly by anti-CD3 MoAb and IL-2, with the percentage of cells in cell cycle (S + G2/M) ranging from 16% to 72%. Normal CD3+ LGL were also stimulated to enter the cell cycle by anti-CD3 and IL-2. These results show that leukemic LGL proliferate in vitro after activation through the T-cell receptor and/or lymphokine.

scholarly journals Derangement of cell cycle markers in peripheral blood mononuclear cells of asthmatic patients as a reliable biomarker for asthma control

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahmood Yaseen Hachim ◽  
Noha Mousaad Elemam ◽  
Rakhee K. Ramakrishnan ◽  
Laila Salameh ◽  
Ronald Olivenstein ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mononuclear Cells ◽  
Bronchial Epithelium ◽  
Acute Attack ◽  
Severe Form ◽  
Peripheral Blood Mononuclear ◽  
Transcriptomic Data ◽  
Asthmatic Patients ◽  
Severe Asthmatic

AbstractIn asthma, most of the identified biomarkers pertain to the Th2 phenotype and no known biomarkers have been verified for severe asthmatics. Therefore, identifying biomarkers using the integrative phenotype-genotype approach in severe asthma is needed. The study aims to identify novel biomarkers as genes or pathways representing the core drivers in asthma development, progression to the severe form, resistance to therapy, and tissue remodeling regardless of the sample cells or tissues examined. Comprehensive reanalysis of publicly available transcriptomic data that later was validated in vitro, and locally recruited patients were used to decipher the molecular basis of asthma. Our in-silicoanalysis revealed a total of 10 genes (GPRC5A, SFN, ABCA1, KRT8, TOP2A, SERPINE1, ANLN, MKI67, NEK2, and RRM2) related to cell cycle and proliferation to be deranged in the severe asthmatic bronchial epithelium and fibroblasts compared to their healthy counterparts. In vitro, RT qPCR results showed that (SERPINE1 and RRM2) were upregulated in severe asthmatic bronchial epithelium and fibroblasts, (SFN, ABCA1, TOP2A, SERPINE1, MKI67, and NEK2) were upregulated in asthmatic bronchial epithelium while (GPRC5A and KRT8) were upregulated only in asthmatic bronchial fibroblasts. Furthermore, MKI76, RRM2, and TOP2A were upregulated in Th2 high epithelium while GPRC5A, SFN, ABCA1 were upregulated in the blood of asthmatic patients. SFN, ABCA1 were higher, while MKI67 was lower in severe asthmatic with wheeze compared to nonasthmatics with wheezes. SERPINE1 and GPRC5A were downregulated in the blood of eosinophilic asthmatics, while RRM2 was upregulated in an acute attack of asthma. Validation of the gene expression in PBMC of locally recruited asthma patients showed that SERPINE1, GPRC5A, SFN, ABCA1, MKI67, and RRM2 were downregulated in severe uncontrolled asthma. We have identified a set of biologically crucial genes to the homeostasis of the lung and in asthma development and progression. This study can help us further understand the complex interplay between the transcriptomic data and the external factors which may deviate our understanding of asthma heterogeneity.

scholarly journals REPLICATION OF HIV-1 SUBTYPE A6 IN THE PRESENCE OF HORMONES INCLUDED IN THE MODERN HORMONAL CONTRACEPTIVES

2019 ◽  
Vol 1 (1) ◽  
pp. 85-90
Author(s):  
M. N. Nosik ◽  
K. A. Ryzhov ◽  
A. V. Potapova
Keyword(s):  
Viral Replication ◽  
Mononuclear Cells ◽  
Virus Production ◽  
Antiretroviral Drugs ◽  
Hiv Treatment ◽  
Hormonal Contraceptives ◽  
Peripheral Blood Mononuclear ◽  
High Concentrations ◽  
Hiv 1

Aim. To study how female hormones included in oral contraceptives (β-estradiol and progesteron) affect HIV-1 replication and efficacy of antiviral drugs. Material and methods. Peripheral blood mononuclear cells (PBMC) and cell lines MT-4, Jurkat were infected with HIV-1 (subtype A6). Afterwards the cells were cultured for 6 days in the presence of β-estradiol/progesteron with or without the presence of antiretroviral drugs Lamivudin (3TC), Etravirin(ETR) and Indinavir (IDV), which are widely used for HIV treatment. Virus production was monitored by p24 levels in culture supernatants on day 6. The experemints were performed in eight repetitions. Results. There was a 1,3-1,8-fold increase of virus replication in the presence of high concentrations of both hormones (26,136 μg/ml). Incomplete suppression of viral replication was observed when infected cells were co-cultivated in the presence of hormones (26 μg, 136 μg) and antiretroviral drugs. The mean suppression rate of viral replication for β-estradiol was 77.3% and 69.8% for progesterone. However, in the absence of hormones the virus production was completely suppressed by those drugs. Conclusion. The high concentrations of steroid hormones induce HIV-1 replication and as a result reduce the efficacy of antiretroviral drugs NVP and IDV in vitro. Thus it is advisable for women at high risk of HIV infection to monitor hormone levels that change during the menstrual cycle and pregnancy before prescribing hormonal contraception.

scholarly journals The NLRP3/eIF2 axis drives cell cycle progression in acute myeloid leukemia

2021 ◽  
Author(s):  
Michela Luciano ◽  
Constantin Blöchl ◽  
Julia Vetter ◽  
Laura Urwanisch ◽  
Theresa Neuper ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Nlrp3 Inflammasome ◽  
Cell Cycle Progression ◽  
Mononuclear Cells ◽  
Inflammasome Activation ◽  
Cycle Progression ◽  
Eif2α Phosphorylation

Aberrant activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome mediates numerous inflammatory diseases. Oncogenes can activate the NLRP3 inflammasome and thereby promote myeloproliferative neoplasia, suggesting a crucial role of NLRP3 in the malignant transformation of hematopoietic cells. Here, we show that bone marrow-derived mononuclear cells of AML patients display enhanced expression of NLRP3, IL-1β; and IL-18 and that high-level expression of NLRP3 is linked to poor survival of AML patients. Pharmacological and genetic inhibition of NLRP3 inflammasome activation attenuated cell proliferation of MOLM-13 AML cells in vitro. In vivo, genetic inhibition of NLRP3 in MOLM-13 AML cells resulted in reduced engraftment potential in xenografts, along with reduced splenomegaly and organ infiltration. Differential proteomic analysis revealed the eIF2 pathway as potential target of NLRP3 in AML, with a significant increase of eIF2α; phosphorylation upon NLRP3 inhibition. NLRP3 inhibition also caused a strong decrease in cyclin - dependent kinases CDK4 and CDK6, accompanied by an upregulation of the CDK inhibitor p21 (CDKN1A) and a marked arrest of cell cycle progression in the G0/G1 phase, consistent with the role of eIF2α; phosphorylation as negative cell cycle regulator. Taken together, we show that inhibition of the NLRP3 inflammasome reduces AML cell proliferation by promoting eIF2α; phosphorylation, which in turn enhances the expression of cell cycle arrest genes such as p21. Thus, the study uncovers the NLRP3/eIF2 axis as new driver of AML proliferation and proposes a novel therapeutic treatment of AML by targeted inhibition of NLRP3 activation.

scholarly journals Activation signals leading to proliferation of normal and leukemic CD3+ large granular lymphocytes

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1282-1285
Author(s):  
JA Aprile ◽  
M Russo ◽  
MS Pepe ◽  
TP Jr Loughran
Keyword(s):  
Cell Cycle ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Interleukin 4 ◽  
Large Granular Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Incorporation Assay ◽  
Granular Lymphocytes

The activation signals leading to proliferation of normal and leukemic CD3+ large granular lymphocytes (LGL) were studied in vitro. Anti-CD3 monoclonal antibody (MoAb) alone (P less than .01) and recombinant interleukin-2 (IL-2) alone (P less than .01) caused significant stimulation of peripheral blood mononuclear cells (PBMC) from four CD3+ LGL leukemia patients, as measured in a 3H-thymidine incorporation assay. Recombinant interleukin-4 (IL-4) alone had no effect (P = .11). The combination signals of anti-CD3 MoAb and either IL-2 or IL-4 produced a proliferative response greater than anti-CD3 MoAb alone (P less than .01) or lymphokine alone (P less than .01). Leukemic LGL, purified by two-color sorting, were subsequently activated by anti-CD3 MoAb and IL-2 and assessed for DNA content by viable Hoechst No. 33342 (HO) staining. Results of these studies demonstrated that leukemic LGL were stimulated directly by anti-CD3 MoAb and IL-2, with the percentage of cells in cell cycle (S + G2/M) ranging from 16% to 72%. Normal CD3+ LGL were also stimulated to enter the cell cycle by anti-CD3 and IL-2. These results show that leukemic LGL proliferate in vitro after activation through the T-cell receptor and/or lymphokine.

scholarly journals CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Jinghan Yang ◽  
Min Cheng ◽  
Bingjie Gu ◽  
Jinghua Wang ◽  
Shushan Yan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Binding ◽  
Mononuclear Cells ◽  
Joint Damage ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Collagen Induced Arthritis ◽  
Peripheral Blood Mononuclear

Abstract A number of circular RNAs (circRNAs) have been implicated in rheumatoid arthritis (RA) pathogenesis; however, little is known about their function and hidden molecular mechanism in immune and inflammation regulation. We investigated the role and the underlying mechanism of circRNA_09505 in RA in this study. Real-time PCR and fluorescence in situ hybridization (FISH) are adopted to estimate the quantitative expression and localization of circRNA_09505 in macrophages. The altering effect of circRNA_09505 on inflammation is investigated in vitro and in vivo by use of macrophage cell models and collagen-induced arthritis (CIA) mice. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) are used to confirm the circRNA_09505/miR-6089 ceRNA network predicted by bioinformatics analysis. Compared with controls, the expression of circRNA_09505 is upregulated in peripheral blood mononuclear cells (PBMCs) from patients with RA. The proliferation and cell cycle are significantly promoted when circRNA_09505 is upregulated in macrophages, whereas knockdown of circRNA_09505 inhibits macrophage proliferation and cell- cycle progression. Besides, circRNA_09505 can act as a miRNA sponge for miR-6089 in macrophages, and promote the production of TNF-α, IL-6, and IL-12 through ceRNA mechanism. Moreover, AKT1 is a direct target of miR-6089. CircRNA_09505 can promote AKT1 expression by acting as a miR-6089 sponge via IκBα/NF-κB signaling pathway in macrophages. Most interestingly, knockdown of circRNA_09505 significantly alleviates arthritis and inflammation in vivo in CIA mice. These data support the hypothesis that circRNA_09505 can function as a miR-6089 sponge and regulate inflammation via miR-6089/AKT1/NF-κB axis in CIA mice.

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