High Expressions of Notch and Survivin in Elderly Patients with Glioma Contribute to an Unfavorable Prognosis

Gliomas account for 24% of all primary brain and central nervous system tumors. To date, elderly patients constitute 10-25% of patients with a diagnosis of glioblastoma multiforme, but limited attention has been put on their optimal treatment, largely due to a very poor expected survival (only 4-6 months). Unraveling the molecular mechanism of gliomas provides an opportunity to develop novel biomarkers and therapeutic targets. In this study, we collected fasting blood samples from elderly patients diagnosed with glioma and who received treatment in our hospital between May 2016 and May 2019 and determined the expression levels of Notch and Survivin proteins in different clinical stages and their relationship with patient survival. A total of 68 healthy volunteers in this hospital during the same period served as healthy controls. Compared with the healthy controls, the expressions of Notch 1, Notch 2, Notch 3, and Survivin protein in the serum of elderly glioma patients were remarkably increased ( P < 0.05 ), but the expression of caspase-3 protein declined ( P < 0.05 ). As the clinical stage of the patient advanced, the expressions of Notch 1, Notch 2, Notch 3, and Survivin increased, and this increase was statistically significant ( P < 0.05 ). It was observed that high expressions of serum Notch 1, Notch 2, Notch 3, and Survivin were associated with poor overall survival of elderly patients with glioma. We used γ-secretase inhibitor MRK-003 and specific ligand Jagged1 to alter the Notch pathway in U251 cells. It was revealed that MRK-003 incubation effectively suppressed the mRNA expression of Survivin in U251 cells, but Jagged1 stimulation significantly promoted the mRNA expression of Survivin in U251 cells. Results of MTT and transwell migration assays revealed reduced U251 cell viability and migration following MRK-003 treatment and enhanced cell viability and migration following Jagged1 stimulation. In conclusion, the finding obtained from these results supports that Notch and Survivin proteins contribute to the development of glioma in elderly patients and could serve as prognostic factors.

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CD4+CD25- effector T cells from healthy controls and MS patients do not differ in mRNA expression of IFN-γ, IL-2, and TNF-α

Aktuelle Neurologie ◽

10.1055/s-2004-833325 ◽

2004 ◽

Vol 31 (S 1) ◽

Author(s):

A Hug ◽

J Haas ◽

A Viehöver ◽

B Fritz ◽

B Storch-Hagenlocher ◽

...

Keyword(s):

T Cells ◽

Mrna Expression ◽

Effector T Cells ◽

Healthy Controls ◽

Tnf Α ◽

Ifn Γ

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THE MODULATION OF DRUG EFFLUX TRANSPORTER BY CURCUMIN IN MCF7 BREAST CANCER CELLS AFTER REPEATED EXPOSURE OF ENDOXIFEN AND ESTRADIOL

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018.v10s1.21 ◽

2018 ◽

Vol 10 (1) ◽

pp. 102

Author(s):

Robby Hertanto ◽

Wilson Bastian ◽

Paramita . ◽

Melva Louisa

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Mrna Expression ◽

Rna Extraction ◽

Efflux Transporters ◽

Drug Efflux ◽

Mcf7 Cells ◽

Total Rna ◽

P Glycoprotein ◽

Drug Efflux Transporters

Objective: The aim of the present study was to determine whether curcumin (CM) can prevent drug sensitivity of breast cancer (BC) cells when E andβ-E2 are administered together and whether the underlying mechanism involves modulation of drug efflux transporters.Methods: MCF7 BC cells were treated with the vehicle only, E+β-E2, or E+β-E2+CM repeatedly for 8 weeks. Afterward, the cells were harvested,counted, and isolated for total RNA extraction. Total RNA was then processed into cDNA and further processed for the determination of mRNAexpression patterns of drug efflux transporters (P-glycoprotein, BCRP, and MRP1).Results: Decreased sensitivity of BC cells was shown by the increased cell viability of MCF7 cells after 8 weeks. This condition was accompanied withincreased mRNA expression of P-glycoprotein, BCRP, and MRP1 in cells treated with E+β-E2, as compared with the vehicle only. CM, administered incombination with E+β-E2, resulted in decreased cell viability versus E and β-E2 and also decreased in mRNA expression of P-glycoprotein, BCRP, andMRP1.Conclusion: CM partially reversed the sensitivity loss of BC cells to E in the presence of β-E2 by modulating drug efflux transporters.

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Notch‐1 and Notch‐3 Mediates Hypoxia‐Induced Synovial Fibroblasts Activation in Rheumatoid Arthritis

Arthritis & Rheumatology ◽

10.1002/art.41748 ◽

2021 ◽

Author(s):

Jianhai Chen ◽

Wenxiang Cheng ◽

Jian Li ◽

Yan Wang ◽

Jingqin Chen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fibroblasts ◽

Notch 1 ◽

Notch 3

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Effects of High Glucose Concentration on Pericyte-Like Differentiated Human Adipose-Derived Mesenchymal Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22094604 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4604

Author(s):

Giuliana Mannino ◽

Anna Longo ◽

Florinda Gennuso ◽

Carmelina Daniela Anfuso ◽

Gabriella Lupo ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mrna Expression ◽

Inflammatory Cytokines ◽

High Glucose ◽

Angiogenic Factors ◽

Diabetic Patients ◽

Ros Production ◽

Migration Ability ◽

And Migration

A pericyte-like differentiation of human adipose-derived mesenchymal stem cells (ASCs) was tested in in vitro experiments for possible therapeutic applications in cases of diabetic retinopathy (DR) to replace irreversibly lost pericytes. For this purpose, pericyte-like ASCs were obtained after their growth in a specific pericyte medium. They were then cultured in high glucose conditions to mimic the altered microenvironment of a diabetic eye. Several parameters were monitored, especially those particularly affected by disease progression: cell proliferation, viability and migration ability; reactive oxygen species (ROS) production; inflammation-related cytokines and angiogenic factors. Overall, encouraging results were obtained. In fact, even after glucose addition, ASCs pre-cultured in the pericyte medium (pmASCs) showed high proliferation rate, viability and migration ability. A considerable increase in mRNA expression levels of the anti-inflammatory cytokines transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) was observed, associated with reduction in ROS production, and mRNA expression of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and angiogenic factors. Finally, a pmASC-induced better organization of tube-like formation by retinal endothelial cells was observed in three-dimensional co-culture. The pericyte-like ASCs obtained in these experiments represent a valuable tool for the treatment of retinal damages occurring in diabetic patients.

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Reply: Comment on: Notch‐1 and Notch‐3 mediates hypoxia‐induced synovial fibroblasts activation in rheumatoid arthritis

Arthritis & Rheumatology ◽

10.1002/art.41904 ◽

2021 ◽

Author(s):

Jianhai Chen ◽

Antonia Sun ◽

Jian Li ◽

Wenxiang Cheng ◽

Peng Zhang

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fibroblasts ◽

Notch 1 ◽

Notch 3

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mRNA expression analysis confirms CD44 splicing impairment in systemic lupus erythematosus patients

Lupus ◽

10.1177/09612033211004725 ◽

2021 ◽

pp. 096120332110047

Author(s):

Andrea Latini ◽

Lucia Novelli ◽

Fulvia Ceccarelli ◽

Cristiana Barbati ◽

Carlo Perricone ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

Mrna Expression ◽

Lupus Erythematosus ◽

Mononuclear Cells ◽

Direct Sequencing ◽

Healthy Controls ◽

Systemic Lupus ◽

Peripheral Tissues ◽

Variant Isoforms

Background Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease characterized by several immunological alterations. T cells have a peculiar role in SLE pathogenesis, moving from the bloodstream to the peripheral tissues, causing organ damage. This process is possible for their increased adherence and migration capacity mediated by adhesion molecules, such as CD44. Ten different variant isoforms of this molecule have been described, and two of them, CD44v3 and CD44v6 have been found to be increased on SLE T cells compared to healthy controls, being proposed as biomarkers of disease and disease activity. The process of alternative splicing of CD44 transcripts is not fully understood. We investigated the mRNA expression of CD44v3 and CD44v6 and also analyzed possible CD44 splicing regulators (ESRP1 molecule and rs9666607 CD44 polymorphism) in a cohort of SLE patients compared to healthy controls. Methods This study involved 18 SLE patients and 18 healthy controls. Total RNA and DNA were extracted by peripheral blood mononuclear cells. The expression study was conducted by quantitative RT-polymerase chain reaction, using SYBR Green protocol. Genotyping of rs9666607 SNP was performed by direct sequencing. Results CD44v6 mRNA expression was higher in SLE patients compared to healthy controls (p = 0.028). CD44v3/v6 mRNA ratio in healthy controls was strongly unbalanced towards isoform v3 compared to SLE patients (p = 0.002) and decreased progressively from healthy controls to the SLE patients in remission and those with active disease (p = 0.015). The expression levels of CD44v3 and CD44v6 mRNA correlated with the disease duration (p = 0.038, Pearson r = 0.493 and p = 0.038, Pearson r = 0.495, respectively). Splicing regulator ESRP1 expression positively correlated with CD44v6 expression in healthy controls (p = 0.02, Pearson r = 0.532) but not in SLE patients. The variant A allele of rs9666607 of CD44 was associated with higher level of global CD44 mRNA (p = 0.04) but not with the variant isoforms. Conclusions In SLE patients, the increase in CD44v6 protein correlates with a higher transcript level of this isoform, confirming an impairment of CD44 splicing in the disease, whose regulatory mechanisms require further investigation.

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The role of CXCR3 and its ligands expression in Brucellar spondylitis

BMC Immunology ◽

10.1186/s12865-020-00390-9 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Xin Hu ◽

Xiaoqian Shang ◽

Liang Wang ◽

Jiahui Fan ◽

Yue Wang ◽

...

Keyword(s):

Protein Expression ◽

Mrna Expression ◽

Mononuclear Cells ◽

Healthy Controls ◽

Inflammatory Infiltration ◽

Peripheral Blood Mononuclear ◽

Expression Levels ◽

Inflammatory Damage ◽

Ifn Γ ◽

Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

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MCPIP1/Regnase-1 Expression in Keratinocytes of Patients with Hidradenitis Suppurativa: Preliminary Results

International Journal of Molecular Sciences ◽

10.3390/ijms22147241 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7241

Author(s):

Piotr K. Krajewski ◽

Weronika Szukała ◽

Agata Lichawska-Cieślar ◽

Łukasz Matusiak ◽

Jolanta Jura ◽

...

Keyword(s):

Western Blot ◽

Mrna Expression ◽

Hidradenitis Suppurativa ◽

Skin Lesions ◽

Healthy Controls ◽

Lesional Skin ◽

Chemotactic Protein ◽

Healthy Control ◽

Mrna And Protein Expression ◽

Skin Biopsies

The pathogenesis of hidradenitis suppurativa (HS) is yet to be fully understood. However, inflammation is a key element in the development of skin lesions. The aim of this study was to evaluate the expression of monocyte chemotactic protein-1-induced protein-1 (MCPIP1) in the skin of patients suffering from HS. Skin biopsies of 15 patients with HS and 15 healthy controls were obtained and processed for immunohistochemistry, western blot, and real time PCR. The highest mean MCPIP1 mRNA expression was found in the inflammatory lesional skin of HS patients. It was significantly higher than MCPIP1 mRNA expression in the biopsies from both healthy controls and non-lesional skin of HS patients. Western blot analysis indicated that expression of MCPIP1 was elevated within both lesional and non-lesional skin compared to the healthy control. The increased MCPIP1 mRNA and protein expression level in HS lesions may indicate its possible role in the disease pathogenesis.

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Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway

BMC Infectious Diseases ◽

10.1186/s12879-020-05713-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ruoyu Wang ◽

Dong Zhang ◽

Kewei Sun ◽

Jianping Peng ◽

Wenfang Zhu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

T Cells ◽

T Cell ◽

Cell Viability ◽

Caspase 3 ◽

Invasion And Migration ◽

Ifn Γ ◽

And Migration ◽

Cellular Immune

Abstract Background Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression. Methods The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays. Results We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment. Conclusion Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.

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