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1.
Cell Death Dis ; 11(10): 833, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028811

RESUMO

A number of circular RNAs (circRNAs) have been implicated in rheumatoid arthritis (RA) pathogenesis; however, little is known about their function and hidden molecular mechanism in immune and inflammation regulation. We investigated the role and the underlying mechanism of circRNA_09505 in RA in this study. Real-time PCR and fluorescence in situ hybridization (FISH) are adopted to estimate the quantitative expression and localization of circRNA_09505 in macrophages. The altering effect of circRNA_09505 on inflammation is investigated in vitro and in vivo by use of macrophage cell models and collagen-induced arthritis (CIA) mice. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) are used to confirm the circRNA_09505/miR-6089 ceRNA network predicted by bioinformatics analysis. Compared with controls, the expression of circRNA_09505 is upregulated in peripheral blood mononuclear cells (PBMCs) from patients with RA. The proliferation and cell cycle are significantly promoted when circRNA_09505 is upregulated in macrophages, whereas knockdown of circRNA_09505 inhibits macrophage proliferation and cell- cycle progression. Besides, circRNA_09505 can act as a miRNA sponge for miR-6089 in macrophages, and promote the production of TNF-α, IL-6, and IL-12 through ceRNA mechanism. Moreover, AKT1 is a direct target of miR-6089. CircRNA_09505 can promote AKT1 expression by acting as a miR-6089 sponge via IκBα/NF-κB signaling pathway in macrophages. Most interestingly, knockdown of circRNA_09505 significantly alleviates arthritis and inflammation in vivo in CIA mice. These data support the hypothesis that circRNA_09505 can function as a miR-6089 sponge and regulate inflammation via miR-6089/AKT1/NF-κB axis in CIA mice.

2.
J Phys Condens Matter ; 32(40): 405402, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32619208

RESUMO

Current understanding of the origin of icosahedral clusters or icosahedral short-range ordering in undercooled metallic liquids or glasses is based on Frank's consideration of an isolated icosahedron whose core has lower potential energy than the shell. Using large scale atomistic simulations and statistical analysis of several bcc (body-centered-cubic) and fcc (face-centered-cubic) metals, here we show that the shells of icosahedrons spontaneously formed inside deeply undercooled metallic liquids or glasses in fact have lower (averaged) potential energy than the cores. The shell potential energy deficiency occurs only to the icosahedral clusters but not to the equilibrium-crystal clusters, and, for icosahedral clusters, this deficiency grows with decreasing temperature. Compared with fcc metals, bcc metals exhibit greater potential energy deficiency on the icosahedral shells and produce significantly more icosahedral clusters upon liquid quenching, which explains the higher tendency of bcc metals to be vitrified observed in ultrafast cooling experiments. Inspecting the potential energy deficiency on the icosahedral shells through computation provides a new avenue to the search for amorphous metals (i.e. metallic glasses) with high glass forming ability and processability.

3.
Cancer Lett ; 488: 18-26, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32473243

RESUMO

MicroRNAs (miRNAs) are gene modulators essential for biological processes. However, the precise functions of miRNAs in growth and development of colon cancer are still elusive. To clarify their role, here we analyzed a miRNA microarray of colon cancer. MiR-182-5p was found markedly downregulated in colon cancer tissues and cells, and strongly correlated with pathological stage, differentiation, and lymphatic metastasis. In vitro, miR-182-5p overexpression repressed colon cancer cell proliferation, colony formation, migration, and invasion, and triggered G1 arrest and apoptosis. MiR-182-5p overexpression also downregulated vascular endothelial growth factor (VEGF)-C and inhibited the activity of a luciferase reporter containing the VEGF-C 3'-untranslated region. Moreover, miR-182-5p overexpression in colon cancer cells and human umbilical vein endothelial cells (HUVECs) downregulated VEGF-A as well as VEGF receptor (VEGFR)-2 and VEGFR-3, thereby inhibiting the phosphorylation of ERK and AKT. In vivo, miR-182-5p overexpression strikingly suppressed oncogenicity of SW620 cells as well as angiogenesis and lymphangiogenesis of xenograft tumors in nude mice. These data indicate that miR-182-5p regulates colon cancer tumorigenesis partially through modulating angiogenesis and lymphangiogenesis by targeting VEGF-C, and inhibiting ERK and AKT signaling pathways.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32424859

RESUMO

The chemical structures and topologies of the crosslinks in supramolecular networks play a crucial role in their properties and functions. Herein, the preparation of a type of poly(N-isopropylacrylamide) (PNIPAAM)-based supramolecular networks crosslinked by emissive hexagonal metallacycles is presented. The topological connections in these networks greatly affect their properties, as evidenced by their differences in absorption, emission, lower critical solution temperature, and modulus along with the variation of crosslinking densities. The integration of PNIPAAM and metallacycles in the networks benefits them improved bioavailability, making them serve as reagents for bacterial imaging and killing. This study provides a strategy to prepare cavity-crosslinked polymer networks for antibacterial applications.

5.
Mediators Inflamm ; 2019: 8128501, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827380

RESUMO

Accumulated studies have implicated microRNAs (miRNAs) exert modifying effects on colorectal cancer (CRC). Protein tyrosine phosphatase, receptor type O (PTPRO) has been identified as a tumor suppressor in several kinds of cancer, including CRC. Previously, we have found that exosome-encapsulated miR-6803-5p is increased in CRC. However, the mechanism of miR-6803-5p in CRC is not clear yet. This study is aimed at elucidating the effect of miR-6803-5p in colorectal carcinogenesis. Expression of miR-6803-5p and PTPRO mRNA in peripheral blood mononuclear cells of CRC patients is estimated by real-time PCR. PTPRO protein in CRC cells is detected by western blot. To verify the association of miR-6803-5p with PTPRO, luciferase reporter assay is performed. CCK-8 and EdU assays are conducted to assess cell proliferation. Real-time PCR and ELISA are applied to detect cytokine expression in CRC cells. Cell invasion and migration assays are evaluated by transwell and scratch tests. Immunofluorescence is carried out to determine the activation of NF-κB in HCT116 cells. Negative correlation is demonstrated between miR-6803-5p and PTPRO in CRC. PTPRO is demonstrated to be a direct target of miR-6803-5p. miR-6803-5p can promote cancer cell proliferation and invasion and enhance inflammation through PTPRO/NF-κB axis in CRC, which serves as a useful target for CRC.

6.
Mediators Inflamm ; 2019: 3120391, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772500

RESUMO

Methyltransferase-like 3 (METTL3), an RNA N6-methyladenosine (m6A) methyltransferase, is essential for the m6A mRNA modification. As a key enzyme of m6A methylation modification, METTL3 has been implicated in immune and inflammation regulation. However, little is known of the role and underlying mechanism of METTL3 in rheumatoid arthritis (RA). The aim of the present study is to elucidate the function and potential mechanism of METTL3 in RA pathogenesis. We used quantitative real-time polymerase chain reaction to detect the expression of METTL3 in RA patients and controls as well as the macrophage cell line. CCK-8 was used for cell proliferation assay. Enzyme-linked immunosorbent assay (ELISA) was adopted to estimate the generation of IL-6 and TNF-α in macrophages. Western blot and immunofluorescence were applied to evaluate the activation of NF-κB in macrophages. The expression of METTL3 was significantly elevated in patients with RA. It was positively associated with CRP and ESR, two common markers for RA disease activity. Besides, LPS could enhance the expression and biological activity of METTL3 in macrophages, while overexpression of METTL3 significantly attenuated the inflammatory response induced by LPS in macrophages. Moreover, the effect of METTL3 on LPS-induced inflammation in macrophages was dependent on NF-κB. This study firstly demonstrates the critical role of METTL3 in RA, which provides novel insights into recognizing the pathogenesis of RA and a promising biomarker for RA.


Assuntos
Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metiltransferases/metabolismo , NF-kappa B/metabolismo , Idoso , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Metiltransferases/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Células THP-1
7.
Front Immunol ; 10: 2218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620132

RESUMO

Accumulating studies have suggested that long non-coding RNAs (lncRNAs) have drawn more and more attention in rheumatoid arthritis (RA), which can function as competitive endogenous RNAs (ceRNAs) in inflammation and immune disorders. Previously, we have found that lncRNA HIX003209 is differentially expressed in RA. However, the precise mechanism of lncRNA HIX003209 in RA is still vague. We aim to elucidate the role and its targeted microRNA of lncRNA HIX003209 in RA as ceRNA. Significantly increased expression of lncRNA HIX003209 was observed in the peripheral blood mononuclear cells (PBMCs) from RA cases. It was positively associated with TLR2 and TLR4 in RA. Besides, peptidoglycan (PGN) and lipopolysaccharide (LPS) could enhance the expression of lncRNA HIX003209, which reversely promoted the proliferation and activation of macrophages through IκBα/NF-κB signaling pathway. Moreover, HIX003209 was involved in TLR4-mediated inflammation via targeting miR-6089 in macrophages. LncRNA HIX003209 functions as a ceRNA and exaggerates inflammation by sponging miR-6089 through TLR4/NF-κB pathway in macrophages, which offers promising therapeutic strategies for RA.

8.
J Cell Physiol ; 234(7): 11149-11155, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30443949

RESUMO

Preeclampsia is a serious complication of pregnancy and leads to maternal hypertension and proteinuria. It remains a major health problem for mothers and babies across the world due to high maternal and fetal morbidity and mortality. Accumulated data have implicated the critical role of microRNA in preeclampsia. However, to date, the role of miR-548c-5p in preeclampsia remains vaguely understood. In this study, we first elucidate the role of miR-548c-5p and its underlying molecular mechanism in preeclampsia. Compared with healthy controls, miR-548c-5p was obviously downregulated in serum exosomes and placental mononuclear cells in patients with preeclampsia. Nonetheless, PTPRO was significantly upregulated and negatively associated with miR-548c-5p in placental mononuclear cells in patients with preeclampsia. PTPRO was a target of miR-548c-5p. PTPRO was downregulated in the miR-548c-5p-overexpressed macrophages. In addition, miR-548c-5p could inhibit the proliferation and activation of LPS-stimulated macrophages, as evidenced by decreased levels of inflammatory cytokines (IL-12 and TNF-α) and less nuclear translocation of pNF-κB in pTHP1 cells. MiR-548c-5p acts as an anti-inflammatory factor in preeclampsia. The axis of miR-548c-5p/PTPRO/NF-κB may provide novel targets for the diagnosis and treatment of preeclampsia.

9.
J Cell Physiol ; 234(2): 1502-1511, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30132861

RESUMO

Exosome-encapsulated microRNAs (miRNAs) have been identified as potential biomarkers in autoimmune diseases. However, little is known about the role of exosome-delivered miRNAs in rheumatoid arthritis (RA). In this study, we investigated the profile of specific exosomal miRNAs by microarray analysis of serum exosomes from three patients with RA and three healthy controls. Quantitative real-time PCR (qRT-PCR) was performed to validate the aberrantly expressed exosomal miRNAs. A total of 20 exosome-encapsulated miRNAs were identified to be differently expressed in the serum of patients with RA compared with controls. Interestingly, we found that exosome-encapsulated miR-6089 was significantly decreased after validation by qRT-PCR in serum exosomes from 76 patients with RA and 20 controls. Besides, miR-6089 could inhibit lipopolysaccharide (LPS)-induced cell proliferation and activation of macrophage-like THP-1 cells. TLR4 was a direct target for miR-6089. MiR-6089 regulated the generation of IL-6, IL-29, and TNF-α by targetedly controlling TLR4 signaling. In conclusion, exosome-encapsulated miR-6089 regulates LPS/TLR4-mediated inflammatory response, which may serve as a novel, promising biomarker in RA.


Assuntos
Artrite Reumatoide/metabolismo , Proliferação de Células , Exossomos/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , MicroRNAs/metabolismo , Receptor 4 Toll-Like/metabolismo , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Exossomos/genética , Feminino , Humanos , Interferons/metabolismo , Interleucina-6/metabolismo , Interleucinas/metabolismo , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Transdução de Sinais , Células THP-1 , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
J Phys Condens Matter ; 31(2): 025401, 2019 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-30521488

RESUMO

Nanoscale metallic glasses (MGs) are frequently used in experimental and computational studies to probe the deformation mechanisms in amorphous metals. Potential consequences of the significant surface to volume ratio in these extremely small materials, nevertheless, are not well understood. Here, using molecular dynamics simulations and novel selective 3D visualization, we show that significant irreversible atomic shear strain condenses on the 3D surface of these materials under low uniaxial stress, while the interior atoms are bearing much lower, mostly reversible shear strain. This is observed for various sample geometries, dimensions, strain rates and temperatures, and attributable to the correlations of atomic shear strain with atomic potential energy and coordination number. The results reveal the profound influence of the surface on the strain partitioning in nanoscale MGs across the 3D volume, critical to the initiation and continuation of plasticity.

11.
Front Immunol ; 10: 3129, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32047497

RESUMO

Rheumatoid arthritis is a common systemic and autoimmune disease characterized by symmetrical and inflammatory destruction of distal joints. Its primary pathological characters are synovitis and vasculitis. Accumulating studies have implicated the critical role of non-coding RNAs (ncRNAs) in inflammation and autoimmune regulation, primarily including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). NcRNAs are significant regulators in distinct physiological and pathophysiological processes. Many validated non-coding RNAs have been identified as promising biomarkers for the diagnosis and treatment of RA. This review will shed some light on RA pathogenesis and be helpful for identifying potential ncRNA biomarkers for RA.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/patologia , RNA não Traduzido , Animais , Biomarcadores , Humanos
12.
J Cell Physiol ; 233(11): 8815-8825, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29806703

RESUMO

We performed a systematic review of genome-wide gene expression datasets to identify key genes and functional modules involved in the pathogenesis of systemic lupus erythematosus (SLE) at a systems level. Genome-wide gene expression datasets involving SLE patients were searched in Gene Expression Omnibus and ArrayExpress databases. Robust rank aggregation (RRA) analysis was used to integrate those public datasets and identify key genes associated with SLE. The weighted gene coexpression network analysis (WGCNA) was adapted to identify functional modules involved in SLE pathogenesis, and the gene ontology enrichment analysis was utilized to explore their functions. The aberrant expressions of several randomly selected key genes were further validated in SLE patients through quantitative real-time polymerase chain reaction. Fifteen genome-wide gene expression datasets were finally included, which involved a total of 1,778 SLE patients and 408 healthy controls. A large number of significantly upregulated or downregulated genes were identified through RRA analysis, and some of those genes were novel SLE gene signatures and their molecular roles in etiology of SLE remained vague. WGCNA further successfully identified six main functional modules involved in the pathogenesis of SLE. The most important functional module involved in SLE included 182 genes and mainly enriched in biological processes, including defense response to virus, interferon signaling pathway, and cytokine-mediated signaling pathway. This study identifies a number of key genes and functional coexpression modules involved in SLE, which provides deepening insights into the molecular mechanism of SLE at a systems level and also provides some promising therapeutic targets.


Assuntos
Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Genoma Humano/genética , Lúpus Eritematoso Sistêmico/genética , Citocinas/genética , Redes Reguladoras de Genes/genética , Humanos , Interferons/genética , Lúpus Eritematoso Sistêmico/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais/genética
13.
J Cell Biochem ; 2018 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-29315763

RESUMO

Currently published studies have implicated that microRNAs (miRNAs) including exosomes-encapsulated miRNAs play a critical role in rheumatoid arthritis (RA). Previously, we have found that exosomes-encapsulated miR-548a-3p was significantly decreased in serum samples from RA patients by miRNAs microarray analysis. However, little is known of the role of miR-548a-3p in the development and progression of RA. In this study, we aim to investigate the underlying molecular mechanisms of miR-548a-3p in RA, which will provide new insight into understanding the pathogenesis of RA and identifying novel therapeutics targets for this disease. As validated by quantitative real-time polymerase chain reaction (qRT-PCR), the expression of miR-548a-3p in serum exosomes and peripheral blood mononuclear cells (PBMCs) of RA patients (n = 76) was obviously down-regulated compared with healthy controls (n = 20). Serum exosomal miR-548a-3p was negatively associated with levels of CRP, RF, and ESR in serum of patients with RA. MiR-548a-3p could inhibit the proliferation and activation of pTHP-1 cells by regulating the TLR4/NF-κB signaling pathway. Accordingly, exosomes-delivered miR-548a-3p may be a critical factor predicting the disease activity of RA. MiR-548a-3p/TLR4/NF-κB axis can serve as promising targets for RA diagnosis and treatment.

14.
J Cell Biochem ; 119(5): 4113-4119, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29240249

RESUMO

Accumulating data have suggested exosome-delivered microRNAs (miRNAs) play critical role in carcinogenesis and cancer progression. However, little is known about the influence of exosomal miR-6803-5p on the development and prognosis of colorectal cancer (CRC). Levels of serum exosomal miR-6803-5p were determined by microarray analysis and verified by quantitative real-time PCR (qRT-PCR). Outcomes of overall survival (OS) and disease-free survival (DFS) of CRC patients were estimated by Kaplan-Meier analysis. We used cox regression analysis to investigate the association between exosomes-encapsulated miR-6803-5p and the clinicopathological factors of CRC patients. The exosomal miR-6803-5p was significantly increased in serum samples from patients with CRC in contrast to healthy controls. Significantly higher levels of serum exosomal miR-6803-5p were observed in CRC patients at later TNM stage or with lymph node metastasis as well as liver metastasis. Patients with elevated levels of serum exosomal miR-6803-5p had much poorer OS and DFS. Cox regression analysis revealed high levels of exosomal miR-6803-5p was associated with poor prognosis in CRC independent of other confounding factors. Thus, exosomal miR-6803-5p is a potential diagnostic and prognostic biomarker for patients with CRC.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Exossomos/metabolismo , MicroRNAs/sangue , RNA Neoplásico/sangue , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Estudos Retrospectivos , Taxa de Sobrevida
15.
J Cell Physiol ; 233(9): 6660-6668, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29206292

RESUMO

Many studies have implicated that microRNAs (miRNAs), as non-coding RNAs, play important roles in the development and progression of colorectal cancer (CRC). However, little is known about the role of a newly identified miRNA, miR-6869-5p, in CRC. We aim to investigate the modifying effects and underlying mechanisms of miR-6869-5 in colorectal carcinogenesis and progression. Significantly reduced levels of miR-6869-5p were observed in both serum exosomes tumor tissue samples from patients with CRC. The prediction of targets of miR-6869-5p in databases of targetscan, microRNA. ORG and miRDBA revealed that toll-like receptor 4 (TLR4) is a potential target for this miRNA. MiR-6869-5p could inhibit cell proliferation and the production of inflammatory cytokines (TNF-α and IL-6) in CRC cells via directly targeting TLR4. The protective effect of miR-6869-5p from colorectal carcinogenesis was dependent on TLR4/NF-κB signaling pathway. In addition, the 3-year survival was poor among CRC patients with decreased levels of miR-6869-5p in serum exosomes. Thus, miR-6869-5p may serve as a tumor suppressor in CRC, and serum exosomal miR-6869-5p is a promising circulating biomarker for the prediction of CRC prognosis.


Assuntos
Neoplasias Colorretais/genética , MicroRNAs/genética , NF-kappa B/genética , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética , Animais , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Exossomos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Células HEK293 , Humanos , Inflamação/genética , Inflamação/patologia , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fator de Necrose Tumoral alfa/genética
16.
Oncotarget ; 8(56): 95280-95292, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29221127

RESUMO

The modifying effects of long noncoding RNAs (lncRNAs) in rheumatoid arthritis (RA) recently have drawn much attention; however, the underlying mechanisms remain largely unknown. Herein, we aim to investigate the expression profile of lncRNAs in RA and identify promising targets for RA diagnosis and treatment. Microarray screening and real-time PCR of lncRNAs were performed by use of serum samples from 3 RA patients and 3 healthy controls. Significantly differentially expressed lncRNAs were verified in serum samples from 43 RA patients and 40 healthy controls by real-time PCR. We found that there were 73 up-regulated and 61 down-regulated lncRNAs as well as 128 up-regulated and 37 down-regulated mRNAs in serum samples of RA patients. Validation in RA clinical samples indicated 5 of these lncRNAs were significantly up-regulated including RNA143598, RNA143596, HIX0032090, IGHCgamma1, and XLOC_002730. Significant association was observed between these lncRNAs and the disease course, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) as well as anti-cyclic citrullinated peptide (anti-CCP) antibody. Additionally, 55 of the differentially expressed mRNAs were associated with 41 lncRNAs and were involved in signaling pathways of toll like receptors (TLRs), nuclear factor-kappa B (NF-κB), and cytokine, especially the IRF3/IRF7 mediated signaling transduction. Our study firstly shows the specific profile of lncRNAs in the serum of RA patients and potential signaling pathways involved in RA pathogenesis, which may provide novel targets for the diagnosis and treatment of patients with RA.

17.
Oncotarget ; 8(36): 60149-60158, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28947960

RESUMO

Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed. Those differentially expressed exosome-encapsulated miRNAs were verified in exosome-enriched serum samples from 77 CRC patients and 20 healthy controls by quantitative real-time PCR (qRT-PCR). A total of 39 aberrantly expressed miRNAs in serum exosomes were identified by microarray analysis. After confirmation by qRT-PCR, we found that 5 exosome-encapsulated miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p and miR-548c-5p) were significantly down-regulated, while 2 exosome-encapsulated miRNAs (miR-486-5p and miR-3180-5p) were significantly up-regulated in serum. Decreased levels of miR-638 in serum exosomes were associated with increased risk of liver metastasis and later TNM stage of CRC. Networks analyses revealed that 5 aberrantly expressed miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p, and miR-548c-5p) might be involved in the process of glucose metabolism in CRC. The present study shows the specific serum profile of exosome-encapsulated miRNAs in CRC. Those specific miRNAs in serum exosomes may serve as disease biomarkers and novel therapeutic targets for CRC.

18.
Int Rev Immunol ; 36(3): 176-181, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28471251

RESUMO

MicroRNAs (miRNAs) are a class of noncoding RNAs and have emerged as critical regulators of gene expression. Some miRNAs play important roles in regulating the function of the immune system and are involved in the pathogenesis of autoimmune diseases. Recent studies suggested that microRNA-22-3p (miR-22-3p) was able to regulate the function of several types of immune cells and may be involved in the development of autoimmune diseases. We systematically reviewed relevant literatures to provide a comprehensive review of the possible roles of miR-22-3p in autoimmune diseases. Published studies suggest that miR-22-3p can act as a novel regulator of autoimmune diseases via several pathways. More studies are needed to further elucidate the exact roles of miR-22-3p in autoimmune diseases. Treatment strategy targeting miR-22-3p is also a promising therapy for autoimmune diseases.


Assuntos
Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Autoimunidade/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Animais , Doenças Autoimunes/terapia , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunidade/genética , Imunomodulação/genética , Terapia de Alvo Molecular
19.
Autoimmun Rev ; 16(7): 756-765, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28483543

RESUMO

BACKGROUND: In the past several years, more and more studies proposed some concerns on the possibly increased risk of autoimmune diseases in individuals receiving vaccinations, but published studies on the associations of vaccinations with risks of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) reported conflicting findings. A systematic review and meta-analysis was carried out to comprehensively evaluate the relationship between vaccinations and risk of SLE and RA. METHODS: Pubmed, Web of Science and Embase were searched for observational studies assessing the associations of vaccinations with risks of RA and SLE. Two authors independently extracted data from those eligible studies. The quality of eligible studies was assessed by using the Newcastle-Ottawa Scale (NOS). The pooled relative risk (RR) with 95% confidence intervals (CIs) was used to measure the risk of RA and SLE associated with vaccinations, and was calculated through random-effect meta-analysis. RESULTS: Sixteen observational studies were finally considered eligible, including 12 studies on the association between vaccinations and SLE risk and 13 studies on the association between vaccinations and RA risk. The pooled findings suggested that vaccinations significantly increased risk of SLE (RR=1.50; 95%CI 1.05-2.12, P=0.02). In addition, there was an obvious association between vaccinations and increased risk of RA (RR=1.32; 95%CI 1.09-1.60, P=0.004). Meta-analysis of studies reporting outcomes of short vaccinated time also suggested that vaccinations could significantly increase risk of SLE (RR=1.93; 95%CI 1.07-3.48, P=0.028) and RA (RR=1.48; 95%CI 1.08-2.03, P=0.015). Sensitivity analyses in studies with low risk of bias also found obvious associations of vaccinations with increased risk of RA and SLE. CONCLUSION: This study suggests that vaccinations are related to increased risks of SLE and RA. More and larger observational studies are needed to further verify the findings above and to assess the associations of vaccinations with other rheumatic diseases.


Assuntos
Artrite Reumatoide/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Vacinação/efeitos adversos , Humanos , Risco
20.
Front Immunol ; 8: 396, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28439272

RESUMO

Autoimmune thyroid diseases (AITD) are a group of both B cell- and T cell-mediated organ-specific autoimmune diseases. Graves' disease and Hashimoto thyroiditis are the two main clinical presentations of AITD. Both genetic and environmental factors have important roles in the development of AITD. Epigenetics have been considered to exert key roles in integrating those genetic and environmental factors, and epigenetic modifications caused by environmental factors may drive genetically susceptibility individuals to develop AITD. Recent studies on the epigenetics of AITD have provided some novel insights into the pathogenesis of AITD. The aim of this review is to provide an overview of recent advances in the epigenetic mechanisms of AITD, such as DNA methylation, histone modifications, and non-coding RNAs. This review highlights the key roles of epigenetics in the pathogenesis of AITD and potential clinical utility. However, the epigenetic roles in AITD are still not fully elucidated, and more researches are needed to provide further deeper insights into the roles of epigenetics in AITD and to uncover new therapeutic targets. Although there are many studies assessing the epigenetic modifications in AITD patients, the clinical utility of epigenetics in AITD remains poorly defined. More studies are needed to identify the underlying epigenetic modifications that can contribute to accurate diagnosis of AITD, adequate choice of treatment approach, and precise prediction of treatment outcomes.

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