Effect of acupuncture on neurovascular units after cerebral infarction in rats through PI3K/AKT signaling pathway

2020 ◽  
Vol 75 (4) ◽  
pp. 387-397
Author(s):  
Linlin Wei ◽  
Kexue Zeng ◽  
Juanjuan Gai ◽  
Feixiong Zhou ◽  
Zhenglin Wei ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Signaling Pathway ◽  
Sham Group ◽  
Escape Latency ◽  
Akt Signaling ◽  
Acupuncture Group ◽  
Akt Signaling Pathway ◽  
Model Group ◽  
Protein Expressions ◽  
The Times

OBJECTIVE: To study the effect of acupuncture on neurovascular units after cerebral infarction (CI) in rats through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. METHODS: A total of 36 Sprague-Dawley rats were randomly divided into sham group (n = 12), model group (n = 12) and acupuncture group (n = 12). The external carotid artery was only exposed in model group, while the post-CI ischemia-reperfusion model was established using the suture method in the other 2 groups. After modeling, the rats in sham group and model group were fixed and sampled, while those in acupuncture group were treated with acupuncture intervention for 2 weeks and sampled. The neurological deficits of rats were evaluated using the Zea-Longa score, and the spatial learning and memory of rats were detected via water maze test. Moreover, the expressions of vascular endothelial growth factor (VEGF), growth associated protein-43 (GAP-43) and synuclein (SYN) in brain tissues were detected via immunohistochemistry, and the relative protein expressions of PI3K p85, PI3K p110 and p-AKT were detected via Western blotting. The messenger ribonucleic acid (mRNA) expressions of VEGF, GAP-43 and SYN were detected via quantitative polymerase chain reaction (qPCR). RESULTS: The Zea-Longa score was significantly increased in model group and acupuncture group compared with that in sham group (p < 0.05), while it significantly declined in acupuncture group compared with that in model group (p < 0.05). The escape latency was significantly prolonged and the times of crossing platform were significantly reduced in model group and acupuncture group compared with those in sham group (p < 0.05), while the escape latency was significantly shortened and the times of crossing platform were significantly increased in acupuncture group compared with those in model group (p < 0.05). The positive expressions of VEGF, GAP-43 and SYN were obviously increased in model group and acupuncture group compared with those in sham group (p < 0.05), while they were obviously increased in acupuncture group compared with those in model group (p < 0.05). Besides, model group and acupuncture group had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than sham group (p < 0.05), while acupuncture group also had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than model group (p < 0.05). The relative mRNA expressions of VEGF, GAP-43 and SYN were remarkably increased in model group and acupuncture group compared with those in sham group (p < 0.05), while they were remarkably increased in acupuncture group compared with those in model group (p < 0.05). CONCLUSION: Acupuncture promotes the repair of neurovascular units after CI in rats through activating the PI3K/AKT signaling pathway, thereby exerting a protective effect on neurovascular units.

scholarly journals Cinnamic hydroxamic acid inhibits the proliferation of gastric cancer cells via upregulation of miR 145 expression and down-regulation of P13K/Akt signaling pathway

2020 ◽  
Vol 19 (5) ◽  
pp. 957-963
Author(s):  
ShanPing Li ◽  
SenMao Hu
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Hydroxamic Acid ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Down Regulation ◽  
Protein Expressions ◽  
Dose Dependent ◽  
Cinnamic Hydroxamic Acid

Purpose: To investigate the anti-proliferative effect of cinnamic hydroxamic acid (CHA) on gastric cancer (GC) cells, and its mechanism of action.Methods: Two GC cell lines (SGC-7901 and MKN1) and normal human gastric epithelial cells (GES1) were used for this study. The GC cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM)supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/streptomycin solution at 37 °C for 24 h in a humidified atmosphere of 5 % CO2 and 95 % air. GES1 cells were cultured in RPMI medium supplemented with 10 % FBS only. Cell viability and apoptosis were determined using 3 (4,5 dimethyl thiazol 2 yl) 2,5 diphenyl 2H tetrazolium bromide (MTT), and flow cytometric assays, respectively. The level of expression of microRNA-145 (miR-145) was determined using real-time quantitative polymerase chain reaction (qRT-PCR). Protein expressions of c-Myc, p-AKT, PI3K, p21, and matrix metalloproteinase (MMP)-2 and MMP-9were determined using Western blotting.Results: Treatment of GC cells with CHA for 72 h led to significant and dose-dependent reduction in their viability, and significant and dose-dependent increase in the number of apoptotic cells (p < 0.05). It also significantly arrested GC cell cycle at G1 phase (p < 0.05). The treatment significantly and dosedependently decreased SGC-7901 and MKN1 cell migration and invasion, and upregulated miR-145 mRNA expression (p < 0.05). The expression of miR-145 mRNA was significantly higher in MKN1 cells than in SGC-7901cells (p < 0.05). Treatment of SGC-7901 and MKN1 cells with CHA significantly downregulated protein expressions of c-Myc, MMP-2/9, PI3K and p-AKT, but upregulated p21 protein expression (p< 0.05).Conclusion: These results show that CHA inhibits the proliferation of GC cells via upregulation of miR-145 expression and down-regulation of  P13K/Akt signaling pathway. Therefore, CHA has a good potential as a therapeutic agent for the management of gastric cancer Keywords: Apoptosis, Cinnamic hydroxamic acid, Gastric cancer, Metastasis, Proliferation

scholarly journals Molecular mechanisms of hydrogen sulfide against uremic accelerated atherosclerosis through cPKCβII/Akt signal pathway

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruifang Xiong ◽  
Xiangxue Lu ◽  
Jinghong Song ◽  
Han Li ◽  
Shixiang Wang
Keyword(s):  
Hydrogen Sulfide ◽  
Signaling Pathway ◽  
Sham Group ◽  
Akt Signaling ◽  
Signal Pathway ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Membrane Translocation ◽  
Enos Expression ◽  
Akt Phosphorylation

Abstract Background Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. The protection mechanism of hydrogen sulfide (H2S) and the specific role of conventional protein kinase C βII (cPKCβII)/Akt signaling pathway in the formation of atherosclerosis is still controversial. Methods 8-week-old male ApoE−/− mice were treated with 5/6 nephrectomy and high-fat diet to make uremia accelerated atherosclerosis (UAAS) model. Mice were divided into normal control group (control group), sham operation group (sham group), UAAS group, L-cysteine group (UAAS+L-cys group), sodium hydrosulfide group (UAAS+NaHS group), and propargylglycine group (UAAS+PPG group). Western blot was used to detect cPKCβII activation, Akt phosphorylation and endothelial nitric oxide synthase (eNOS) expression in mice aorta. Results The membrane translocation of cPKCβII in UAAS group was higher than sham group, and L-cys or NaHS injection could suppress the membrane translocation, but PPG treatment resulted in more membrane translocation of cPKCβII (P < 0.05, n = 6 per group). Akt phosphorylation and the eNOS expression in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation and the eNOS expression, but PPG treatment resulted in more decrease in the Akt phosphorylation and the eNOS expression (P < 0.05, n = 6 per group). Conclusion Endogenous cystathionine-γ-lyase (CSE)/H2S system protected against the formation of UAAS via cPKCβII/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule eNOS, which may be mediated by cPKCβII/Akt signaling pathway.

scholarly journals miR-146b-3p regulates PI3K/AKT signaling pathway in septic mice with acute respiratory distress syndrome

2020 ◽  
Author(s):  
Yao Liu ◽  
Jinqiang Zhu ◽  
Xiaohong Jin ◽  
Meiping Dong ◽  
Junfen Zheng
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Signaling Pathway ◽  
Distress Syndrome ◽  
Akt Signaling ◽  
Normal Group ◽  
Akt Signaling Pathway ◽  
Model Group ◽  
Caspase 1

Abstract Background: This study aimed to explore the effect of miR-146b-3p on acute respiratory distress syndrome in septic mice by regulating PI3K/AKT signaling pathway. Methods: Seventy C57BL/6 mice were divided into normal group ( n = 10) and modeling group ( n = 60, mice for constructing septic mice models with acute respiratory distress syndrome). Model mice were subdivided into model group (without any treatment), negative control (NC) mimic group (injection with miRNA NC), miR-146b-3p mimic group (injection with miR-146b-3p mimic), si-NC group (injection with PI3Kγ siRNA NC), si-PI3Kγ group (injection with PI3Kγ interference sequence), and miR-146b-3p mimic + oe-PI3Kγ group (injection with miR-146b-3p mimic + PI3Kγ overexpression plasmid). Dual-luciferase reporter assay was conducted to determine the target relationship between miR-146b-3p and PI3Kγ. Wet weight/dry weight (W/D) ratio of the left lung was measured. Hematoxylin and eosin stain was used to detect the pathological change of mouse lung. ELISA was employed to measure serum interleukin (IL) -1β and IL-18 levels. miR-146b-3p and PI3Kγ expressions were detected by qRT-PCR. PI3Kγ, AKT, NLRP3, apoptosis-associated speck-like protein caspase recruitment domain (ASC) and Caspase-1 protein expressions were detected by Western blotting. Results: miR-146b-3p negatively regulated PI3Kγ. The lung tissues in other groups compared with normal group had down-regulated miR-146b-3p, up-regulated PI3Kγ, p-AKT, ASC, NLRP3 and Caspase-1 proteins, higher W/D ratio, and more serum IL-1β and IL-18 (all P < 0.05). All indicators in miR-146b-3p mimic group and si-PI3Kγ group were significantly improved as compared to model group (all P < 0.05). Up-regulated PI3Kγ, p-AKT, ASC, NLRP3 and Caspase-1 proteins and higher W/D ratio and IL-1β and IL-18 levels in serum existed in miR-146b-3p mimic + oe-PI3Kγ group compared with miR-146b-3p mimic group (all P < 0.05). Conclusions: Up-regulation of miR-146b-3p can restrain PI3K/AKT signaling pathway, thereby improving acute respiratory distress syndrome in septic mice.

scholarly journals Acupuncture Reduces Apoptosis of Granulosa Cells in Rats with Premature Ovarian Failure Via Restoring the PI3K/Akt Signaling Pathway

2019 ◽  
Vol 20 (24) ◽  
pp. 6311 ◽  
Author(s):  
Shiqi Wang ◽  
Shujun Lin ◽  
Mingmin Zhu ◽  
Chenglu Li ◽  
Shulian Chen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Premature Ovarian Failure ◽  
Akt Signaling ◽  
Ovarian Failure ◽  
Acupuncture Group ◽  
Female Rats ◽  
Akt Signaling Pathway ◽  
Expression Levels

Acupuncture is widely recognized as an effective therapy for premature ovarian failure (POF) in clinical, but information about its potential mechanisms is rarely explored. To investigate the mechanism, fifty SD female rats were randomly divided into normal group, POF group, POF+estradiol-valerate group (abbreviated as estradiol group), and POF+acupuncture group (abbreviated as acupuncture group). The estrous cycle of the rats was tracked by vaginal smears. Their ovaries morphology was observed by hematoxylin-eosin staining. The apoptotic level of granulosa cells was detected by in situ TUNEL fluorescence staining assay. Serum follicle-stimulating hormone (FSH) and estrogen (E2) levels were measured by enzyme-linked-immunosorbent-assay (ELISA). Protein and gene expression of PI3K, Akt, bcl-2, and bax were detected by Western blotting and qPCR. In the acupuncture and estradiol groups, compared with the POF group as controls, the apoptosis number of granulosa cells was significantly decreased (p < 0.05). FSH levels were decreased, while E2 levels were increased (p > 0.05). The gene and protein expression levels of PI3K, Akt, and bcl-2 were increased, while the expression levels of bax were decreased (p < 0.05), and the protein expression level of p-Akt increased. There was no significant difference between the acupuncture group and the estradiol group (p > 0.05). Acupuncture was able to regulate hormone levels in POF rats, up-regulate PI3K/Akt signaling pathway, and reduce the apoptosis of granulosa cells. This may be one of the mechanisms of acupuncture treating premature ovarian failure.

scholarly journals MiR-28-3p enhances healing of fracture via negative regulation of the target gene Sox6 and activation of PI3K/Akt signaling pathway

2020 ◽  
Vol 19 (10) ◽  
pp. 2061-2066
Author(s):  
Wei Li ◽  
Xin Dong ◽  
Jian Zhao
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Negative Regulation ◽  
Control Group ◽  
Akt Signaling Pathway ◽  
Over Expression ◽  
Expression Control ◽  
Protein Expressions ◽  
Inhibition Control

Purpose: To investigate the effect of miR-28-3p on fracture healing, and the involvement of Sox6 gene and PI3K/Akt signaling pathway in the process.Methods: Mouse osteoblast cell lines were cultured in vitro, and miR-28-3p over-expression and inhibitory plasmids were separately added to the medium. The corresponding control groups were set up. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure the mRNA expressions of the osteogenesis-related genes Col1a1, Col-Ⅱ and Col-X in osteoblasts. The protein expressions of Sox6, Col1a1, Col-Ⅱ, Col-X, PI3K, p-PI3K, Akt and p-Akt in rat cartilage tissue were determined with Western blotting assay.Results: The expression of Sox6 protein in the miR-28-3p over-expression group was significantly reduced, when compared with the miR-28 overexpression control, but Sox6 protein expression in the miR-28-3p inhibition group was significantly increased, relative to inhibition control group (p < 0.05). In the miR-28-3p over-expression and Sox6 over-expression groups, Col1a1 protein expression was significantly increased, while Col-Ⅱ and Col-X protein expressions decreased, when compared with the respective over-expression control group (p < 0.05). Over-expression of miR-28-3p markedly upregulated phosphorylation levels of PI3K and Akt, relative to over-expression control group, while miR-28-3p inhibition significantly downregulated the phosphorylations of PI3K and Akt, relative to the inhibition control group (p < 0.05).Conclusion: Over-expression of miR-28-3p may enhance the healing of fractures by induction of PI3K/Akt signaling route via negative regulation of the expression of Sox6 gene. Keywords: MiR-28-3p, Sox6, PI3K/Akt signaling pathway, Fracture healing

scholarly journals Xiaotan Jieyu Prescription Alleviates Breast Precancerous Lesions through PI3K/Akt Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jing Zhao ◽  
Tao Pang ◽  
Jian-peng Jiao ◽  
Bin Wang ◽  
Xuan Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Rat Model ◽  
Precancerous Lesions ◽  
Precancerous Lesion ◽  
Akt Signaling ◽  
Occurrence Rate ◽  
Akt Signaling Pathway ◽  
Protein Expressions

Background/Aims. In previous studies, it has been observed that Xiaotan Jieyu (XTJY) prescription may inhibit the proliferation of human breast precancerous lesion MCF-10AT cells by inhibiting the PI3K/Akt signaling pathway. The purpose of this study is to further verify the therapeutic effect and the possible mechanism of XTJY on precancerous lesions of breast cancer in vivo. Methods. The successfully established breast precancerous lesion rat model and normal healthy rats were randomly assigned into the blank (BLA), model (MOD), XTJY-low (LD), XTJY-medium (MD), XTJY-high (HD), and tamoxifen (TAM) groups. Different concentrations of XTJY and saline were supplied by intragastric administration for 4 consecutive weeks to assess the protective effect of XTJY on the progress of the breast precancerous lesion in rats involving the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Results. In this study, it determined that 10 mg/each rat DMBA-combined estrogen and progesterone induction for 10 weeks was the optimal condition for the establishment of the breast precancerous lesion rat model. In vivo administration of XTJY or TAM was found to inhibit the development of the breast precancerous lesion, and the occurrence rate of breast invasive carcinomas was decreased by about 50%. Furthermore, XTJY or TAM markedly reduced protein expressions of PI3K and p-Akt and increased protein expressions of PTEN. Conclusion. These data indicated that XTJY can significantly alleviate the development of breast precancerous lesions by inhibiting the activation of the PI3K/Akt signaling pathway. XTJY may be a promising drug for the treatment of precancerous lesions in breast cancer.

Expression of Galectins-1 in Rat Traumatic Osteoarthritis and Its Regulation Mechanism

2019 ◽  
Vol 9 (12) ◽  
pp. 1724-1730
Author(s):  
Yaheng Wei ◽  
Zuoming Yang ◽  
Pengfei Guan ◽  
Lifeng Zhang
Keyword(s):  
Cell Migration ◽  
Real Time ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Akt Signaling ◽  
Control Group ◽  
Regulation Mechanism ◽  
Akt Signaling Pathway ◽  
Model Group ◽  
Chondrocyte Proliferation

Traumatic arthritis is a common orthopedic surgery disease that seriously affects the health of patients. The expression and role of Galectins in traumatic osteoarthritis remains unclear. SD rats were divided into control group and osteoarthritis model group. Real-time PCR and ELISA were used to analyze Galectins-1 expression. Chondrocytes were isolated and cultured and divided into control group, Galectins-1 siRNA group and Galectins-1 group followed by analysis of proliferation of chondrocytes by MTT assay, cell migration by Transewell chamber, expression of RUNX2 and ADAMTS-4/5 by Real-time PCR, and PI3K/Akt by Western blot. Galectins-1 mRNA and secretion in synovial fluid was significantly reduced in model group compared to control (P < 0.05). Transfection of Galectins-1-pcDNA3.1 plasmid into chondrocytes of osteoarthritic rats significantly increased the expression of Galectins-1, promoted chondrocyte proliferation and cell migration, and downregulated RUNX2 and ADAMTS-4/5 (P < 0.05). Up-regulation of Galectins-1 blocked the expression of PI3K/Akt signaling pathway. Transfection of Galectins-1 siRNA significantly reduced the expression of Galectins-1, inhibited chondrocyte proliferation and cell migration, and upregulated RUNX2 and ADAMTS-4/5 (P < 0.05). Down-regulation of Galectins-1 up-regulated PI3K/Akt signaling pathway. Galectins-1 expression is reduced in joint tissues in rat model of traumatic osteoarthritis. Up-regulation of Galectins-1 expression can promote chondrocyte proliferation and migration by regulating PI3K/Akt signaling pathway, which may reduce chondrocyte damage in rats with traumatic osteoarthritis.

scholarly journals LianXia Formula Granule Attenuates Cardiac Sympathetic Remodeling in Rats with Myocardial Infarction via the NGF/TrKA/PI3K/AKT Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Sai-Sai Li ◽  
Nan Kang ◽  
Xiang-Lei Li ◽  
Jing Yuan ◽  
Ruby Ling ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Western Blot ◽  
Real Time ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Plasma Catecholamines ◽  
Akt Signaling ◽  
Nerve Fibers ◽  
Akt Signaling Pathway ◽  
Model Group

Sympathetic remodeling may cause severe arrhythmia after myocardial infarction (MI). Thus, targeting this process may be an effective strategy for clinical prevention of arrhythmias. LianXia Formula Granule (LXFG) can effectively improve the symptoms of patients with arrhythmia after MI, and modern pharmacological studies have shown that Coptidis Rhizoma and Rhizoma Pinelliae Preparata, the components of LXFG, have antiarrhythmia effects. Here, we investigated whether LXFG can mitigate sympathetic remodeling and suppress arrhythmia and then elucidated its underlying mechanism of action in rats after MI. Sprague-Dawley (SD) rats that had undergone a myocardial infarction model were randomly divided into 6 groups, namely, sham, model, metoprolol, and LXFG groups, with high, medium, and low dosages. We exposed the animals to 30 days of treatment and then evaluated incidence of arrhythmia and arrhythmia scores in vivo using programmed electrical stimulation. Moreover, we determined plasma catecholamines contents via enzyme-linked immunosorbent assay and detected expression of tyrosine hydroxylase (TH) at infarcted border zones via western blot, real-time PCR, and immunohistochemical analyses to assess sympathetic remodeling. Finally, we measured key molecules involved in the NGF/TrKA/PI3K/AKT pathways via western blot and real-time PCR. Compared with the model group, treatment with high dose of LXFG suppressed arrhythmia incidence and arrhythmia scores. In addition, all the LXFG groups significantly decreased protein and mRNA levels of TH, improved the average optical density of TH-positive nerve fibers, and reduced the levels of plasma catecholamines relative to the model group. Meanwhile, expression analysis revealed that key molecules in the NGF/TrKA/PI3K/AKT pathways were downregulated in the LXFG group when compared with model group. Overall, these findings indicate that LXFG suppresses arrhythmia and attenuates sympathetic remodeling in rats after MI. The mechanism is probably regulated by suppression of the NGF/TrKA/PI3K/AKT signaling pathway.

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