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1.
Article in Chinese | WPRIM | ID: wpr-879620

ABSTRACT

OBJECTIVE@#To construct the differential expression profile of microRNA (miRNA) in plasma of patients with type 2 diabetes mellitus (T2DM) and explore the possibility of using miRNA as the target for diagnosis and treatment of T2DM.@*METHODS@#Agilent miRNA microarray was used to determine the expression profiles of miRNA in the plasma of patients with T2DM (FC> 2, P< 0.05). The result was verified by real-time quantitative PCR (RT-qPCR). Candidate miRNA was analyzed by bioinformatic tools.@*RESULTS@#In total 122 differentially expressed miRNAs were identified. Among these, 14 were selected by multi-source intersection screening, which included 5 up-regulated genes and 9 down regulated genes. RT-qPCR showed that the expression of hsa-miR-185-5p and hsa-miR-328-5p have significantly increased in T2DM patients (P< 0.05). Bioinformatic analysis suggested that these miRNAs may be involved in the pathogenesis of T2DM through insulin secretion and PI3K-AKT signaling pathway.@*CONCLUSION@#Differential expression of hsa-miR-185-5p and hsa-miR-328-5p in the plasma may be closely associated with the pathogenesis of T2DM.


Subject(s)
Computational Biology , Diabetes Mellitus, Type 2/genetics , Humans , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases , Signal Transduction
2.
Article in Chinese | WPRIM | ID: wpr-879573

ABSTRACT

The development of female germ cells can be mainly divided into two stages: fetal germ cells and oocytes in folliculogenesis after puberty. Mitosis-meiosis transition, meiosis arrest and re-activation are the key phases of the development. Several phases may be characterized by their distinct molecular events, which involve precise regulation of gene expression and interaction with corresponding gonadal niche cells. In recent years, single-cell transcriptome studies have clarified phase-specific patterns of gene expression, signaling pathways and epigenetic modification during oogenesis and folliculogenesis. These works have provided important insights into the development of female germ cells and pathogenesis of germ-cell related diseases, which may promote clinical application of reproductive genetic research.


Subject(s)
Female , Germ Cells , Humans , Meiosis , Oocytes , Oogenesis/genetics , Signal Transduction
3.
Frontiers of Medicine ; (4): 178-207, 2021.
Article in English | WPRIM | ID: wpr-880961

ABSTRACT

Breast cancer is one of the most common malignancies that seriously threaten women's health. In the process of the malignant transformation of breast cancer, metabolic reprogramming and immune evasion represent the two main fascinating characteristics of cancer and facilitate cancer cell proliferation. Breast cancer cells generate energy through increased glucose metabolism. Lipid metabolism contributes to biological signal pathways and forms cell membranes except energy generation. Amino acids act as basic protein units and metabolic regulators in supporting cell growth. For tumor-associated immunity, poor immunogenicity and heightened immunosuppression cause breast cancer cells to evade the host's immune system. For the past few years, the complex mechanisms of metabolic reprogramming and immune evasion are deeply investigated, and the genes involved in these processes are used as clinical therapeutic targets for breast cancer. Here, we review the recent findings related to abnormal metabolism and immune characteristics, regulatory mechanisms, their links, and relevant therapeutic strategies.


Subject(s)
Breast Neoplasms , Cell Proliferation , Cell Transformation, Neoplastic , Energy Metabolism , Female , Humans , Lipid Metabolism , Signal Transduction
4.
Frontiers of Medicine ; (4): 292-301, 2021.
Article in English | WPRIM | ID: wpr-880958

ABSTRACT

The high- and the low-molecular weight hyaluronic acids (HMW-HA and LMW-HA, respectively) showed different biological activities in inflammation. However, the role of LMW-HA in inflammatory response is controversial. In this study, we aimed to investigate the effect of bioactive hyaluronan (B-HA) on lipopolysaccharide (LPS)-induced inflammatory responses in human macrophages and mice. B-HA was produced from HA treated with glycosylated recombinant human hyaluronidase PH20. Human THP-1 cells were induced to differentiate into macrophages. THP-1-derived macrophages were treated with B-HA, LPS, or B-HA + LPS. The mRNA expression and the production of inflammatory cytokines were determined using quantitative real-time PCR and enzyme-linked immunosorbent assay. The phosphorylation levels of proteins in the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and IRF-3 signaling pathways were measured using Western blot. The in vivo efficacy of B-HA was assessed in a mouse model of LPS-induced inflammation. Results showed that B-HA inhibited the expression of TNF-α, IL-6, IL-1, and IFN-β, and enhanced the expression of the antiinflammatory cytokine IL-10 in LPS-induced inflammatory responses in THP-1-derived macrophages and in vivo. B-HA significantly suppressed the phosphorylation of the TLR4 signaling pathway proteins p65, IKKα/β, IκBα, JNK1/2, ERK1/2, p38, and IRF-3. In conclusion, our results demonstrated that the B-HA attenuated the LPS-stimulated inflammatory response by inhibiting the activation of the TLR4 signaling pathway. B-HA could be a potential anti-inflammatory drug in the treatment of inflammatory disease.


Subject(s)
Animals , Cytokines , Hyaluronic Acid , Lipopolysaccharides , Mice , NF-kappa B/metabolism , Signal Transduction , Toll-Like Receptor 4
5.
Protein & Cell ; (12): 29-38, 2021.
Article in English | WPRIM | ID: wpr-880916

ABSTRACT

Prostate cancer is the most commonly diagnosed non-cutaneous cancers in North American men. While androgen deprivation has remained as the cornerstone of prostate cancer treatment, resistance ensues leading to lethal disease. Forkhead box A1 (FOXA1) encodes a pioneer factor that induces open chromatin conformation to allow the binding of other transcription factors. Through direct interactions with the Androgen Receptor (AR), FOXA1 helps to shape AR signaling that drives the growth and survival of normal prostate and prostate cancer cells. FOXA1 also possesses an AR-independent role of regulating epithelial-to-mesenchymal transition (EMT). In prostate cancer, mutations converge onto the coding sequence and cis-regulatory elements (CREs) of FOXA1, leading to functional alterations. In addition, FOXA1 activity in prostate cancer can be modulated post-translationally through various mechanisms such as LSD1-mediated protein demethylation. In this review, we describe the latest discoveries related to the function and regulation of FOXA1 in prostate cancer, pointing to their relevance to guide future clinical interventions.


Subject(s)
Amino Acid Sequence , Epigenesis, Genetic , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Hepatocyte Nuclear Factor 3-alpha/metabolism , Histone Demethylases/metabolism , Histones/metabolism , Humans , Male , Mutation , Prostate/pathology , Prostatic Neoplasms/pathology , Protein Binding , Protein Processing, Post-Translational , Receptors, Androgen/metabolism , Signal Transduction , Transcription, Genetic
6.
Article in English | WPRIM | ID: wpr-880866

ABSTRACT

As an important component of the tumor microenvironment, cancer-associated fibroblasts (CAFs) secrete energy metabolites to supply energy for tumor progression. Abnormal regulation of long noncoding RNAs (lncRNAs) is thought to contribute to glucose metabolism, but the role of lncRNAs in glycolysis in oral CAFs has not been systematically examined. In the present study, by using RNA sequencing and bioinformatics analysis, we analyzed the lncRNA/mRNA profiles of normal fibroblasts (NFs) derived from normal tissues and CAFs derived from patients with oral squamous cell carcinoma (OSCC). LncRNA H19 was identified as a key lncRNA in oral CAFs and was synchronously upregulated in both oral cancer cell lines and CAFs. Using small interfering RNA (siRNA) strategies, we determined that lncRNA H19 knockdown affected proliferation, migration, and glycolysis in oral CAFs. We found that knockdown of lncRNA H19 by siRNA suppressed the MAPK signaling pathway, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and miR-675-5p. Furthermore, the lncRNA H19/miR-675-5p/PFKFB3 axis was involved in promoting the glycolysis pathway in oral CAFs, as demonstrated by a luciferase reporter system assay and treatment with a miRNA-specific inhibitor. Our study presents a new way to understand glucose metabolism in oral CAFs, theoretically providing a novel biomarker for OSCC molecular diagnosis and a new target for antitumor therapy.


Subject(s)
Cancer-Associated Fibroblasts/metabolism , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Glycolysis , Head and Neck Neoplasms , Humans , MicroRNAs/metabolism , Mouth Neoplasms/genetics , Phosphofructokinase-2/genetics , RNA, Long Noncoding/genetics , Signal Transduction , Tumor Microenvironment
7.
Article in English | WPRIM | ID: wpr-880858

ABSTRACT

During embryonic development, organs undergo distinct and programmed morphological changes as they develop into their functional forms. While genetics and biochemical signals are well recognized regulators of morphogenesis, mechanical forces and the physical properties of tissues are now emerging as integral parts of this process as well. These physical factors drive coordinated cell movements and reorganizations, shape and size changes, proliferation and differentiation, as well as gene expression changes, and ultimately sculpt any developing structure by guiding correct cellular architectures and compositions. In this review we focus on several craniofacial structures, including the tooth, the mandible, the palate, and the cranium. We discuss the spatiotemporal regulation of different mechanical cues at both the cellular and tissue scales during craniofacial development and examine how tissue mechanics control various aspects of cell biology and signaling to shape a developing craniofacial organ.


Subject(s)
Cell Differentiation , Morphogenesis , Signal Transduction , Skull , Tooth
8.
Article in Chinese | WPRIM | ID: wpr-880827

ABSTRACT

OBJECTIVE@#To investigate the role of NDUFA13 inactivation in the pathogenesis of spontaneous hepatitis in mice and explore the possible mechanisms.@*METHODS@#Hepatocyte-specific NDUFA13 knockout (NDUFA13@*RESULTS@#Liver-specific NDUFA13 heterozygous knockout mice were successfully constructed as verified by PCR results. HE staining revealed severe liver damage in both 4- week-old and 2-year-old NDUFA13@*CONCLUSIONS@#Hepatocytes-specific NDUFA13 ablation can trigger spontaneous hepatitis in mice possibly mediated by the activation of ROS/NF-κB/NLRP3 signaling.


Subject(s)
Animals , Hepatitis , Inflammasomes , Mice , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Signal Transduction
9.
Article in Chinese | WPRIM | ID: wpr-880182

ABSTRACT

Acute intestinal graft-versus-host disease is a refractory disease which can affect implantation and become a threat to life in severe cases. Autophagy is an intracellular degradation pathway necessary for maintaining cellular energy homeostasis. In recent years, a large number of studies have found that it is closely related to the pathogenesis and process of acute intestinal graft-versus-host disease. The main mechanisms may involve that inflammatory factor storm after pretreatment and infusion of donor cells induces disordered intestinal immune tolerance, and abnormal oxidative stress damages intestinal mucosal barrier, leading to intestinal rejection of acute graft-versus-host disease via mTOR signal pathway of autophagy, disordered mitophagy and other related pathways.


Subject(s)
Autophagy , Graft vs Host Disease , Humans , Immune Tolerance , Oxidative Stress , Signal Transduction
10.
Article in Chinese | WPRIM | ID: wpr-880114

ABSTRACT

OBJECTIVE@#To investigate the damaging of human umbilical vein endothelial cells (HUVEC) induced by antiplatelet integrin β3 antibodies in vitro.@*METHODS@#The serum from 36 chronic ITP patients were collected, flow cytometry and monoclonal antibody specific immobilization of platelet antigen (MAIPA) assay were used to collect antiplatelet integrin β3 antibodies from the serum of the patients. After HUVEC were treated by ITP patient serum (PS) containing anti-integrin β3 antibodies, the cell damage was detected by Lactate dehydrogenase (LDH) assay, cell apoptosis was detected by flow cytometry, the expression of apoptosis-related gene Bax was detected by Reverse transcription-Quantitative real-time PCR (RT-qPCR), and expression of Apoptosis-related signaling pathway protein Akt and related protein Bax were detected by Western blot. HUVEC were treated by PS combined with Akt activator SC79, the cells damage were detected by LDH assay, apoptosis of the cells were detected by flow cytometry, the expression of apoptosis-related gene Bax was detected by RT-qPCR.@*RESULTS@#Among 36 cases of serum from the chronic ITP patients, 5 patients' serum containing anti-integrin β3 antibodies were collected. After HUVEC was treated by PS, the viability of LDH was significant increased(P<0.05), so as for the apoptosis of the cells(P<0.05), the expression of gene and protein of Bax was increased up-regulated(P<0.05), the protein expression of pAkt was down-regulated(P<0.05). Comparing with HUVEC cultured with PS alone, the viability of LDH of HUVEC treated by PS combined with SC79 was significantly reduced(P<0.05), so as for the apoptosis of the cells(P<0.05), and gene expression of Bax was significantly decreased(P<0.05).@*CONCLUSION@#Anti-integrin β3 serum can cause the damage and apoptosis of HUVEC through Akt signaling pathway,the apoptotic effects of anti-integrin β3 antibodies to HUVEC was effectively reversed by SC79.


Subject(s)
Apoptosis , Cells, Cultured , Human Umbilical Vein Endothelial Cells , Humans , Integrin beta3 , Signal Transduction
11.
Article in Chinese | WPRIM | ID: wpr-880102

ABSTRACT

OBJECTIVE@#To investigate the effect of long non-coding RNA-TUC338 on the proliferation and migration of lymphoma cells.@*METHODS@#The expression of TUC338 in different lymphoma cells was detected by fluorescence quantitative PCR, cell proliferation by sulforhodamine B (SRB) assay, migration of lymphoma cells by transwell assay, and protein expression in PI3K/AKT signaling pathway by Western blot.@*RESULTS@#The expression levels of TUC338 in lymphoma cells Daudi, U937, BC-3, and Raji significantly increased in comparison with human normal T lymphocytes H9 (t=13.277, 10.103, 16.200, and 26.687, P=0.002, 0.005, 0.001, and 0.000). Compared with NC-siRNA group, the number of cells crossing the chamber of TUC338-siRNA group was significantly reduced (t=30.508, P=0.000), the protein expression levels of p-PI3K and p-AKT significantly decreased (t=16.872 and 18.371, P=0.000 and 0.000), and OD@*CONCLUSION@#The expression of TUC338 significantly increases in lymphoma cells, and silence of TUC338 effectively inhibits the activation of PI3K/AKT signaling pathway, thereby inhibiting the proliferation and migration of lymphoma cells, which has a potential application value in diagnosis and treatment of lymphoma.


Subject(s)
Cell Line, Tumor , Cell Movement , Cell Proliferation , Humans , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/genetics , Signal Transduction
12.
Article in Chinese | WPRIM | ID: wpr-880073

ABSTRACT

In recent years, it is found that the classical IKKα and IKKβ pathway were closely relates with hematological tumors, except the classical pathogenesis, moreover the classical IKKβ pathway is deeply studied. The studies indicated that the IKKβis activated to phosphorylate the NF-κB through multiple cascades under the effect of extracellular IL-6, TNF-α and other stimulating factors. At the cellular level, the classical IKKβcan promote the tumor cell survival and proliferation, reduce the cell apoptosis, and promote the angiogenesis and cell transfer. Although the classical IKKα plays a role in regulating IKKβ activity, but its role in non-classical pathway is more prominent. This review briefly summarizes the latest advance of researches on the pathogenesis of hematological malignancies in term of IKKα and IKKβpathway, so as to provide the theoretic basis for deeply understanding and studying the pathogenesis of hematologic tumors. At present, blocking the classical IKKα and IKKβ pathway has become a new target for treatment of hematological tumors, moreover, some specific inhibitor for IKKα and IKKβpathway have been developed, for example, LY2409881, BMS 345541 and so on. Most of these drugs are in clinical trials and display some good anti-tumor effects.


Subject(s)
Cell Survival , Hematologic Neoplasms , Humans , I-kappa B Kinase/metabolism , NF-kappa B/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha
13.
Article in English | WPRIM | ID: wpr-879959

ABSTRACT

: To assess the () recombinant gingivalis gingipain R2 (rRgpB)-induced Ca mobilization in human gingival fibroblast (HGF) mediated by protease-activated receptor (PAR) and its downstream signal transduction pathways. : Flow cytometry was used to detect the expression of PAR in HGF. The proliferation of HGF was measured by CCK-8. The dynamic changes of intracellular Ca concentration in HGF induced by rRgpB and the blocking effect of PAR-1 antagonist were observed by laser confocal microscopy. Western blot was performed to determine the phosphorylation levels of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) 1/2, p38 mitogen-activated protein kinase (p38 MAPK) and p65 in HGF. : PAR-1 and PAR-3 were expressed in HGF, and the rRgpB could promote the proliferation of HGF. rRgpB caused a transient increase in [Ca], which could be completely suppressed by vorapaxar, a PAR-1 antagonist. The phosphorylation levels of JNK, ERK1/2 and p65 were significantly up-regulated after the induction of rRgpB for and (all <0.05), which was completely inhibited by vorapaxar. However, the phosphorylation level of p38 MAPK had no significant change after rRgpB stimulation. : rRgpB causes an increase in [Ca] in HGF mediated by PAR-1. JNK, ERK1/2 and nuclear factor-κB may be involved in intracellular signal transduction after PAR-1 activation.


Subject(s)
Fibroblasts , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , MAP Kinase Signaling System , Phosphorylation , Signal Transduction , p38 Mitogen-Activated Protein Kinases/metabolism
14.
Article in English | WPRIM | ID: wpr-879958

ABSTRACT

The primary cilium, a sensory organelle that protrudes from the surface of most eukaryotic cells, receives and transduces various critical signals that are essential for normal development and homeostasis. Structural or functional disruption of primary cilia causes a number of human diseases, including cancer. Primary cilia has cross talks with cell cycle and it may act as a cell cycle checkpoint to suppress cancer development. Moreover, primary cilia has cross-regulation with autophagy, which may affect tumor progression. We then discuss the association of the primary cilia with several oncogenic signaling pathways, including Shh, Wnt, Notch and platelet-derived growth factor receptor (PDGFR). Since these signaling pathways are often over-activated in many types of human cancers, primary cilia are likely to play a role in the tumorigenesis by modulating these pathways. Finally, we summarize current progress on the role of cilia during tumorigenesis and the challenges that the cilia-cancer field faces.


Subject(s)
Autophagy , Carcinogenesis , Cilia , Homeostasis , Humans , Signal Transduction
15.
Article in English | WPRIM | ID: wpr-879949

ABSTRACT

The gene is frequently mutated and abnormally activated in many cancers,and plays an important role in cancer development. Metabolic reprogramming occurs in malignant tumors,which can be one of the key targets for anti-tumor therapy. gene can regulate lipid metabolism through AKT-mTORC1 single axis or multiple pathways,such as lipid synthesis pathways and degradation pathways. Similarly,lipid metabolism can also modify and activate RAS protein and its downstream signaling pathways. This article overviews the current research progress on the interaction between lipid metabolism and ,to provide insight in therapeutic strategies of lipid metabolism for -driven tumors.


Subject(s)
Genes, ras , Humans , Lipid Metabolism/genetics , Neoplasms/genetics , Signal Transduction , ras Proteins/metabolism
16.
Article in Chinese | WPRIM | ID: wpr-879849

ABSTRACT

OBJECTIVE@#To study the role and mechanism of histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2) in mouse neuronal development.@*METHODS@#The mice with Synapsin1-Cre recombinase were bred with @*RESULTS@#The mice with @*CONCLUSIONS@#Deletion of


Subject(s)
Animals , Blotting, Western , Histone Deacetylase 1/genetics , Histone Deacetylase 2 , Histone Deacetylases/genetics , Immunohistochemistry , Mice , Neurons/metabolism , Signal Transduction
17.
Mem. Inst. Oswaldo Cruz ; 116: e200326, 2021. tab, graf
Article in English | LILACS | ID: biblio-1250363

ABSTRACT

BACKGROUND Schistosomiasis is a disease caused by Schistosoma. Due to its complex life cycle, evolutionary position and sexual dimorphism, schistosomes have several mechanisms of gene regulation. MicroRNAs (miRNAs) are short endogenous RNAs that regulate gene expression at the post-transcriptional level by targeting mRNA transcripts. OBJECTIVES Here, we tested 12 miRNAs and identified their putative targets using a computational approach. METHODS We performed the expression profiles of a set of miRNAs and their putative targets during the parasite's life cycle by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). FINDINGS Our results showed differential expression patterns of the mature miRNAs sma-miR-250; sma-miR-92a; sma-miR-new_4-3p; sma-miR-new_4-5p; sma-miR-new_5-5p; sma-miR-new_12-5p; sma-miR-new_13-3p and sma-miR-new_13-5p. Interestingly, many of the putative target genes are linked to oxidative phosphorylation and are up-regulated in adult-worms, which led us to suggest that miRNAs might play important roles in the post-transcriptional regulation of genes related to energetic metabolism inversion during parasite development. It is noteworthy that the expression of sma-miR-new_13-3p exhibited a negative correlation on SmNADH:ubiquinone oxidoreductase complex I. MAIN CONCLUSIONS Our analysis revealed putative miRNA genes related to important biological processes, such as transforming growth factor beta (TGF-β) signaling, proteasome regulation, glucose and lipid metabolism, immune system evasion and transcriptional regulation.


Subject(s)
Animals , MicroRNAs/genetics , Schistosoma mansoni/genetics , Signal Transduction , Gene Expression Regulation/genetics , Gene Expression Profiling , Life Cycle Stages/genetics
18.
Braz. j. med. biol. res ; 54(5): e10637, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153548

ABSTRACT

Transcription factors control, coordinate, and separate the functions of distinct network modules spatially and temporally. In this review, we focus on the transcription factor 21 (TCF21) network, a highly conserved basic-helix-loop-helix (bHLH) protein that functions to integrate signals and modulate gene expression. We summarize the molecular and biological properties of TCF21 control with an emphasis on molecular and functional TCF21 interactions. We suggest that these interactions serve to modulate the development of different organs at the transcriptional level to maintain growth homeostasis and to influence cell fate. Importantly, TCF21 expression is epigenetically inactivated in different types of human cancers. The epigenetic modification or activation and/or loss of TCF21 expression results in an imbalance in TCF21 signaling, which may lead to tumor initiation and, most likely, to progression and tumor metastasis. This review focuses on research on the roles of TCF21 in development and tumorigenesis systematically considering the physiological and pathological function of TCF21. In addition, we focus on the main molecular bases of its different roles whose importance should be clarified in future research. For this review, PubMed databases and keywords such as TCF21, POD-1, capsulin, tumors, carcinomas, tumorigenesis, development, and mechanism of action were utilized. Articles were selected within a historical context as were a number of citations from journals with relevant impact.


Subject(s)
Humans , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Carcinogenesis/genetics , Signal Transduction , Cell Differentiation , Cell Transformation, Neoplastic/genetics
19.
Clinics ; 76: e2484, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153996

ABSTRACT

OBJECTIVES: To investigate the role of miR-139-5p and the TLR4/MyD88/NF-κB signaling pathway in acute lung injury in septic mice. METHOD: A total of 140 healthy male SPF C57BL/6 mice were divided into seven groups, i.e., Normal, Control, NC, miR-139-5p mimic, miR-139-5p inhibitor, TAK-242, and miR-139-5p inhibitor+TAK-242 groups. The levels of miR-139-5p, proteins related to the TLR4/MyD88/NF-κB signaling pathway (TLR4, MyD88, and p-NF-κB p50), and MPO, SOD, GSH, and MDA in lung tissue were measured. The lung tissue wet-to-dry mass ratio (W/D), arterial oxygen partial pressure (PaO2), and carbon dioxide partial pressure (PaCO2) were measured. RESULTS: A web-based bioinformatic tool predicted that MyD88 was a target of miR-139-5p, which was verified by a dual luciferase reporter assay. Compared with those in the Normal group, the levels of miR-139-5p, PaO2, SOD, and GSH were significantly lower, while those of TLR4, MyD88, p-NF-κB p50, W/D, PaCO2, IL-1β, TNF-α, IL-6, MPO, and MDA were higher in all other groups. Moreover, compared with their levels in the Control group, these indicators exhibited contrasting results in the miR-139-5p mimic and TAK-242 groups, but were similar in the miR-139-5p inhibitor group. In the miR-139-5p inhibitor+TAK-242 group, acute lung injury, aggravated by miR-139-5p inhibitor, was partially rescued by TAK-242. CONCLUSION: miR-139-5p inhibits the TLR4/MyD88/NF-κB signaling pathway to alleviate acute lung injury in septic mice.


Subject(s)
Animals , Male , Rats , Sepsis/genetics , MicroRNAs/genetics , Acute Lung Injury/genetics , Signal Transduction , NF-kappa B/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Mice, Inbred C57BL
20.
Clinics ; 76: e2348, 2021. graf
Article in English | LILACS | ID: biblio-1153978

ABSTRACT

OBJECTIVES: TTP488, an antagonist of the receptor for advanced glycation end-products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer's disease (AD). However, the mechanism underlying the protective action of TTP488 against AD has not yet been fully explored. METHODS: Healthy male rats were exposed to aberrant amyloid β (Aβ) 1-42. Lipopolysaccharide (LPS) and the NOD-like receptor family pyrin domain containing 1 (NLRP1) overexpression lentivirus were injected to activate the NLRP1 inflammasome and exacerbate AD. TTP488 was administered to reverse AD injury. Finally, tofacitinib and fludarabine were used to inhibit the activity of Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) to prove the relationship between the JAK/STAT signaling pathway and TTP488. RESULTS: LPS and NLRP1 overexpression significantly increased the NLRP1 levels, reduced neurological function, and aggravated neuronal damage, as demonstrated by the impact latency time of, time spent by, and length of the platform covered by, the mice in the Morris water maze assay, Nissl staining, and immunofluorescence staining in rats with AD. CONCLUSIONS: TTP488 administration successfully reduced AD injury and reversed the aforementioned processes. Additionally, tofacitinib and fludarabine administration could further reverse AD injury after the TTP488 intervention. These results suggest a new potential mechanism underlying the TTP488-mediated alleviation of AD injury.


Subject(s)
Animals , Male , Mice , Rats , Janus Kinases/metabolism , Alzheimer Disease/drug therapy , Tyrosine , Transducers , Signal Transduction , Amyloid beta-Peptides , Janus Kinase 2 , Receptor for Advanced Glycation End Products , Imidazoles
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