Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 4.123
Filter
1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
J. appl. oral sci ; 29: e20210209, 2021. graf
Article in English | LILACS | ID: biblio-1340103

ABSTRACT

Abstract Objective Oral squamous cell carcinoma (OSCC) is one of the common type of cancer that leads to death; and is becoming a global concern. Due to the lack of efficient chemotherapeutic agents for patients with oral cancer, the prognosis remains poor. 6-shogaol, a bioactive compound of ginger, has a broad spectrum of bioactivities and has been widely used to relieve many diseases. However, its effects on human oral cancer have not yet been fully evaluated. In our study, we investigated the anticancer effects of 6-shogaol on the proliferation, migration, invasion, apoptosis, and underlying mechanisms within human OSCC cell lines. Methodology We investigated the effect of 6-shogaol on the growth of OSCC cells by cell viability and soft agar colony formation assay. Migration and invasion assays were conducted to confirm the effect 6-shogaol on OSCC cell metastasis. Apoptosis was detected by flow cytometry and the underlying mechanism on the antigrowth effect of 6-shogaol in OSCC cells was assessed using western blotting. Results In our results, 6-shogaol not only suppressed proliferation and anchorage-independent cell growth in OSCC cells, but also induced apoptosis by regulating the apoptosis-associated factors such as p53, Bax, Bcl-2, and cleaved caspase-3. Migration and invasion of OSCC cells were inhibited following the regulation of E-cadherin and N-cadherin by 6-shogaol. Additionally, 6-shogaol treatment significantly inhibited the PI3K/AKT signaling pathway. Conclusion Therefore, our results may provide critical evidence that 6-shogaol can be a potential new therapeutic candidate for oral cancer.


Subject(s)
Humans , Mouth Neoplasms/metabolism , Catechols/pharmacology , Squamous Cell Carcinoma of Head and Neck/metabolism , Signal Transduction , Cell Movement , Apoptosis , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Cell Proliferation , Proto-Oncogene Proteins c-akt/metabolism
8.
Braz. j. med. biol. res ; 54(9): e10390, 2021. graf
Article in English | LILACS | ID: biblio-1249337

ABSTRACT

Sorafenib (SOR) resistance is still a significant challenge for the effective treatment of hepatocellular carcinoma (HCC). The mechanism of sorafenib resistance remains unclear. Several microRNAs (miRNAs) have been identified as playing a role in impairing the sensitivity of tumor cells to treatment. We examined the mechanism behind the role of miR-92b in mediating sorafenib resistance in HCC cells. We detected that miR-92b expression was significantly upregulated in SOR-resistant HepG2/SOR cells compared to parental HepG2/WT cells. After transfection with miR-92b inhibitor, the proliferation of HepG2/SOR cells was remarkably weakened and rates of apoptosis significantly increased. PTEN was considered to be a functional target of miR-92b according to a luciferase reporter assay. Knockdown of PTEN significantly impaired the ability of miR-92b inhibitor on increasing sorafenib sensitivity of HepG2/SOR cells. Furthermore, we confirmed by western blotting and immunofluorescence that miR-92b can mediate sorafenib resistance by activating the PI3K/AKT/mTOR pathway in HCC cells by directly targeting PTEN. These findings further validate the mechanism of miR-92b in SOR resistance in HCC treatment.


Subject(s)
Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/drug therapy , Drug Resistance, Neoplasm , MicroRNAs/genetics , Sorafenib/pharmacology , Liver Neoplasms/genetics , Liver Neoplasms/drug therapy , Signal Transduction , Gene Expression Regulation, Neoplastic , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Cell Proliferation , PTEN Phosphohydrolase/genetics , TOR Serine-Threonine Kinases
9.
Braz. j. med. biol. res ; 54(8): e11184, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285676

ABSTRACT

Hypertrophic scar (HS) formation is a common complication that develops after skin injury; however, there are few effective and specific therapeutic approaches for HS. Emodin has previously been reported to inhibit mechanical stress-induced HS inflammation. Here, we investigated the molecular mechanisms underlying the inhibitory effects of emodin on HS formation. First, we conducted in vitro assays that revealed that emodin inhibited M1 and M2 polarization in rat macrophages. We subsequently established a combined rat model of tail HS and dorsal subcutaneous polyvinyl alcohol (PVA) sponge-induced wounds. Rats were treated with emodin or vehicle (DMEM). Tail scar specimens were harvested at 14, 28, and 42 days post-incision and subjected to H&E staining and Masson's trichrome staining. Histopathological analyses confirmed that emodin attenuated HS formation and fibrosis. Macrophages were separated from wound cells collected from the PVA sponge at 3 and 7 days after implantation. Flow cytometry analysis demonstrated that emodin suppressed in vivo macrophage recruitment and polarization at the wound site. Finally, we explored the molecular mechanisms of emodin in modulating macrophage polarization by evaluating the expression levels of selected effectors of the Notch and TGF-β pathways in macrophages isolated from PVA sponges. Western blot and qPCR assays showed that Notch1, Notch4, Hes1, TGF-β, and Smad3 were downregulated in response to emodin treatment. Taken together, our findings suggested that emodin attenuated HS formation and fibrosis by suppressing macrophage polarization, which is associated with the inhibition of the Notch and TGF-β pathways in macrophages.


Subject(s)
Animals , Rats , Emodin/pharmacology , Cicatrix, Hypertrophic/pathology , Cicatrix, Hypertrophic/drug therapy , Signal Transduction , Transforming Growth Factor beta , Macrophages
10.
Braz. j. med. biol. res ; 54(7): e10236, 2021. graf
Article in English | LILACS | ID: biblio-1249317

ABSTRACT

This work aimed to research the function of MARVEL domain-containing protein 1 (MARVELD1) in glioma as well as its functioning mode. Bioinformatics analysis was utilized to assess the MARVELD1 expression in glioma tissues and its relationship with grade and prognosis, based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) databases. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays were carried out to determine the impact of MARVELD1 on malignant biological behavior of glioma, such as proliferation, invasion, and migration. qRT-PCR was carried out to test the mRNA level of MARVELD1. Western blot assay was performed to measure the protein expression of MARVELD1 and JAK/STAT pathway-related proteins. MARVELD1 was expressed at high levels in glioma tissues and cell lines. Kaplan-Meier survival analysis revealed that the higher MARVELD1 expression, the shorter the survival time of patients with glioma. Also, the MARVELD1 expression in WHO IV was significantly enhanced compared to that in WHO II and WHO III. Furthermore, the functional analysis of MARVELD1 in vitro revealed that knockdown of MARVELD1 in U251 cells restrained cell proliferation, migration, and invasion, while up-regulation of MARVELD1 in U87 cells presented opposite outcomes. Finally, we found that JAK/STAT signaling pathway mediated the function of MARVELD1 in glioma. MARVELD1 contributed to promoting the malignant progression of glioma, which is the key driver of activation of JAK/STAT signaling pathway in gliomas.


Subject(s)
Humans , Animals , Rats , Brain Neoplasms , Glioma , Phenotype , Signal Transduction , Gene Expression Regulation, Neoplastic , Up-Regulation , Cell Movement , Cell Line, Tumor , Cell Proliferation , MARVEL Domain-Containing Proteins , Membrane Proteins , Mice, Nude , Microtubule-Associated Proteins
11.
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
12.
Braz. j. med. biol. res ; 54(3): e10023, 2021. graf
Article in English | LILACS | ID: biblio-1153521

ABSTRACT

The objective of this study was to investigate the inhibitory effect of miR-135a in regulating JAK/STAT signaling pathway on airway inflammation in asthmatic mice. An asthma model was established by sensitization and stimulation with ovalbumin (OVA), and the corresponding drug intervention was given from the day of stimulation by means of nasal drops. Airway hyperresponsiveness was tested. The content of miR-135a in the lung tissue of mice was detected by RT-PCR. The pathological changes of lung tissue were evaluated by HE staining. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-5, and eotaxin in bronchoalveolar lavage fluid (BALF) and lung tissue were detected by ELISA and immunohistochemistry, respectively. The expression of JAK/STAT signaling pathway-related protein in lung tissue was detected by western blot. To further validate the effect of miR-135a overexpression on the JAK/STAT signaling pathway, pathway activators and inhibitors were added. Compared with the OVA group, the airway hyperresponsiveness of the mice was significantly decreased after treatment with the miR-135a agonist. The expression of miR-135a was significantly increased in the lung tissue and the pathological changes of the lung tissue were alleviated. The contents of TNF-α, IL-6, IL-5, and eotaxin in BALF and lung tissues were decreased. The expression of JAK/STAT signaling pathway-related proteins p-JAK3/JAK3, p-STAT1/STAT1, and p-STAT3/STAT3 were significantly reduced in lung tissue (P<0.05). Addition of JAK inhibitor AG490 reduced airway inflammation in asthmatic mice. miR-135a agonists inhibit airway inflammation in asthmatic mice by regulating the JAK/STAT signaling pathway.


Subject(s)
Animals , Rats , Asthma/drug therapy , Bronchoalveolar Lavage Fluid , Signal Transduction , Ovalbumin , MicroRNAs , Disease Models, Animal , Lung , Mice, Inbred BALB C
13.
Braz. j. med. biol. res ; 54(3): e9206, 2021. graf
Article in English | LILACS | ID: biblio-1153519

ABSTRACT

Renal fibrosis is one of the most significant pathological changes after ureteral obstruction. Transforming growth factor-β (TGF-β) signaling pathway plays essential roles in kidney fibrosis regulation. The aims of the present study were to investigate effects of microRNA-302b (miR-302b) on renal fibrosis, and interaction between miR-302b and TGF-β signaling pathway in murine unilateral ureteral obstruction (UUO) model. Microarray dataset GSE42716 was downloaded by retrieving Gene Expression Omnibus database. In accordance with bioinformatics analysis results, miR-302b was significantly down-regulated in UUO mouse kidney tissue and TGF-β1-treated HK-2 cells. Masson's trichrome staining showed that miR-302b mimics decreased renal fibrosis induced by UUO. The increased mRNA expression of collagen I and α-smooth muscle actin (α-SMA) and decreased expression of E-cadherin were reversed by miR-302b mimics. In addition, miR-302b up-regulation also inhibited TGF-β1-induced epithelial mesenchymal transition (EMT) of HK-2 cells by restoring E-cadherin expression and decreasing α-SMA expression. miR-302b mimics suppressed both luciferase activity and protein expression of TGF-βR2. However, miR-302b inhibitor increased TGF-βR2 luciferase activity and protein expression. Meanwhile, miR-302b mimics inhibited TGF-βR2 mRNA expression and decreased Smad2 and Smad3 phosphorylation in vivo and in vitro. Furthermore, over-expression of TGF-βR2 restored the miR-302b-induced decrease of collagen I and α-SMA expression. In conclusion, this study demonstrated that miR-302b attenuated renal fibrosis by targeting TGF-βR2 to suppress TGF-β/Smad signaling activation. Our findings showed that elevating renal miR-302b levels may be a novel therapeutic strategy for preventing renal fibrosis.


Subject(s)
Humans , Animals , Rats , Ureteral Obstruction/pathology , Signal Transduction , Transforming Growth Factor beta/metabolism , MicroRNAs/genetics , Smad Proteins , Kidney Diseases/genetics , Fibrosis , Cell Line , Epithelial-Mesenchymal Transition , Kidney/pathology , Kidney Diseases/pathology
14.
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
15.
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
16.
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
17.
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
18.
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
19.
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
20.
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
SELECTION OF CITATIONS
SEARCH DETAIL