scholarly journals Ocimum sanctum Linn. Extract Improves Cognitive Deficits in Olfactory Bulbectomized Mice via the Enhancement of Central Cholinergic Systems and VEGF Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xoan Thi Le ◽  
Hien Thu Nguyen ◽  
Tai Van Nguyen ◽  
Hang Thi Nguyet Pham ◽  
Phuong Thi Nguyen ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Ex Vivo ◽  
Hippocampal Neurogenesis ◽  
Ocimum Sanctum ◽  
Vegf Receptor ◽  
Vegf Expression ◽  
Reference Drug ◽  
Expression Levels ◽  
Cholinergic Systems ◽  
Gene And Protein Expression

This study aimed to clarify the antidementia effects of ethanolic extract of Ocimum sanctum Linn. (OS) and its underlying mechanisms using olfactory bulbectomized (OBX) mice. OBX mice were treated daily with OS or a reference drug, donepezil (DNP). Spatial and nonspatial working memory performance was measured using a modified Y maze test and a novel object recognition test, respectively. Brain tissues of the animals were subjected to histochemical and neurochemical analysis. OS treatment attenuated OBX-induced impairment of spatial and nonspatial working memories. OBX induced degeneration of septal cholinergic neurons, enlargement of the lateral ventricles, and suppression of hippocampal neurogenesis. OS and DNP treatment also depressed these histological damages. OS administration reduced ex vivo activity of acetylcholinesterase in the brain. OBX diminished the expression levels of genes coding vascular endothelial growth factor (VEGF) and VEGF receptor type 2 (VEGFR2). Treatment with OS and DNP reversed OBX-induced decrease in VEGF gene and protein expression levels without affecting the expression of the VEGFR2 gene. These results demonstrate that the administration of OS can lessen the cognitive deficits and neurohistological damages of OBX and that these actions are, at least in part, mediated by the enhancement of central cholinergic systems and VEGF expression.

scholarly journals Oxidative Stress Induces a VEGF Autocrine Loop in the Retina: Relevance for Diabetic Retinopathy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1452
Author(s):  
Maria Grazia Rossino ◽  
Matteo Lulli ◽  
Rosario Amato ◽  
Maurizio Cammalleri ◽  
Massimo Dal Monte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Ex Vivo ◽  
Hypoxia Inducible Factor ◽  
Related Factor ◽  
Vegf Receptor ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Autocrine Loop ◽  
Retinal Explants

Background: Oxidative stress (OS) plays a central role in diabetic retinopathy (DR), triggering expression and release of vascular endothelial growth factor (VEGF), the increase of which leads to deleterious vascular changes. We tested the hypothesis that OS-stimulated VEGF induces its own expression with an autocrine mechanism. Methods: MIO-M1 cells and ex vivo mouse retinal explants were treated with OS, with exogenous VEGF or with conditioned media (CM) from OS-stressed cultures. Results: Both in MIO-M1 cells and in retinal explants, OS or exogenous VEGF induced a significant increase of VEGF mRNA, which was abolished by VEGF receptor 2 (VEGFR-2) inhibition. OS also caused VEGF release. In MIO-M1 cells, CM induced VEGF expression, which was abolished by a VEGFR-2 inhibitor. Moreover, the OS-induced increase of VEGF mRNA was abolished by a nuclear factor erythroid 2-related factor 2 (Nrf2) blocker, while the effect of exo-VEGF resulted Nrf2-independent. Finally, both the exo-VEGF- and the OS-induced increase of VEGF expression were blocked by a hypoxia-inducible factor-1 inhibitor. Conclusions: These results are consistent with the existence of a retinal VEGF autocrine loop triggered by OS. This mechanism may significantly contribute to the maintenance of elevated VEGF levels and therefore it may be of central importance for the onset and development of DR.

scholarly journals IL-6 Promotes FSH-Induced VEGF Expression Through JAK/STAT3 Signaling Pathway in Bovine Granulosa Cells

2017 ◽  
Vol 44 (1) ◽  
pp. 293-302 ◽  
Author(s):  
Meng Yang ◽  
Lei Wang ◽  
Xurong Wang ◽  
Xuezhi Wang ◽  
Zhiqiang Yang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Promoting Effect ◽  
Expression Levels ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Gene And Protein Expression

Background/Aims: Vascular endothelial growth factor (VEGF) has been demonstrated to play a pivotal role in the regulation of angiogenesis in ovarian follicular development, particularly during the preovulatory period. Although numerous studies have shown that interleukin-6 (IL-6) is one of the major inducing factors that regulate the expression of VEGF in non-ovarian cells, whether it involved in regulating the expression of VEGF in normal ovarian granulosa cells is still unknown. The aim of this study was to elucidate the mechanisms underlying the effect of IL-6 on FSH-induced VEGF expression in bovine granulosa cells derived from large follicles. Methods: VEGF mRNA expression in granulosa cells after IL-6 with/without inhibitors treatment was analyzed by RT-qPCR. Phosphorylation levels of ERK1/2 and STAT3 proteins induced by IL-6 were analyzed by western blotting. The protein levels produced by granulosa cells were detected by ELISA. Results: High concentration of IL-6 (10ng/ml) can significantly up-regulate FSH-induced VEGF gene and protein expression levels in granulosa cells, and also promote the VEGF upstream regulators HIF-1α and COX2 mRNA expression. VEGF expression levels were significantly decreased after specifically blocking HIF-1α and COX2 by using inhibitors. The up-regulation effect of IL-6 on FSH-induced VEGF expression in granulosa cells mainly through activating the JAK/STAT3 signaling pathway, which can be impaired by JAK inhibitors. Conclusion: IL-6 can promote FSH-induced VEGF expression in granulosa cells, which is mainly achieved by increasing the expression of HIF-1α and COX2.This promoting effect is mediated by activating the JAK/STAT3 pathway. Moreover, there may be a synergistic relationship between FSH and IL-6 in the regulation of VEGF expression.

scholarly journals Antifungal Effect of Long Noncoding RNA 9708-1 in the Vulvovaginal Candidiasis Murine Model

2021 ◽  
Vol 186 (2) ◽  
pp. 177-188
Author(s):  
Ying Wu ◽  
Lisha Jiang ◽  
Lingling Zhang ◽  
Xia Liu ◽  
Lina Yan ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Basal Layer ◽  
Vulvovaginal Candidiasis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Blank Control Group ◽  
Candida Spp ◽  
Expression Levels ◽  
Gene And Protein Expression

AbstractVulvovaginal candidiasis (VVC) caused by Candida spp. affects 70–75% of women at least once during their lives. We aim to elucidate the potential mechanism of VVC and investigate the therapeutic effects of long noncoding RNA 9708-1. Female BALB/c mice were randomized to four treatment groups, including the blank control group, VVC control group, vehicle control group and lncRNA 9708-1-overexpressed group. Mice were euthanized on Day 4, Day 7 and Day 14 after treatment. Colony-forming unit (CFU) was measured, and the inflammation was detected by hematoxylin and eosin (H&E). Gene and protein expression levels of lncRNA 9708-1 and FAK were determined by real-time PCR, Western blot and immunohistochemistry. The overexpression of lncRNA 9708-1 significantly decreased the fungal load from Day 4 to 7. H&E staining indicated that the impaired histological profiles were improved in lncRNA 9708-1-overexpressed group. LncRNA 9708-1 led to a significant increase in FAK level of vagina tissue which is expressed mainly in epithelial basal layer. This study suggests that lncRNA 9708-1 played a protective role on murine experimental VVC by upregulating the expression levels of FAK.

scholarly journals Activated STAT3 Is a Novel Regulator of the XRCC1 Promoter and Selectively Increases XRCC1 Protein Levels in Triple Negative Breast Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5475
Author(s):  
Griffin Wright ◽  
Manoj Sonavane ◽  
Natalie R. Gassman
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Excision Repair ◽  
Strand Break ◽  
Xrcc1 Gene ◽  
Single Strand Break ◽  
Expression Levels ◽  
Constitutive Activation ◽  
Gene And Protein Expression

Base Excision Repair (BER) addresses base lesions and abasic sites induced by exogenous and endogenous stressors. X-ray cross complementing group 1 (XRCC1) functions as a scaffold protein in BER and single-strand break repair (SSBR), facilitating and coordinating repair through its interaction with a host of critical repair proteins. Alterations of XRCC1 protein and gene expression levels are observed in many cancers, including colorectal, ovarian, and breast cancer. While increases in the expression level of XRCC1 are reported, the transcription factors responsible for this up-regulation are not known. In this study, we identify the signal transducer and activator of transcription 3 (STAT3) as a novel regulator of XRCC1 through chromatin immunoprecipitation. Activation of STAT3 through phosphorylation at Y705 by cytokine (IL-6) signaling increases the expression of XRCC1 and the occupancy of STAT3 within the XRCC1 promoter. In triple negative breast cancer, the constitutive activation of STAT3 upregulates XRCC1 gene and protein expression levels. Increased expression of XRCC1 is associated with aggressiveness and resistance to DNA damaging chemotherapeutics. Thus, we propose that activated STAT3 regulates XRCC1 under stress and growth conditions, but constitutive activation in cancers results in dysregulation of XRCC1 and subsequently BER and SSBR.

scholarly journals Enhancing Anti-Tumoral Potential of CD-NHF by Modulating PI3K/Akt Axis in U87 Ex Vivo Glioma Model

2021 ◽  
Vol 22 (8) ◽  
pp. 3873
Author(s):  
Gabriel Luta ◽  
Mihail Butura ◽  
Adrian Tiron ◽  
Crina E. Tiron
Keyword(s):  
Cell Line ◽  
Ex Vivo ◽  
Glioma Cells ◽  
In Vitro Study ◽  
Immunofluorescent Staining ◽  
Expression Levels ◽  
Disease Diagnostics ◽  
Phosphorylated Akt ◽  
Significant Impairment

Background: In the latest years, there has been an increased interest in nanomaterials that may provide promising novel approaches to disease diagnostics and therapeutics. Our previous results demonstrated that Carbon-dots prepared from N-hydroxyphthalimide (CD-NHF) exhibited anti-tumoral activity on several cancer cell lines such as MDA-MB-231, A375, A549, and RPMI8226, while U87 glioma tumor cells were unaffected. Gliomas represent one of the most common types of human primary brain tumors and are responsible for the majority of deaths. In the present in vitro study, we expand our previous investigation on CD-NHF in the U87 cell line by adding different drug combinations. Methods: Cell viability, migration, invasion, and immunofluorescent staining of key molecular pathways have been assessed after various treatments with CD-NHF and/or K252A and AKTVIII inhibitors in the U87 cell line. Results: Association of an inhibitor strongly potentiates the anti-tumoral properties of CD-NHF identified by significant impairment of migration, invasion, and expression levels of phosphorylated Akt, p70S6Kinase, or by decreasing expression levels of Bcl-2, IL-6, STAT3, and Slug. Conclusions: Using simultaneously reduced doses of both CD-NHF and an inhibitor in order to reduce side effects, the viability and invasiveness of U87 glioma cells were significantly impaired.

scholarly journals Diagnostic impact of promoter methylation and E-cadherin gene and protein expression levels in laryngeal carcinoma

2013 ◽  
Vol 3 ◽  
pp. 263-271
Author(s):  
Katarzyna Starska ◽  
Ewa Forma ◽  
Iwona Lewy-Trenda ◽  
Paweł Papież ◽  
Jan Woś ◽  
...  
Keyword(s):  
Protein Expression ◽  
Promoter Methylation ◽  
Laryngeal Carcinoma ◽  
Expression Levels ◽  
Diagnostic Impact ◽  
Gene And Protein Expression ◽  
E Cadherin

Abstract 358: First Trimester Human Umbilical Cord Perivascular Cells (FTM HUCPVCs) Maintain High Expression Levels of Angiogenic Factors and Have Superior Pro-angiogenic Effects on Endothelial Networks When Compared to Term HUCPVCs and BMSCs in an ex-vivo Rat Aortic Ring Assay

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Farwah Iqbal ◽  
Peter Szaraz ◽  
Shlomit Kenigsberg ◽  
Andree Gauthier-Fisher ◽  
Clifford Librach
Keyword(s):  
Ex Vivo ◽  
Human Growth ◽  
Aortic Ring ◽  
Angiogenic Factors ◽  
High Expression ◽  
Loop Formation ◽  
Expression Levels ◽  
Vascular Regeneration ◽  
Aortic Ring Assay ◽  
Qpcr Array

Introduction: Features of an ideal cell type, that would be conducive to vascular regeneration include (1) expression of pro-angiogenic genes (2) secretion of factors that promote developing or regenerating vasculature, and (3) maintenance of pro-angiogenic properties in the microvascular niche. Hypothesis: FTM HUCPVCs, a young rich source of mesenchymal stromal-like cells (MSCs) are ideal candidates for vascular regeneration due to their high expression of pro-angiogenic factors. Methods: The paracrine angiogenic potential of 3 types of MSCs was evaluated and compared using ex vivo tissue culture of rat aortic rings. Aorta sections were embedded into Matrigel™, cells were added to transwell membranes (pore=0.1μm, EBM 2% FBS) and combined with aortic rings (Day 0). Radial network growth and total loop formation were monitored by microscopy. Endothelial networks were quantified by ImageJ TM software. p values were calculated using ANOVA. (N=3 experiments, n=3 replicates). At day 7, the MSCs were isolated from transwells, human cytokine gene expression levels were measured using human growth factor profiler qPCR array (Qiagen, normalizers: GAPDH, βACT). Ct>35 considered negligible. Results: In the transwell aortic ring assay, FTM HUCPVCs induced significantly greater network growths when compared to term HUCPVCs (p≤0.0001), BMSCs (p≤0.0001) and untreated rings (p≤0.05). Quantification of network loop formation showed that FTM HUCPVCs induced greater numbers of closed loops when compared to term HUCPVCs (p≤0.0001), BMSCs (p≤0.0001) and untreated networks (p≤0.0001). Human growth factor qPCR array showed a high expression of angiogenic factors (Ct<25 cycle) both at day0 and day7 of co-culture, including BMP1, GDNF, MDK, NRG1, PDGFc, VEGFa, and VEGFc. Most cytokine expression levels were maintained up to 7 days in co-culture with 1 gene upregulated (BMP6 ΔCt>3), and 3 downregulated genes (FGF19, FGF9, NRTN ΔCt>3) at day 7 when compared to day 1. Conclusion: Compared to older sources of MSCs, FTM HUCPVCs promote developing endothelial networks in vitro via paracrine mechanisms and maintain the high expression of pro-angiogenic factors when cultures with endothelial cells.

scholarly journals Antioxidant Role of PRGF on RPE Cells after Blue Light Insult as a Therapy for Neurodegenerative Diseases

2020 ◽  
Vol 21 (3) ◽  
pp. 1021 ◽  
Author(s):  
Carlota Suárez-Barrio ◽  
Susana del Olmo-Aguado ◽  
Eva García-Pérez ◽  
María de la Fuente ◽  
Francisco Muruzabal ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Human Cell Line ◽  
Antioxidant Effect ◽  
Age Related Macular Degeneration ◽  
Strong Impact ◽  
Retinal Diseases ◽  
Age Related ◽  
Gene And Protein Expression

Oxidative stress has a strong impact on the development of retinal diseases such as age-related macular degeneration (AMD). Plasma rich in growth factors (PRGF) is a novel therapeutic approach in ophthalmological pathologies. The aim of this study was to analyze the antioxidant effect of PRGF in retinal epithelial cells (EPR) in in vitro and ex vivo retinal phototoxicity models. In vitro analyses were performed on ARPE19 human cell line. Viability and mitochondrial status were assessed in order to test the primary effects of PRGF. GSH level, and protein and gene expression of the main antioxidant pathway (Keap1, Nrf2, GCL, HO-1, and NQO1) were also studied. Ex vivo analyses were performed on rat RPE, and HO-1 and Nrf2 gene and protein expression were evaluated. The results show that PRGF reduces light insult by stimulating the cell response against oxidative damage and modulates the antioxidant pathway. We conclude that PRGF’s protective effect could prove useful as a new therapy for treating neurodegenerative disorders such as AMD.

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