scholarly journals Hair Growth Effect of Emulsion Extracted Brevilin A, a JAK3 Inhibitor, from Centipeda minima

Processes ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 767
Author(s):  
Byoung Ha Kim ◽  
Won-Yung Lee ◽  
Tuy An Trinh ◽  
Jae Sung Pyo ◽  
Sooyeun Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hair Growth ◽  
Mapk Signaling ◽  
Janus Kinase ◽  
Gene Set Enrichment Analysis ◽  
Herbal Extract ◽  
Growth Effect ◽  
Dependent Manner ◽  
Centipeda Minima ◽  
Jak3 Inhibitor

Janus kinase 3 (JAK3) inhibitors have been used effectively in the treatment of several cases of alopecia universalis and its variants. Our study aims to evaluate whether the emulsion extract of brevilin A from Centipeda minima (CMX) stimulates hair regrowth in a clinical trial, as a JAK3 inhibitor, combined with network pharmacology-based analysis. CMX showed potent inhibition of JAK3 in a concentration-dependent manner. Significant differences in total hair count, terminal hair count, and anagen hair count from the baseline to 24 weeks were observed between the placebo and CMX subjects. The gene set enrichment analysis showed that the targets of CMX are mainly associated with the JAK-STAT signaling pathway, cytokine–cytokine receptor interactions, and the MAPK signaling pathway. This study suggests that the medicinal herbal extract CMX is useful in the treatment of mild to moderate vertex balding that contribute to the visible improvements in hair growth observed in treated patients.

The defense response of Caenorhabditis elegans to Cutibacterium acnes SK137 via the TIR-1-p38 MAPK signaling pathway

2021 ◽  
Author(s):  
Ayano Tsuru ◽  
Yumi Hamazaki ◽  
Shuta Tomida ◽  
Mohammad Shaokat Ali ◽  
Eriko Kage-Nakadai
Keyword(s):  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Defense Response ◽  
Mapk Pathway ◽  
Defense Responses ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Healthy Skin ◽  
Cutibacterium Acnes

Abstract Cutibacterium acnes plays roles in both acne disease and healthy skin ecosystem. We observed that mutations in the tir-1/SARM1 and p38 MAPK cascade genes significantly shortened Caenorhabditis elegans lifespan upon Cutibacterium acnes SK137 infection. Antimicrobial molecules were induced by SK137 in a TIR-1-dependent manner. These results suggest that defense responses against SK137 involve the TIR-1-p38 MAPK pathway in Caenorhabditis elegans.

scholarly journals Intracerebral Injection of Heme Induces Lipid Peroxidation, Neuroinflammation, and Sensorimotor Deficits

Stroke ◽  
2021 ◽  
Author(s):  
Luiz Ricardo C. Vasconcellos ◽  
Letícia Martimiano ◽  
Danillo Pereira Dantas ◽  
Filipe Mota Fonseca ◽  
Hilton Mata-Santos ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Signaling Pathway ◽  
Brain Damage ◽  
Autologous Blood ◽  
Mapk Signaling ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
In Vivo Models ◽  
Sensorimotor Deficits ◽  
The Brain

Background and Purpose: Heme is a red blood cell component released in the brain parenchyma following intracerebral hemorrhage. However, the study of the pathophysiological mechanisms triggered by heme in the brain is hampered by the lack of well-established in vivo models of intracerebral heme injection. This study aims to optimize and characterize a protocol of intrastriatal heme injection in mice, with a focus on the induction of lipid peroxidation, neuroinflammation and, ultimately, sensorimotor deficits. We also evaluated the involvement of NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), an inflammasome sensor, in the behavior deficits induced by heme in this model. Methods: Mice were injected with heme in the striatum for the evaluation of neuroinflammation and brain damage through histological and biochemical techniques. Immunoblot was used to evaluate the expression of proteins involved in heme/iron metabolism and antioxidant responses and the activation of the MAPK (mitogen-activated protein kinase) signaling pathway. For the assessment of neurological function, we followed-up heme-injected mice for 2 weeks using the rotarod, elevated body swing, and cylinder tests. Mice injected with the vehicle (sham), or autologous blood were used as controls. Results: Heme induced lipid peroxidation and inflammation in the brain. Moreover, heme increased the expression of HO-1 (heme oxygenase-1), ferritin, p62, and superoxide dismutase 2, and activated the MAPK signaling pathway promoting pro-IL (interleukin)-1β production and its cleavage to the active form. Heme-injected mice exhibited signs of brain damage and reactive astrogliosis around the injection site. Behavior deficits were observed after heme or autologous blood injection in comparison to sham-operated controls. In addition, behavior deficits and IL-1β production were reduced in Nlrp3 knockout mice in comparison to wild-type mice. Conclusions: Our results show that intracerebral heme injection induces neuroinflammation, and neurological deficits, in an NLRP3-dependent manner, suggesting that this is a feasible model to evaluate the role of heme in neurological disorders.

scholarly journals Differential gene expression in articular cartilage between rheumatoid arthritis and endemic Kashin–Beck disease

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Zongqiang Gao ◽  
Chen Duan ◽  
Fang-fang Yu ◽  
Xiong Guo
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Articular Cartilage ◽  
Signaling Pathway ◽  
Differential Gene Expression ◽  
Mapk Signaling ◽  
Janus Kinase ◽  
Ppi Network ◽  
Differential Gene ◽  
Beck Disease

AbstractKashin–beck disease (KBD) is endemic chronic osteoarthrosis and its pathogenesis is still unclear. The present study aimed to explore differential gene expression in articular cartilage between patients with rheumatoid arthritis (RA) and KBD. Articular cartilages were collected from KBD and RA patients, and differentially expressed genes (DEGs) were analyzed by RNA-seq. The signaling pathway and biological process (BP) of the DEGs were identified by enrichment analysis. The protein–protein interaction (PPI) network of DEGs and the key genes of KBD were identified by network analysis with STRING and cytoscape software. We identified 167 immune-related DEGs in articular cartilage samples from KBD patients compared with RA. The up-regulation of MAPK signaling pathway and the down-regulation of signaling pathways such as toll-like receptor, janus kinase-signal transducers and activators of transcription, leukocyte migration, T-cell receptor and chemokine, and antigen processing and presentation were involved in KBD. We identified 137 genes nodes related with immune and mapped the PPI network diagram. BP analysis revealed that immune response, calcium ion homeostasis, blood vessel morphogenesis, inflammatory response, lymphocyte proliferation, and MAPK activation were involved in KBD. In conclusion, gene expression profiling can be used to identify the different mechanism of pathogenesis between KBD and RA.

scholarly journals G protein pathway suppressor 2 enhanced the renal large-conductance Ca2+-activated potassium channel expression via inhibiting ERK1/2 signaling pathway

2018 ◽  
Vol 315 (3) ◽  
pp. F503-F511 ◽  
Author(s):  
Zhizhi Zhuang ◽  
Jia Xiao ◽  
Xinxin Chen ◽  
Xiaohan Hu ◽  
Ruidian Li ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
G Protein ◽  
Mapk Signaling ◽  
Bk Channels ◽  
Bk Channel ◽  
Mapk Signaling Pathway ◽  
Dependent Manner ◽  
Channel Activity ◽  
Open Probability

G protein pathway suppressor 2 (GPS2) is a multifunctional protein and transcriptional regulation factor that is involved in the G protein MAPK signaling pathway. It has been shown that the MAPK signaling pathway plays an important role in the regulation of renal large-conductance Ca2+-activated potassium (BK) channels. In this study, we investigated the effects of GPS2 on BK channel activity and protein expression. In human embryonic kidney (HEK) BK stably expressing cells transfected with either GPS2 or its vector control, a single-cell recording showed that GPS2 significantly increased BK channel activity ( NPo), increasing BK open probability ( Po), and channel number ( N) compared with the control. In Cos-7 cells and HEK 293 T cells, GPS2 overexpression significantly enhanced the total protein expression of BK in a dose-dependent manner. Knockdown of GPS2 expression significantly decreased BK protein expression, while increasing ERK1/2 phosphorylation. Knockdown of ERK1/2 expression reversed the GPS2 siRNA-mediated inhibition of BK protein expression in Cos-7 cells. Pretreatments of Cos-7 cells with either the lysosomal inhibitor bafilomycin A1 or the proteasomal inhibitor MG132 partially reversed the inhibitory effects of GPS2 siRNA on BK protein expression. In addition, feeding a high-potassium diet significantly increased both GPS2 and BK protein abundance in mice. These data suggest that GPS2 enhances BK channel activity and its protein expression by reducing ERK1/2 signaling-mediated degradation of the channel.

scholarly journals Differential Roles of ASK1 and TAK1 in Helicobacter pylori-Induced Cellular Responses

2013 ◽  
Vol 81 (12) ◽  
pp. 4551-4560 ◽  
Author(s):  
Yoku Hayakawa ◽  
Yoshihiro Hirata ◽  
Hiroto Kinoshita ◽  
Kosuke Sakitani ◽  
Hayato Nakagawa ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Critical Role ◽  
Cellular Responses ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Content Type ◽  
H Pylori ◽  
Jnk Activation

ABSTRACTThe mitogen-activated protein kinase (MAPK) signaling pathway regulates various cellular functions, including those induced byHelicobacter pylori. TAK1 is an upstream MAPK kinase kinase (MAP3K) required forH. pylori-induced MAPK and NF-κB activation, but it remains unclear whether other MAP3Ks are involved inH. pylori-induced cellular responses. In this study, we focused on the MAP3K ASK1, which plays a critical role in gastric tumorigenesis. In gastric epithelial cells,H. pyloriactivates ASK1 in a reactive oxygen species (ROS)- andcagpathogenicity island-dependent manner, and ASK1 regulates sustained JNK activation and apoptosis induced byH. pylori. In contrast, TAK1 regulatesH. pylori-mediated early JNK activation and cytokine production. We also found reciprocal regulation between ASK1 and TAK1 inH. pylori-related responses, whereby inhibition of TAK1 or downstream p38 MAPK activates ASK1 through ROS production, and ASK1 suppresses TAK1 and downstream NF-κB activation. We identified ROS/ASK1/JNK as a new signaling pathway induced byH. pylori, which regulates apoptotic cell death. The balance of ASK1-induced apoptosis and TAK1-induced antiapoptotic or inflammatory responses may determine the fate of epithelial cells infected withH. pyloriand thus be involved in the pathogenesis of gastritis and gastric cancer.

scholarly journals Aloesin Suppresses Cell Growth and Metastasis in Ovarian Cancer SKOV3 Cells through the Inhibition of the MAPK Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Li-qian Zhang ◽  
Rong-wei Lv ◽  
Xiang-dong Qu ◽  
Xian-jun Chen ◽  
Hong-sheng Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Therapeutic Drug ◽  
Dependent Manner ◽  
Skov3 Cells

Aloesin is an active constituent of the herb aloe vera and plays a crucial role in anti-inflammatory activity, ultraviolet protection, and antibacterium. We investigated the role and possible mechanisms of aloesin in the cell growth and metastasis of ovarian cancer. It was found that aloesin inhibited cell viability and cell clonality in a dose-dependent manner. It arrests the cell cycle at the S-phase and induced apoptosis in SKOV3 cells. In an in vivo experiment, it was observed that aloesin inhibited tumor growth. Moreover, it inhibited migration and invasion of cancer in SKOV3 cells. Interestingly, members from the mitogen-activated protein kinase (MAPK) signaling family became less phosphorylated as the aloesin dose increased. This suggests that aloesin exerts its anticancer effect through the MAPK signaling pathway. Our data also highlights the possibility of using aloesin as a novel therapeutic drug for ovarian cancer treatment.

scholarly journals Hydrogen sulfide upregulates acid-sensing ion channels via the MAPK-Erk1/2 signaling pathway

Function ◽  
2021 ◽  
Author(s):  
Zhong Peng ◽  
Stephan Kellenberger
Keyword(s):  
Hydrogen Sulfide ◽  
Ion Channels ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Mammalian Cells ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Membrane Expression ◽  
Concentration Dependent Manner ◽  
Acid Sensing Ion Channels

Abstract Hydrogen sulfide (H2S) emerged recently as a new gasotransmitter and was shown to exert cellular effects by interacting with proteins, among them many ion channels. Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive Na+ channels activated by extracellular protons. ASICs are involved in many physiological and pathological processes, such as fear conditioning, pain sensation and seizures. We characterize here the regulation of ASICs by H2S. In transfected mammalian cells, the H2S donor NaHS increased the acid-induced ASIC1a peak currents in a time- and concentration-dependent manner. Similarly, NaHS potentiated also the acid-induced currents of ASIC1b, ASIC2a and ASIC3. An upregulation induced by the H2S donors NaHS and GYY4137 was also observed with the endogenous ASIC currents of cultured hypothalamus neurons. In parallel with the effect on function, the total and plasma membrane expression of ASIC1a was increased by GYY4137, as determined in cultured cortical neurons. H2S also enhanced the phosphorylation of extracellular signal-regulated kinase, which belongs to the family of mitogen-activated protein kinases (MAPKs). Pharmacological blockade of the MAPK signaling pathway prevented the GYY4137-induced increase of ASIC function and expression, indicating that this pathway is required for ASIC regulation by H2S. Our study demonstrates that H2S regulates ASIC expression and function, and identifies the involved signaling mechanism. Since H2S shares several roles with ASICs, as e.g. facilitation of learning and memory, protection during seizure activity and modulation of nociception, it may be possible that H2S exerts some of these effects via a regulation of ASIC function.

scholarly journals HBeAg mediates inflammatory functions of macrophages by TLR2 contributing to hepatic fibrosis

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaoyu Xie ◽  
Huanran Lv ◽  
Chenxi Liu ◽  
Xiaonan Su ◽  
Zhen Yu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Macrophage Activation ◽  
Stellate Cells ◽  
Mapk Signaling ◽  
Functional Domain ◽  
Dependent Manner ◽  
Core Domain ◽  
Direct Binding

Abstract Background We and others have confirmed activation of macrophages plays a critical role in liver injury and fibrogenesis during HBV infection. And we have also proved HBeAg can obviously induce the production of macrophage inflammatory cytokines compared with HBsAg and HBcAg. However, the receptor and functional domain of HBeAg in macrophage activation and its effects and mechanisms on hepatic fibrosis remain elusive. Methods The potentially direct binding receptors of HBeAg were screened and verified by Co-IP assay. Meanwhile, the function domain and accessible peptides of HBeAg for macrophage activation were analyzed by prediction of surface accessible peptide, construction, and synthesis of truncated fragments. Furthermore, effects and mechanisms of the activation of hepatic stellate cells induced by HBeAg-treated macrophages were investigated by Transwell, CCK-8, Gel contraction assay, Phospho Explorer antibody microarray, and Luminex assay. Finally, the effect of HBeAg in hepatic inflammation and fibrosis was evaluated in both human and murine tissues by immunohistochemistry, immunofluorescence, ELISA, and detection of liver enzymes. Results Herein, we verified TLR-2 was the direct binding receptor of HBeAg. Meanwhile, C-terminal peptide (122-143 aa.) of core domain in HBeAg was critical for macrophage activation. But arginine-rich domain of HBcAg hided this function, although HBcAg and HBeAg shared the same core domain. Furthermore, HBeAg promoted the proliferation, motility, and contraction of hepatic stellate cells (HSCs) in a macrophage-dependent manner, but not alone. PI3K-AKT-mTOR and p38 MAPK signaling pathway were responsible for motility phenotype of HSCs, while the Smad-dependent TGF-β signaling pathway for proliferation and contraction of them. Additionally, multiple chemokines and cytokines, such as CCL2, CCL5, CXCL10, and TNF-α, might be key mediators of HSC activation. Consistently, HBeAg induced transient inflammation response and promoted early fibrogenesis via TLR-2 in mice. Finally, clinical investigations suggested that the level of HBeAg is associated with inflammation and fibrosis degrees in patients infected with HBV. Conclusions HBeAg activated macrophages via the TLR-2/NF-κB signal pathway and further exacerbated hepatic fibrosis by facilitating motility, proliferation, and contraction of HSCs with the help of macrophages.

scholarly journals The role of andrographolide and its derivative in COVID-19 associated proteins and immune system

2020 ◽  
Author(s):  
Yadu Nandan Dey ◽  
Pukar Khanal ◽  
B. M. Patil ◽  
Manish M. Wanjari ◽  
Bhavana Srivast ◽  
...  
Keyword(s):  
Immune System ◽  
Signaling Pathway ◽  
Immune Modulation ◽  
Killer Cell ◽  
Mapk Signaling ◽  
Binding Energies ◽  
Gene Set Enrichment Analysis ◽  
Spike Protein ◽  
Network Pharmacology ◽  
Receptor Interaction

Abstract Aim: In view of the strong immunomodulatory and antiviral activity of andrographolide and its derivative, the present study aimed to investigate the binding affinities of andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide with 3 major targets of COVID-19 i.e. 3CLpro, PLpro and spike protein followed by their gene-set enrichment analysis with special reference to immune modulation.Materials and methods: SMILES of the compounds were retrieved from DigepPred database and the proteins identified were queried in STRING to evaluate the protein-protein interaction and modulated pathways were identified concerning the KEGG database. Drug-likeness and ADMET profiles were evaluated using MolSoft and admet SAR 2.0, respectively. Molecular docking was carried using autodock 4.0.Results: Andrographolide and 14-Deoxy-11,12-didehydroandrographolide were predicted to have a high binding affinity with papain-like protease i.e. -6.7 kcal/mol and -6.5 kcal/mol, respectively while they interact with equal binding energies with 3clpro (-6.8 kcal/mol) and spike protein (-6.9 kcal/mol). Network pharmacology analysis revealed that both compounds modulated the immune system through the regulation of chemokine signaling pathway, Rap1 signaling pathway, Cytokine-cytokine receptor interaction, MAPK signaling pathway, NF-kappa B signaling pathway, Rassignaling pathway, p53 signaling pathway, HIF-1 signaling pathway, and Natural killer cell-mediated cytotoxicity. Although the 14-deoxy-11,12-didehydroandrographolide scored higher drug-likeness character, it showed less potency to interaction with targeted proteins of COVID-19.Conclusion: The study suggests the strong interaction of the andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide against target proteins associated with COVID-19. Further, network pharmacology analysis elucidated the different pathways of immunomodulation. However, clinical research should be conducted to confirm the current findings.

scholarly journals Diagnosis and Prognostic Value of SPARC in Gastric Carcinoma: database mining for GCTA

2020 ◽  
Author(s):  
Diqi Ying ◽  
Ding Li ◽  
Xiao Jin
Keyword(s):  
Gastric Carcinoma ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Wnt Signaling Pathway ◽  
Mapk Signaling ◽  
Gene Set Enrichment Analysis ◽  
Signal Pathways ◽  
Potential Biomarker ◽  
Incidence And Mortality ◽  
Sparc Expression

Abstract Gastric carcinoma (GC) remains high incidence and mortality both in developed and developing countries. SPARC is extracellular non-structural matrix glycoprotein. Previous studies were closely associated with bone disease. However, the role of SPARC in GC remains largely unclear. In our study, we explored the diagnosis, prognosis and pathway enrichments value of SPARC in GC. Here, with the data from The Cancer Genome Atlas (TCGA), we used receiver operating characteristic (ROC) curve analysis to estimate the diagnosis value of the SPARC expression, Univariate and multivariate analysis to the prognosis, Gene set enrichment analysis (GSEA) to the signal pathway enrichments. As a result, SPARC expression was significantly higher in the GC tissue samples. Those with high SPARC expression of GC patients were worse prognosis. GSEA shows the gene sets related signal pathways including transforming growth factor (TGF) beta signaling pathway, pathways in cancer, Wnt signaling pathway, Mitogen-activated protein kinase (MAPK) signaling pathway etc. In brief, those results suggest that SPARC can serve as a potential biomarker for GC in diagnosis and prognosis.

Sign in / Sign up

Export Citation Format

Share Document