scholarly journals The Impact of the Ca2+-Independent Phospholipase A2β (iPLA2β) on Immune Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 577
Author(s):  
Tayleur D. White ◽  
Abdulaziz Almutairi ◽  
Ying Gai Tusing ◽  
Xiaoyong Lei ◽  
Sasanka Ramanadham
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Immune Cells ◽  
Neurological Disorders ◽  
Male Fertility ◽  
Metabolic Disorders ◽  
Potential Contribution ◽  
Biological Processes ◽  
Membrane Remodeling ◽  
The Impact

The Ca2+-independent phospholipase A2β (iPLA2β) is a member of the PLA2 family that has been proposed to have roles in multiple biological processes including membrane remodeling, cell proliferation, bone formation, male fertility, cell death, and signaling. Such involvement has led to the identification of iPLA2β activation in several diseases such as cancer, cardiovascular abnormalities, glaucoma, periodontitis, neurological disorders, diabetes, and other metabolic disorders. More recently, there has been heightened interest in the role that iPLA2β plays in promoting inflammation. Recognizing the potential contribution of iPLA2β in the development of autoimmune diseases, we review this issue in the context of an iPLA2β link with macrophages and T-cells.

scholarly journals Analysis of the use of photosensitization in human glioblastoma multiforme to induce cell death

2019 ◽  
Vol 98 (Suppl) ◽  
pp. 25-25
Author(s):  
Mario Minor Murakami Junior ◽  
Yollanda E. Moreira Franco ◽  
Maurício Da Silva Baptista ◽  
Suely Kazue Nagahashi Marie
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Methylene Blue ◽  
Cell Proliferation ◽  
Cell Death ◽  
Acridine Orange ◽  
Light Irradiation ◽  
Rt Pcr ◽  
Low Concentration ◽  
The Impact

Introduction: The most frequent primary tumor of the central nervous system is the malignant glioma, being the glioblastoma (GBM), grade IV astrocytoma, the most aggressive and lethal glioma. Malignant astrocytomas are responsive for therapy targeting autophagy as temozolomide, the standard adjuvant treatment which induces autophagic cell death. Autophagy is a homeostatic intracellular process that eliminate old proteins and recycle cellular components. Mitophagy is a subtype of autophagy that regulates the removal of damaged, dysfunctional or redundant mitochondria. Parallel damage against lysosomes and mitochondria membranes using photosensitized oxidations and strong redox stress leads to activation of mitophagy and malfunction of autophagy. This mechanism of photosensitization, ultimately, causes cell death. Challenging cells with a low concentration of a photosensitizer as 1,9-dimethyl methylene blue (DMMB) combined with light- irradiation of 12 joules/cm2 have induced mitochondrial damage with activation of mitophagy and concomitant lysosome damage, in skin-derived cell lines. This experimental design was applied to U87MG GBM cells to verify if tumor cell death may be obtained with combined mitochondrial and lysosomal damages to open new therapeutic strategies for GBM and to better understand the mechanisms of mitophagy.Objectives: Our primary objective is to analyze the impact of challenging GBM cells with a low concentration of 1,9-dimethyl methylene blue (DMMB) with combined light- irradiation of 12 joules/cm2.Methodology: U87MG a human GBM cell line was used. The photodamage was performed using DMMB photosensitized by a LED with maximum emission wavelength at 630 nm providing 12 J/cm2. Cell proliferation and viability assays were performed using MTT to assess whether there was proliferation inhibition and/or alteration of cell viability after photosensitization. Quantification of cells in different stages of apoptosis, and in the various phases of the cell cycle were analyzed using flow cytometry after photosensitization. Acridine orange assay was used to assess lysosome damage. RT-PCR and Western Blotting were performed to evaluate the expression levels of the main autophagy and mitophagy genes and proteins.Partial Results: Cell proliferation and viability assays demonstrated that the concentration of DMMB to cause 50% inhibition of biological activity of cells (IC50) was 10 nM after 48h. The apoptosis and cell cycle experiments were performed in this concentration. Increase in apoptosis was observed after 24hs of photosensitization. Currently, the cell cycle flow cytometry assay has been performed, followed by the quantification of lysosomes damage by Acridine Orange assay. The genes and proteins involved in the mechanisms of autophagy and mitophagy will be determined by expression analysis through RT-PCR and Western blot assays.Discussion and Conclusion: For a future perspective, if this prove of concept is achieved, i.e. death of tumor cells by the combined approach of photosensitizer with irradiation, a new therapeutic strategy of light-activated drugs may be offered to cancer patients.

scholarly journals A Review on the Role of miR-1290 in Cell Proliferation, Apoptosis and Invasion

2021 ◽  
Vol 8 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Tayyebeh Khoshbakht ◽  
Bashdar Mahmud Hussen ◽  
Mohammad Taheri ◽  
Mohammad Samadian
Keyword(s):  
Cell Proliferation ◽  
Present Review ◽  
Molecular Pathways ◽  
Biological Processes ◽  
Affect Expression ◽  
Non Coding Rnas ◽  
The Impact

MicroRNAs (miRNAs) have been shown to affect expression of several genes contributing in important biological processes. miR-1290 a member of this family with crucial roles in the carcinogenesis. This miRNA is transcribed from MIR1290 gene on chromosome 1p36.13. This miRNA has interactions with a number of mRNA coding genes as well as non-coding RNAs SOCS4, GSK3, BCL2, CCNG2, KIF13B, INPP4B, hMSH2, KIF13B, NKD1, FOXA1, IGFBP3, CCAT1, FOXA1, NAT1, SMEK1, SCAI, ZNF667-AS1, ABLIM1, Circ_0000629 and CDC73. miR-1290 can also regulate activity of JAK/STAT3, PI3K/AKT, Wnt/β-catenin and NF-κB molecular pathways. Most evidence indicates the oncogenic roles of miR-1290, yet controversial evidence also exists. In the present review, we describe the results of in vitro, animal and human investigations about the impact of miR-1290 in the development of malignancies.

scholarly journals iPLA2β and its role in male fertility, neurological disorders, metabolic disorders, and inflammation

2019 ◽  
Vol 1864 (6) ◽  
pp. 846-860 ◽  
Author(s):  
John Turk ◽  
Tayleur D. White ◽  
Alexander J. Nelson ◽  
Xiaoyong Lei ◽  
Sasanka Ramanadham
Keyword(s):  
Neurological Disorders ◽  
Male Fertility ◽  
Metabolic Disorders

scholarly journals HPV16 E1 dysregulated cellular genes involved in cell proliferation and host DNA damage: A possible role in cervical carcinogenesis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260841
Author(s):  
Fern Baedyananda ◽  
Arkom Chaiwongkot ◽  
Shankar Varadarajan ◽  
Parvapan Bhattarakosol
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Cell Death ◽  
Cellular Proliferation ◽  
Host Gene ◽  
Cervical Carcinogenesis ◽  
Host Gene Expression ◽  
The Impact

HPV16 is the most prominent cause of cervical cancer. HPV16 E1, a helicase required for HPV replication exhibits increased expression in association with cervical cancer progression, suggesting that E1 has a similar effect on the host as the HPV16 E6 and E7 oncoproteins. This study aimed to determine whether expression of HPV16 E1 correlated with carcinogenesis by modulating cellular pathways involved in cervical cancer. HEK293T cells were transfected with pEGFP, pEGFPE1 or truncated forms of HPV16 E1. Cell proliferation, cell death, and the impact of HPV16 E1 on host gene expression was then evaluated. HPV16 E1 overexpression resulted in a significant reduction of cell viability and cellular proliferation (p-value<0.0001). Moreover, prolonged expression of HPV16 E1 significantly induced both apoptotic and necrotic cell death, which was partially inhibited by QVD-OPH, a broad-spectrum caspase inhibitor. Microarray, real time RT-PCR and kinetic host gene expression analyses revealed that HPV16 E1 overexpression resulted in the downregulation of genes involved in protein synthesis (RPL36A), metabolism (ALDOC), cellular proliferation (CREB5, HIF1A, JMJDIC, FOXO3, NFKB1, PIK3CA, TSC22D3), DNA damage (ATR, BRCA1 and CHEK1) and immune response (ISG20) pathways. How these genetic changes contribute to HPV16 E1-mediated cervical carcinogenesis warrants further studies.

scholarly journals ADP-ribosylation signalling and human disease

Open Biology ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 190041 ◽  
Author(s):  
Luca Palazzo ◽  
Petra Mikolčević ◽  
Andreja Mikoč ◽  
Ivan Ahel
Keyword(s):  
Neurological Disorders ◽  
Fine Tuning ◽  
Molecular Medicine ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Adp Ribosylation ◽  
Damage Repair ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
The Impact

ADP-ribosylation (ADPr) is a reversible post-translational modification of proteins, which controls major cellular and biological processes, including DNA damage repair, cell proliferation and differentiation, metabolism, stress and immune responses. In order to maintain the cellular homeostasis, diverse ADP-ribosyl transferases and hydrolases are involved in the fine-tuning of ADPr systems. The control of ADPr network is vital, and dysregulation of enzymes involved in the regulation of ADPr signalling has been linked to a number of inherited and acquired human diseases, such as several neurological disorders and in cancer. Conversely, the therapeutic manipulation of ADPr has been shown to ameliorate several disorders in both human and animal models. These include cardiovascular, inflammatory, autoimmune and neurological disorders. Herein, we summarize the recent findings in the field of ADPr, which support the impact of this modification in human pathophysiology and highlight the curative potential of targeting ADPr for translational and molecular medicine.

scholarly journals Follicular helper-T cells restore CD8+-dependent antitumor immunity and anti-PD-L1/PD-1 efficacy

2021 ◽  
Vol 9 (6) ◽  
pp. e002157
Author(s):  
Julie Niogret ◽  
Hélène Berger ◽  
Cédric Rebe ◽  
Romain Mary ◽  
Elise Ballot ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mouse Cell ◽  
Dependent Manner ◽  
Follicular Helper ◽  
The Impact

BackgroundT follicular helper cells (Tfh) are essential to shape B cell response during germinal center formation. Tfh accumulation has been reported in various human cancers, with positive or negative prognostic roles. However, the mechanisms explaining the accumulation of Tfh and their role in cancer remain obscure.MethodsIn vitro differentiated and mouse cell sorted Tfh phenotype was evaluated by flow cytometry and quantitative PCR (qPCR). Antitumor effect of Tfh was evaluated by adoptive transfer in different tumor-bearing mice models. The involvement of immune cells, cytokines and chemokines was evaluated, using depleting antibodies. Chemokines and cytokines expression and production were evaluated by qPCR and ELISA. In human, the impact of immune cells and chemokines on survival was evaluated by analyzing transcriptomic data from public databases and from our own patient cohorts.ResultsIn this study, we show that Tfh exert an antitumor immune effect in a CD8+-dependent manner. Tfh produce interleukin-21, which sustains proliferation, viability, cytokine production and cytotoxic functions of exhausted T cells. The presence of Tfh is required for efficacy of antiprogrammed cell death ligand-1 therapy. Tfh accumulate in the tumor bed and draining lymph nodes in different mouse cancer models. This recruitment is due to the capacity of transforming growth factor β to drive Chemokine (C-X-C motif) Ligand 13 expression, a chemoattractant of Tfh, by intratumor CD8+ T cells. Accumulation of Tfh and exhausted CD8+ T cells predicts cancer outcome in various cancer types. In patients treated with anti-programmed cell death-1 mAb, accumulation of Tfh and CD8+ at the tumor site is associated with outcome.ConclusionThis study provides evidence that CD8+/Tfh crosstalk is important in shaping antitumor immune response generated by immunotherapy.

scholarly journals miR-130-3p Promotes MTX-Induced Immune Killing of Hepatocellular Carcinoma Cells by Targeting EPHB4

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Liangtian Shao ◽  
Qing Ye ◽  
Moyang Jia
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Target Gene ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Block Type ◽  
Immunogenic Cell Death ◽  
Immune Cell Infiltration ◽  
Drug Induced ◽  
The Impact

The vast majority of primary hepatocellular cancer is hepatocellular carcinomas (HCCs). Currently, HCC is one of the more common cancers in humans, and it has a high mortality and disability rate. Mitoxantrone (MTX) is an antitumor drug that can block type II topoisomerase. It has been reported that immunogenic cell death evoked by MTX can induce the discharge of damage associated with molecular patterns (DAMPs) and subsequently influence immune cell infiltration in the tumor microenvironment. High mobilities aggregation box 1 (HMGB1) is the prototypical extracellular DAMP. Many cellular processes have been reported to involve EPHB4 receptor tyrosine kinases, but the relation of DAMP and EPHB4 is uncertain. In this research, we assessed the impact of miR-130-3p by Edu incorporation test on cell proliferation, and we have proven its impact on HCC cell migration through Transwell and wound healing tests. Flow cytometry was applied to study its influence on apoptosis. Luciferase report test was integrated in detecting the miR-130-3p target gene. The influence of miR-130-3p on the manifestation of classical DAMPs was studied, such as HMGB1, ATP, and Calreticulin. A coculture experiment was carried out to further confirm its effects on immune cell infiltration. The result displayed that miR-130-3p overexpression considerably facilitates apoptosis and suppresses the migration or proliferation of HCC cells. EPHB4 was confirmed as the target gene of miR-130-3p. Overexpression of this target gene promotes emission of Calreticulin, ATP, and HMGB1 and subsequently promotes DCs maturation and proliferation of CD4+ T cells. In summary, our results demonstrated that miR-130-3p inhibits HCC cell proliferation and migration by targeting EPHB4 and promotes drug-induced immunogenic cell death.

scholarly journals Neutrophil Metabolic Shift during Their Lifecycle: Impact on Their Survival and Activation

2019 ◽  
Vol 21 (1) ◽  
pp. 287 ◽  
Author(s):  
Louise Injarabian ◽  
Anne Devin ◽  
Stéphane Ransac ◽  
Benoit S. Marteyn
Keyword(s):  
Bone Marrow ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Pentose Phosphate ◽  
Neutrophil Activation ◽  
Population Heterogeneity ◽  
Polymorphonuclear Neutrophils ◽  
Potential Contribution ◽  
Plasma Fraction ◽  
The Impact

Polymorphonuclear neutrophils (PMNs) are innate immune cells, which represent 50% to 70% of the total circulating leukocytes. How PMNs adapt to various microenvironments encountered during their life cycle, from the bone marrow, to the blood plasma fraction, and to inflamed or infected tissues remains largely unexplored. Metabolic shifts have been reported in other immune cells such as macrophages or lymphocytes, in response to local changes in their microenvironment, and in association with a modulation of their pro-inflammatory or anti-inflammatory functions. The potential contribution of metabolic shifts in the modulation of neutrophil activation or survival is anticipated even though it is not yet fully described. If neutrophils are considered to be mainly glycolytic, the relative importance of alternative metabolic pathways, such as the pentose phosphate pathway, glutaminolysis, or the mitochondrial oxidative metabolism, has not been fully considered during activation. This statement may be explained by the lack of knowledge regarding the local availability of key metabolites such as glucose, glutamine, and substrates, such as oxygen from the bone marrow to inflamed tissues. As highlighted in this review, the link between specific metabolic pathways and neutrophil activation has been outlined in many reports. However, the impact of neutrophil activation on metabolic shifts’ induction has not yet been explored. Beyond its importance in neutrophil survival capacity in response to available metabolites, metabolic shifts may also contribute to neutrophil population heterogeneity reported in cancer (tumor-associated neutrophil) or auto-immune diseases (Low/High Density Neutrophils). This represents an active field of research. In conclusion, the characterization of neutrophil metabolic shifts is an emerging field that may provide important knowledge on neutrophil physiology and activation modulation. The related question of microenvironmental changes occurring during inflammation, to which neutrophils will respond to, will have to be addressed to fully appreciate the importance of neutrophil metabolic shifts in inflammatory diseases.

scholarly journals Death and Proliferation of Lymphocytes in Immune Response and Tumor Cells Are Controlled by pH Balance

2021 ◽  
Author(s):  
Wei-ping Zeng
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Unified Theory ◽  
Biological Processes ◽  
Proliferating Cells ◽  
Proliferation Of Lymphocytes ◽  
The Warburg Effect ◽  
Acid Treatments

Many biological processes are controlled by cell death and proliferation. Previous evidence suggests that cell proliferation and death by apoptosis are regulated by separate pathways. The present study found that cellular pH was positively correlated with proliferation but negatively with cell death. Alkaline treatments enhanced lymphocyte proliferation in response to antigen challenge in vivo and in in vitro cultures, whereas acid treatments induced cell death. Low pH was incompatible with the survival of highly proliferating cells, and the susceptibility to the acid-induced death was determined in part by the proliferative status of the lymphocytes. Likewise, alkaline treatments maintained tumor cell proliferation whereas acid treatments induced death. These data support a unified theory for the regulation of cell death and proliferation where a cellular pH balance controls both events, and the mitochondria as proton generators act as pH-stats. Thus, the Warburg effect is viewed as necessary for proliferating cells to have a high cellular pH environment to both survive and accelerate proliferation.

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