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1.
Proc Natl Acad Sci U S A ; 119(49): e2205013119, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36442102

RESUMO

Zika virus (ZIKV) targets the neural progenitor cells (NPCs) in brain during intrauterine infections and consequently causes severe neurological disorders, such as microcephaly in neonates. Although replicating in the cytoplasm, ZIKV dysregulates the expression of thousands of host genes, yet the detailed mechanism remains elusive. Herein, we report that ZIKV encodes a unique DNA-binding protein to regulate host gene transcription in the nucleus. We found that ZIKV NS5, the viral RNA polymerase, associates tightly with host chromatin DNA through its methyltransferase domain and this interaction could be specifically blocked by GTP. Further study showed that expression of ZIKV NS5 in human NPCs markedly suppressed the transcription of its target genes, especially the genes involved in neurogenesis. Mechanistically, ZIKV NS5 binds onto the gene body of its target genes and then blocks their transcriptional elongation. The utero electroporation in pregnant mice showed that NS5 expression significantly disrupts the neurogenesis by reducing the number of Sox2- and Tbr2-positive cells in the fetal cortex. Together, our findings demonstrate a molecular clue linking to the abnormal neurodevelopment caused by ZIKV infection and also provide intriguing insights into the interaction between the host cell and the pathogenic RNA virus, where the cytoplasmic RNA virus encodes a DNA-binding protein to control the transcription of host cell in the nuclei.


Assuntos
Infecção por Zika virus , Zika virus , Humanos , Feminino , Gravidez , Animais , Camundongos , Cromatina/genética , Zika virus/genética , Infecção por Zika virus/genética , DNA , RNA Polimerases Dirigidas por DNA/genética , Transcrição Gênica
2.
J Gene Med ; 26(1): e3649, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282155

RESUMO

BACKGROUND: Ovarian cancer is one of the most common cancers in women. Profiles changes of microRNAs (miRNAs) are closely linked to malignant tumors. In the present study, we investigated expression of miR-451a in high-grade serous ovarian cancer (HGSOC). We also investigated the potential pathological roles and the likely mechanism of miR-451a in the development of HGSOC using animal models and cell lines. METHODS: Using bioinformatics techniques and a real-time PCR, we analyzed differently expressed miRNAs in HGSOC compared to normal tissue. MTT (i.e. 3-[4, 5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide), EDU (i.e. 5-ethynyl-2'-deoxyuridine) and transwell assays were performed to investigate the effect of miR-451a on the proliferation and migration of HGSOC SKOV-3 cells. A dual luciferase reporter assay was performed to verify the targeting relationship of miR-451 and RAB5A (one of the Rab GTPase proteins that regulates endocytosis and vesicle transport). Also, we analyzed levels of the RAB5A mRNA and protein by real-time PCR, western blotting and immunohistochemistry assays in HGSOC cells and tissues. Finally, we performed in vivo experiments using HGSOC mice. RESULTS: miR-451a was substantially upregulated in HGSOC and associated with favorable clinical characteristics. miR-451a knockdown significantly increased growth and metastasis of HGSOC cell line SKOV-3 through Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. In addition, RAB5A, an early endosome marker, was shown to be a direct target of miR-451a. Moreover, RAB5A is correlated with unfavorable clinical features and shows independent prognostic significance in HGSOC. CONCLUSIONS: We found that the miR-451a/RAB5A axis is associated with tumorigenesis and progression through the Ras/Raf/MEK/ERK pathway, providing prognostic indicators and therapeutic targets for patients with HGSOC.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Proteínas rab5 de Ligação ao GTP , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Neoplasias Ovarianas/genética , Proteínas rab5 de Ligação ao GTP/genética
3.
Pancreatology ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38853072

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the digestive malignancy with poor prognosis, and there is still a lack of effective diagnostic biomarkers. OBJECTIVE: We aimed to explore the diagnostic efficiency of DNA methylation in peripheral blood monocytes (PBMCs) in PDAC. METHODS: 850K BeadChips were used to detect genome-wide methylation of PBMCs. For the selected sites, MethylTarget assays was used for further verification. The support vector machine was used to establish the combined panel. RESULTS: A total of 167 PDAC patients and 113 healthy controls were included in this study and were divided into three sets. In the discovery set, we found 4625 differentially methylated positions (DMPs) between cancer group and healthy controls. ZFHX3 (0.16 ± 0.04 vs. 0.18 ± 0.04, P = 0.001), cg01904886 (0.84 ± 0.05 vs. 0.81 ± 0.04, P = 0.02) and NUMBL (0.96 ± 0.005 vs. 0.957 ± 0.005, P = 0.04) were found to be significantly different in training set. The locus with more significant differences, namely ZFHX3, was used for further validation and to establish a combined diagnostic panel with CA19-9. In the validation set, the ROC curve indicated that the AUC value of ZFHX3 was 0.75. The AUC value of the combined model (AUC = 0.92) was higher than that of CA19-9 alone (AUC = 0.88). In patients with normal CA19-9 levels, the ZFHX3 methylation biomarker still maintained good diagnostic efficacy (AUC = 0.71). CONCLUSION: Our study preliminarily suggests that ZFHX3 methylation combined with CA19-9 can improve the detection rate of PDAC. Especially in patients with normal CA19-9, ZFHX3 methylation can maintain stable diagnostic efficacy. The diagnostic value of ZFHX3 methylation still needs to be prospectively validated.

4.
J Environ Manage ; 351: 119869, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142596

RESUMO

The stacking of phosphogypsum has caused considerable phosphorus pollution in water bodies near phosphogypsum yards through surface runoff and underground infiltration. The phosphate oxygen isotope (δ18Op) tracing method has served as a valuable tool for tracing phosphorus pollution in water. However, the existing δ18Op enrichment and purification methods are complex, costly, and inefficient for phosphate recovery, particularly for phosphogypsum leachate with complex compositions. Herein, a simplified and optimized pretreatment method for δ18Op measurement in phosphogypsum leachate was developed. Zirconium/polyvinyl alcohol (Zr/PVA) gel beads showed good selectivity for phosphate enrichment from water at different initial phosphate concentrations with appropriate Zr/PVA dosage. The optimal enrichment pH value was <7, and the concentrated phosphate on the Zr/PVA gel beads could be effectively eluted in an alkaline environment. Compared with the traditional Fe or Mg coprecipitation enrichment methods, impurities in the solution showed no obvious adverse effects on the phosphate enrichment process. Further, the phosphate solution eluted from the Zr/PVA gel beads was purified by a simple adjustment of the pH instead of cation exchange in the traditional purification process. Magnesium ions in the solution could be completely removed when the pH ranged from 3.17 to 6.15, and the phosphate recovery rate could reach 98.66% when the eluent pH was 5.02. Fourier-transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy revealed that similar to traditional pretreatment method, the proposed method can obtain high-purity Ag3PO4 solids for δ18OP measurement and no isotope fractionation of δ18OP was observed. Therefore, this study provides a promising and reliable pretreatment method for δ18OP measurement, especially in complex phosphogypsum leachate.


Assuntos
Sulfato de Cálcio , Fosfatos , Fósforo , Isótopos de Oxigênio , Fósforo/química , Água
5.
J Environ Manage ; 360: 121108, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754189

RESUMO

A novel air-lifting loop reactor combines anoxic, oxic, and settling zones to achieve organic and nutrient removal, as well as solid-liquid separation. To address sludge settling ability and operation stability issues caused by low dissolved oxygen in aerobic zones, this study proposes using modified polypropylene carriers to establish a fixed-film activated sludge (IFAS) system. A pilot-scale demonstration of the IFAS-based air-lifting loop reactor is conducted, and the results show successful operation for approximately 300 days. The pilot-scale reactor achieves a maximum aerobic granulation ratio of 16% in the bulk liquid. The IFAS system contributes to efficient removal of organic matter (96%) and nitrogen (94%) by facilitating simultaneous nitrification and denitrification, as well as fast solid-liquid separation with a low sludge volume index of 34 mL/g. Microbial analysis reveals enrichment of functional bacteria involved in nitrification, denitrification, and flocculation throughout the operation process.


Assuntos
Reatores Biológicos , Nitrogênio , Esgotos , Eliminação de Resíduos Líquidos , Águas Residuárias , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Desnitrificação , Nitrificação , Projetos Piloto
6.
Anal Chem ; 95(28): 10644-10654, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37403970

RESUMO

The efficacy of radiotherapy (RT) is usually restricted by the hypoxic microenvironment and the poor radiation attenuation coefficient of tumor tissue. Theranostic probes that simultaneously evaluate the hypoxia degree and sensitize cancer cells toward RT are promising for improving the treatment efficacy and avoiding overtreatment. We rationally designed a metal-organic framework (MOF)-derived multifunctional nanoprobe for hypoxia imaging-guided radiosensitization. Hf-MOF was carbonized to obtain a porous carbonous nanostructure containing ultrasmall HfO2 (HfC); then, a fluorophore-labeled HIF-α mRNA antisense sequence was readily adsorbed and quenched by HfC to obtain the nanoprobe (termed HfC-Hy). The antisense sequence could easily hybridize with HIF-α mRNA and recover its fluorescence signal to evaluate the degree of hypoxia, while the HfC nanostructure could deposit more radiation energy in cancer cells for radiosensitization. A series of in vitro and in vivo experiments demonstrated that the nanoprobe could be successfully utilized for imaging the hypoxic degree of cancer cells/tumor tissue and guiding radiosensitization. This work not only developed a highly efficient and safe nanosensitizer but also offered a potential solution for customized clinical RT.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Humanos , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/química , Linhagem Celular Tumoral , Hipóxia , Diagnóstico por Imagem , Neoplasias/patologia , RNA Mensageiro , Microambiente Tumoral
7.
Inorg Chem ; 62(41): 16825-16831, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37779255

RESUMO

By harnessing the power of coordination self-assembly, crystalline materials can act as carriers for photoacids. Unlike their solution-based counterparts, these photoacids are capable of altering the properties of the crystalline material under light and can even generate proton transfer in a solid-state environment. Due to the photoinduced proton transfer and charge transfer processes within this functional material, this crystal exhibits powerful absorption spanning the visible to near-infrared spectrum upon light irradiation. This feature enables reproducible, significant chromatic variation, near-infrared photothermal conversion, and photocontrollable conductivity for this photoresponsive material. The findings suggest that the synthesis of pyranine photoacid-based crystalline materials via coordination self-assembly can not only enhance light-harvesting efficiency but also enable excited-state proton transfer processes within solid crystalline materials, thereby maintaining and even improving the properties of photoacids.

8.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36982414

RESUMO

Long noncoding RNAs (lncRNAs) play crucial roles in various biological processes, and they are considered to be closely associated with the pathogenesis of intestinal diseases. However, the role and expression of lncRNAs in intestinal damage during weaning stress remain unknown. Herein, we investigated the expression profiles of jejunal tissue from weaning piglets at 4 and 7 d after weaning (groups W4 and W7, respectively) and from suckling piglets on the same days (groups S4 and S7, respectively). Genome-wide analysis of lncRNAs was also performed using RNA sequencing technology. A total of 1809 annotated lncRNAs and 1612 novel lncRNAs were obtained from the jejunum of piglets. In W4 vs. S4, a total of 331 lncRNAs showed significant differential expression, and a total of 163 significantly differentially expressed lncRNAs (DElncRNAs) was identified in W7 vs. S7. Biological analysis indicated that DElncRNAs were involved in intestinal diseases, inflammation, and immune functions, and were mainly enriched in the Jak-STAT signaling pathway, inflammatory bowel disease, T cell receptor signaling pathway, B cell receptor signaling pathway and intestinal immune network for IgA production. Moreover, we found that lnc_000884 and target gene KLF5 were significantly upregulated in the intestine of weaning piglets. The overexpression of lnc_000884 also significantly promoted the proliferation and depressed apoptosis of IPEC-J2 cells. This result suggested that lnc_000884 may contribute to repairing intestinal damage. Our study identified the characterization and expression profile of lncRNAs in the small intestine of weaning piglets and provided new insights into the molecular regulation of intestinal damage during weaning stress.


Assuntos
RNA Longo não Codificante , Suínos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Desmame , Intestino Delgado/metabolismo , Jejuno
9.
Biochem Biophys Res Commun ; 632: 1-9, 2022 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-36191371

RESUMO

OBJECTIVE: This study aimed to determine the role of COL17A1 in tumor progression and predict the prognosis of pancreatic cancer (PC). METHODS: RNA-seq data from The Cancer Genome Atlas and Genotype-Tissue Expression were analyzed using bioinformatics methods. "Limma" package was used to screen differentially expressed genes (DEGs). Prognostic-associated data were further analyzed using univariate Cox regression and verified using the GSE28375 and GSE62452 datasets. Protein-protein interaction (PPI) network analysis was integrated to screen for hub genes. In vitro quantitative real-time PCR (qPCR) and western blotting were used to detect gene expression. The functional attributes of PC cells were verified by wound healing assays, migration and invasion assays, Cell Counting Kit 8 (CCK8), and 5-ethynyl-2'-deoxyuridine (EdU) assay. RESULTS: On analyzing PC data, 4637 DEGs were identified. Of these, 2399 genes were upregulated and 2238 were downregulated. Through PPI network analysis, we identified that COL17A1 expression was highly correlated with poor prognosis of patients with PC. Functional attribute assays in the in vitro study showed that COL17A1 knockdown inhibited PC cell proliferation, migration, and invasion. CONCLUSIONS: According to our results, COL17A1 promotes PC cell proliferation, migration, and invasion mediated by the epithelial-mesenchymal transition (EMT) pathway. Thus, COL17A1 could be used as a prognostic marker in PC.


Assuntos
Neoplasias Pancreáticas , Humanos , Movimento Celular/genética , Linhagem Celular Tumoral , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Transição Epitelial-Mesenquimal/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas
10.
Int J Mol Sci ; 23(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36012290

RESUMO

Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain (FTH1) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR, respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.


Assuntos
Carcinoma de Células Escamosas , Ferroptose , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Anticorpos Monoclonais/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Neoplasias da Língua/tratamento farmacológico
11.
Curr Psychol ; : 1-11, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36531197

RESUMO

This study aimed to examine the relations between perceived teacher emotional support, Covid-19 anxiety, resilience, and mental well-being among Chinese vocational college students during Covid-19 pandemic. A sample of Chinese vocational college students (n = 1469) were surveyed with an online questionnaire composed of Teacher Emotional Support, Covid-19 Anxiety Scale, Brief Resilience Scale and Mental Well-being in Chinese version. Path analysis was employed in the study and the results showed that teacher emotional support was an important promoter for building up mental well-being but not a buffer for Covid-19 within Chinese cultural context, and the Covid-19 anxiety was significantly and negatively related to mental well-being. Resilience hindered the incidences of Covid-19 anxiety and was a significant protector for mental well-being. Covid-19 anxiety mediated the both relations between teacher emotional support and mental well-being, and resilience and mental well-being. These findings provided practical implications for coping with psychological problems and flourishing mental well-being among Chinese vocational college students. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-04112-9.

12.
Cancer Sci ; 112(10): 4220-4233, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34363722

RESUMO

The ascites that develops in advanced OC, both at diagnosis and upon recurrence, is a rich source of multicellular spheroids/aggregates (MCSs/MCAs), which are the major seeds of tumor cell dissemination within the abdominal cavity. However, the molecular mechanism by which specific ascites-derived tumor cells survive and metastasize remains largely unknown. In this study, we elucidated cancer stem cell (CSC) properties of ascites-derived MCSs, concomitant with enhanced malignancy, induced EMT, and low KLF9 (Krüppel-like factor 9) expression, compared with PTCs. KLF9 was also downregulated in OC cell line-derived spheroids and the CD117+ CD44+ subpopulation in MCSs. Functional experiments demonstrated that KLF9 negatively modulated stem-like properties in OC cells. Mechanistic studies revealed that KLF9 reduced the transcriptional expression of Notch1 by directly binding to the Notch1 promoter, thereby inhibiting the function of slug in a CSL-dependent manner. Clinically, expression of KLF9 was associated with histological grade and loss of KLF9 predicts poor prognosis in OC.


Assuntos
Ascite/patologia , Fatores de Transcrição Kruppel-Like/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/patologia , Receptor Notch1/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Esferoides Celulares/patologia , Linhagem Celular Tumoral , Movimento Celular , Regulação para Baixo , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , Fatores de Transcrição Kruppel-Like/fisiologia , Gradação de Tumores , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Prognóstico , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-kit/metabolismo , Transdução de Sinais , Esferoides Celulares/metabolismo
13.
Anal Chem ; 93(45): 15150-15158, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34738799

RESUMO

Mimicking enzyme specificity via construction of on-demand geometric structures on nanozymes is of great interest in recent years. Although building substrate-specific polymers on nanozymes has achieved great success, polymer-blocked active sites would inevitably lead to decreased activity of nanozymes. Here, we have developed three photoactive metal-organic framework (MOF)-based nanozymes (called 2D-TCPP, 3D-TCPP, and AD-TCPP), which have different geometric structures as well as unshielded active sites. Together with their structural variations and excellent photoresponsive oxidase-like activities, these photoactive nanozymes exhibit structure-dependent specificity for three kinds of substrates (typical oxidase substrates, organic pollutants, and antioxidants). Moreover, AD-TCPP and 3D-TCPP show potential applications for environmental protection and bioanalysis, respectively. This work offers a promising approach to the development of nanozymes with enzyme-like specificity.


Assuntos
Estruturas Metalorgânicas , Nanoestruturas , Catálise , Oxirredutases , Especificidade por Substrato
14.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445601

RESUMO

Ferroptosis, an iron-dependent form of programmed cell death, has excellent potential as an anti-cancer therapeutic strategy in different types of tumors, especially in RAS-mutated ones. However, the function of ferroptosis for inhibiting neuroblastoma, a common child malignant tumor with minimal treatment, is unclear. This study investigated the anti-cancer function of ferroptosis inducer Erastin or RSL3 in neuroblastoma N2A cells. Our results show that Erastin or RSL3 induces ROS level and cell death and, therefore, reduces the viability of RAS-proficient N2A cells. Importantly, inhibitors to ferroptosis, but not apoptosis, ameliorate the high ROS level and viability defect in Erastin- or RSL3-treated cells. In addition, our data also show that N2A cells are much more sensitive to ferroptosis inducers than primary mouse cortical neural stem cells (NSCs) or neurons. Moreover, a higher level of ROS and PARylation is evidenced in N2A, but not NSCs. Mechanically, ferritin heavy chain 1 (Fth), the ferroxidase function to oxidate redox-active Fe2+ to redox-inactive Fe3+, is likely responsible for the hypersensitivity of N2A to ferroptosis induction since its expression is lower in N2A compared to NSCs; ectopic expression of Fth reduces ROS levels and cell death, and induces expression of GPX4 and cell viability in N2A cells. Most importantly, neuroblastoma cell lines express a significantly low level of Fth than almost all other types of cancer cell lines. All these data suggest that Erastin or RSL3 induce ferroptosis cell death in neuroblastoma N2A cells, but not normal neural cells, regardless of RAS mutations, due to inadequate FTH. This study, therefore, provides new evidence that ferroptosis could be a promising therapeutic target for neuroblastoma.


Assuntos
Ferritinas/metabolismo , Ferroptose , Células-Tronco Neurais/patologia , Neuroblastoma/patologia , Oxirredutases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas ras/metabolismo , Animais , Apoptose , Feminino , Ferritinas/genética , Ferro/metabolismo , Peroxidação de Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Oxirredução , Oxirredutases/genética , Piperazinas/metabolismo , Proteínas ras/genética
15.
Dev Dyn ; 249(7): 794-815, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32314458

RESUMO

BACKGROUND: Craniofacial anomalies are among the most frequent birth defects worldwide, and are thought to be caused by gene-environment interactions. Genetically manipulated zebrafish simulate human diseases and provide great advantages for investigating the etiology and pathology of craniofacial anomalies. Although substantial advances have been made in understanding genetic factors causing craniofacial disorders, limited information about the etiology by which environmental factors, such as teratogens, induce craniofacial anomalies is available in zebrafish. RESULTS: Zebrafish embryos displayed craniofacial malformations after teratogen treatments. Further observations revealed characteristic disruption of chondrocyte number, shape and stacking. These findings suggested aberrant development of cranial neural crest (CNC) cells, which was confirmed by gene expression analysis of the CNC. Notably, these observations suggested conserved etiological pathways between zebrafish and mammals including human. Furthermore, several of these chemicals caused malformations of the eyes, otic vesicle, and/or heart, representing a phenocopy of neurocristopathy, and these chemicals altered the expression levels of the responsible genes. CONCLUSIONS: Our results demonstrate that chemical-induced craniofacial malformation is caused by aberrant development of neural crest. This study indicates that zebrafish provide a platform for investigating contributions of environmental factors as causative agents of craniofacial anomalies and neurocristopathy.


Assuntos
Anormalidades Craniofaciais/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Crista Neural/citologia , Teratogênicos , Peixe-Zebra/embriologia , Peixe-Zebra/crescimento & desenvolvimento , Animais , Apoptose , Cartilagem/efeitos dos fármacos , Cartilagem/embriologia , Diferenciação Celular , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Anormalidades Craniofaciais/induzido quimicamente , Modelos Animais de Doenças , Olho/efeitos dos fármacos , Olho/embriologia , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Interação Gene-Ambiente , Masculino , Exposição Materna , Crista Neural/efeitos dos fármacos , Organogênese/efeitos dos fármacos , Organogênese/genética , Crânio , Proteínas de Peixe-Zebra/genética
16.
Reproduction ; 158(5): 441-452, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31546232

RESUMO

It is well documented that granulosa cell apoptosis is the main reason for follicular atresia and death; however, increasing evidence suggests that autophagy plays an important role in the fate of granulosa cells. miR-21-3p regulates many fundamental biological processes and is pivotal in the autophagy of tumor cells; nevertheless, the autophagy in cattle ovary and how miR-21-3p regulates the follicular cells is unknown. In this study, we aimed to elucidate the autophagy and the role of miR-21-3p in cattle ovary using bovine primary ovarian granulosa cells (BGCs). The results showed the autophagy for the first time in BGCs in large follicle according to autophagic gene transcript of LC3, BECN-1, ATG3, protein expression of LC3, P62 and LC3 puncta, a standard marker for autophagosomes. miR-21-3p was identified as a novel miRNA that repressed BGCs autophagy according to the results from plasmids transfection of miR-21-3p mimics and inhibitor. Meanwhile, VEGFA was confirmed to be a validated target of miR-21-3p in BGCs using luciferase reporter assays and the results of VEGFA expression decreased with transfection of miR-21-3p mimics, while it increased with transfection of miR-21-3p inhibitor. In addition, small interference-mediated knockdown of VEGFA significantly inhibits BGCs autophagy signaling; however, overexpression of VEGFA in BGCs promoted autophagy in the presence of miR-21-3p. Finally, the results of AKT and its phosphorylation suggested that miR-21-3p suppressed VEGFA expression through downregulating AKT phosphorylation signaling. In summary, this study demonstrates that miR-21-3p inhibits BGCs autophagy by targeting VEGFA and attenuating PI3K/AKT signaling.


Assuntos
Autofagia/genética , Células da Granulosa/fisiologia , MicroRNAs/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Bovinos , Células Cultivadas , Regulação para Baixo , Feminino , Regulação da Expressão Gênica , Fosforilação , Cultura Primária de Células , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Langmuir ; 35(29): 9493-9503, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31240936

RESUMO

We have computed the free energy per unit area (i.e., interfacial tension) between a solid surface and two coexisting polymer solutions, where there is no specific interaction between the particles and either polymer, via self-consistent field calculations. Several different systems have been studied, including those where the two polymers differ in molecular weight (Mw) by a factor of ∼2 or where the polymers have the same Mw, but one set of chains is branched with the other linear. In the absence of any enthalpic contribution resulting from adsorption on the solid particle surface, the differences in the free energy per unit area resulting from the polymer-depleted regions around the particles in the two coexisting phases are found to be ∼1 µN m-1. Although this value may seem rather small, this difference is more than capable of inducing the partitioning of particles of 100 nm in size (or larger) into the phase with the lower interfacial free energy at the solid surface. By examining the density profile variation of the polymers close to the surface, we can also infer information about the wettability and contact angle (θ) of solid particles at the interface between the two coexisting phases. This leads to the conclusion that for all systems of this type, when the incompatibility between the two polymers is sufficiently large, θ will be close to 90°.

18.
Nanotechnology ; 30(42): 425301, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31315092

RESUMO

In situ exsolved nanoparticles (NPs) on surfaces perform well in many catalytic applications. Herein, an emerging technique of pulsed electric current (PEC) for facilitating NPs exsolution was firstly utilized in functional materials towards tailoring structure and morphology of materials. PEC facilitated Ni NPs exsolution in situ and the exposed active sites were highly dispersed on the LaCrO3 substrate surface. Such result was confirmed by combining x-ray diffraction, scanning electron microscopy, and high-resolution transmission electron microscopy. As a consequence, PEC-treated and untreated LaCrO3 perovskite samples were employed as electrocatalysts for oxygen evolution reaction (OER). The PEC-treated samples exhibit obviously improved OER activity (lower overpotential, smaller Tafel slope) and lower reaction resistance than the untreated samples. This illustrates that the exsolved Ni NPs driven by PEC are beneficial for the OER performance and are probably the components of the OER active sites.

19.
J Clin Monit Comput ; 33(3): 419-429, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30073444

RESUMO

Recently, we developed a novel endotracheal catheter with functional cuff (ECFC). Using such an ECFC and a regular ICU ventilator, we were able to generate clinically relevant tidal volume in a lung model and adult human sized animal. This ECFC allows co-axial ventilation without using a jet ventilator. The aim of this study was to determine if ECFC also could generate clinically relevant positive end expiratory pressure (PEEP). The experiment was conducted on a model lung and artificial trachea. Lung model respiratory mechanics were set to simulate those of an adult human being. The tip of the distal end of ECFC 14 or 19 Fr catheter was positioned in the artificial trachea 3 cm above the carina. The proximal end of ECFC was connected to an ordinary ICU ventilator. With 14 Fr catheter at respiratory rate 10 bpm, PEEP 0, 2.9, 8.2, 12.9 cmH2O was generated at preset PEEP 0, 5, 10, 15 cmH2O respectively and tidal volume was up to 393.4 ml. With 19 Fr catheter, PEEP was 0, 2.8, 7.6, 12.3 cmH2O, at preset PEEP 0, 5, 10, 15 cmH2O respectively and the tidal volume was up to 667.3 ml. With 14 Fr catheter at respiratory rate 20 bpm, PEEP was 0, 3.9, 9.6, 14.6 cmH2O at preset PEEP 0, 5, 10, 15 cmH2O respectively and tidal volume was up to 188.8 ml. With 19 Fr catheter, PEEP was 0, 3.6, 8.9, 13 cmH2O, at preset PEEP 0, 5, 10, 15 cmH2O respectively and tidal volume was up to 345.3 ml. ECFC enables clinicians to generate not only adequate tidal volume but also clinically relevant PEEP via co-axial ventilation using an ordinary ICU ventilator.


Assuntos
Respiração com Pressão Positiva/instrumentação , Mecânica Respiratória , Taxa Respiratória , Volume de Ventilação Pulmonar , Ventiladores Mecânicos , Calibragem , Cateterismo , Cuidados Críticos/métodos , Desenho de Equipamento , Humanos , Unidades de Terapia Intensiva , Pulmão/fisiologia , Troca Gasosa Pulmonar , Respiração Artificial , Traqueia/patologia , Traqueia/fisiologia
20.
Opt Express ; 26(13): 17185-17198, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-30119533

RESUMO

In this paper, a compact four-degree-of-freedom (4-DOF) measurement system is presented. With a special optical configuration, the pitch error, yaw error, and two straightness errors of the moving target are able to be detected by only a single laser beam from a collimated laser diode. A 2D hybrid mirror angle steering mount is designed to perform the large angle turning for the axis alignment and very fine angle tuning by PZT actuators for real-time beam drift compensation. A series of calibration and comparison experiments have been carried out to verify the performance of the proposed system. The developed active compensation system could effectively suppress the beam's angular drift to within ± 0.01 arc-sec in both of yaw and pitch directions. The developed 4-DOF measuring system is compact, low cost, and suitable for long distance geometric error measurement of linear stages.

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