Acupuncture Regulates Serum Differentially Expressed Proteins in Patients with Chronic Atrophic Gastritis: A Quantitative iTRAQ Proteomics Study

Objective. To identify differentially expressed proteins (DEPs) in sera of patients with chronic atrophic gastritis (CAG) using isobaric tags for relative and absolute quantitation (iTRAQ) and to explore acupuncture’s mechanism in CAG. Methods. Peripheral sera from 8 healthy volunteers (HC), 8 chronic nonatrophic gastritis (NAG) patients, 8 CAG patients, and 8 CAG patients who underwent acupuncture treatment (CAG + ACU) were collected followed by labeling with iTRAQ reagent for protein identification and quantification using two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS). Representative DEPs were selected through bioinformatics, and proteins were verified by enzyme-linked immunosorbent assay (ELISA). Results. A total of 4,448 unique peptides were identified, corresponding to 816 nonredundant proteins. A 1.4-fold difference was used as the threshold. Compared with the HC group, 75 and 106 DEPs were identified from CAG and NAG groups, respectively. Compared with the CAG group, 110 and 66 DEPs were identified from the NAG and CAG + ACU groups, respectively. The DEPs were mainly involved in protein binding and the Notch signaling pathway-related proteins, and the upregulated proteins included actin-binding proteins (thymosin beta-4, tropomyosin-4, profilin-1, transgelin-2), while the downregulated proteins included Notch2 and Notch3. After acupuncture, the expression of these proteins in CAG patients was less differentiated from that in healthy people. The level of the above 6 proteins were verified by ELISA, and the results were similar to the results of iTRAQ analysis. Conclusions. Actin-binding proteins and Notch signaling pathway-related proteins were correlated with the development and progression of CAG and thus are potential diagnostic markers for CAG. Acupuncture may play a role in regulating actin-binding proteins and Notch signaling pathway-related proteins to play a therapeutic role in CAG.

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Propofol Alleviates Neuropathic Pain in CCI Rat Model via the miR-140-3p/JAG1/Notch Signaling Pathway

10.21203/rs.3.rs-404901/v1 ◽

2021 ◽

Author(s):

Fang Cheng ◽

Wei Qin ◽

Ai-xing Yang ◽

Feng-feng Yan ◽

Yu chen ◽

...

Keyword(s):

Neuropathic Pain ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Pathway ◽

Thermal Hyperalgesia ◽

Underlying Mechanism ◽

Notch Signaling Pathway ◽

Mechanical Threshold ◽

Tnf Α ◽

Related Proteins

Abstract As a renowned anesthetic, propofol exerts excellent analgesic function in nerve injury. However, the underlying mechanism of propofol on neuropathic pain (NP) remains unknown. The research aims to analyze propofol’s analgesia mechanism to alleviate NP in CCI rats. The chronic constriction injury (CCI) of sciatic nerve was used to established NP rat models. CCI rats were treated with propofol and its paw withdrawal mechanical threshold (PMWT) and paw withdraw thermal latency (PWTL) were measured. The expressions of TNF-α, IL-1β and IL-10 were detected. CCI rats with propofol treatment were injected with antagomiR-140-3p. After the targeting relationship between miR-140-3p and JAG1 was checked, JAG1 expression was detected. Propofol-treated CCI rats were further injected with Ad-JAG1. Finally, the levels of JAG1 and Notch pathway-related proteins were detected. As a result, propofol could alleviate NP, including thermal hyperalgesia and mechanical pain threshold, and ameliorate neuroinflammation. Mechanically, propofol enhanced the level of miR-140-3p in CCI rats. JAG1 was a direct target of miR-140-3p. The downregulation of miR-140-3p or upregulation of JAG1 could reduce the protective effect of propofol against NP. Propofol inhibited activation of Notch signaling via miR-140-3p/JAG1. Overall, Propofol could inhibit the neuroinflammation and Notch signaling pathway via miR-140-3p/JAG1 to alleviate NP.

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Notch Signaling Pathway Is Activated by Sulfate Reducing Bacteria

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.695299 ◽

2021 ◽

Vol 11 ◽

Author(s):

Sudha B. Singh ◽

Cristina N. Coffman ◽

Amanda Carroll-Portillo ◽

Matthew G. Varga ◽

Henry C. Lin

Keyword(s):

Protein Expression ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Pathway ◽

Sulfate Reducing Bacteria ◽

Notch Signaling Pathway ◽

Sulfate Reducing ◽

Inflammatory Conditions ◽

Related Proteins ◽

Reducing Bacteria

Sulfate Reducing Bacteria (SRB), usually rare residents of the gut, are often found in increased numbers (called a SRB bloom) in inflammatory conditions such as Inflammatory Bowel Disease (IBD), pouchitis, and periodontitis. However, the underlying mechanisms of this association remain largely unknown. Notch signaling, a conserved cell-cell communication pathway, is usually involved in tissue development and differentiation. Dysregulated Notch signaling is observed in inflammatory conditions such as IBD. Lipolysaccharide and pathogens also activate Notch pathway in macrophages. In this study, we tested whether Desulfovibrio, the most dominant SRB genus in the gut, may activate Notch signaling. RAW 264.7 macrophages were infected with Desulfovibrio vulgaris (DSV) and analyzed for the expression of Notch signaling pathway-related proteins. We found that DSV induced protein expression of Notch1 receptor, Notch intracellular domain (NICD) and p21, a downstream Notch target, in a dose-and time-dependent manner. DSV also induced the expression of pro-IL1β, a precursor of IL-1β, and SOCS3, a regulator of cytokine signaling. The gamma secretase inhibitor DAPT or Notch siRNA dampened DSV-induced Notch-related protein expression as well the expression of pro-IL1β and SOCS3. Induction of Notch-related proteins by DSV was not affected by TLR4 -IN -C34(C34), a TLR4 receptor antagonist. Additionally, cell-free supernatant of DSV-infected macrophages induced NICD expression in uninfected macrophages. DSV also activated Notch pathway in the human epithelial cell line HCT116 and in mouse small intestine. Thus, our study uncovers a novel mechanism by which SRB interact with host cells by activating Notch signaling pathway. Our study lays a framework for examining whether the Notch pathway induced by SRB contributes to inflammation in conditions associated with SRB bloom and whether it can be targeted as a therapeutic approach to treat these conditions.

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Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02418-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zhixiao Lin ◽

Congying Zhao ◽

Zhanjun Lei ◽

Yuheng Zhang ◽

Rong Huang ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Notch Signaling ◽

Signaling Pathway ◽

Notch Signaling Pathway ◽

Skin Defect ◽

Epidermal Stem Cells ◽

Nanofiber Scaffold ◽

Related Proteins

Abstract Background Epidermal stem cells (EpSCs) play a vital role in wound healing and skin renewal. Although biomaterial scaffolds have been used for transplantation of EpSCs in wound healing, the ex vivo differentiation of EpSCs limits their application. Methods To inhibit the differentiation of EpSCs and maintain their stemness, we developed an electrospun polycaprolactone (PCL)+cellulose acetate (CA) micro/nanofiber for the culture and transplantation of EpSCs. The modulation effect on EpSCs of the scaffold and the underlying mechanism were explored. Liquid chromatography-tandem mass spectrometry for label-free quantitative proteomics was used to analyze proteomic changes in EpSCs cultured on scaffolds. In addition, the role of transplanted undifferentiated EpSCs in wound healing was also studied. Results In this study, we found that the PCL+CA micro/nanofiber scaffold can inhibit the differentiation of EpSCs through YAP activation-mediated inhibition of the Notch signaling pathway. Significantly differentially expressed proteomics was observed in EpSCs cultured on scaffolds and IV collagen-coated culture dishes. Importantly, differential expression levels of ribosome-related proteins and metabolic pathway-related proteins were detected. Moreover, undifferentiated EpSCs transplanted with the PCL+CA scaffold can promote wound healing through the activation of the Notch signaling pathway in rat full-thickness skin defect models. Conclusions Overall, our study demonstrated the role of the PCL+CA micro-nanofiber scaffold in maintaining the stemness of EpSCs for wound healing, which can be helpful for the development of EpSCs maintaining scaffolds and exploration of interactions between biomaterials and EpSCs.

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Sanpodo and Notch act in opposition to Numb to distinguish sibling neuron fates in the Drosophila CNS

Development ◽

10.1242/dev.125.10.1857 ◽

1998 ◽

Vol 125 (10) ◽

pp. 1857-1865 ◽

Cited By ~ 16

Author(s):

J.B. Skeath ◽

C.Q. Doe

Keyword(s):

Notch Signaling ◽

Signaling Pathway ◽

Binding Protein ◽

Notch Signaling Pathway ◽

Actin Binding ◽

Actin Binding Protein ◽

Cns Neurons

In Drosophila, most neuronal siblings have different fates ('A/B'). Here we demonstrate that mutations in sanpodo, a tropomodulin actin-binding protein homologue, equalize a diverse array of sibling neuron fates ('B/B'). Loss of Notch signaling gives the same phenotype, whereas loss of numb gives the opposite phenotype ('A/A'). The identical effect of removing either sanpodo or Notch function on the fates of sibling CNS neurons indicates that sanpodo may act in the Notch signaling pathway. In addition, sanpodo and numb show dosage-sensitive interactions and epistasis experiments indicate that sanpodo acts downstream of numb. Taken together, these results show that interactions between sanpodo, the Notch signaling pathway and numb enable CNS sibling neurons to acquire different fates.

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