scholarly journals Peptidomics Analysis Discloses That Novel Bioactive Peptides Participate in Necrotizing Enterocolitis in a Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yiwen Liu ◽  
Changlin Wang ◽  
Renqiang Yu ◽  
Jianfeng Fan ◽  
Weilai Jin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Necrotizing Enterocolitis ◽  
Molecular Mechanisms ◽  
Gastrointestinal Disease ◽  
Wnt Signaling Pathway ◽  
Mapk Signaling ◽  
Intestinal Epithelial ◽  
Endogenous Peptides ◽  
Liquid Chromatography Tandem Mass ◽  
Peptide Expression

Necrotizing enterocolitis (NEC) is a common devastating gastrointestinal disease in premature infants, the molecular mechanisms of which have not been fully elucidated. Recently, endogenous peptides have garnered much attention owing to their role in diagnosis and treatment. However, changes in the peptide expression of NEC intestinal tissues remain poorly understood. In the present study, a comparative peptidomics profiling analysis was performed between NEC and control intestinal tissues via liquid chromatography-tandem mass spectrometry (LC-MS). In total, 103 upregulated and 73 downregulated peptides were identified in the intestinal tissues ( fold   change ≥ 1.5 , p < 0.05 ). Bioinformatics analysis revealed that these differentially expressed peptides were significantly associated with NEC pathophysiology, including apoptosis, the TGF-β signaling pathway, the Wnt signaling pathway, and the MAPK signaling pathway. Furthermore, two putative peptides could inhibit apoptosis and promote the migration of intestinal epithelial cells induced by lipopolysaccharide; these peptides were derived from the protein domains MT1 and EZRI, respectively. In conclusion, our study revealed that endogenous peptides are involved in the pathophysiologic mechanism of NEC; nevertheless, further exploration is required in this regard.

scholarly journals Genome-Wide Regulation of Acupuncture and Moxibustion on Ulcerative Colitis Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zhaoqin Wang ◽  
Yan Huang ◽  
Di Wang ◽  
Rumeng Wang ◽  
Kunshan Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Clinical Effects ◽  
Sprague Dawley ◽  
Acupuncture And Moxibustion

Acupuncture and moxibustion have definite clinical effects on treating ulcerative colitis (UC), but their mechanism is still unclear. To investigate the molecular mechanisms, we applied herb-partitioned moxibustion or electroacupuncture at the Tianshu (ST25) points on UC rats and used RNA sequencing to identify molecular consequences. Male Sprague Dawley (SD) rats were divided into 6 groups randomly: the normal control (NC) group, the control + herb-partitioned moxibustion (NCHM) group, the control + electroacupuncture (NCEA) group, the model (UC) group, the model + herb-partitioned moxibustion (UCHM) group, and the model + electroacupuncture (UCEA) group. Compared to the UC group, HE staining in the UCHM group and UCEA group indicated that colitis was relieved, the histopathological score and MPO were both significantly reduced, and the serum hs-CRP concentration was decreased significantly. The results of RNA-seq suggested that, compared to the NC group, 206 upregulated genes and 167 downregulated genes were identified in colon tissues from the UC group; compared to the UC group, the expression levels of some genes were both affected in the UCHM group and the UCEA group (684 differentially expressed genes were identified in the UCHM group, and 1182 differentially expressed genes were identified in the UCEA group). KEGG signal pathway analysis indicated that the differentially expressed genes in the UCHM group were associated with the JAK-STAT signaling pathway and cell adhesion molecule (CAM); the differentially expressed genes in the UCEA group were associated with the NF-κB signaling pathway, the toll-like receptor signaling pathways, the PI3K-Akt signaling pathway, the MAPK signaling pathway, and the Wnt signaling pathway. This is the first study to reveal the gene expression characteristics of the anti-inflammatory effect of UC rats from the perspective of acupuncture and moxibustion control, which provide a clue for further investigation into the molecular mechanisms of UC treatment by acupuncture and moxibustion.

scholarly journals Serum Glycoproteomics and Identification of Potential Mechanisms Underlying Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Naphatthakarn Kerdsaeng ◽  
Sittiruk Roytrakul ◽  
Suwannee Chanprasertyothin ◽  
Piangporn Charernwat ◽  
Sirintorn Chansirikarnjana ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Cytokine Signaling ◽  
Control Group ◽  
Protein Protein Interactions ◽  
Liquid Chromatography Tandem Mass

Objectives. This study compares glycoproteomes in Thai Alzheimer’s disease (AD) patients with those of cognitively normal individuals. Methods. Study participants included outpatients with clinically diagnosed AD ( N = 136 ) and healthy controls without cognitive impairment ( N = 183 ). Blood samples were collected from all participants for biochemical analysis and for Apolipoprotein   E (APOE) genotyping by real-time TaqMan PCR assays. Comparative serum glycoproteomic profiling by liquid chromatography-tandem mass spectrometry was then performed to identify differentially abundant proteins with functional relevance. Results. Statistical differences in age, educational level, and APOE ɛ3/ɛ4 and ɛ4/ɛ4 haplotype frequencies were found between the AD and control groups. The frequency of the APOE ɛ4 allele was significantly higher in the AD group than in the control group. In total, 871 glycoproteins were identified, including 266 and 259 unique proteins in control and AD groups, respectively. There were 49 and 297 upregulated and downregulated glycoproteins, respectively, in AD samples compared with the controls. Unique AD glycoproteins were associated with numerous pathways, including Alzheimer’s disease-presenilin pathway (16.6%), inflammation pathway mediated by chemokine and cytokine signaling (9.2%), Wnt signaling pathway (8.2%), and apoptosis signaling pathway (6.7%). Conclusion. Functions and pathways associated with protein-protein interactions were identified in AD. Significant changes in these proteins can indicate the molecular mechanisms involved in the pathogenesis of AD, and they have the potential to serve as AD biomarkers. Such findings could allow us to better understand AD pathology.

scholarly journals Comparative Transcriptome Analysis Identifies Candidate Genes Related to Black-Spotted Pattern Formation in Spotted Scat (Scatophagus argus)

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 765
Author(s):  
Xiaozhan Lin ◽  
Changxu Tian ◽  
Yang Huang ◽  
Hongjuan Shi ◽  
Guangli Li
Keyword(s):  
Signaling Pathway ◽  
Fish Species ◽  
Molecular Mechanisms ◽  
Skin Pigmentation ◽  
Wnt Signaling Pathway ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Marine Aquaculture ◽  
Pigment Synthesis ◽  
Scatophagus Argus

Spotted scat (Scatophagus argus) is an economically important marine aquaculture and ornamental fish species in Asia, especially in southeast China. In this study, skin transcriptomes of S. argus were obtained for three types of skin, including black-spotted skin (A), non-spotted skin (B) and caudal fin (C). A total of nine complementary DNA (cDNA) libraries were obtained by Illumina sequencing. Bioinformatics analysis revealed that 1358, 2086 and 487 genes were differentially expressed between A and B, A and C, and B and C, respectively. The results revealed that there were 134 common significantly differentially expressed genes (DEGs) and several key genes related to pigment synthesis and pigmentation, including tyrp1, mitf, pmel, slc7a2, tjp1, hsp70 and mart-1. Of these, some DEGs were associated with pigmentation-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as tyrosine metabolism, melanogenesis, the Wnt signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway. The results will facilitate understanding the molecular mechanisms of skin pigmentation differentiation in S. argus and provide valuable information for skin coloration, especially the formation of spotted patterns on other marine fish species.

scholarly journals DNA methylation mediated RSPO2 to promote follicular development in mammals

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xiaofeng Zhou ◽  
Yingting He ◽  
Nian Li ◽  
Guofeng Bai ◽  
Xiangchun Pan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Cpg Island ◽  
Wnt Signaling Pathway ◽  
Follicular Development ◽  
Expression Level

AbstractIn female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.

scholarly journals Spirulina Crude Protein Promotes the Migration and Proliferation in IEC-6 Cells by Activating EGFR/MAPK Signaling Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 205
Author(s):  
Su-Jin Jeong ◽  
Jeong-Wook Choi ◽  
Min-Kyeong Lee ◽  
Youn-Hee Choi ◽  
Taek-Jeong Nam
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Crude Protein ◽  
Cell Cycle Progression ◽  
Intestinal Epithelial Cells ◽  
Mapk Signaling ◽  
S Phase ◽  
Intestinal Epithelial ◽  
Cycle Progression

Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells.

Evaluation of MACF1-regulatory non-coding RNA as a potential therapeutic target in Colorectal Cancer

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Rowaida Mohammed Reda M. M Aboushahba ◽  
Fayda Ibrahim Abdel Motaleb ◽  
Ahmed Abdel Aziz Abou-Zeid ◽  
Enas Samir Nabil ◽  
Dalia Abdel-Wahab Mohamed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Potential Therapeutic Target

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P &lt; 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.

scholarly journals Identifying Main Genes and Pathways by Using Gene Expression Profiling in Primary Immunodeficiency HOIL-1/RBCK1 Disorder Patients

2021 ◽  
Author(s):  
Khyber Shinwari ◽  
Guojun Liu ◽  
Mikhail Bolkov ◽  
Monib Ullah ◽  
Irina Tuzankina
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Signaling Pathway ◽  
Focal Adhesion ◽  
Molecular Mechanisms ◽  
Kegg Pathway ◽  
Wnt Signaling Pathway ◽  
Negative Regulation ◽  
Coagulation Cascade ◽  
Bacterial Disease

HOIL-1/RBCK1 deficiency is a new autosomal receiving disorder with dysfunctional cellular responses to pro-inflammatory cytokines, leading to auto-inflammation, pyogenic bacterial disease, and muscle amylopectinosis growth. Our study with integrated bioinformatics studies of the feature genes and the correlative gene functions, investigated the molecular mechanisms of RBCK1 deficiency. GSE31064 dataset expression profile was downloaded from the Omnibus Gene Expression database. Between RBCK1, MYDK88, NEMO deficient fibroblast, and healthy fibroblast specimens, differentially expressed genes (DEGs) were defined. Gene ontology (GO) gene role enrichment analysis and the Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed using the Annotation, Visualization and Integrated Discovery Database (DAVID). The protein-protein interaction (PPI) of these DEGs was visualized using Cytoscape. GO analysis revealed that the “Skeletal system development, Extracellular matrix organization, Positive regulation of cell migration, Negative regulation of canonical Wnt signaling pathway, Cell adhesion, Angiogenesis and Negative regulation of BMP signaling pathway, Serine-type carboxypeptidase activity, Polysaccharide binding, Calcium ion binding, frizzled binding, Neuropilin binding, and cell adhesion molecule binding, extracellular exosome, extracellular space, extracellular region, lysosomal lumen, endoplasmic reticulum lumen, cell surface and focal adhesion to BP, MF, and CC, respectively. The study of the KEGG pathway showed that the complement and coagulation cascade, interactions of the ECM receptor, PI3K-Akt signaling pathway, PPAR signaling pathway, TGF-beta signaling pathway, cancer pathway, viral carcinogenesis and focal adhesion pathway were closely correlated with the incidence of RBCK1 deficiency. Importantly, it has been predicted that TK1, AURKB, CDCA2, UBE2C, KIFC1, CEP55, CDCA3, GINS2, MCM6 and CDC45 are significantly associated with RCBK1 deficiency. Our study offers a record of damaged genes and pathways in RCBK1, which will boost the understanding of RBCK1 deficiency pathogenesis and other inherent immunodeficiency diseases. This research has the potential and can possibly use in the clinic for diagnosis and targeted therapy of HOIL-1/RBCK1 disorder and other inherent immunodeficiencies.

scholarly journals Anticancer Effects of Emodin on HepG2 Cell: Evidence from Bioinformatic Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Rui-sheng Zhou ◽  
Xiong-Wen Wang ◽  
Qin-feng Sun ◽  
Zeng Jie Ye ◽  
Jian-wei Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Ion Concentration ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Mrna Levels ◽  
Hub Genes ◽  
Positive Regulation

Hepatocellular carcinoma (HCC) is a primary cause of cancer-related death in the world. Despite the fact that there are many methods to treat HCC, the 5-year survival rate of HCC is still at a low level. Emodin can inhibit the growth of HCC cells invitroand invivo. However, the gene regulation of emodin in HCC has not been well studied. In our research, RNA sequencing technology was used to identify the differentially expressed genes (DEGs) in HepG2 cells induced by emodin. A total of 859 DEGs were identified, including 712 downregulated genes and 147 upregulated genes in HepG2 cells treated with emodin. We used DAVID for function and pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING, and Cytoscape was used for module analysis. The enriched functions and pathways of the DEGs include positive regulation of apoptotic process, structural molecule activity and lipopolysaccharide binding, protein digestion and absorption, ECM-receptor interaction, complement and coagulation cascades, and MAPK signaling pathway. 25 hub genes were identified and pathway analysis revealed that these genes were mainly enriched in neuropeptide signaling pathway, inflammatory response, and positive regulation of cytosolic calcium ion concentration. Survival analysis showed that LPAR6, C5, SSTR5, GPR68, and P2RY4 may be involved in the molecular mechanisms of emodin therapy for HCC. A quantitative real-time PCR (qRT-PCR) assay showed that the mRNA levels of LPAR6, C5, SSTR5, GPR68, and P2RY4 were significantly decreased in HepG2 cells treated with emodin. In conclusion, the identified DEGs and hub genes in the present study provide new clues for further researches on the molecular mechanisms of emodin.

scholarly journals miR-3188 Regulates Cell Proliferation, Apoptosis, and Migration in Breast Cancer by Targeting TUSC5 and Regulating the p38 MAPK Signaling Pathway

2018 ◽  
Vol 26 (3) ◽  
pp. 363-372 ◽  
Author(s):  
Xiaowen Chen ◽  
Jianli Chen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
And Migration ◽  
Mcf 7

This study intended to investigate the effects of miR-3188 on breast cancer and to reveal the possible molecular mechanisms. miR-3188 was upregulated and TUSC5 was downregulated in breast cancer tissues and MCF-7 cells compared to normal tissue and MCF-10 cells. After MCF-7 cells were transfected with miR-3188 inhibitor, cell proliferation and migration were inhibited, whereas apoptosis was promoted. Luciferase reporter assay suggested that TUSC5 was a target gene of miR-3188. In addition, miR-3188 overexpression increased the p-p38 expression, while miR-3188 suppression decreased the p-p38 expression significantly. miR-3188 regulated breast cancer progression via the p38 MAPK signaling pathway. In conclusion, miR-3188 affects breast cancer cell proliferation, apoptosis, and migration by targeting TUSC5 and activating the p38 MAPK signaling pathway. miR-3188 may serve as a potential therapeutic agent for the treatment of breast cancer.

scholarly journals Small RNA Sequencing Reveals Differentially Expressed miRNAs in Necrotizing Enterocolitis in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ren-qiang Yu ◽  
Min Wang ◽  
Shan-yu Jiang ◽  
Ying-hui Zhang ◽  
Xiao-yu Zhou ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Rna Sequencing ◽  
Necrotizing Enterocolitis ◽  
Small Rna ◽  
Mirna Expression ◽  
Expression Patterns ◽  
Wnt Signaling Pathway ◽  
Differentially Expressed ◽  
Small Rna Sequencing

Necrotizing enterocolitis (NEC) is the leading cause of death due to gastrointestinal disease in preterm infants. The role of miRNAs in NEC is still unknown. The objective of this study was to identify differentially expressed (DE) miRNAs in rats with NEC and analyze their possible roles. In this study, a NEC rat model was established using Sprague-Dawley rat pups. Small RNA sequencing was used to analyze the miRNA expression profiles in the NEC and control rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to identify target mRNAs for the DE miRNAs and to explore their potential roles. The DE miRNAs were verified by real-time quantitative PCR (RT-qPCR). The status of intestinal injury and the elevated levels of inflammatory cytokines in the NEC group confirmed that the NEC model was successfully established. The 16 miRNAs were found to be differentially expressed between the NEC group and the control group of rats. Bioinformatics analysis indicated that the parental genes of the DE miRNAs were predominantly implicated in the phosphorylation, cell migration, and protein phosphorylation processes. Moreover, the DE miRNAs were mainly found to be involved in the pathways of axon guidance, endocytosis, and focal adhesion, as well as in the Wnt signaling pathway, which is related to colitis. The expression patterns of the candidate miRNAs (rno-miR-27a-5p and rno-miR-187-3p), as assessed by RT-qPCR, were in accordance with the expression patterns obtained by miRNA-sequencing. The miRNA/mRNA/pathway network revealed that rno-miR-27a-5p and rno-miR-187-3p might be involved in NEC via the Wnt signaling pathway. We found an altered miRNA expression pattern in rats with NEC. We hypothesize that rno-miR-27a-5p and rno-miR-187-3p might mediate the NEC pathophysiological processes via the Wnt signaling pathway.

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