Effect of key enzyme inhibition of glycolysis on synovial fibroblasts in Rheumatoid Arthritis

2021 ◽  
Vol 2 (1) ◽  
pp. 020-026
Author(s):  
Fuxue Meng ◽  
Xiaomai Tao
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Citric Acid ◽  
Pyruvate Kinase ◽  
Inflammatory Factors ◽  
Human Rheumatoid Arthritis ◽  
Atp Content ◽  
Tnf Α ◽  
Cell Proliferation Activity ◽  
Proliferation Activity

Objective: To observe effects of glycolysis on human rheumatoid arthritis Fibroblast-like synoviocytes (HFLS-RA) by inhibiting glycolysis. Methods: Hexokinase inhibitor (3-bromopyruvate, 3-BrPa), 6-phosphofructokinase 1 inhibitor citric acid and pyruvate kinase inhibitor shikonin were applied to HFLS-RA respectively. Cell count 8 Kit detects cell proliferation activity, the activity of hexokinase, 6-phosphofructokinase 1, and pyruvate kinase, as well as the cellular glucose, lactate and ATP content were detected by kits, and the ELISA kit detects the expression of cellular inflammatory factors TNF-α and TGF-β. Results: 10 μg/mL 3-BrPa, 160 μg/mL citric acid and 5 μg/mL shikonin significantly inhibited cell proliferation activity (P<0.001); and significantly inhibited HFLS-RA hexokinase and fructose 6-phosphate Kinase 1 and pyruvate kinase activity; Glucose, lactate and ATP content decreased; TNF-α expression decreased, while TGF-β expression increased. Conclusion: This study explored the changes in glucose metabolism and the expression of inflammatory factors in HFLS-RA by inhibiting the key enzymes of glycolysis, further confirming the important role of glycolysis in HFLS-RA, and laying a theoretical basis for a deep understanding of the pathogenesis of RA.

scholarly journals Novel H2S Donor Proglumide-ADT-OH Protects HUVECs From ox-LDL-Induced Injury Through NF-κB and JAK/SATA Pathway

2020 ◽  
Author(s):  
Xuelan Ou ◽  
Chunyan Yang ◽  
Chunlei Yu ◽  
Shipeng Zhang ◽  
Rong Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Superoxide Dismutase ◽  
Protective Effect ◽  
Damage Model ◽  
Protective Mechanism ◽  
Physiological Effects ◽  
Tnf Α ◽  
Cell Proliferation Activity ◽  
Proliferation Activity ◽  
Stat Pathway

Abstract Introduction: As a gaseous me dilator, hydrogen sulfide (H2S) has many physiological effects and pathological effects in atherosclerosis. In recent years, many exogenous H2S donors have been synthesized to study atherosclerosis diseases. Methods: Proglumide-(5-(4-Hydroxyphenyl)-3H-1, 2-dithiole-3-thione) (P-A) was synthesized as a H2S donor. The protective effect and mechanism of P-A on HUVEC that injured by ox-LDL was detected. Results: The HUEVCs was affected by 100μmol/L P-A for 24 hours, the release of H2S was the largest. After 100μmol/L P-A acted on HUVEC damage model for 12h, the cell proliferation activity was the best. The results showed that P-A can down regulate the expression of p-NF-кBp65 protein and reduce the amount of TNF-α and IL-6 and promote the formation of IL-10 by inhibiting the NF-кB pathway, and also induce the expression of superoxide dismutase (SOD) to protect HUVEC from ox-LDL injury. P-A can also regulate JAK/STAT pathway to reduce the expression of p-JAK2 protein and reduce the production of IL-6 and TNF-α. Conclusion: P-A has protective effect on HUVEC injured by ox-LDL, and the protective mechanism is related to the regulation of JAK/STAT pathway and NF-кB pathway.

scholarly journals Novel H2S donor proglumide-ADT-OH protects HUVECs from ox-LDL-induced injury through NF-κB and JAK/SATA pathway

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1318-1327
Author(s):  
Xuelan Ou ◽  
Tianqin Xia ◽  
Chunyan Yang ◽  
Chunlei Yu ◽  
Shipeng Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Superoxide Dismutase ◽  
Protective Effect ◽  
Damage Model ◽  
Protective Mechanism ◽  
Physiological Effects ◽  
Tnf Α ◽  
Cell Proliferation Activity ◽  
Proliferation Activity ◽  
Stat Pathway

Abstract As a gaseous mediator, hydrogen sulfide (H2S) has many physiological effects and pathological effects in atherosclerosis. In recent years, many exogenous H2S donors have been synthesized to study atherosclerosis diseases. In this study, proglumide-(5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione) (P-A) was synthesized as a H2S donor. The protective effect and mechanism of P-A on HUVEC that was injured by ox-LDL were detected. The HUEVCs were affected by 100 μmol/L P-A for 24 h; the release of H2S was the largest. After 100 μmol/L P-A acted on HUVEC damage model for 12 h, the cell proliferation activity was the best. The results showed that P-A can downregulate the expression of p-NF-кBp65 protein and reduce the amount of TNF-α and IL-6 and promote the formation of IL-10 by inhibiting the NF-кB pathway, and also induce the expression of superoxide dismutase (SOD) to protect HUVEC from ox-LDL injury. P-A can also regulate JAK/STAT pathway to reduce the expression of p-JAK2 protein and reduce the production of IL-6 and TNF-α. P-A has protective effect on HUVEC injured by ox-LDL, and the protective mechanism is related to the regulation of JAK/STAT pathway and NF-кB pathway.

scholarly journals Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 587
Author(s):  
Fu-Tzu Pai ◽  
Cheng-You Lu ◽  
Chia-Hsin Lin ◽  
John Wang ◽  
Ming-Cheng Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Suppressor Cells ◽  
Clinical Severity ◽  
Histopathological Analysis ◽  
Human Rheumatoid Arthritis ◽  
Psoralea Corylifolia ◽  
Collagen Induced Arthritis ◽  
Tnf Α ◽  
Synovial Tissues ◽  
Orthopedic Diseases

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

Cyclin D1 expression in astrocytomas is associated with cell proliferation activity and patient prognosis

1999 ◽  
Vol 188 (3) ◽  
pp. 289-293 ◽  
Author(s):  
Satu-Leena Sallinen ◽  
Pauli K. Sallinen ◽  
Juha T. Kononen ◽  
Kirsi M. Syrj�koski ◽  
Nina N. Nupponen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cyclin D1 ◽  
Cell Proliferation Activity ◽  
Proliferation Activity ◽  
Patient Prognosis

MicroRNA-16-5p Promoted Fibroblast-Like Synoviocyte Proliferation and Suppressed Apoptosis via Targeting Suppressor of Cytokine Signaling 6 (SOCS6) in Human Rheumatoid Arthritis

2021 ◽  
Vol 11 (9) ◽  
pp. 1744-1751
Author(s):  
Deqian Meng ◽  
Wenyou Pan ◽  
Ju Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Cytokine Signaling ◽  
Human Rheumatoid Arthritis ◽  
Reporter Assay ◽  
Functional Roles ◽  
Proliferation And Apoptosis ◽  
Fibroblast Like Synoviocytes

Accumulating evidence have indicated that MicroRNAs (miRNAs) are key regulators in human rheumatoid arthritis (RA). The aim of this study was to explore the functional roles of miR-16-5p in proliferation, inflammation, and apoptosis of fibroblast-like synoviocytes (FLS). The expression of miR-16-5p and SOCS6 in FLA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry, respectively. Luciferase reporter assay was used to verify the direct target of miR-16-5p. Western blot analysis was performed to analysis the levels of SOCS6, Bcl-2, Bax and cleaved caspase 3. miR-16-5p expression was significantly upregulated while SOCS6 level was decreased in RA-FLS compared with normal FLS. In addition, luciferase reporter assay confirmed that SOCS6 was the target of miR-16-5p. Silencing of miR-16-5p inhibited cell proliferation, releases of TNF-α, IL-1β, IL-6 and IL-8, and induced the apoptosis. The effects of miR-16-5p silencing on RA-FLS were reversed by downregulation of SOCS6. In summary, knockdown of miR-16-5p could suppress cell proliferation and accelerate the apoptosis of RA-FLS through targeting SOCS6, which may provide a potential therapeutic target for patients with RA.

scholarly journals The Activity of Combination of Hydrolyzed Virgin Coconut Oil and Chitosan Toward Wound Healing Parameters on NIH 3T3 Cells Using in Vitro Methods

1970 ◽  
Vol 7 (3) ◽  
pp. 14-19 ◽  
Author(s):  
Hekdin Marsius Sipayung ◽  
Jansen Silalahi ◽  
Yuandani Y
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Protein Expression ◽  
Scratch Wound ◽  
Cell Proliferation Activity ◽  
Proliferation Activity ◽  
Cox 2 ◽  
Nih 3T3 ◽  
Vegf Protein

Objectives: The objective of this study was to investigate the activity of combination of hydrolyzed VCO (HVCO) and chitosan on NIH 3T3 cell proliferation activity, NIH 3T3 cell migration, COX-2 and VEGF protein expression. Design: In vitro cytotoxic assay was determined by MTT (MicrocultureTetrazoliumTehnique) assay, cell proliferation activity was measured by calculating cell viability incubated 24 hours, 48 hours and 72 hours, wound closure percentage was tested by scratch wound healing method, expression of COX-2 protein and VEGF protein were measured by immunocytochemical method. Interventions: The variable that was intervened in this study was the concentration of HVCO and chitosan. Main Outcome Measures: The main measurements carried out in this study were the absorbance value of HVCO and chitosan which was converted into viability cell, proliferation activity, percentage of wound closure, and percentage of COX-2 and VEGF protein expression. Results: Cytotoxic activity of HVCO and chitosan resulted the best concentration at 31.25 μg/ml, scratch wound healing assay from a combination HVCO and chitosan resulted the best migration of fibroblast cells at a ratio of 1:1 with HVCO 62.5 μg/ml and chitosan 62.5 μg/ml, combination of HVCO 62.5 μg/ml and chitosan 62.5 μg/ml (1:1) increased expression of COX-2 and VEGF. Conclusion: Combination of HVCO and chitosan could increase NIH 3T3 cell migration, COX-2 and VEGF protein expression. Combination of HVCO and chitosan had better wound healing activity in vitro than single use. Keywords: Rhizomucor miehei, viability, proliferation, migration, expression

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