Forkhead Box O1-p21 Mediates Macrophage Polarization in Postoperative Cognitive Dysfunction Induced by Sevoflurane

2020 ◽  
Vol 17 (1) ◽  
pp. 79-85
Author(s):  
Jun-Bao Fu ◽  
Zhi-Hua Wang ◽  
Yong-Ying Ren
Keyword(s):  
Cognitive Dysfunction ◽  
Macrophage Polarization ◽  
Postoperative Cognitive Dysfunction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Sevoflurane Anesthesia ◽  
Expression Levels ◽  
Forkhead Box ◽  
Anesthesia Group ◽  
Tnf Α

Purpose: The current study was conducted in order to investigate the role of Forkhead box O1 and p21-mediated macrophage polarization in postoperative cognitive dysfunction induced by sevoflurane. Methods: There involved a total of 30 healthy mice that were randomly divided into two groups: control group (without any treatment) and anaesthesia group (treated with sevoflurane inhalation). The effects of sevoflurane on cognitive function (memory) in mice were studied by trace fear conditioned reflex, and the effects of systemic inflammation and behavior after operation were measured by enzyme-linked immunosorbent assay (ELISA), the concentrations of CD163 and tumor necrosis factor-α (TNF-α) were measured. The expression of macrophage phenotype was observed by immunofluorescence staining, the expression levels of M1 and M2 markers mRNA were detected by real-time fluorescence quantitative PCR (RT-PCR), and the expression levels of FoxO1 and p21 were analyzed by immunoblotting (Western blot). Results: Compared with the control group, the freezing time in the anesthesia group was lower than that in the control group (P<0.01), indicating that sevoflurane anesthesia led to the decrease of cognitive ability. The blood concentrations of CD163 and TNF-α increased significantly at 24 h after the operation with sevoflurane anesthesia (P<0.05). Fluorescence microscopic observation showed that M2 was the main type of macrophages in normal tissues, while M1 and M2 phenotypes were highly expressed in sevoflurane anesthetized tissues at the same time, especially in M1 phenotypes (P<0.01). The polarization of macrophages in the anesthetic group showed the high level of M1 mRNA, and the expression levels of TNF-α, monocyte chemotactic protein 1(MCP-1) and Interleukin-6 (IL-6)mRNA in the anesthetic group were significantly higher than those in the control group (P<0.05). The expression levels of M2 mRNA such as transforming growth factor-β (TGF-β) and IL-10 were significantly lower than those in the control group (P<0.05). Compared with the control group, the expression of FoxO1 and p21 protein in the anesthesia group was significantly lower than that in the control group with a significant statistical difference (P<0.01). Conclusion: This study offers a theoretical basis and insight for further understanding of the prevention and treatment of cognitive dysfunction induced by anesthetic drugs.

Macrophage M1/M2 polarization in patients with pregnancy-induced hypertension

2018 ◽  
Vol 96 (9) ◽  
pp. 922-928 ◽  
Author(s):  
Yan Li ◽  
Zhen Xie ◽  
Yaning Wang ◽  
Hongyi Hu
Keyword(s):  
Macrophage Polarization ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Lipoprotein Cholesterol ◽  
Lower Percentage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Pregnancy Induced Hypertension ◽  
Tnf Α ◽  
Induced Hypertension

This study aimed to validate whether macrophage polarization imbalance and abnormal cytokines production occurred in pregnancy-induced hypertension (PIH) patients. PIH women (n = 26) were enrolled and the level of biochemical parameters were determined. The percentage of CD86- and CD163-positive cells, representing M1 and M2 macrophages, were determined by flow cytometry. The concentrations of cytokines (TNF-α, IL-1β, IL-4, IL-13, and IL-10) were determined using enzyme-linked immunosorbent assay kit. THP-1 cells were incubated with 10% serum from PIH and control groups, and then macrophage polarization and cytokines production were analyzed. The levels of high-density lipoprotein cholesterol and apolipoprotein A1 were significantly lower, and the levels of fasting blood glucose, total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein a were significantly higher in the PIH group than that in the control group. The PIH group contained a significant higher percentage of CD86-positive cells (M1) and a significant lower percentage of CD163-positive cells (M2), representing higher M1/M2 ratio, than the control group. The PIH group expressed higher concentrations of TNF-α and IL-1β, and expressed lower concentrations of IL-4, IL-10, and IL-13 than the control group. The in vitro experiment also showed macrophage polarization imbalance and abnormal cytokines production in THP-1 cells treated with PIH serum as compared with that treated with control serum. Macrophage polarization imbalance and abnormal cytokines production occurred in PIH patients and in THP-1 cells treated with PIH serum.

scholarly journals Boeravinone B promotes fracture healing in ovariectomyinduced osteoporotic rats via the regulation of NF-κB p65/IκB-α/SIRT-1 signaling pathway

2021 ◽  
Vol 18 (5) ◽  
pp. 955-960
Author(s):  
Jianlin Zhang ◽  
Longze Zong ◽  
Dongyu Bai
Keyword(s):  
Fracture Healing ◽  
Signaling Pathway ◽  
Normal Control ◽  
Bone Mineral ◽  
Normal Control Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Type I ◽  
Expression Levels ◽  
Tnf Α

Purpose: To investigate the fracture-healing effect of boeravinone B in ovariectomy-induced (OVX) osteoporotic rats. Methods: Adult female Wistar rats (n = 30) were ovariectomized and after three months, the unilateral cross-tibial fractures were fixed with intramedullary nails. The rats were then randomly assigned to three groups of 10 rats each: normal control group, OVX group and 100 mg/kg body weight boeravinone B group. Boeravinone B was orally administered for a period of 5 weeks. The effect of boeravinone B on indices of bone formation and resorption was assessed. Levels of inflammatory cytokines including tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1β) were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine the expression levels of NF-κB p65, IкB-α and SIRT1 proteins. Results: There were significant increases in the activities of tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP), and collagen type I fragment (CTX) level and serum osteocalcin (OC) of OVX group, when compared with normal control group (p < 0.05). However, treatment with boeravinone B significantly reduced the activities and levels of these parameters, relative to OVX group (p < 0.05). The levels of TNF-α and IL-1β significantly increased in OVX group, relative normal control group, but were significantly lower following treatment with boeravinone B (p < 0.05). Bone mineral content (BMC) was not significantly altered in OVX and boeravinone B-treated groups, when compared with normal control group (p > 0.05). There was significant reduction in bone mineral density (BMD) of OVX group relative to normal control group (p < 0.05). However, treatment with boeravinone B significantly increased the BMD, when compared with OVX group (p < 0.05). After Week 5 of treatment, boeravinone B significantly enhanced bone remodeling and formation of callus. Treatment with boeravinone B significantly reduced the expression levels of NF-κB p65 and IκB-α proteins, and significantly upregulated the expression of SIRT-1 (p < 0.05). Conclusion: The results obtained in this study suggest that boeravinone B promotes the healing of fracture caused by osteoporosis via a mechanism involving NF-κB p65/IκB-α/SIRT-1 signaling pathway.

scholarly journals Dezocine attenuates neuropathic pain by inhibiting ERK1/2 signaling in rats

2019 ◽  
Author(s):  
Chan Shen ◽  
Shi Sheng ◽  
Ling Yu ◽  
Naixing Xin
Keyword(s):  
Neuropathic Pain ◽  
Quantitative Polymerase Chain Reaction ◽  
Mammalian Target Of Rapamycin ◽  
Life Quality ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Expression Levels ◽  
Withdrawal Threshold ◽  
Tnf Α ◽  
Cox 2

Abstract Background Neuropathic pain severely impacts patients’ life quality. Dezocine can be used for the treatment of pain. The present study intended to explore the effects of dezocine in chronic constriction injury (CCI) induced neuropathic pain as well as the possible responsible molecules in rats. Methods There were 3 subgroups, ie, control group, CCI group and dezocine+CCI group. The values of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in rats were determined by a dynamic plantar esthesiometer. The ipsilateral lumbar spinal cords in rats were extracted for the detection of protein levels of phosphorylated-mammalian target of rapamycin (p-mTOR) and p-extracellular signal-regulated kinase 1/2 (p-ERK1/2) by western blot analysis; and the mRNA and protein expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and cyclooxygenase-2 (COX-2) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results In comparison with control group, there were lower values of PWT and PWL in CCI group, which were partially reversed by dezocine. In addition, compared to control group, the expression levels of p-mTOR, p-ERK1/2, IL-6, TNF-α and COX-2 were upregulated by CCI, which were attenuated by dezocine. Conclusions In conclusion, the analgesic effect of dezocine on CCI induced neuropathic pain might be correlated with inhibiting of the p-mTOR and p-ERK1/2 signaling pathway.

scholarly journals Electroacupuncture for the Prevention of Postoperative Cognitive Dysfunction Among Older Adults Undergoing Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2022 ◽  
Vol 8 ◽  
Author(s):  
Liang Ou ◽  
Zhen Shen ◽  
Tiantian Zhang ◽  
Zehua Chen ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Cognitive Dysfunction ◽  
Knee Replacement ◽  
Meta Analysis ◽  
Postoperative Cognitive Dysfunction ◽  
Control Group ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Tnf Α

Background: Postoperative cognitive dysfunction (POCD) is a common surgical complication in elderly patients undergoing hip and knee replacement. Electroacupuncture (EA) may have a protective effect on postoperative cognitive function, but relevant evidence remains uncertain.Objective: To systematically evaluate the evidence of EA for the prevention of POCD after total joint arthroplasty.Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, and Chinese Biomedical Literature Database (CBM) databases were searched until May 1, 2021. Randomized controlled trials (RCTs) in which patients undergoing hip and knee replacement pretreated with EA for preventing POCD were included. The risk of bias was assessed by the Cochrane Collaboration tool. Meta-analysis was performed using Review Manager version 5.4.Results: A total of 11 RCTs with 949 patients were identified. Meta-analysis showed that compared with controls, EA pretreatment significantly reduced the incidence of POCD at 1, 3, and 7 days and 3 and 6 months after the operation. EA was also superior in improving the Mini-Mental State Examination (MMSE) scores on the third postoperative day, but not on the first postoperative day. Neuron-specific enolase (NSE) and interleukin-1β (IL-1β) in the EA group were significantly lower than that in the control group. There was no difference in S100β between the EA group and the control group. Compared to the control group, tumor necrosis factor-α (TNF-α) levels were not significantly lower in the EA group at postoperative hour 0, while significantly decreased at postoperative hours 24 and 48.Conclusion: Our results suggest that EA pretreatment is an effective adjunctive therapy for reducing the incidence of POCD for patients receiving total joint replacement surgery. Its effect was embodied in improving the MMSE scores and NSE, IL-1β, and TNF-α levels, whereas it had no significant effect on S100β levels. Meanwhile, the benefits of EA for improving POCD need further strengthening and support from more large-scale, high-quality, and good-homogeneity RCTs.Systematic Review Registration:https://osf.io/xb3e8.

Expression and Significance of Th17 Cells and Related Factors in Patients with Autoimmune Hepatitis

2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An
Keyword(s):  
Autoimmune Hepatitis ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Treg Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Total Bilirubin ◽  
Study Group ◽  
Related Factors ◽  
Tnf Α

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.

scholarly journals Pirfenidone attenuates synovial fibrosis and postpones the progression of osteoarthritis by anti-fibrotic and anti-inflammatory properties in vivo and in vitro

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qilu Wei ◽  
Ning Kong ◽  
Xiaohui Liu ◽  
Run Tian ◽  
Ming Jiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fast Green ◽  
Expression Levels ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Safranin O ◽  
Tgf Β1

Abstract Background Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. Methods Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-β1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson’s trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. Results The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-β1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-β1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-β1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson’s trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. Conclusions PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.

scholarly journals Glycyrrhizin Attenuates Carcinogenesis by Inhibiting the Inflammatory Response in a Murine Model of Colorectal Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2609
Author(s):  
Guifeng Wang ◽  
Keiichi Hiramoto ◽  
Ning Ma ◽  
Nobuji Yoshikawa ◽  
Shiho Ohnishi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Stem Cell ◽  
Inflammatory Response ◽  
Murine Model ◽  
Licorice Root ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Stem Cell Markers ◽  
Tnf Α

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.

Oxydative stress markers and cytokine levels in rosuvastatin-medicated hypercholesterolemia patients

2018 ◽  
Vol 44 (4) ◽  
pp. 530-538
Author(s):  
Aysun Çetin ◽  
İhsan Çetin ◽  
Semih Yılmaz ◽  
Ahmet Şen ◽  
Göktuğ Savaş ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Interleukin 1 ◽  
Paraoxonase 1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Phenotypic Effect ◽  
Necrosis Factor Alpha ◽  
Stress Markers ◽  
Tnf Α ◽  
Before And After

Abstract Background Limited research is available concerning the relationship between oxidative stress and inflammation parameters, and simultaneously the effects of rosuvastatin on these markers in patients with hypercholesterolemia. We aimed to investigate the connection between cytokines and oxidative stress markers in patients with hypercholesterolemia before and after rosuvastatin treatment. Methods The study consisted of 30 hypercholesterolemic patients diagnosed with routine laboratory tests and 30 healthy participants. The lipid parameters, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), paraoxonase-1 (PON1) and malondialdehyde (MDA) levels in controls and patients with hypercholesterolemia before and after 12-week treatment with rosuvastatin (10 mg/kg/day), were analyzed by means of enzyme-linked immunosorbent assay. Results It was found that a 12-week cure with rosuvastatin resulted in substantial reductions in IL-1β, IL-6 and TNF-α and MDA levels as in rising activities of PON1 in patients with hypercholesterolemia. Before treatment, the PON1 levels were significantly negatively correlated with TNF-α and IL-6 in control group, while it was positively correlated with TNF-α in patients. Conclusion Our outcomes provide evidence of protected effect of rosuvastatin for inflammation and oxidative damage. It will be of great interest to determine whether the correlation between PON1 and cytokines has any phenotypic effect on PON1.

scholarly journals Effects of L-655,708 on expression changes of GABA, glutamate, and beta-endorphin induced by propofol anesthesia in rats

2018 ◽  
Vol 16 ◽  
pp. 205873921879670
Author(s):  
Jin Wang ◽  
Xinyi Li ◽  
Huisheng Wu ◽  
Jianjuan Ke ◽  
Zongze Zhang ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Cognitive Dysfunction ◽  
Sham Group ◽  
Postoperative Cognitive Dysfunction ◽  
Expression Level ◽  
Control Group ◽  
Beta Endorphin ◽  
Anesthetized Rats ◽  
Significant Difference ◽  
Dentate Gyrus Region

Anesthetics are considered to be one of the important inducing factors of postoperative cognitive dysfunction (POCD). The hippocampal region of the rat is one of the action sites of general anesthesia drugs. L 655,708, a reverse agonist of gamma aminobutyric acid (GABA) receptor, can significantly improve short-term memory dysfunction in mice after anesthetized with isoflurane. So the purpose of this study is to investigate the effects of L-655,708 on expression of GABA, glutamate (GLU), and beta-endorphin (β-EP) in the dentate gyrus region of the hippocampus and cognition of rats anesthetized with propofol. In all, 30 male Sprague–Dawley (SD) rats were randomly allocated into the control group, sham group, and L-655,708 group, with 10 in each group. The cognitive function of rats was measured by Morris water maze before and 1 h after administration. Then the rats were sacrificed for brain tissues. Immunohistochemistry was used to study the expression of GABA, GLU, and β-EP in the hippocampus of anesthetized rats in each group. Compared with the control group, the latency of the sham group and L-655,708 group were significantly prolonged after administration ( P < 0.05). However, L-655,708 could shorten the prolonged latency ( P < 0.05). There was no significant difference in times of accessing original platform area between the three groups before and after medication ( P > 0.05). The expression level of GABA in the dentate gyrus region of hippocampus of rats in the sham group was significantly higher than that in the control group ( P < 0.05), while the expression level in the L-655,708 group was significantly lower than that in the sham group ( P < 0.05). No significant difference was found in the expression of GLU in the dentate gyrus region of hippocampus of rats in each group ( P > 0.05). Compared with the control group, the expression of β-EP was significantly lower in the dentate gyrus region of the hippocampus of sham group rats ( P < 0.05). However, the expression of β-EP in the L-655,708 group was significantly higher than that in the sham group ( P < 0.05). Cognitive dysfunction in rats anesthetized with propofol may be related to high expression of GABA and low expression of β-EP in the hippocampus. The mechanism of L-655,708 in reducing the cognitive impairment in propofol anesthetized rats may be bound up with down-regulating the expression of GABA and increasing the expression of β-EP in the hippocampus.

Sign in / Sign up

Export Citation Format

Share Document