scholarly journals GPER Agonist G-1 Disrupts Tubulin Dynamics and Potentiates Temozolomide to Impair Glioblastoma Cell Proliferation

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3438
Author(s):  
Alex Hirtz ◽  
Nolwenn Lebourdais ◽  
Fabien Rech ◽  
Yann Bailly ◽  
Athénaïs Vaginay ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Patient Survival ◽  
Protective Role ◽  
Chemotherapy Treatment ◽  
Sensitive Cell Line ◽  
Standard Chemotherapy ◽  
Current Standard ◽  
First Time ◽  
G Protein Coupled

Glioblastoma (GBM) is the most common brain tumor in adults, which is very aggressive, with a very poor prognosis that affects men twice as much as women, suggesting that female hormones (estrogen) play a protective role. With an in silico approach, we highlighted that the expression of the membrane G-protein-coupled estrogen receptor (GPER) had an impact on GBM female patient survival. In this context, we explored for the first time the role of the GPER agonist G-1 on GBM cell proliferation. Our results suggested that G-1 exposure had a cytostatic effect, leading to reversible G2/M arrest, due to tubulin polymerization blockade during mitosis. However, the observed effect was independent of GPER. Interestingly, G-1 potentiated the efficacy of temozolomide, the current standard chemotherapy treatment, since the combination of both treatments led to prolonged mitotic arrest, even in a temozolomide less-sensitive cell line. In conclusion, our results suggested that G-1, in combination with standard chemotherapy, might be a promising way to limit the progression and aggressiveness of GBM.

scholarly journals Differential Activation of Fetal Hofbauer Cells in Primigravidas Is Associated with Decreased Birth Weight in Symptomatic Placental Malaria

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Stephanie L. Gaw ◽  
Bethann S. Hromatka ◽  
Sadiki Ngeleza ◽  
Sirirak Buarpung ◽  
Nida Ozarslan ◽  
...  
Keyword(s):  
Birth Weight ◽  
Placental Malaria ◽  
Perinatal Outcomes ◽  
Protective Role ◽  
Cross Sectional ◽  
Macrophage Response ◽  
Hofbauer Cells ◽  
Infant Birth ◽  
First Time

Background. Placental malaria is a leading global cause of low birth weight neonates, especially in first-time mothers. To better understand the role of innate immunity in placental malaria, we investigated the relationships between histopathological markers of placental malaria, fetal and maternal macrophage responses, and perinatal outcomes in a cross-sectional case control study of pregnant women presenting with symptomatic malaria at the time of delivery. Results. Primigravidas showed increased hemozoin deposition in placental villi (p=0.02), syncytiotrophoblasts (p=0.01), and fetal Hofbauer cells (p=0.01). The percentage of hemozoin-positive villi negatively correlated with infant birth weight (regression coefficient [b] = -0.03 kg decrease in birth weight per % increase in hemozoin-positive villi, p=0.035). Malaria-infected placentas showed a twofold increase in Hofbauer cells (p<0.001) and maternal macrophages (p<0.001). Placental malaria was associated with a threefold increase in the percentage of M2 maternal macrophages (19.2% vs 6.4%, p=0.01). Primigravidas showed a significant decrease in the Hofbauer cell M2-percentage in placental malaria (92.7% vs. 97.0%, p=0.04), which was predictive of infant birth weight (b=0.08 kg increase in birth weight per % increase in M2 Hofbauer cells, p=0.001). There was no association between maternal macrophage response and infant birth weights. Conclusions. Placentas with malarial infection had increased numbers of fetal Hofbauer cells in the villous stroma and maternal macrophages in the intervillous space. In primigravidas, decreased anti-inflammatory M2-type Hofbauer cells were predictive of lower birth weight. M2-type maternal macrophages were increased in placental malaria, but there was no association with gravidity or birth weight. These results suggested a protective role of M2 Hofbauer cells in fetal growth restriction.

scholarly journals Physical Activity Prevents Cartilage Degradation: A Metabolomics Study Pinpoints the Involvement of Vitamin B6

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1374 ◽  
Author(s):  
Deiana ◽  
Malerba ◽  
Dalle Carbonare ◽  
Cheri ◽  
Patuzzo ◽  
...  
Keyword(s):  
Physical Activity ◽  
Vitamin B6 ◽  
Cartilage Degradation ◽  
Protective Role ◽  
Before And After ◽  
Metabolomics Study ◽  
Cartilage Cells ◽  
First Time ◽  
Chondrosarcoma Cell Line

Osteoarthritis (OA) is predominantly characterized by the progressive degradation of articular cartilage, the connective tissue produced by chondrocytes, due to an imbalance between anabolic and catabolic processes. In addition, physical activity (PA) is recognized as an important tool for counteracting OA. To evaluate PA effects on the chondrocyte lineage, we analyzed the expression of SOX9, COL2A1, and COMP in circulating progenitor cells following a half marathon (HM) performance. Therefore, we studied in-depth the involvement of metabolites affecting chondrocyte lineage, and we compared the metabolomic profile associated with PA by analyzing runners’ sera before and after HM performance. Interestingly, this study highlighted that metabolites involved in vitamin B6 salvage, such as pyridoxal 5’-phosphate and pyridoxamine 5’-phosphate, were highly modulated. To evaluate the effects of vitamin B6 in cartilage cells, we treated differentiated mesenchymal stem cells and the SW1353 chondrosarcoma cell line with vitamin B6 in the presence of IL1β, the inflammatory cytokine involved in OA. Our study describes, for the first time, the modulation of the vitamin B6 salvage pathway following PA and suggests a protective role of PA in OA through modulation of this pathway.

scholarly journals Modulation of Dendritic Cell Apoptosis and CD8+Cytotoxicity by Histamine: Role of Protein Kinase C

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Julieta Alcain ◽  
Enrique Podaza ◽  
María Soledad Gori ◽  
Gabriela Salamone ◽  
Mónica Vermeulen
Keyword(s):  
T Lymphocytes ◽  
Inflammatory Responses ◽  
Cytolytic Activity ◽  
Cross Presentation ◽  
Kinase C ◽  
Histocompatibility Complex ◽  
First Time ◽  
G Protein Coupled ◽  
Pkc Activation

Dendritic cells (DC) are able to present extracellular antigens associated with the molecules of the major histocompatibility complex class I. In a previous work, we demonstrated that the histamine (HIS), acting through H1/H4 receptors, increases the cross-presentation of soluble ovalbumin by murine DC and can enhance the recruitment of specific CD8+T lymphocytes during the development of chronic inflammatory responses. Here, we studied in more depth the mechanisms underlying this enhancement. We showed that the cytotoxicity of specific CD8+lymphocytes is increased in HIS-treated DC and it is lost by inhibition of vacuolar-ATPase that prevents endosome acidification. It is known that HIS acts through G protein-coupled receptors. The H1/H4 receptors are associated with a Gqsubunit, which involves PKC signaling, a pathway related to the apoptotic process. Interestingly, we demonstrated for the first time that HIS prevents DC apoptosis induced by heat shock through the inhibition of caspase-3, a mechanism dependent on PKC activation, since it is reversed by its inhibition. By contrast, cytolytic activity of T lymphocytes induced by HIS-stimulated DC was independent of PKC pathway.

scholarly journals miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jianlei Zhang ◽  
Wei Liu ◽  
Yabo Wang ◽  
Shengnan Zhao ◽  
Na Chang
Keyword(s):  
Cell Proliferation ◽  
Glycogen Synthase ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Protective Effects ◽  
Inflammatory Cytokine Production ◽  
Protein Levels

miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson’s disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP+-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF-α and IL-1β in SH-SY5Y cells in the presence of MPP+. Luciferase reporter assay demonstrated that GSK3β was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3β activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP+-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3β in MPP+-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.

Abstract 293: Role Of G-protein Coupled Receptor Signaling In Cardio-renal Injury

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Fadia A Kamal ◽  
Joshua G Travers ◽  
Qing Ma ◽  
Prasad Devarajan ◽  
Burns C Blaxall
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
G Protein ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Collagen Iii ◽  
Mechanistic Investigation ◽  
G Protein Coupled

The kidneys play an important role in cardiovascular disease (CVD), where renal co-morbidities accompany CVD in a large proportion of patients thus complicating their treatment regimen. Moreover, the incidence of acute renal injury after cardiac surgery plays an important role in disease progression. Emerging data suggest the importance of understanding the mechanisms of cardio-renal injury and the development of novel therapies that can be safely used with cardiovascular and renal co-existing pathologies. Although the role of G-protein coupled receptors (GPCRs) in CVD has been broadly recognized, their role in renal injury remains poorly understood. We have found, in a chronic mouse model of heart failure, attenuated renal fibrosis and attenuated pathologic RAAS activation by the small molecule GPCR-Gβγ inhibitor “gallein”. To investigate the direct effects of GPCR-Gβγ inhibition on renal injury, we utilized an acute renal ischemia-reperfusion (RIR) mouse model. Gβγ inhibition by gallein pretreatment attenuated the histopathological profile of RIR, including attenuation of tubular hypertrophy, apoptosis, cast formation, and tissue Lipocalin2 expression. This was accompanied by attenuated inflammation, reflected by reduced CCL2 and ICAM1 gene expression and cellular infiltration, in addition to reduced Collagen III gene expression. These preliminary results suggest a promising protective role for Gβγ inhibition in renal injury and remodeling. Future mechanistic investigation of this possible protective effect will provide better understanding of the role of GPCR-Gβγ signaling in cardio-renal injury and remodeling and possible novel therapeutic targets.

scholarly journals Herpes Viral Origin of the Parsonage-Turner Syndrome: Highlighting of Serological Immune Anti-Herpes Deficiency Cured by Anti-Herpes Therapy

2015 ◽  
Vol 7 (2) ◽  
pp. 110-114
Author(s):  
Jacqueline Le Goaster ◽  
Patrice Bourée ◽  
Charles Ifergan ◽  
Frederic Tangy ◽  
René Olivier ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Normal Values ◽  
Respiratory Function Tests ◽  
Herpes Viruses ◽  
Chemotherapy Treatment ◽  
Viral Origin ◽  
The Family ◽  
Genetic Deficiency ◽  
First Time

In 2012, a 50 year-old athletic male presented with weakness, pain and unilateral phrenic paralysis, followed by bilateral phrenic paralysis with deep dyspnea. In 2013, the Parsonage-Turner syndrome was diagnosed. When the patient was seen in September 2014 for the first time, he was facing phrenic neuromuscular failure, which led to the hypothesis of neurotropic herpes viruses. A control of the global serological anti-Herpes immunity to analyze his antibody (Ab) levels confirmed herpes immune genetic deficiency. An appropriate herpes chemotherapy treatment was proposed. Immediately, a spectacular recovery of the patient was observed, and after a few weeks, the respiratory function tests showed normal values. The hypothesis of the inductive role of viruses of the herpes family in the Parsonage-Turner syndrome was thus substantiated. The patient's immune deficiency covers the HSV2, HHV3, HHV4, HHV5 and HHV6 Ab levels. This led to the control of herpes in the family lineage: indeed, his daughter presented alterations of her serological herpes Ab levels.

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