Angiogenesis-modulating properties of ethanolic extract of Ferula assa-foetida oleo-gum-resin

Objectives: Angiogenesis has been known to have a critical role in the tumour growth. Different studies indicated that angiogenesis was stimulated by hypoxia. In the present study, we assessed the anti-angiogenesis activity of ethanolic extract of Ferula assa-foetida (EEFA) on hypoxic-induced human umbilical vein endothelial cells (HUVECs). Materials and Methods: The F. assa-foetida gum extract was characterised by total phenolic contents (TPC) and total flavonoids content (TFC). The active compounds of EEFA were determined by high-performance liquid chromatography (HPLC). Then, cytotoxic effects of EEFA on the growth of HUVECs were assessed using MTT assay, wound healing and cell cycle analysis. The expression of Vascular endothelial growth factor (VEGF), Akt,HIF-1, VEGF receptor 1 (VEGFR-1) and VEGFR-2 genes was also quantified by Real-Time PCR. GeneMANIA and EnrichR databases were used to predict gene network interactions for the studied genes and their mechanism. Results: The TFC and TPC of the extract were 26 mg gallic acid equivalent per gram of extract and 5.45 mg quercetin/g, respectively. HPLC analysis revealed the presence of anti-angiogenic components in EEFA. Our data showed that EEFA had no cytotoxicity effect on HUVECs. The obtained results also indicated that EEFA prevented the proliferation and migration of HUVECs. Expression analysis showed that EEFA significantly decreased the VEGF-A mRNA level in the hypoxia-induced HUVECs. No change was found in the VEGFR-2 gene expression following treatment with EEFA in the HUVECs. However, the significantly upregulation of the VEGFR-1 gene expression was observed in the EEFA-treated HUVECs. The bioinformatics analysis of gene-gene interaction network also showed that the studied genes play an essential role in the regulatory pathways of angiogenesis and cancer. Conclusion: These findings provided evidence about the anti-angiogenesis role of EEFA, suggesting that this could be considered in the cancer therapy.

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Stanniocalcin-1 regulates endothelial gene expression and modulates transendothelial migration of leukocytes

AJP Renal Physiology ◽

10.1152/ajprenal.00219.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. F895-F904 ◽

Cited By ~ 36

Author(s):

Arup Chakraborty ◽

Heddwen Brooks ◽

Ping Zhang ◽

Wayne Smith ◽

Matthew R. McReynolds ◽

...

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

B Lymphocytes ◽

Tissue Injury ◽

Umbilical Vein ◽

Critical Role ◽

Inflammatory Cells ◽

Transendothelial Migration ◽

Calcium Signal ◽

Apical Surface

The mammalian counterpart of the fish calcium-regulating hormone stanniocalcin-1 (STC1) inhibits monocyte chemotactic protein-1- and stromal-derived factor-1α (SDF-1α)-mediated chemotaxis and diminishes chemokinesis in macrophage-like RAW264.7 and U937 cells in a manner that may involve attenuation of the intracellular calcium signal. STC1 is strongly induced in the kidney following obstructive injury. We hypothesized that STC1 may serve to attenuate the influx of inflammatory cells to the site of tissue injury. In this study, we examined the effect of STC1 on the migration of freshly isolated human macrophages, neutrophils, and T and B lymphocytes through quiescent or IL-1β-treated human umbilical vein endothelial cell (HUVEC) monolayers. STC1 inhibited transmigration of macrophages and T lymphocytes through quiescent or IL-1β-activated HUVECs but did not attenuate the transmigration of neutrophils and B lymphocytes. STC1 regulates gene expression in cultured endothelial cells and is detected on the apical surface of endothelial cells in vivo. The data suggest that STC1 plays a critical role in transendothelial migration of inflammatory cells and is involved in the regulation of numerous aspects of endothelial function.

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Biological Activities of Selected Plants and Detection of Bioactive Compounds from Ardisia elliptica Using UHPLC-Q-Exactive Orbitrap Mass Spectrometry

Molecules ◽

10.3390/molecules25133067 ◽

2020 ◽

Vol 25 (13) ◽

pp. 3067

Author(s):

Pei Lou Wong ◽

Nurul Azila Fauzi ◽

Siti Norhamimah Mohamed Yunus ◽

Nur Ashikin Abdul Hamid ◽

Siti Zulaikha Abd Ghafar ◽

...

Keyword(s):

High Performance ◽

Biological Activities ◽

Ethanolic Extract ◽

Dry Weight ◽

Total Phenolic ◽

Glucosidase Inhibitors ◽

Long Time ◽

Ic50 Values ◽

Q Exactive ◽

Ardisia Elliptica

Plants and plant-based products have been used for a long time for medicinal purposes. This study aimed to determine the antioxidant and anti-α-glucosidase activities of eight selected underutilized plants in Malaysia: Leucaena leucocephala, Muntingia calabura, Spondias dulcis, Annona squamosa, Ardisia elliptica, Cynometra cauliflora, Ficus auriculata, and Averrhoa bilimbi. This study showed that the 70% ethanolic extract of all plants exhibited total phenolic content (TPC) ranging from 51 to 344 mg gallic acid equivalent (GAE)/g dry weight. A. elliptica showed strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging activities, with half maximal inhibitory concentration (IC50) values of 2.17 and 49.43 μg/mL, respectively. Most of the tested plant extracts showed higher inhibition of α-glucosidase enzyme activity than the standard, quercetin, particularly A. elliptica, F. auriculata, and M. calabura extracts with IC50 values of 0.29, 0.36, and 0.51 μg/mL, respectively. A total of 62 metabolites including flavonoids, triterpenoids, benzoquinones, and fatty acids were tentatively identified in the most active plant, i.e., A. elliptica leaf extract, by using ultra-high-performance liquid chromatography (UHPLC)–electrospray ionization (ESI) Orbitrap MS. This study suggests a potential natural source of antioxidant and α-glucosidase inhibitors from A. elliptica.

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Epigenetic mechanisms shape the underlining expression regulatory mechanisms of the STAT3 in multiple sclerosis disease

BMC Research Notes ◽

10.1186/s13104-020-05427-1 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Arezoo Hosseini ◽

Zohreh Babaloo ◽

Tohid Gharibi ◽

Navid Shomali ◽

Faroogh Marofi ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Diseases ◽

Mrna Level ◽

Critical Role ◽

Methylation Status ◽

Significant Negative Correlation ◽

Treg Cells ◽

Immunological Tolerance ◽

Dna Hypermethylation ◽

T Helper 17

Abstract Objectives Immunological tolerance is mediated by CD4+CD25+ regulatory T (Treg) cells. Studies have shown that thymic and peripheral generations of Treg cells depend on the CD28 signaling pathway. T helper 17 (Th17) cells are involved in the pathophysiology of various inflammatory diseases. Cytokines, such as interleukin (IL)-6 and TGF-β, regulate the reciprocal development of Th17 and Treg cells. In CD4+ T cells, signal transducer and activator of transcription 3 (STAT3) play a critical role in the induction of Th17 cell differentiation and inhibition of Treg cell development. Results In this study, we investigated the STAT3 methylation and gene expression status in patients with MS. Our study demonstrated that the level of STAT3 methylation decreased in relapsing–remitting MS patient compared to control groups, which the decreases were statistically significant. STAT3 gene expression increased in patient group relative to healthy one, and the increases were found to be statistically significant. According to our findings, it can be suggested that DNA hypermethylation of STAT3 affects the gene expression. In addition, there is a strong and significant negative correlation between the methylation status and mRNA level of STAT3.

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P048 Mucosal macrophages express elevated levels of HDAC9 in inflamed and uninflamed mucosa of Crohn’s disease, but not ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.177 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S157-S157

Author(s):

M Ghiboub ◽

J de Bruyn ◽

K Reedquist ◽

T Radstake ◽

C Wichers ◽

...

Keyword(s):

Gene Expression ◽

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Histone Deacetylases ◽

Cell Function ◽

Mrna Level ◽

Critical Role ◽

Histone Deacetylation ◽

Inflamed Tissue

Abstract Background Histone deacetylases (HDACs) are a group of enzymes that control histone and non-histone deacetylation and influence inflammatory gene transcription. Certain members of the HDAC family control the function of macrophages and play an important role in immune response. In this study, we aimed to study the expression of HDACs in mucosal macrophages isolated from inflammatory bowel diseases (IBD) patients. Methods Both macroscopically inflamed and non-inflamed colon resection tissue were collected from 15 Crohn’s disease (CD) and nine ulcerative colitis (UC) patients operated on for therapy refractory disease. Of the CD patients, 53% had ileal and 47% ileocolonic disease. Of the UC patients, 44% had left-sided colitis and 56% pancolitis. Lamina propria was separated from the muscularis externa, and a targeted array for epigenetic enzymes was performed. To assess the relevance of HDAC9 gene expression in terms of protein level, immunofluorescence staining of HDAC9 protein was undertaken in tissue sections from inflamed and non-inflamed mucosa. CD68 was used as a pan-macrophage marker. Results From our array, expression of HDAC9 was significantly higher in the inflamed mucosa of CD patients compared with UC patients (p = 0.005). Gene expression of HDAC9 in non-inflamed mucosa from CD was elevated compared with non-inflamed mucosa from UC. In addition, in CD, HDAC9 mRNA level was increased in inflamed tissue in comparison to non-inflamed tissue (p = 0.046). In conjunction with the expression data, HDAC9 protein was found highly expressed in inflamed tissue. HDAC9 was predominantly localised in the cytoplasmic compartment of macrophages in non-inflamed tissue whilst HDAC9 localised to the nucleus of macrophages in inflamed tissue. Conclusion HDAC9 is member of class IIA HDAC superfamily that exerts pro-inflammatory properties. The inhibition of HDAC9 in experimental murine colitis clearly enhances regulatory T-cell function, suggesting a critical role for HDAC9 in breaching immune homeostasis (de Zoeten EF et al, 2009). We suggest here that HDAC9 can serve as an additional marker to distinguish CD from UC in tissue biopsies. Furthermore, we show for the first time that HDAC9 protein is expressed in mucosal macrophages of CD patients, indicating its potential in mediating macrophage inflammatory function in IBD. Further studies are currently being undertaken to elucidate the role of HDAC9 in CD pathogenesis.

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Activity of Serbian Aronia prunifolia against Prototheca wickerhamii and Prototheca zopfii

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.80797 ◽

2017 ◽

Vol 45 (1) ◽

pp. 9

Author(s):

Ljiljana Suvajdžić ◽

Tamara Krstić ◽

Srđan Stojanović ◽

Nevena Grujić-Letić ◽

Olgica Milankov ◽

...

Keyword(s):

High Performance ◽

Dry Matter ◽

Ethanolic Extract ◽

Break Point ◽

Total Phenolic ◽

Dilution Method ◽

Prototheca Zopfii ◽

Minimal Inhibitory Concentrations ◽

Antialgal Activity ◽

Prototheca Wickerhamii

Background: Beneficial effects of berries have been known from 16th century, but their antimicrobial effects have been explained scientifically only recently. The two most common aronia species are black chokeberry, Aronia melanocarpa [Michx.] Elliot and red chokeberry, Aronia arbutifolia [L.] Elliot. Purple chokeberry (Aronia prunifolia) is a hybrid of these two species. Protothecosis is a disease caused by achlorophyllous algae Prototheca species. Infections with Prototheca species are more common in veterinary medicine. The purpose of this study was to investigate the activity of Aronia prunifolia berries against Prototheca zopfii (P. zopfii) and Prototheca wickerhamii (P. wickerhamii).Materials, Methods & Results: Purple chokeberry juice was made by squeezing the fruits and evaporated to dryness. Extracts of purple aronia were obtained by maceration with ethanol 80 % (v/v) for 24 h. Prototheca zopfii was obtained from udder of cow with mastitis and Prototheca wickerhamii was isolated from human oral cavity. Total phenolic and flavonoid contents were analized using spectrophotometric methods. The chemical composition of the tested substances was determined by a high performance liquid chromatography (HPLC) method. The examination was conducted by a micro-dilution method according to the guidelines of Clinical and Laboratory Standards Institute (CLSI). Microsoft Excel program 2007 was used for statistical analysis. The antialgal activity was expressed as minimal inhibitory concentrations MIC99, MIC90 and MIC80, the lowest concentration which kills 99%, 90% and 80% of organisms, respectively. Furthermore, minimal algaecide concentration (MAC), the lowest concentration which kills 99.9% of organisms is determined, as well as break point, the lowest concentration at which there is no algal growth.Discussion: The content of ascorbic acid was twice as high in the ethanolic extract as in the juice. Content of polyphenolic compounds was high in both juice and ethanolic extract. The quantity of phenocarbonic acids in juice and ethanolic extract was relatively low. Some of them were found only in juice (ellagic, coumaric and gentisic acids) as opposed to others found only in ethanolic extract (chlorogenic acid). Flavonoids were also detected in juice and ethanolic extract. Extract was much richer in flavonoid content when compared to aronia juice. Catechin was present in concentration of 186.3 mg/ 100 g of dry matter in the aronia juice, and 680.65 mg/ 100 g of dry matter in the ethanolic extract, which was more than 3.6 times higher. Quercetin was found only in the extract. The rutin content was 12 times and the chrysin content was 2.5 times higher in the aronia extract. The biggest difference could be noted in the quantitative contents of anthocyanins, 26 times higher concentration in extract than in juice. In general, higher content of bioactive compounds could be observed in the extract than in the juice. The results showed that the ethanolic extract of aronia fruits exhibited antialgal activity against both Prototheca species, while the juice showed no antialgal activity. This difference in antialgal effect is presumably related to the high content of several groups of biocompounds, especially catechin and anthocyanins, present in the ethanolic extract, and probably their synergistic action. There is no comparable data of antialgal effects of aronia in literature.

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Coordinated alteration of hepatic gene expression in fatty acid and triglyceride synthesis in LCAT-null mice is associated with altered PUFA metabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00597.2004 ◽

2006 ◽

Vol 290 (1) ◽

pp. E17-E25 ◽

Cited By ~ 17

Author(s):

Hui Song ◽

Liping Zhu ◽

Clive M. Picardo ◽

Graham Maguire ◽

Vincent Leung ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Knockout Mice ◽

Target Genes ◽

Mrna Level ◽

Triglyceride Synthesis ◽

Altered Expression ◽

Regulatory Pathways ◽

Hepatic Expression ◽

Pufa Metabolism

Complete lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with fasting hypertriglyceridemia (HTG). We recently reported that, in ldlr−/−×lcat−/− mice, fasting HTG is associated with hepatic triglyceride overproduction in association with an upregulation of the hepatic srebp1 gene and altered expression of its target genes in lipogenesis and gluconeogenesis. We further investigated the role of hepatic polyunsaturated fatty acid (PUFA) metabolism in the modulation of the lipid phenotypes. In the ldlr−/−×lcat−/− mice, using the ldlr−/−×lcat+/+ littermate as controls, the hepatic level of cholesterol esters (CE) were reduced by 61.0% whereas the 20:4-CE and 22:6-CE contents were each reduced by >80%. In contrast, the hepatic levels of 20:4- and 22:6-containing phospholipid (PL) species were either unchanged or mildly elevated. Similar alterations of the hepatic PUFA in CE and in PL were also observed in the lcat−/− mice compared with their wild-type controls. In ldlr−/−×lcat−/− mice, hepatic mRNA level was markedly reduced for Δ-6 desaturase ( fads2) (70.2%) and acyl-CoA:cholesterol acyltransferase-2 ( soat2) (57.0%). A similar pattern of gene expression change was also observed in the lcat−/− single-knockout mice. In contrast, the acyl-CoA:diacylglycerol acyltransferase-2 ( dgat2) mRNA level was 1.7-fold upregulated in the double-knockout mice. In summary, we observed coordinated alterations in hepatic expression of the gene for fads2, soat2, and dgat2, resulting in a reduction in total hepatic PUFA pool and differentially in the PUFA-CE pool, in association with an increase in dgat2 gene expression for promoting triglyceride synthesis and secretion. Some of the phenotypes are not readily explained by known mechanisms and may represent novel regulatory pathways.

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Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms22168885 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8885 ◽

Cited By ~ 1

Author(s):

Jolanta Kryczka ◽

Jakub Kryczka ◽

Karolina H. Czarnecka-Chrebelska ◽

Ewa Brzeziańska-Lasota

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Cisplatin Resistance ◽

Interaction Network ◽

Tumour Microenvironment ◽

Acquired Drug Resistance ◽

Active Efflux ◽

Regulatory Pathways

Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm, and epigenetic regulation by microRNAs (miRNAs). Because it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced, and the cancer cells may have acquired drug resistance. This review summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin-resistant non-small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly dysregulated TP53, MDM2, and CDKN1A genes as they encode the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

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Identification of Diagnostic Markers for Breast Cancer Based on Differential Gene Expression and Pathway Network

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.811585 ◽

2022 ◽

Vol 9 ◽

Author(s):

Shumei Zhang ◽

Haoran Jiang ◽

Bo Gao ◽

Wen Yang ◽

Guohua Wang

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Differentially Expressed Genes ◽

Interaction Network ◽

Enrichment Analysis ◽

Gene Interaction ◽

Diagnostic Markers ◽

Differentially Expressed ◽

Breast Cancer Patients ◽

Gene Interaction Network

Background: Breast cancer is the second largest cancer in the world, the incidence of breast cancer continues to rise worldwide, and women’s health is seriously threatened. Therefore, it is very important to explore the characteristic changes of breast cancer from the gene level, including the screening of differentially expressed genes and the identification of diagnostic markers.Methods: The gene expression profiles of breast cancer were obtained from the TCGA database. The edgeR R software package was used to screen the differentially expressed genes between breast cancer patients and normal samples. The function and pathway enrichment analysis of these genes revealed significant enrichment of functions and pathways. Next, download these pathways from KEGG website, extract the gene interaction relations, construct the KEGG pathway gene interaction network. The potential diagnostic markers of breast cancer were obtained by combining the differentially expressed genes with the key genes in the network. Finally, these markers were used to construct the diagnostic prediction model of breast cancer, and the predictive ability of the model and the diagnostic ability of the markers were verified by internal and external data.Results: 1060 differentially expressed genes were identified between breast cancer patients and normal controls. Enrichment analysis revealed 28 significantly enriched pathways (p < 0.05). They were downloaded from KEGG website, and the gene interaction relations were extracted to construct the gene interaction network of KEGG pathway, which contained 1277 nodes and 7345 edges. The key nodes with a degree greater than 30 were extracted from the network, containing 154 genes. These 154 key genes shared 23 genes with differentially expressed genes, which serve as potential diagnostic markers for breast cancer. The 23 genes were used as features to construct the SVM classification model, and the model had good predictive ability in both the training dataset and the validation dataset (AUC = 0.960 and 0.907, respectively).Conclusion: This study showed that the difference of gene expression level is important for the diagnosis of breast cancer, and identified 23 breast cancer diagnostic markers, which provides valuable information for clinical diagnosis and basic treatment experiments.

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FCGR2A Could Function as a Prognostic Marker and Correlate with Immune Infiltration in Head and Neck Squamous Cell Carcinoma

BioMed Research International ◽

10.1155/2021/8874578 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Yongmei Dai ◽

Wenhan Chen ◽

Junpeng Huang ◽

Tongjian Cui

Keyword(s):

Gene Expression ◽

Head And Neck ◽

Protein Interaction ◽

Protein Interaction Network ◽

Mrna Level ◽

Interaction Network ◽

Progression Free Survival ◽

Tissue Samples ◽

Protein Protein Interaction ◽

Protein Protein Interaction Network

Objective. We aim to investigate the correlation between FCGR2A mRNA level and prognosis of head and neck squamous cancer (HNSC) in public databases. In addition, we investigated the correlation between FCGR2A expression and clinicopathological characteristics and tumor-infiltrating immune cells in HNSC patients. Methods. FCGR2A mRNA expression in multiple cancers was analyzed based on Gene Expression Profiling Interactive Analysis. A protein-protein interaction network was obtained based on the STRING database. The 10 proteins most closely related to FCGR2A (i.e., CD3G, PLCG2, LAT, LYN, SYK, FCGR3A, PIK3R1, HCK, ITGAM, and ITGB2) were screened, followed by establishing the protein-protein interaction network. The correlation between FCGR2A expression and immunocytes was investigated, together with the effects of FCGR2A on the metastasis, recurrence, and survival of HNSC. Results. FCGR2A expression in several carcinoma tissues was significantly higher than that of adjacent tissues. Significant differences were noticed in the HNSC samples and the adjacent tissue samples except the seven samples of grade 4. There were statistical differences between the FCGR2A expression in tissues of grade 1, grade 2, and grade 3 ( P < 0.05 ). In the tissues of grade 4, the expression of FCGR2A was the lowest. The FCGR2A protein was a type of II-a receptor in γFc of the low-affinity immunoglobulin, which could bind with the Fc region of the immunoglobulin γ. There was a correlation between the FCGR2A gene and the distal HNSC metastasis. FCGR2A gene expression was correlated with the survival and prognosis. The GSE65858 dataset was selected for the validation. The FCGR2A expression was significantly correlated with total survival ( P = 0.0107 ) and progression-free survival ( P = 0.0362 ). Conclusions. Our findings shed light on the importance of FCGR2A in HNSC and illustrated a potential relationship between FCGR2A and tumor-immune interactions.

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