scholarly journals The effects of UCP2 on autophagy through the AMPK signaling pathway in septic cardiomyopathy and the underlying mechanism

2021 ◽  
Vol 9 (3) ◽  
pp. 259-259
Author(s):  
Jia-Yu Mao ◽  
Long-Xiang Su ◽  
Dong-Kai Li ◽  
Hong-Min Zhang ◽  
Xiao-Ting Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Underlying Mechanism ◽  
Septic Cardiomyopathy ◽  
Ampk Signaling

scholarly journals Exogenous stromal cell-derived factor-1 (SDF-1) suppresses the NLRP3 inflammasome and inhibits pyroptosis in synoviocytes from osteoarthritic joints via activation of the AMPK signaling pathway

2021 ◽  
Author(s):  
Shuya Wang ◽  
Ali Mobasheri ◽  
Yue Zhang ◽  
Yanli Wang ◽  
Tianqi Dai ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Stromal Cell ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Healthy Individuals ◽  
Mtor Signaling Pathway ◽  
Ampk Signaling ◽  
Stromal Cell Derived Factor

Abstract Objective NLRP3 inflammasome may play a key role in OA pathogenesis. Stromal cell-derived factor-1 (SDF-1) is a homeostatic CXC chemokine. Since the role of SDF-1 in OA has not been explored, this study aimed to examine the effect of SDF-1 on NLRP3 inflammasome and pyroptosis in synoviocytes from OA joints. Materials and methods Human synovium was obtained from OA patients for isolation of primary synoviocytes and a murine model of collagenase-induced OA was established for testing intra-articular injections of SDF-1. Immunoblotting assays were used to examine the effects and underlying mechanism of action of SDF-1 on NLRP3 inflammasome and synoviocyte pyroptosis in synoviocytes. Inhibitors of AMPK and PI3K–mTOR were utilized to investigate the key signaling pathways involved in SDF-1-mediated OA inflammasome formation and pyroptosis. Results Synoviocytes from OA joints exhibited significantly higher expression of NLRP3 inflammasome and biomarkers of synoviocyte pyroptosis relative to healthy individuals. This was confirmed in the collagenase-induced OA model, where OA synoviocytes had a significantly lower SDF-1 expression than healthy ones. SDF-1 treatment in synoviocytes of OA patients and collagenase-induced OA led to significant downregulation in the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers. Inhibition of the AMPK signaling pathway significantly suppressed the inhibitory effect of SDF-1 on NLRP3 inflammasome expression of OA synoviocytes. However, blocking the SDF-1-activated PI3K–mTOR signaling pathway could still suppress the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers. Conclusions SDF-1 ameliorates NLRP3 inflammasome and pyroptosis in OA synoviocytes through activation of the AMPK signaling pathway. Therefore, SDF-1 may be a novel therapeutic target for OA.

scholarly journals Exogenous Stromal Cell-Derived Factor-1 (SDF-1) Suppresses the NLRP3 Inflammasome and Inhibits Pyroptosis in Synoviocytes from Osteoarthritic Joints via Activation of the AMPK Signaling Pathway

2021 ◽  
Author(s):  
Shuya Wang ◽  
Ali Mobasheri ◽  
Yue Zhang ◽  
Yanli Wang ◽  
Tianqi Dai ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Stromal Cell ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Healthy Individuals ◽  
Mtor Signaling Pathway ◽  
Ampk Signaling ◽  
Stromal Cell Derived Factor

Abstract ObjectiveNLRP3 inflammasome may play a key role in OA pathogenesis. Stromal cell-derived factor-1 (SDF-1) is a homeostatic CXC chemokine. Since the role of SDF-1 in OA has not been explored, this study aimed to examine the effect of SDF-1 on NLRP3 inflammasome and pyroptosis in synoviocytes from OA joints.Materials and MethodsHuman synovium was obtained from OA patients for isolation of primary synoviocytes and a murine model of collagen-induced OA was established for testing intra-articular injections of SDF-1. Immunoblotting assays were used to examine the effects and underlying mechanism of action of SDF-1 on NLRP3 inflammasome and synoviocyte pyroptosis in synoviocytes. Inhibitors of AMPK and PI3K-mTOR were utilized to investigate the key signaling pathways involved in SDF-1-mediated OA inflammasome formation and pyroptosis.ResultsSynoviocytes from OA joints exhibited significantly higher expression of NLRP3 inflammasome and biomarkers of synoviocyte pyroptosis relative to healthy individuals. This was confirmed in the collagen-induced OA model, where OA synoviocytes had a significantly lower SDF-1 expression than healthy ones. SDF-1 treatment in synoviocytes of OA patients and collagen-induced OA led to significant downregulation in the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers. Inhibition of the AMPK signaling pathway significantly suppressed the inhibitory effect of SDF-1 on NLRP3 inflammasome expression of OA synoviocytes. However, blocking the SDF-1-activated PI3K-mTOR signaling pathway could still suppress the expression of NLRP3 inflammasome and synoviocyte pyroptosis biomarkers.ConclusionsSDF-1 ameliorates NLRP3 inflammasome and pyroptosis in OA synoviocytes through activation of the AMPK signaling pathway. Therefore, SDF-1 may be a novel therapeutic target for OA.

scholarly journals LHPP inhibits cell growth and migration and triggers autophagy in papillary thyroid cancer by regulating the AKT/AMPK/mTOR signaling pathway

2020 ◽  
Vol 52 (4) ◽  
pp. 382-389 ◽  
Author(s):  
Wenyu Sun ◽  
Kai Qian ◽  
Kai Guo ◽  
Lili Chen ◽  
Jun Xiang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Lines ◽  
Underlying Mechanism ◽  
Mtor Pathway ◽  
Human Thyroid ◽  
Papillary Thyroid ◽  
Cell Growth And Migration ◽  
Ampk Signaling ◽  
Normal Tissues ◽  
And Migration

Abstract In recent decades, the incidence rate of papillary thyroid carcinoma (PTC) has been rapidly increasing. However, the molecular mechanism of the physiological and pathological processes of PTC is still largely unknown. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a tumor suppressor and exerts anti-tumor effect in several human cancers, while the role and underlying mechanism of LHPP in PTC remain vague. In this study, we firstly evaluated the roles of LHPP in PTC and explored its underlying mechanism. Using clinical tissue samples, we detected the level of LHPP in PTC tissues and in matched adjacent normal tissues. Lower level of LHPP was found in PTC tissues than in matched adjacent normal tissues. Similar LHPP expression pattern was found in PTC cell lines when compared with that in normal human thyroid follicular epithelial cells. Then, we over-expressed LHPP in three PTC cell lines and results showed that ectopic LHPP expression consistently reduced cell viability, proliferation, and migration and triggered cell autophagy. Furthermore, over-expression of LHPP inhibited the activation of the AKT/mTOR pathway and promoted the AMPK signaling pathway. In addition, the activation of AKT/mTOR and inhibition of AMPK signaling pathways restored the role of ectopic LHPP expression in PTC cell lines, indicating that LHPP exerts its anti-tumor activity through regulating the AKT/AMPK/mTOR pathway. Ultimately, we illustrated that ectopic LHPP expression inhibited PTC tumor growth in vivo. In conclusion, we revealed that LHPP has an anti-tumor effect in PTC and indicated that LHPP might serve as an effective diagnostic and therapeutic target for PTC.

Gabapentin Reduces Alcohol Intake in Rats by Regulating NF-κB Signaling Pathway Via PPAR γ

2021 ◽  
Author(s):  
Jing Li ◽  
Kewei Xu ◽  
Hao Ding ◽  
Qiaozhen Xi
Keyword(s):  
Locomotor Activity ◽  
Signaling Pathway ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Ethanol Consumption ◽  
Diglycidyl Ether ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Tnf Α

Abstract Aims Increasing preclinical and clinical reports have demonstrated the efficacy of gabapentin (GBP) in treating alcohol use disorder (AUD). However, the mechanism of the effects of GBP in AUD is largely unknown. Herein, we sought to investigate the effect of GBP in a rat model of AUD and explore the underlying mechanism. Methods The intermittent access to 20% ethanol in a 2-bottle choice (IA2BC) procedure was exploited to induce high voluntary ethanol consumption in rats. The rats were treated daily for 20 days with different doses of GBP, simultaneously recording ethanol/water intake. The locomotor activity and grooming behavior of rats were also tested to evaluate the potential effects of GBP on confounding motor in rats. The levels of IL-1β and TNF-α in serum and hippocampus homogenate from the rats were detected by using ELISA. The expressions of peroxisome proliferator-activated-receptor γ (PPAR-γ) and nuclear factor-κB (NF-κB) in the hippocampus were determined by immunofluorescence and western blot. Results GBP reduced alcohol consumption, whereas increased water consumption and locomotor activity of rats. GBP was also able to decrease the levels of IL-1β and TNF-α in both serum and hippocampus, in addition to the expression of NF-κB in the hippocampus. Furthermore, these effects attributed to GBP were observed to disappear in the presence of bisphenol A diglycidyl ether (BADGE), a specific inhibitor of PPAR-γ. Conclusions Our findings revealed that GBP could activate PPAR-γ to suppress the NF-κB signaling pathway, contributing to the decrease of ethanol consumption and ethanol-induced neuroimmune responses.

Identification of Potential Genes Associated with Vemurafenib Efficacy and Melanoma Prognosis

2021 ◽  
Vol 24 ◽  
Author(s):  
Yue Qi ◽  
GuiE Ma
Keyword(s):  
Signaling Pathway ◽  
Estrogen Signaling ◽  
Akt Signaling Pathway ◽  
Ppi Network ◽  
Hub Genes ◽  
Ampk Signaling ◽  
Melanoma Patients ◽  
Key Genes ◽  
Neurotrophin Signaling ◽  
Upregulated Genes

Objective: This work aimed to investigate the molecular mechanisms underlying the efficacy of vemurafenib as a treatment for melanoma. Methods: The GSE52882 dataset, which includes A375 and A2058 melanoma cell lines treated with vemurafenib and dimethyl sulfoxide (DMSO), and clinical information associated with melanoma patients, were acquired from the Gene Expression Omnibus (GEO) database and University of California Santa Cruz (UCSC), respectively. Functional enrichment analysis, protein-protein interaction (PPI) network construction, sub-module analysis, and transcriptional regulation analysis were performed on overlapping differentially expressed genes (DEGs) identified in both cell lines. Finally, we performed a survival analysis based on the genes identified. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Conclusion: MMP2, CXCL8, PIK3R3, ITGB3, and LEF1 may play roles in the efficacy of vemurafenib treatment in melanoma; for example, MMP2 and PIK3R3 are likely associated with vemurafenib resistance. These findings will contribute to the development of novel therapies for melanoma.

scholarly journals DNA methylation mediates the association between breastfeeding and early-life growth trajectories

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Laurent Briollais ◽  
Denis Rustand ◽  
Catherine Allard ◽  
Yanyan Wu ◽  
Jingxiong Xu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Signaling Pathway ◽  
Exclusive Breastfeeding ◽  
Child Growth ◽  
Postnatal Period ◽  
Overweight And Obesity ◽  
Breastfeeding Duration ◽  
Ampk Signaling ◽  
Cpg Sites ◽  
Genome Wide

Abstract Background The role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence. Using extensive DNA methylation data from the ALSPAC child cohort, we characterized the genome-wide landscape of DNA methylation variations associated with the duration of exclusive breastfeeding and assessed whether these variations mediate the association between exclusive breastfeeding and BMI over different epochs of child growth. Results Exclusive breastfeeding elicits more substantial DNA methylation variations during infancy than at other periods of child growth. At the genome-wide level, 13 CpG sites in girls (miR-21, SNAPC3, ATP6V0A1, DHX15/PPARGC1A, LINC00398/ALOX5AP, FAM238C, NATP/NAT2, CUX1, TRAPPC9, OSBPL1A, ZNF185, FAM84A, PDPK1) and 2 CpG sites in boys (IL16 and NREP), mediate the association between exclusive breastfeeding and longitudinal BMI. We found enrichment of CpG sites located within miRNAs and key pathways (AMPK signaling pathway, insulin signaling pathway, endocytosis). Overall DNA methylation variation corresponding to 3 to 5 months of exclusive breastfeeding was associated with slower BMI growth the first 6 years of life compared to no breastfeeding and in a dose–response manner with exclusive breastfeeding duration. Conclusions Our study confirmed the early postnatal period as a critical developmental period associated with substantial DNA methylation variations, which in turn could mitigate the development of overweight and obesity from infancy to early childhood. Since an accelerated growth during these developmental periods has been linked to the development of sustained obesity later in life, exclusive breastfeeding could have a major role in preventing the risks of overweight/obesity and children and adults through DNA methylation mechanisms occurring early in life.

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