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1.
J Biochem Mol Toxicol ; 37(6): e23346, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36988443

RESUMO

The protection of the blood-brain barrier (BBB) is the key direction to improving subarachnoid hemorrhage (SAH). Therefore, developing appropriate targeted drugs and therapies has become an urgent task for SAH patients. In this study, we investigated the role of dendritic cells (DCs) exosomal miR-3064-5p in repairing the BBB, providing a new basis for treating SAH. We detected the expression of miR-3064-5p in exosomes secreted by DCs (DCs-exo). An SAH rat model was constructed by intravascular perforation and characterized by HE and TUNEL-IF staining. We found that overexpression of miR-3064-5p in SAH rats suppressed iNOS expression and promoted the accumulation of tight junction proteins (Occludin, Claudin-3, ZO-1), whereas knockdown of miR-3064-5p exerted the opposite effect. Dual-LUC assay confirmed that miR-3064-5p could target and inhibit SIRT6. Knockdown of SIRT6 inhibited inflammatory cytokine (IL-6, IL-1ß, IFN-γ, and TGF-ß1) levels and apoptosis. The results of the co-IP assay showed that SIRT6 interacted with PCSK9, and knockdown of SIRT6 suppressed the expression of PCSK9. Moreover, DCs-exo reduced brain edema, upregulated miR-3064-5p and downregulated SIRT6 and PCSK9 in SAH rats. DCs-exo reduced inflammatory factors and increased tight junction proteins in SAH rats. Overexpression of miR-3064-5p enhanced the protective effect of DCs-exo, while overexpression of SIRT6 partially counteracted the effect. This study confirmed that DCs could secrete miR-3064-5p to ameliorate BBB damage after SAH. Mechanistically, miR-3064-5p alleviated BBB damage by targeting and inhibiting SIRT6/PCSk9 signaling pathway.


Assuntos
MicroRNAs , Sirtuínas , Hemorragia Subaracnóidea , Ratos , Animais , Barreira Hematoencefálica/metabolismo , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Ratos Sprague-Dawley , Pró-Proteína Convertase 9/metabolismo , Pró-Proteína Convertase 9/farmacologia , Pró-Proteína Convertase 9/uso terapêutico , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo , Células Dendríticas/metabolismo
2.
Bioresour Technol ; 359: 127346, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35605776

RESUMO

In this study, baffled anaerobic-aerobic reactors (AOBRs) with modified basalt fiber (MBF) carriers and felt were used to treat domestic wastewater (DWW). The influent was first treated in anaerobic compartments, with the NH4+-N containing digestate refluxed into aerobic compartment for nitrification. The nitrified liquid was channeled to the anaerobic compartments for further denitrification. Under optimal conditions, AOBR with MBF carriers could remove 91% chemical oxygen demand (COD) and 81% total nitrogen (TN), with biomass production increased by 7.6%, 4.5% and 8.7% in three successive anaerobic compartments compared to the control. Biological viability analysis showed that live cells outnumbered dead cells in bio-nests. Metagenomics analysis showed that multiple metabolic pathways accounted for nitrogen conversion in anaerobic and aerobic compartments. More importantly, low COD/TN ratio digestate facilitated heterotrophic nitrification-aerobic denitrification (HN-AD) species growth in aerobic compartment. This study provides a promising strategy to source treatment of DWW from urban communities.


Assuntos
Desnitrificação , Nitrogênio , Anaerobiose , Reatores Biológicos , Carbono , Processos Heterotróficos , Nitrificação , Nitrogênio/metabolismo , Águas Residuárias/análise
3.
Sci Total Environ ; 805: 150212, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34536867

RESUMO

The traditional biological nitrogen removal (BNR) follows the conventional scheme of sequential nitrification and denitrification. In recent years, novel processes such as anaerobic ammonia oxidation (anammox), complete oxidation of ammonia to nitrate in one organism (comammox), heterotrophic nitrification and aerobic denitrification (HN-AD), and dissimilatory nitrate reduction to ammonium (DNRA) are gaining tremendous attention after the discovery of metabolically versatile bacteria. Among them, HN-AD offers several advantages because individual bacteria could achieve one-stage nitrogen removal under aerobic conditions in the presence of organic carbon. In this review, besides classical BNR processes, we summarized the existing literature on HN-AD bacteria which have been isolated from diverse habitats. A particular focus was given on the diversity and physiology of HN-AD bacteria, influences of physiological and biochemical factors on their growth, nitrogen removal performances, as well as limitations and strategies in unraveling HN-AD metabolic pathways. We also presented case studies of HN-AD application in wastewater treatment facilities, pointed out forthcoming challenges of HN-AD in these systems, and presented modulation strategies for HN-AD application in engineering. This review may help improve the existing design of wastewater treatment plants by harnessing HN-AD bacteria for effective nitrogen removal.


Assuntos
Nitrificação , Purificação da Água , Aerobiose , Desnitrificação , Processos Heterotróficos , Nitrogênio/análise , Águas Residuárias
4.
Int J Neurosci ; 131(12): 1162-1172, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32532171

RESUMO

BACKGROUND: Ischemic stroke (IS) is a major public health issue causing mortality and disability and is more difficult to treat than other cerebral diseases. Previous study reported that miR-376a was upregulated in the serum of stroke patients, indicating that miR-376a played potential role in occurrence and development of stroke. METHODS: IS cell model was induced by oxygen-glucose deprivation (OGD) exposed HCMEC/D3 cells. The mRNA level of SNHG1, miR-376a and inflammatory cytokines were detected by q-PCR. Protein level of CBS, apoptotic proteins were examined by Western blot. Apoptosis was analyzed by flow cytometry, and H2S level was measured by kit. Interaction among lncRNA, miRNA and target gene was validated by luciferase assay. RESULTS: Our research revealed that mRNA level of SNHG1 and CBS in HCMEC/D3 cells was downregulated while miR-376a was upregulated under OGD conditions. Further results demonstrated that miR-376a overexpression promoted apoptosis and inflammation while SNHG1 overexpressing alleviated such processes. Mechanistically, SNHG1 directly targeted miR-376a, and CBS was a target of miR-376a. Moreover, SNHG1 exert its function via inhibiting miR-376a to regulate CBS expression. CONCLUSION: LncRNA SNHG1 depressed apoptosis and inflammation of IS cell model via inhibiting miR-376a and upregulating CBS/H2S signal. These results show light on underlying mechanisms of IS and provide potential targets for IS therapy.


Assuntos
Apoptose/fisiologia , Cistationina beta-Sintase/metabolismo , Citocinas/metabolismo , Sulfeto de Hidrogênio/metabolismo , Inflamação/metabolismo , AVC Isquêmico/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Células Cultivadas , Regulação para Baixo , Humanos , Hipoglicemia/metabolismo , Hipóxia/metabolismo , Transdução de Sinais/fisiologia
5.
Int Immunopharmacol ; 83: 106336, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32213460

RESUMO

BACKGROUND: Dendritic cell (DC)-based vaccination has been suggested to be promising for glioblastoma. However, the evidence in randomized controlled trials (RCTs) is inconsistent. We aimed to systematically evaluate the efficacy and safety of DC vaccine for glioblastoma via a meta-analysis of RCTs. METHODS: Related randomized controlled trials (RCTs) were identified via a search of PubMed, Embase, and Cochrane's Library. We used a random-effect model to pool the results. RESULTS: Six phase II RCTs with 347 patients with newly diagnosed or recurrent glioblastoma that underwent conventional treatments were included. Compared to the control group with placebo or blank treatment, DC vaccine was associated with significantly improved overall survival in patients with glioblastoma (hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.49 to 0.97, p = 0.03) with moderate heterogeneity (p for Cochrane's Q test = 0.07, I2 = 51%). A trend of improved progression-free survival was also detected in patients allocated to the DC vaccine group compared to those in the control group (HR: 0.76, 95% CI: 0.56 to 1.02, p = 0.07), with no significant heterogeneity (I2 = 0%). Moreover, the incidence of adverse events was not significant between patients treated with DC vaccine or control (odds ratio = 1.52, 95% CI: 0.88 to 2.62, p = 0.14; I2 = 0%). CONCLUSIONS: Evidence based on phase II RCTs suggests that DC vaccine may improve the survival of patients with glioblastoma. Large-scale RCTs are needed to validate the findings and determine the optimal regimens for DC vaccine.


Assuntos
Neoplasias Encefálicas/terapia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Glioblastoma/terapia , Imunoterapia Adotiva/métodos , Animais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Células Dendríticas/transplante , Glioblastoma/imunologia , Glioblastoma/mortalidade , Humanos , Recidiva Local de Neoplasia , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
6.
Genomics ; 112(1): 1021-1029, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31226483

RESUMO

Glioma is one of the most common and aggressive malignant primary brain tumor with invariably poor 5-year survival rates. Because of the high recurrence rate and mortality rate, effective therapies for glioma are still weak. Recently, several studies has been proved that long non-coding RNAs (lncRNAs) have been identified to play regulatory mediators in the tumorigenesis of glioma. Nevertheless, the role of lncRNAs and their downstream transcripts are still elusive in the progression of glioma. Small nucleolar RNA host gene 16 (SNHG16), a newly identified lncRNA, has been verified to be up-regulated in human malignant carcinomas. In the present study, we confirmed that lncRNA SNHG16 was highly expressed in glioma and may exert oncogenic function as a competing endogenous RNA (ceRNA) to regulate EGFR by sponging of miR-373-3p through activating PI3K/AKT pathway, which providing a new insight of the regulatory network of lncRNA SNHG16 in the development of glioma.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Glioma/patologia , Humanos , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/fisiologia , Transdução de Sinais
7.
Pathol Oncol Res ; 26(2): 1021-1028, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30972632

RESUMO

Glioma is a malignant brain tumor that accounts for 30% of all brain tumors and 80% of malignant brain tumors. This poor clinical outcome makes the study of molecular mechanisms in glioma as an urgent subject. However, the certain mechanism remains unclear. Long non-coding RNAs (lncRNAs) plays a key role in glioma development and progression. In the present study, we aimed to explore the potential mechanisms of lncRNA SNHG16 in glioma. The levels of lncRNA SNHG16 were qualified in both glioma tissues and cell lines using qRT-PCR assay. The ability of cell proliferation was tested via CCK-8 and colony formation assays. Transfections were performed to knockdown SNHG16 and its target gene p21. The cell cycles and cell apoptosis were evaluated using flow cytometry, and the expression of SNHG16, p21 and apoptosis biomarkers were qualified with qRT-PCR and western blot assays. The expression of SNHG16 were up-regulated in both glioma tissues and cell lines. Knockdown of SNHG16 was associated with poor proliferation, decreased monoclonal formation rates, but increased apoptosis rates, which also caused the high expression of p21. Moreover, p21 could mediate cell proliferation and monoclonal formation, promote cell apoptosis in glioma, which was negatively correlated with lncRNA SNHG16. The molecule mechanism experiments revealed that SNHG16 could not only inhibit the expression of p21 but also suppressed the level of caspase 3 and 9, while promoted cyclinD1 and cyclinB1 expression. lncRNA SNHG16 could promote the cell proliferation and inhibit the apoptosis of glioma through suppressing p21, indicating that lncRNA SNHG16 might be quite vital for the diagnosis and progression of glioma and could even be a novel therapeutic target for glioma.


Assuntos
Neoplasias Encefálicas/patologia , Carcinogênese/genética , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Glioma/patologia , RNA Longo não Codificante/genética , Apoptose/genética , Neoplasias Encefálicas/genética , Proliferação de Células/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioma/genética , Humanos
8.
Colloids Surf B Biointerfaces ; 177: 454-461, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30802829

RESUMO

Surface properties of carrier are critical for microorganism initial adhesion and biofilm formation in wastewater treatment. Until now, there are few reports on adhesion behaviors between bacteria and inorganic fiber surface. In this study, inorganic basalt fiber (BF) was modified with cationic polyacrylamide (CPAM) to make surface more hydrophilic and positively charged. The initial adhesion behaviors of BF modified with CPAM (CMBF) were interpreted by thermodynamics and extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. According to the total interaction energy calculated by the extended DLVO theory, insurmountable energy barrier between BF and Escherichia coli (E. coli) made irreversible adhesion unachievable due to hydrophobicity and electronegativity of BF, but allowed reversible adhesion at second minimum. By contrast, the energy barrier between CMBF and E. coli could be overcome allowing irreversible bacterial adhesion and thus a huge amount of biomass because of hydrophilicity and electropositivity of CMBF. The results showed the total interaction energies were dominated by Lewis acid-base and electrostatic interactions and coating BF with CPAM could promote initial bacterial adhesion on carrier surface. Overall, the extended DLVO theory provides a comprehensive tool to interpret initial adhesion behaviors between bacteria and inorganic fibers.


Assuntos
Aderência Bacteriana , Escherichia coli/química , Modelos Químicos , Silicatos/química , Termodinâmica , Resinas Acrílicas/química , Tamanho da Partícula , Propriedades de Superfície
9.
Biomed Res Int ; 2013: 695179, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24392454

RESUMO

Raf-1 kinase inhibitor protein (RKIP) is a tumor and metastasis suppressor in cancer cells. MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on antimetastasis strategy. In this study, we found that the expression of RKIP and miR-98 in glioma tissues were significantly lower than that in normal brain tissues. Overexpression of RKIP upregulated miR-98 expression and inhibited glioma cell invasion and miR-98 target gene HMGA2 but had no effect in glioma cell proliferation. Moreover, forced expression of miR-98 accelerated the inhibition of glioma cell invasion and the expression of HMGA2 also had no effect in glioma cell proliferation. Our findings newly described RKIP/miR-98 to HMGA2 link and provided a potential mechanism for glioma cell invasion. RKIP and miR-98 may illustrate the potential therapeutic utility of signaling pathway signatures.


Assuntos
Glioma/genética , MicroRNAs/genética , Invasividade Neoplásica/genética , Proteína de Ligação a Fosfatidiletanolamina/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Glioma/patologia , Proteína HMGA2/genética , Humanos , MicroRNAs/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Transdução de Sinais/genética
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