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1.
Cell Prolif ; 54(8): e13088, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34240781

RESUMO

OBJECTIVES: Breast cancer-amplified sequence 3 (BCAS3) was initially found to be amplified in human breast cancer (BRCA); however, there has been little consensus on the functions of BCAS3 in breast tumours. MATERIALS AND METHODS: We analysed BCAS3 expression in BRCA using bio-information tools. Affinity purification and mass spectrometry were employed to identify BCAS3-associated proteins. GST pull-down and ubiquitination assays were performed to analyse the interaction mechanism between BCAS3/p53 and CUL4A-RING E3 ubiquitin ligase (CRL4A) complex. BCAS3 was knocked down individually or in combination with p53 in MCF-7 cells to further explore the biological functions of the BCAS3/p53 axis. The clinical values of BCAS3 for BRCA progression were evaluated via semiquantitative immunohistochemistry (IHC) analysis and Cox regression. RESULTS: We reported that the expression level of BCAS3 in BRCA was higher than that in adjacent normal tissues. High BCAS3 expression promoted growth, inhibited apoptosis and conferred chemoresistance in breast cancer cells. Mechanistically, BCAS3 overexpression fostered BRCA cell growth by interacting with the CRL4A complex and promoting ubiquitination and proteasomal degradation of p53. Furthermore, BCAS3 could regulate cell growth, apoptosis and chemoresistance through a p53-mediated mechanism. Clinically, BCAS3 overexpression was significantly correlated with a malignant phenotype. Moreover, higher expression of BCAS3 correlates with shorter overall survival (OS) in BRCA. CONCLUSIONS: The functional characterization of BCAS3 offers new insights into the oncogenic properties and chemotherapy resistance in breast cancer.


Assuntos
Neoplasias da Mama/patologia , Proteínas de Neoplasias/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células , Proteínas Culina/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Taxa de Sobrevida , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
2.
Aging (Albany NY) ; 13(13): 17302-17315, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226298

RESUMO

The molecular mechanism of bone metastasis in breast cancer is largely unknown. Herein, we aimed to identify the key genes and long non-coding RNAs (lncRNAs) related to the bone metastasis of breast cancer using a bioinformatics approach. We screened differentially expressed genes and lncRNAs between normal breast and breast cancer bone metastasis samples using the GSE66206 dataset from the Gene Expression Omnibus. We also constructed a differentially expressed lncRNA-mRNA interaction network and analyzed the node degrees to identify the driving genes. After finding potential pathogenic modules of breast cancer bone metastasis, we identified breast cancer bone metastasis-related modules and functional enrichment analysis of the genes and lncRNAs in the modules. Based on the above analysis, we constructed a differentially expressed lncRNA-mRNA network related to bone metastasis in breast cancer and identified core driver genes, including BNIP3 and the lncRNA RP11-317-J19.1. The role of core driver genes and lncRNAs in the network implies their biological functions in regulating bone development and remodeling. Thus, targeting the core driver genes and lncRNAs in the network may be a promising therapeutic strategy to manage bone metastasis.


Assuntos
Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Biologia Computacional , Regulação Neoplásica da Expressão Gênica/genética , Genes Neoplásicos/genética , RNA Longo não Codificante/genética , Desenvolvimento Ósseo/genética , Remodelação Óssea/genética , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/genética , Humanos , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas/genética
3.
Cell Death Differ ; 28(9): 2818-2836, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33953349

RESUMO

The biological function of PRMT5 remains poorly understood in cervical cancer metastasis. Here, we report that PRMT5 physically associates with the transcription factor Snail and the NuRD(MTA1) complex to form a transcriptional-repressive complex that catalyzes the symmetrical histone dimethylation and deacetylation. This study shows that the Snail/PRMT5/NuRD(MTA1) complex targets genes, such as TET1 and E-cadherin, which are critical for epithelial-mesenchymal transition (EMT). This complex also affects the conversion of 5mC to 5hmC. This study demonstrates that the Snail/PRMT5/NuRD(MTA1) complex promotes the invasion and metastasis of cervical cancer in vitro and in vivo. This study also shows that PRMT5 expression is upregulated in cervical cancer and various human cancers, and the PRMT5 inhibitor EPZ015666 suppresses EMT and the invasion potential of cervical cancer cells by disinhibiting the expression of TET1 and increasing 5hmC, suggesting that PRMT5 is a potential target for cancer therapy.

4.
Adv Sci (Weinh) ; 8(10): 2001515, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34026424

RESUMO

Cullin4B (CUL4B) is a scaffold protein of the CUL4B-Ring E3 ligase (CRL4B) complex. However, the role of CUL4B in the development of breast cancer remains poorly understood. Here it is shown that CRL4B interacts with multiple histone deacetylase (HDAC)-containing corepressor complexes, including MTA1/NuRD, SIN3A, CoREST, and NcoR/SMRT complexes. It is demonstrated that CRL4B/NuRD(MTA1) complexes cooccupy the E-cadherin and AXIN2 promoters, and could be recruited by transcription factors including Snail and ZEB2 to promote cell invasion and tumorigenesis both in vitro and in vivo. Remarkably, CUL4B responded to transformation and migration/invasion stimuli and is essential for multiple epithelial-mesenchymal transition (EMT) signaling pathways such as hypoxia. Furthermore, the transcription of CUL4B is directedly activated by hypoxia-inducible factor 1α (HIF1α) and repressed by the ERα-GATA3 axis. Overexpressing of CUL4B successfully induced CSC-like properties. Strikingly, CUL4B expression is markedly upregulated during breast cancer progression and correlated with poor prognosis. The results suggest that CUL4B lies at a critical crossroads between EMT and stem cell properties, supporting CUL4B as a potential novel target for the development of anti-breast cancer therapy.

5.
Clin Epigenetics ; 13(1): 113, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001246

RESUMO

Epigenetics studies heritable genomic modifications that occur with the participation of epigenetic modifying enzymes but without alterations of the nucleotide structure. Small-molecule inhibitors of these epigenetic modifying enzymes are known as epigenetic drugs (epi-drugs), which can cause programmed death of tumor cells by affecting the cell cycle, angiogenesis, proliferation, and migration. Epi-drugs include histone methylation inhibitors, histone demethylation inhibitors, histone deacetylation inhibitors, and DNA methylation inhibitors. Currently, epi-drugs undergo extensive development, research, and application. Although epi-drugs have convincing anti-tumor effects, the patient's sensitivity to epi-drug application is also a fundamental clinical issue. The development and research of biomarkers for epi-drugs provide a promising direction for screening drug-sensitive patients. Here, we review the predictive biomarkers of 12 epi-drugs as well as the progress of combination therapy with chemotherapeutic drugs or immunotherapy. Further, we discuss the improvement in the development of natural ingredients with low toxicity and low side effects as epi-drugs.

6.
J Biomed Nanotechnol ; 17(3): 382-398, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875073

RESUMO

Multidrug resistance (MDR) remains a significant impediment to chemotherapy during cancer therapy. In this study, the amphiphilic biomaterials PEI-TOS and HA-QU were synthesized to self-assemble into PEI-TOS/HA-QU core-shell micelles for the targeted codelivery of paclitaxel (PTX) and quercetin (QU) to alleviate multidrug drug resistance and enhance therapeutic efficacy. The PTX-loaded micelles possessed a uniform particle size (167.60 ± 8.185 nm), stable negative charge (-19.13 ± 0.321 mV), and pH-responsive drug release with good compatibility. The drug-loaded micelles increased the chemosensitivity of MDR tumor cells (MDA-MB-231/MDR1) to PTX and activated mitochondria-dependent apoptotic pathways (the IC50 was 2.22-fold lower than that of PTX alone). Moreover, PEI-TOS/HA-QU micelles increased the cellular uptake of lipophilic antitumor drugs by downregulating P-gp expression in MDA-MB-231/MDR1 cells. Compared with Taxol, PTX-loaded PEI-TOS/HA-QU micelles presented excellent antitumor efficacy in tumor-bearing mice, with an average tumor size that was 3.7-fold lower than that of the control group. The drug-loaded formulation showed low in vitro / in vivo toxicity and better tumor accumulation than the free drug, which led to a high tumor inhibition rate of 80.56% and considerable biocompatibility. This work describes a new platform for the codelivery of lipophilic anticancer drugs and natural active ingredients such as PTX and QU for the treatment of MDR cancer cells.


Assuntos
Neoplasias da Mama , Paclitaxel , Animais , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Resistência a Múltiplos Medicamentos , Humanos , Ácido Hialurônico , Hidrogênio , Camundongos , Micelas , Polietilenoimina , Quercetina , Succinatos , alfa-Tocoferol
7.
Theranostics ; 11(5): 2058-2076, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500709

RESUMO

Histone deacetylases (HDACs) are involved in key cellular processes and have been implicated in cancer. As such, compounds that target HDACs or drugs that target epigenetic markers may be potential candidates for cancer therapy. This study was therefore aimed to identify a potential epidrug with low toxicity and high efficiency as anti-tumor agents. Methods: We first screened an epigenetic small molecule inhibitor library to screen for an epidrug for breast cancer. The candidate was identified as PCI-24781 and was characterized for half maximal inhibitory concentration (IC50), for specificity to breast cancer cells, and for effects on carcinogenesis and metastatic properties of breast cancer cell lines in vitro. A series of in silico and in vitro analyses were further performed of PCI-24781 to identify and understand its target. Results: Screening of an epigenetic inhibitor library in MDA-MB-231 cells, a malignant cancer cell line, showed that PCI-24781 is a potential anti-tumor drug specific to breast cancer. Ca2+ related pathways were identified as a potential target of PCI-24781. Further analyses showed that PCI-24781 inhibited Gαq-PLCß3-mediated calcium signaling by activating the expression of regulator of G-protein signaling 2 (RGS2) to reduce cell proliferation, metastasis, and differentiation, resulting in cell death in breast cancer. In addition, RGS2 depletion reversed anti-tumor effect and inhibition of calcium influx induced by PCI-24781 treatment in breast cancer cells. Conclusions: We have demonstrated that PCI-24781 is an effective anti-tumor therapeutic agent that targets calcium signaling by activating RGS2. This study also provides a novel perspective into the use of HDAC inhibitors for cancer therapy.


Assuntos
Benzofuranos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cálcio/metabolismo , Proliferação de Células , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Animais , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Protoplasma ; 258(2): 361-370, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33106960

RESUMO

As the by-products of edible oil production with rich lignin, the reserves of Camellia oleifera shell were abundant and had a great economic value. Lignin was the most important limiting factor during the conversion of plant biomass to pulp or biofuels, which mainly deposited in the stone cells of C. oleifera shells. Thus, its lignin deposition made the function of stone cells in the ripening process of the shell clearer, and provided a theoretical basis for the potential utilization of the biomass of C. oleifera shells. In this study, the paraffin embedding method was used to investigate the development and difference of stone cell in the fruitlet. The lignin deposition characteristics of stone cell were analyzed by the fluorescence microscopy and Wiesner and Mäule method. The chemical-functional group types of lignin in the stone cell of C. oleifera shell were examined by the ultraviolet spectrophotometer and transform infrared spectroscopy. The stone cells, vessels, parenchyma, and vascular tissue had existed during the young fruit growing period. The anatomical characteristics and the cell tissue ratio inverse relationship between stone cell and parenchymal cell suggested that stone cells developed from parenchymal cells. With the growth of shell, the stone cell wall thickened, and thickness-to-cavity ratio from 0 to 3.6. The fluorescent results showed that lignin content increased continuously; during shell development, the mean brightness of stone cell wall from 0 to 77.9 sections was stained with phloroglucinol-HCl, and Mäule revealed the presence of G-S-lignin in stone cells, and ImageJ results showed that G-lignin was distributed in the entire stone cell wall, while S-lignin deposition accounted for 48.59% of the cell wall area. In the FTIR spectra, the shell was identified as containing G-S-lignin.

9.
Hum Exp Toxicol ; 40(5): 882-894, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33233951

RESUMO

Exogenous and endogenous formaldehyde (FA) both play an important role in cell growth and migration; however, their potential role in osteoblasts remains largely unclear. Cell counting kit-8 (CCK-8) and wound-healing assays revealed that FA exposure at naturally occurring concentrations inhibited the proliferation and migration of mouse preosteoblast MC3T3-E1 cells. Moreover, RNA sequencing (RNA-seq) analysis revealed that FoxO1 signaling pathway components displayed distinct expression patterns upon FA exposure, reflected through significant enrichment of cell migration. In particular, FoxO1-, Sirt1-, and FA-induced protein expression, which was closely associated with cell proliferation and migration, was confirmed by western blotting. The results obtained indicated that the FoxO1 pathway is involved in FA-induced inhibition of cell growth and migration.

10.
Aging (Albany NY) ; 13(2): 2519-2538, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33318294

RESUMO

Breast cancer is one of the leading causes of cancer-associated mortality in women worldwide and has become a major public health problem. Although the definitive cause of breast cancer is not known, many genes sensitive to breast cancer have been detected using advanced technologies. Our study identified 3301 differentially expressed lncRNAs and mRNAs between tumor and normal samples from The Cancer Genome Atlas database. Based on the gene expression analysis and clinical traits as well as weighted gene co-expression network analysis, the co-expression Brown module was found to be key for breast cancer prognosis. A total of 453 genes in the Brown module were used for functional enrichment, protein-protein interaction analysis, lncRNA-miRNA-mRNA ceRNA network, and lncRNA-RNA binding protein-mRNA network construction. GRM4, SSTR2, PARD6B, PRR15, COX6C, and lncRNA DSCAM-AS1 were the hub genes according to protein-protein interaction, lncRNA-miRNA-mRNA and lncRNA-RNA binding protein-mRNA network. Their high expression was found to be correlated with breast cancer development, according to multiple databases. In conclusion, this study provides a framework of the co-expression gene modules of breast cancer and identifies several important biomarkers in breast cancer development and prognosis.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Taxa de Sobrevida
11.
Artigo em Inglês | MEDLINE | ID: mdl-32565857

RESUMO

Background: Luhong formula (LHF)-a traditional Chinese medicine containing Cervus nippon Temminck, Carthamus tinctorius L., Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Codonopsis pilosula (Franch.) Nannf., Cinnamomum cassia Presl, and Lepidium apetalum Willd-is used in the treatment of heart failure, but little is known about its mechanism of action. We have investigated the effects of LHF on antifibrosis. Methods: Forty-eight SD male rats were randomly assigned into six groups (n = 8), model group, sham-operation group, perindopril group (0.036 mg/ml), LHF high doses (LHF-H, 1.44 g/mL), LHF middle doses (LHF-M, 0.72 g/mL), and LHF low doses (LHF-L, 0.36 g/mL). Except the sham-operation group, the other groups were received an abdominal aorta constriction to establish a model of myocardial hypertrophy. The HW and LVW were measured to calculate the LVW/BW and HW/BW. ELISA was used to detect the serum concentration of BNP. The expressions of eNOS, TGF-ß1, caspase-3, VEGF, and VEGFR2 in heart tissues were assessed by western blot analysis. mRNA expressions of eNOS, Col1a1, Col3a1, TGF-ß1, VEGF, and VEGFR2 in heart tissues were measured by RT-PCR. The specimens were stained with hematoxylin-eosin (HE) and picrosirius red staining for observing the morphological characteristics and collagen fibers I and III of the myocardium under a light microscope. Results: LHF significantly lowered the rat's HW/BW and LVM/BW, and the level of BNP in the LHF-treated group compared with the model group. Histopathological and pathomorphological changes of collagen fibers I and III showed that LHF inhibited myocardial fibrosis in heart failure rats. Treatment with LHF upregulated eNOS expression in heart tissue and downregulated Col1a1, Col3a1, TGF-ß1, caspase-3, VEGF, and VEGFR2 expression. Conclusion: LHF can improve left ventricular remodeling in a pressure-overloaded heart failure rat model; this cardiac protective ability may be due to cardiac fibrosis and attenuated apoptosis. Upregulated eNOS expression and downregulated Col1a1, Col3a1, TGF-ß1, caspase-3, VEGF, and VEGFR2 expression may play a role in the observed LHF cardioprotective effect.

12.
J Transl Med ; 18(1): 175, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312307

RESUMO

BACKGROUND: Kidney ischemia reperfusion injury (IRI) is a common cause of acute kidney injury and an unavoidable consequence of kidney transplantation and still lacks specific therapeutics. Recently, mesenchymal stem cell (MSC) has been emerging as a promising cell-based therapy for IRI in the context of transplantation. MSC negatively regulates the secretion of pro-inflammatory as well as the activation of immune cells during IRI through its unique immunosuppressive property. METHODS: We employed mice kidney IRI model and MSC cell line to monitor the IRI related checkpoints. siRNAs were utilized to knock down the potential key factors for mechanistic analysis. Statistical analysis was performed by using one-way ANOVA with Tukey's post hoc procedure by SPSS. RESULTS: The expression of high-mobility group box 1 protein (HMGB1) is increased in the acute phase as well as the recovery stage of IRI. Importantly, the HMGB1 upregulation is correlated with the injury severity. HMGB1 diminishes the MSC induced immunosuppressive capacity in the presence of pro-inflammatory cytokines in vitro. Toll like receptor 4 (TLR4)-mediated inducible nitric oxide synthase (iNOS) inhibition contributes to the negative effect of HMGB1 on MSCs. HMGB1-TLR4 signaling inhibition augments the therapeutic efficacy of MSCs in mice renal IRI model. CONCLUSIONS: These findings demonstrate that HMGB1 plays a crucial role in shaping the immunoregulatory property of MSCs within the microenvironments, providing novel insights into the crosstalk between MSCs and microenvironment components, suggesting HMGB1 signals as a promising target to improve MSC-based therapy.


Assuntos
Injúria Renal Aguda , Proteína HMGB1 , Células-Tronco Mesenquimais , Traumatismo por Reperfusão , Injúria Renal Aguda/terapia , Animais , Rim , Camundongos , Traumatismo por Reperfusão/terapia
13.
Artigo em Inglês | MEDLINE | ID: mdl-31827566

RESUMO

Background: Ventricular remodelling is a common pathological change at all stages of heart disease. Luhong granules are widely used in patients with chronic ventricular remodelling after myocardial infarction and can alleviate chest tightness, shortness of breath, and other symptoms. However, its effect on ventricular remodelling remains to be studied. Purpose: In this study, we investigated the effects of these granules on myocardial fibrosis in a rat model of myocardial infarction in vivo. Methods: Male Wistar rats were randomly divided into four groups: the sham operation group, the acute myocardial infarction (AMI) group, the Luhong granule group, and the vancomycin group, with a sample size (n) of 10 rats in each group. The AMI model was established in all rats by ligation of the left anterior descending (LAD) coronary artery (the sham operation group did not undergo ligation). Luhong granules (0.5 ml·kg-1·d-1), vancomycin (0.075 g·ml-1·d-1), and 0.9% saline (5 ml·kg-1·d-1 for the sham operation and AMI groups) were administered orally for 6 weeks. Echocardiography was used to check cardiac structure and function. Myocardial and small intestinal tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson's trichrome to analyse myocardial fibrosis. 16S rDNA sequencing was performed to detect changes in the gut flora. The level of trimethylamine N-oxide (TMAO) in plasma samples was quantified by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS). Results: H&E and Masson's trichrome staining of cardiac tissues showed that Luhong granules could partially reverse ventricular remodelling and improve intestinal barrier function (P < 0.05). Echocardiographic analysis showed that, compared with the AMI group, the left ventricular ejection fraction (LVEF) in the Luhong granule group was increased (P < 0.05). Stool sequencing and microbiological analysis showed changes in Bacteroidales, Alistipes, Phascolarctobacterium, etc., which can produce TMAO. We found that Luhong granules can reduce Bacteroidales, Alistipes, and Phascolarctobacterium at the genus level. The levels of TMAO and lipopolysaccharides (LPS) in plasma samples were reduced in the Luhong granule group (P < 0.05). Conclusions: Our results indicate that Luhong granules reduce TMAO and LPS levels in circulating blood by improving intestinal flora and intestinal barrier function to delay ventricular remodelling after myocardial infarction.

14.
Biomater Sci ; 7(12): 5238-5246, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31602440

RESUMO

Due to unsatisfactory tumor-targeting efficiency, hitch-hiking nanomedicines with tumor "smelling" immune cells have rapidly evolved to achieve a more precision delivery. However, the current research tends to default to the smelling capacity of neutrophils and largely overlooks the capacity of those immune cells that are heavily dependent on the pathogen exposure history of individuals. By avoiding risky strategies, such as altering the housing environment of mice for the improved activity of immune cells, we propose a new concept of nano-immunotraining strategy to quickly activate neutrophil tumor tropism and thereby give an enhanced tumor-targeting capacity. Such a strategy involves a facile construction of a vaccine-like nano-CpG adjuvant, followed by pre-immunizing on mice periodically to mimic the pathogen exposure. The results demonstrated that a significantly enhanced tumor-targeting accumulation of neutrophils harvested from nano-immunotrained mice could be achieved, either by intraperitoneal or intravenous injection. This easily accessed, reproducible, and biosafe nano-immunotraining strategy holds a great promise for more precision delivery of nanomedicines.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Neoplasias/terapia , Neutrófilos/metabolismo , Oligodesoxirribonucleotídeos/administração & dosagem , Adjuvantes Imunológicos/química , Animais , Linhagem Celular Tumoral , Feminino , Imunização , Camundongos , Nanopartículas , Neoplasias/imunologia , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Ecotoxicol Environ Saf ; 175: 74-82, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30889402

RESUMO

Lead (Pb) is a type of toxic metal that can hurt the immune system. Selenium (Se) can reduce the damage caused by heavy metals. To investigate the effects of Se against Pb on bird immune cells, as well as the immunotoxin mechanism of Pb, Se supplementation and/or Pb poisoning chicken models were established. One hundred eighty 1-year-old broiler chickens were randomly divided into four groups (n = 6). The four groups were the control group, the selenium-rich group (Se group), the Pb supplementation group (Pb group) and the Se and Pb compound group (Se + Pb group). The peripheral blood lymphocytes of chickens were collected to test the selenoproteins and cytokine mRNA levels at 30 and 60 d. Determination of the content of Se and Pb in the serum, principal component analysis and ingenuity pathway analysis were performed at the two time points. As a result, Pb exposure increased the content of Pb, activating the Th1/Th2 pathway in peripheral blood lymphocytes. Additionally, this experiment showed that Se supplementation and Pb exposure could influence the mRNA levels of selenoproteins and cytokines in the peripheral blood lymphocytes of chickens. However, all of the parameters that we detected in the experiment indicated that Se supplementation could alleviate the increase of selenoproteins and cytokine mRNA levels and the Th1/Th2 imbalance induced by Pb in peripheral blood lymphocytes. In summary, Se can alleviate the toxic effects caused by Pb in the peripheral blood lymphocytes of chickens, suggesting the antagonism between Se and Pb.


Assuntos
Galinhas/imunologia , Chumbo/toxicidade , Selênio/metabolismo , Equilíbrio Th1-Th2/efeitos dos fármacos , Animais , Galinhas/metabolismo , Citocinas/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , RNA Mensageiro/metabolismo , Distribuição Aleatória , Selenoproteínas/metabolismo
16.
J Cell Physiol ; 234(4): 4095-4103, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30144391

RESUMO

Selenium and selenoproteins are identified as potential determinants in pathological cellular hypertrophy. Cardiomyocytes hypertrophy is a compensatory form of heart disease characterized by increased size of cardiomyocytes. However, the link between cardiac hypertrophy and Se-specific microRNA (miRNA) remains to be characterized. In the current study, we established a miR-200a-5p mimic and an inhibitor cardiomyocytes model. Cardiomyocytes hypertrophy was induced in the miR-200a-5p mimic group. Hence, we detected the glucose level of cardiomyocytes to estimate the cellular glucose uptake. The effect of miR-200a-5p overexpression and the low expression on 25 selenoproteins mRNA levels was further explored using reverse transcription polymerase chain reaction. Overexpression of miR-200a-5p elevated glucose uptake and Txnrd2, 3 expression and reduced Sepp1, Seln, Selt, and Sep15 expression in cardiomyocytes. Contrary results were observed in cardiomyocytes with the knockdown of miR-200a-5p. We next assessed glucose metabolism-related genes in cardiomyocytes. The results showed that miR-200a-5p had a negative correlation with insulin-like growth factor gene-1, insulin-like growth factor binding protein (IGFBP)1, IGFBP2, IGFBP3, IGFBP4, and IGFBP5 and had a positive correlation with Akt, glucose transporter family (GLUT)2, GLUT3, and GLUT4. These results support the involvement of selenoproteins and glucose metabolism in the control of cardiomyocytes hypertrophy by Se-specific miRNA, suggesting that miR-200a-5p inhibited the expression of stress-related selenoproteins to alter glucose transport leading to glucose metabolism disorder, eventually inducing cardiomyocytes hypertrophy. Our finding highlights a pivotal role of Se-specific miRNA and selenoproteins in cardiac hypertrophy.


Assuntos
Proteínas Aviárias/metabolismo , Cardiomegalia/metabolismo , Crescimento Celular , Glucose/metabolismo , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Selenoproteínas/metabolismo , Animais , Proteínas Aviárias/genética , Cardiomegalia/genética , Cardiomegalia/patologia , Células Cultivadas , Embrião de Galinha , Regulação da Expressão Gênica , MicroRNAs/genética , Miócitos Cardíacos/patologia , Selenoproteínas/genética , Transdução de Sinais
17.
Nat Commun ; 9(1): 3407, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30143602

RESUMO

The faithful storage and coherent manipulation of quantum states with matter-systems would enable the realization of large-scale quantum networks based on quantum repeaters. To achieve useful communication rates, highly multimode quantum memories are required to construct a multiplexed quantum repeater. Here, we present a demonstration of on-demand storage of orbital-angular-momentum states with weak coherent pulses at the single-photon-level in a rare-earth-ion-doped crystal. Through the combination of this spatial degree-of-freedom (DOF) with temporal and spectral degrees of freedom, we create a multiple-DOF memory with high multimode capacity. This device can serve as a quantum mode converter with high fidelity, which is a fundamental requirement for the construction of a multiplexed quantum repeater. This device further enables essentially arbitrary spectral and temporal manipulations of spatial-qutrit-encoded photonic pulses in real time. Therefore, the developed quantum memory can serve as a building block for scalable photonic quantum information processing architectures.

18.
J Inorg Biochem ; 186: 235-245, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29990747

RESUMO

Selenium (Se) is an important nutritional element in the diet. Apoptosis is one of the characteristic pathological changes in liver tissue resulting from Se deficiency. MicroRNA (miRNA) plays an important role in cell proliferation, differentiation, apoptosis and tumorigenesis. However, why apoptosis occurs during Se deficiency and how miRNA regulates hepatocyte apoptosis in broilers requires further study. We used a dual luciferase reporter assay system and quantitative real-time PCR (qPCR) to screen hepatocytes in Se-deficient broilers for the specificity of hepatocyte apoptosis miRNA and its target protein. We tested the apoptosis of Se-deficient broiler livers and microRNA-193b-transfected primary hepatocytes using qPCR, western blot (WB) and flow cytometry. Our studies revealed that Se deficiency led to microRNA-193b-3p (miR-193b-3p) overexpression and increased apoptosis-related gene expression, resulting in broiler hepatocyte apoptosis. Mastermind-like protein 1 (MAML1) was one of the miR-193b-3p targets, and its expression was down-regulated in miR-193b-3p-overexpressing hepatocytes. Further studies have shown that miR-193b-3p overexpression induced changes of apoptosis-related gene expression by inhibiting the release of MAML1. Interestingly, when we overexpressed miR-193b-3p, which was added to the Signal transducers and activators of transcription-1 (STAT1) inhibitor fludarabine (Flu), hepatocyte apoptosis was significantly reduced. When these results were combined, they indicated that miR-193b-3p is involved in broiler hepatocyte apoptosis in Se deficiency by regulating the target protein MAML1. This finding may provide new ideas for studying the mechanism of hepatocyte injury due to Se deficiency.


Assuntos
Apoptose , Proteínas Aviárias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Hepatócitos/metabolismo , MicroRNAs/metabolismo , Selênio/deficiência , Animais , Embrião de Galinha , Galinhas , Hepatócitos/patologia
19.
Biochem Biophys Res Commun ; 503(2): 757-762, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29913150

RESUMO

Pulmonary fibrosis (PF) is a fatal respiratory disease with no effective medical treatments available. TGF-ß/Smads signaling has been implicated to play an essential in the pathogenesis of PF, in which Smad3 act as the integrator of pro-fibrosis signals. In this study, we determined the effect of SIS3, a specific inhibitor of Smad3, in an experimental mouse model of lung fibrosis. We observed that SIS3 treatment significantly reduced bleomycin (BLM)-induced pathological changes and collagen deposition in the lung as indicated by Masson staining, real-time PCR and hydroxyproline content assay. As expected, the levels of Smad3 phosphorylation were decreased in the lung of mice treated with SIS3. Furthermore, SIS3 treatment also suppressed BLM-induced infiltration of inflammatory cells in the lung. Taken together, our results suggest that SIS3 ameliorated BLM-induced PF in mouse lungs. Thus, targeting Smad3 with SIS3 may be an effective approach for treatment of fibrotic disorders.


Assuntos
Isoquinolinas/uso terapêutico , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/tratamento farmacológico , Piridinas/uso terapêutico , Pirróis/uso terapêutico , Proteína Smad3/antagonistas & inibidores , Animais , Bleomicina , Colágeno Tipo I/análise , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Proteína Smad3/análise
20.
Cancer Lett ; 431: 22-30, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29803788

RESUMO

Tuberculosis (TB) is one of the most fatal infectious diseases, affecting one third of the world's population. The causative agent, Mycobacterium tuberculosis (Mtb), has a well-established ability to circumvent the host's immune system for its long-term intracellular survival. MicroRNAs (miRNAs) are crucial post-transcriptional regulators of immune response. They act by negatively regulating the expression levels of important genes in both innate and adaptive immunity. It has been established in recent studies that the host immune response against Mtb is regulated by many miRNAs, most of which are induced by Mtb infection. Moreover, differential expression of miRNA in tuberculosis (TB) patients may help distinguish between TB patients and healthy individuals or latent TB. In this review, we present the recent advancements on the miRNA regulation of the host responses against Mtb infection, as well as the potential of miRNAs to as biomarkers for TB diagnosis.


Assuntos
Sistema Imunitário , MicroRNAs/metabolismo , Mycobacterium tuberculosis , Tuberculose/genética , Tuberculose/imunologia , Imunidade Adaptativa , Autofagia , Biomarcadores/metabolismo , Células Dendríticas/metabolismo , Regulação Bacteriana da Expressão Gênica , Predisposição Genética para Doença , Humanos , Imunidade Inata , Macrófagos/metabolismo , Fagocitose , Polimorfismo Genético , Transdução de Sinais
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