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1.
Arch Biochem Biophys ; 760: 110108, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39084281

RESUMO

Maternal inflammation can lead to premature birth and fetal brain damage. CircRNA_19038 and lncRNA-AK016022 have been shown to be significantly reduced in brain tissues of preterm mice, while whether they are involved in the regulation of preterm white matter injury remains to be explored. Pregnant mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish a preterm brain injury model. Healthy mice born at term served as controls. Lentivirus-mediated circ_19038 overexpression vector (LV-circ_19038), LV-lnc-AK016022, LV-Sirt1 and LV-sh-Sirt1 were administered to preterm mice through the ventricles. The expression levels of circ_19038, lnc-AK016022 and Sirt1 in the brain tissues of preterm mice were significantly lower than those of full-term healthy mice, and circ_19038 and lnc-AK016022 were co-localized in the brain tissues. Upregulation of circ_19038 or/and lnc-AK016022 promoted remyelination and alleviated white matter structural damage, neuroinflammation, and long-term cognitive and motor deficits in preterm mice, and the combined effect of circ_19038 and lnc-AK016022 showed better results. Primary mouse neuronal cells were isolated to investigate the regulatory effects of circ_19038 and lnc-AK016022 on Sirt1. Circ_19038 and lnc-AK016022 jointly promoted the expression of Sirt1 by adsorbing miR-1b and miR-328, respectively. Moreover, silencing Sirt1 antagonized the beneficial effects of circ_19038 or/and lnc-AK016022 on brain white matter injury in preterm mice. In conclusion, circ_19038 and lnc-AK016022 synergistically regulated Sirt1 expression to promote remyelination and alleviate white matter injury in preterm mice.


Assuntos
RNA Circular , RNA Longo não Codificante , Sirtuína 1 , Substância Branca , Animais , Sirtuína 1/metabolismo , Sirtuína 1/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Camundongos , Substância Branca/metabolismo , Substância Branca/patologia , Substância Branca/lesões , Feminino , Gravidez , RNA Circular/genética , RNA Circular/metabolismo , Remielinização , Camundongos Endogâmicos C57BL , Lipopolissacarídeos/toxicidade , Nascimento Prematuro , Encéfalo/metabolismo , Encéfalo/patologia
2.
Biochem Genet ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376577

RESUMO

The aim of this study was to investigate the role and mechanism of circ-RNF111 in the human ovarian cancer cell line SKOV-3. First, qRT-PCR was used to detect circ-RNF111 and miR-556-5p expression levels in human normal ovarian epithelial cells IOSE80 and human ovarian cancer cells SKOV-3. CCK-8 and colony formation assays were adopted to determine the proliferation rate and cell viability of SKOV-3 cells, respectively. Additionally, in an attempt to reveal the mechanism of circ-RNF111, we predicted the targeting relationship between miR-556-5p and circ-RNF111 as well as miR-556-5p and CCND1 using the circinteractome and TargetScan databases, respectively, and validated their relationship by dual-luciferase reporter assay. The protein expression levels of CCND1 in SKOV-3 cells were detected by Western blot. Based on the above experiments, the expression of circ-RNF111 was found to be up-regulated in SKOV-3, and the knockdown of circ-RNF111 significantly inhibited the proliferation and viability of SKOV-3 cells. Then we confirmed that circ-RNF111 sponged miR-556-5p in SKOV-3 cells to up-regulate CCND1 expression. In addition, simultaneous inhibition of miR-556-5p or overexpression of CCND1 in SKOV-3 cells with knockdown of circ-RNF111 reversed the inhibitory effect of knockdown of circ-RNF111 on the protein expression level of CCND1, cell proliferation rate, and cell viability. In summary, circ-RNF111 promotes the proliferation of SKOV-3 cells by targeting the miR-556-5p/CCND1 axis. Circ-RNF111 may serve as a potential target for ovarian cancer therapy.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 432-436, 2024 Apr 15.
Artigo em Zh | MEDLINE | ID: mdl-38660910

RESUMO

The patient, a male newborn, was admitted to the hospital 2 hours after birth due to prematurity (gestational age 27+5 weeks) and respiratory distress occurring 2 hours postnatally. After admission, the infant developed fever and elevated C-reactive protein levels. On the fourth day after birth, metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis (9 898 reads). On the eighth day, a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis (56 806 reads). The diagnosis of purulent meningitis caused by Mycoplasma hominis was established, and the antibiotic treatment was switched to moxifloxacin [5 mg/(kg·day)] administered intravenously for a total of 4 weeks. After treatment, the patient's cerebrospinal fluid tests returned to normal, and he was discharged as cured on the 76th day after birth. This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis, introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.


Assuntos
Lactente Extremamente Prematuro , Moxifloxacina , Mycoplasma hominis , Humanos , Mycoplasma hominis/isolamento & purificação , Recém-Nascido , Masculino , Moxifloxacina/uso terapêutico , Moxifloxacina/administração & dosagem , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Meningites Bacterianas/diagnóstico , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/diagnóstico , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem
4.
PLoS Pathog ; 17(3): e1009347, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33647067

RESUMO

In the field, many insect-borne crop viral diseases are more suitable for maintenance and spread in hot-temperature areas, but the mechanism remains poorly understood. The epidemic of a planthopper (Sogatella furcifera)-transmitted rice reovirus (southern rice black-streaked dwarf virus, SRBSDV) is geographically restricted to southern China and northern Vietnam with year-round hot temperatures. Here, we reported that two factors of endoplasmic reticulum-associated degradation (ERAD) machinery, the heat shock protein DnaJB11 and ER membrane protein BAP31, were activated by viral infection to mediate the adaptation of S. furcifera to high temperatures. Infection and transmission efficiencies of SRBSDV by S. furcifera increased with the elevated temperatures. We observed that high temperature (35°C) was beneficial for the assembly of virus-containing tubular structures formed by nonstructural protein P7-1 of SRBSDV, which facilitates efficient viral transmission by S. furcifera. Both DnaJB11 and BAP31 competed to directly bind to the tubule protein P7-1 of SRBSDV; however, DnaJB11 promoted whereas BAP31 inhibited P7-1 tubule assembly at the ER membrane. Furthermore, the binding affinity of DnaJB11 with P7-1 was stronger than that of BAP31 with P7-1. We also revealed that BAP31 negatively regulated DnaJB11 expression through their direct interaction. High temperatures could significantly upregulate DnaJB11 expression but inhibit BAP31 expression, thereby strongly facilitating the assembly of abundant P7-1 tubules. Taken together, we showed that a new temperature-dependent protein quality control pathway in the ERAD machinery has evolved for strong activation of DnaJB11 for benefiting P7-1 tubules assembly to support efficient transmission of SRBSDV in high temperatures. We thus deduced that ERAD machinery has been hitchhiked by insect-borne crop viruses to enhance their transmission in tropical climates.


Assuntos
Temperatura Alta/efeitos adversos , Insetos Vetores/virologia , Doenças das Plantas/virologia , Reoviridae/imunologia , Animais , Degradação Associada com o Retículo Endoplasmático/imunologia , Insetos Vetores/imunologia , Orthoreovirus/patogenicidade
5.
Microb Pathog ; 176: 105993, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36657690

RESUMO

Edwardsiella tarda is a causative pathogen of edwardsiellosis in fish. Our previous studies on high (NUF251) and low (NUF194) virulent strains of E. tarda demonstrated that NUF251 strain induced significantly higher levels of NO and TNF-α from fish and mouse macrophages than NUF194 strain. Subsequent studies suggested that a flagellin-like protein secreted from E. tarda might be a responsible factor for the macrophage-stimulating activities. To evaluate the activities of flagellins of E. tarda, in this study, the flagellin genes of NUF251 and NUF194 strains were isolated by PCR and cloned into pQE-30 and pCold I expression vectors, and then the recombinant flagellins of two strains were overexpressed in E. coli JM109 and pG-Tf/BL21, respectively. The molecular weight of the purified recombinant flagellins of NUF251 and NUF194 strains were estimated to be 45 kDa and 37 kDa, respectively on SDS-PAGE analysis. Referring the three-dimensional structure of Salmonella flagellin, which has been reported to have 4 domains (D0, D1, D2, and D3), high sequence homology between two flagellins of E. tarda was observed at conservative domain (D0 and D1) regions, whereas the sequences equivalent to D2 and D3 domains were different, and even equivalent to 57 amino acids were deleted in NUF194. Both recombinant flagellins induced NO production, mRNA expression level of inducible NO synthase (iNOS), and intercellular ROS production in mouse macrophage cell line RAW264.7 cells. Also, the secretion of TNF-α and its mRNA expression level were increased by treatment of both recombinant flagellins. These results indicate that the recombinant flagellins from different virulent E. tarda strains can stimulate macrophages with nearly equal levels as judged by the parameters tested, even though they are differences in the structure and molecular weight, suggesting that conservative D0 and D1 domains are sufficient structural elements for the recombinant flagellins to induce a certain level of macrophage-stimulation in vitro. Further studies are necessary focusing on the role of D2 and D3 domain regions of the recombinant flagellins as macrophage-stimulating agent as well as their influence on host immune system in vivo.


Assuntos
Infecções por Enterobacteriaceae , Doenças dos Peixes , Animais , Camundongos , Flagelina/genética , Edwardsiella tarda/genética , Sequência de Bases , Virulência , Fator de Necrose Tumoral alfa/genética , Escherichia coli/genética , Macrófagos , Peixes/genética , Clonagem Molecular
6.
Molecules ; 28(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36677713

RESUMO

Malus hupehensis (MH), as a natural resource, contains various active ingredients such as polyphenols, polysaccharides, proteins, amino acids, volatile substances, and other components. Increasingly, studies have indicated that MH showed a variety of biological activities, including antioxidant, hypoglycemic, hypolipidemic, anti-cancer, anti-inflammatory activities, and other activities. Hence, MH has attracted wide interest because of its high medical and nutritional value. It is necessary to review the active components and biological activities of MH. This paper systematically reviewed the chemical substances, biological activities, and potential problems of MH to further promote the related research of MH and provide an important reference for its application and development in medicine and food.


Assuntos
Malus , Malus/química , Polifenóis/farmacologia , Polifenóis/metabolismo , Antioxidantes/química , Hipoglicemiantes/metabolismo
7.
J Sep Sci ; 44(9): 1843-1851, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33595167

RESUMO

For a rapid enrichment and separation of minor components from Malus hupehensis, the selection of suitable solvent system is the great challenge for liquid-liquid extraction with a three-phase solvent system and high-speed counter-current chromatography. According to the concept of "like dissolves like," the similarity of the average polarity between solvent system and target compounds was the significant characteristic of liquid-liquid extraction with a three-phase solvent system and high-speed counter-current chromatography separation. The polarity parameter model provides a way to calculate the polarity of unknown compounds. Under the guidance of the polarity, an efficient enrichment and separation approach was established through liquid-liquid extraction and high-speed counter-current chromatography with solvent systems composed of n-hexane-ethyl acetate-acetonitrile-water (5:3:5:7, v/v), n-hexane-ethyl acetate-methanol-water (1:2:1:2, v/v), respectively. Thus, the total content of minor compounds was increased from 2.6% to 17.2%, and two novel compounds (6´´-O-coumaroyl-2´-O-glucopyranosylphloretin and 3´´´-methoxy-6´´-O-feruloy-2´-glucopyranosylphloretin) were obtained. The discovery of the new dihydrochalcones expanded the structural diversity of compounds produced by the genus Malus. The experimental results demonstrated that compound polarity can be described by the polarity parameter model and is an important reference for investigating optimum solvent systems for liquid-liquid extraction with a three-phase solvent system and high-speed counter-current chromatography.


Assuntos
Extração Líquido-Líquido , Malus/química , Fenóis/isolamento & purificação , Acetatos/química , Acetonitrilas/química , Distribuição Contracorrente , Hexanos/química , Metanol/química , Fenóis/química , Solventes/química , Água/química
8.
Molecules ; 26(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921423

RESUMO

Malus hupehensis (M. hupehensis), an edible and medicinal plant with significant antioxidant and hypoglycemic activity, has been applied to new resource foods. However, the structural characterization and biological effects of its polysaccharides (MHP) are less known. The optimum extraction parameters to achieve the highest extraction efficiency (47.63%), the yield (1.68%) and purity of MHP (89.6%) by ultrasonic-assisted aqueous two-phase system (ATPS) were obtained under the liquid-to-solid ratio of 23 g/mL, ultrasonic power of 65 W, and ultrasonic time of 33 min. According to the analysis results, MHP was composed of Man, GlcA, Rha, GalA, Glc, Gal, Xyl, Ara, and Fuc, in which Ara and Gal were the main components, and the content of GlcA was the lowest. In in vitro activity analysis, MHP showed a significant antioxidant capacity, and an inhibition activity of α-glucosidase and the advanced glycation end products (AGEs) formation in the BSA/Glc reaction model. MHP interacted with α-glucosidase and changed the internal microenvironment of the enzyme, and inhibited the AGEs formation, which provides more evidence for the antihyperglycemic mechanism of MHP. The results suggest that ATPS is an efficient and environmentally friendly solvent system, and M. hupehensis has broad application prospects in functional foods, healthcare products, and pharmaceuticals.


Assuntos
Malus/química , Polissacarídeos/isolamento & purificação , Ultrassom , Água/química , Antioxidantes/farmacologia , Dicroísmo Circular , Etanol/química , Produtos Finais de Glicação Avançada/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Monossacarídeos/análise , Extratos Vegetais/farmacologia , Sais/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
9.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(6): 563-568, 2021 Jun.
Artigo em Zh | MEDLINE | ID: mdl-34130776

RESUMO

OBJECTIVE: To study the association of neonatal blood calcium levels with perinatal factors and neonatal urinary calcium levels measured by an intelligent urine test system. METHODS: The medical data of 96 full-term singleton neonates with mild diseases were collected by a cross-sectional survey, who were hospitalized in the Department of Neonatology, The First Affiliated Hospital of Xi'an Jiaotong University, from June to August 2018. Urinary calcium levels measured by an intelligent urine test system, total blood calcium levels, ionized calcium levels, and the mother's calcium and vitamin D supplementation during pregnancy were recorded. RESULTS: Compared with the group without vitamin D supplementation for the mother (17 neonates), the group with vitamin D supplementation for the mother (79 neonates) had significantly higher levels of total blood calcium and ionized calcium (P < 0.05).The group with both vitamin D and calcium supplementation for the mother (68 neonates) had significantly higher levels of ionized calcium than controls (28 neonate) (P=0.05). There was no significant difference in the levels of total blood calcium and ionized calcium between the group with calcium supplementation for the mother (74 neonates) and the group without calcium supplementation for the mother (22 neonates) (P > 0.05). The hypothermia group (5 neonates) had a significantly lower level of total blood calcium than the normal body temperature group (91 neonates) (P < 0.05). There was a significantly positive correlation between the maternal blood total calcium level and the neonatal blood total calcium and ionized calcium levels (r=0.881 and 0.703 respectively; P < 0.05). The neonatal urinary calcium level measured by the intelligent urine test system was significantly correlated with the blood ionized calcium level (r=0.526, P=0.025). CONCLUSIONS: Vitamin D supplementation during pregnancy can increase the blood levels of total calcium and ionized calcium in neonates, and calcium supplementation alone cannot increase the blood levels of total calcium or ionized calcium in neonates. Hypothermia in neonates might cause the reduction in blood calcium levels. The urinary calcium level measured by the intelligent urine test system is positively correlated with the blood level of ionized calcium.


Assuntos
Cálcio , Deficiência de Vitamina D , Cálcio da Dieta , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Gravidez , Vitamina D
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(7): 730-734, 2021 Jul.
Artigo em Zh | MEDLINE | ID: mdl-34266532

RESUMO

OBJECTIVE: To determine the association of circular RNA (circRNA) and circRNA-microRNA (miRNA) network regulation with brain injury induced by inflammation in preterm mice. METHODS: Pregnant mice were treated with intraperitoneally injected lipopolysaccharide to establish a preterm mouse model of brain injury induced by inflammation (inflammation preterm group with 3 mice). Preterm mice born to normal pregnant mice by cesarean section were selected as controls (non-inflammation preterm group with 3 mice). The gene microarray technique was used to screen out the circRNAs associated with brain injury in preterm mice. The miRNA target prediction software was used to predict the binding sites between circRNAs and miRNAs and analyze the regulatory mechanism. RESULTS: A total of 365 differentially expressed circRNAs were screened out between the inflammation preterm and non-inflammation preterm groups (fold change > 1.5, P < 0.05), among which there were 206 upregulated circRNAs and 159 downregulated circRNAs. Further analysis of the circRNAs with a fold change of > 4 showed that these circRNAs could bind to miRNAs and regulate their activity, thereby regulating the expression of the genes associated with the nervous system. CONCLUSIONS: Inflammation induces a significant change in the expression profile of circRNAs in the brain tissue of mice, and the change in the expression of circRNAs plays an important role in brain injury induced by inflammation and subsequent brain development in preterm mice.


Assuntos
Lesões Encefálicas , MicroRNAs , Animais , Cesárea , Feminino , Perfilação da Expressão Gênica , Inflamação/genética , Camundongos , MicroRNAs/genética , Gravidez , RNA/genética , RNA Circular
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(6): 582-587, 2021 Jun.
Artigo em Zh | MEDLINE | ID: mdl-34130779

RESUMO

OBJECTIVE: To evaluate the efficacy of sepsis risk calculator (SRC) in guiding antibiotic use in neonates with suspected early-onset sepsis (EOS). METHODS: A total of 284 neonates with a gestational age of ≥ 35 weeks were enrolled as the control group, who were hospitalized in the Children's Hospital of Chongqing Medical University from March to July, 2019 and were suspected of EOS. Their clinical data were retrospectively collected and the use of antibiotics was analyzed based on SRC. A total of 170 neonates with a gestational age of ≥ 35 weeks were enrolled as the study group, who were admitted to the hospital from July to November, 2020 and were suspected of EOS. SRC was used prospectively for risk scoring to assist the decision making of clinical antibiotic management. The two groups were compared in terms of the rate of use of antibiotics, blood culture test rate, clinical outcome, and adherence to the use of SRC. RESULTS: Compared with the control group, the study group had a significantly higher SRC score at birth and on admission (P < 0.05). The rate of use of antibiotics in the study group was significantly lower than that in the control group[84.7% (144/170) vs 91.5% (260/284), 6.8% decrease; P < 0.05]. The blood culture test rate in the study group was also significantly lower than that in the control group (85.3% vs 91.9%, P < 0.05). There was no significant difference between the two groups in the incidence rate of adverse outcomes and the final diagnosis of EOS (P > 0.05). CONCLUSIONS: The use of SRC reduces the rate of empirical use of antibiotics in neonates with suspected EOS and does not increase the risk of adverse outcomes, and therefore, it holds promise for clinical application.


Assuntos
Sepse Neonatal , Sepse , Antibacterianos/uso terapêutico , Criança , Humanos , Lactente , Recém-Nascido , Sepse Neonatal/diagnóstico , Sepse Neonatal/tratamento farmacológico , Estudos Retrospectivos , Medição de Risco , Sepse/diagnóstico , Sepse/tratamento farmacológico
12.
Nanotechnology ; 31(5): 055706, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31614344

RESUMO

Highly dispersed CoTe electrode material were successfully prepared by using a facile one-step solvothermal process without any surfactants. Compared with the conventional hydrothermally prepared irregularly-shaped CoTe, a regular nanowire-formed CoTe can be obtained by a solvothermal process using ethylene glycol as a solvent. The prepared CoTe nanowire electrode can exhibit a relatively high specific capacity of 643.6 F g-1 at a current density of 1 A g-1 and remarkable cyclic stability with 76.9% of its specific capacitance retention after 5000 cycles at a high current density of 5 A g-1. Besides, even at the high current density of 20 A g-1, the specific capacitance of CoTe nanowire electrode still has 90.2% retention relative to 1 A g-1, showing an excellent rate performance. In order to enlarge the potential window to increase the energy density, an asymmetric supercapacitor (ASC) is assembled by applying CoTe nanowires and activated carbon as the positive electrode and the negative electrode in 3 M KOH, which can enlarge the operating voltage to as high as 1.6 V, and shows a specific capacity of 92.5 F g-1 with an energy density of 32.9 Wh kg-1 and power density of 800.27 W kg-1 at 1 A g-1, and even after 5000 cycles of charge/discharge at 5 A g-1, the ASC still retains 90.5% of its initial specific capacitance, showing excellent cycle stability.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(5): 441-445, 2020 May.
Artigo em Zh | MEDLINE | ID: mdl-32434638

RESUMO

OBJECTIVE: To compare intranasal midazolam and intramuscular phenobarbital sodium for their sedative effect in neonates undergoing magnetic resonance imaging (MRI). METHODS: A total of 70 neonates who underwent cranial MRI from September 2017 to March 2019 were randomized into an observation group and a control group, with 35 cases in each group. The observation group received intranasal drops of midazolam (0.3 mg/kg), and the control group received intramuscular injection of phenobarbital sodium (10 mg/kg). The sedation status of the neonates was evaluated using the Ramsay Sedation Scale. Meanwhile, the two groups were compared for the success rate of MRI procedure and incidence of adverse reactions. RESULTS: In the observation group, the sedation score was the highest at 20 minutes post administration, then was gradually decreasing, and decreased to the lowest level at 70 minutes post administration. In the control group, the sedation score was the lowest at 10 minutes post administration, then was gradually increasing, and increased to the highest level at 40 minutes and 50 minutes post administration, followed by a gradual decrease. Comparison of the sedation score at each time period suggested that the sedation score was significantly higher in the observation group than in the control group within 40 minutes post administration (P<0.05), while there were no significant differences between the two groups in the sedation score after 40 minutes post administration (P>0.05). The success rate of MRI procedure was significantly higher in the observation group than in the control group (89% vs 69%, P<0.05). There was no significant difference between the two groups in the incidence of adverse reactions (P>0.05). CONCLUSIONS: Intranasal midazolam is superior to intramuscular phenobarbital sodium in the sedative effect in neonates undergoing MRI, with the benefits of being fast, convenient, safe, and effective.


Assuntos
Hipnóticos e Sedativos/farmacologia , Humanos , Recém-Nascido , Espectroscopia de Ressonância Magnética , Midazolam , Estudos Prospectivos , Método Simples-Cego
14.
Biochem Biophys Res Commun ; 513(4): 875-882, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31003769

RESUMO

The injury of oligodendrocyte precursor cells (OPCs) contributes to the pathology of hypoxic-ischemic encephalopathy in newborns. MicroRNAs (miRNAs) have emerge as critical regulators of hypoxic-ischemic encephalopathy; however, the role of miRNAs in regulating OPC injury remains largely unknown. MiRNA-146b-5p (miR-146b-5p) has been reported to exert a cytoprotective function under various pathological conditions. In this study, we aimed to investigate the potential function of miR-146b-45p in regulating oxygen/glucose deprivation (OGD)-induced injury of OPCs and explore the underlying mechanism. Herein, we found that miR-146b-5p expression was reduced in OPCs exposed to OGD. Functional experiments showed that miR-146b-5p overexpression promoted cell growth and viability, and reduced the apoptosis and oxidative stress in OGD-injured OPCs, while miR-146b-5p inhibition showed an opposite effect. Interestingly, bromodomain-containing protein 4 (Brd4) was identified as a target gene of miR-146b-5p. Brd4 expression was negatively modulated by miR-146b-5p in OPCs. Moreover, the inhibition of Brd4 showed a protective effect in OGD-injured OPCs. Notably, miR-146b-5p overexpression or Brd4 inhibition down-regulated kelch-like ECH-associated protein 1 (Keap1) expression, but promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear expression and enhanced the transcriptional activity of the antioxidant response element (ARE). However, the overexpression of Brd4 significantly abrogated miR-146b-5p mediated protection effect in OGD exposed OPCs. Taken together, these results demonstrate that the overexpression of miR-146b-5p attenuates OGD-induced injury in OPCs through targeting Brd4 and regulating Keap1/Nrf2/ARE antioxidant signaling, suggesting a potential role of miR-146b-5p/Brd4 in the pathophysiology of neonatal hypoxic-ischemic brain injury.


Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , MicroRNAs/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Células Precursoras de Oligodendrócitos/efeitos dos fármacos , Fatores de Transcrição/antagonistas & inibidores , Elementos de Resposta Antioxidante/efeitos dos fármacos , Células Cultivadas , Glucose/deficiência , Humanos , Hipóxia , Hipóxia-Isquemia Encefálica/metabolismo , Substâncias Protetoras/farmacologia
15.
J Org Chem ; 84(22): 14911-14918, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31621323

RESUMO

A one-pot novel strategy is described for the construction of various oxazolo[4,5-c]quinoline derivatives starting from the isocyano(triphenylphosphoranylidene)acetates, aldehydes, amines, and 2-azidobenzoic acids. The reactions generated the target products directly in moderate to good yields via a sequential Ugi/Wittig/aza-Wittig cyclization process. The salient features of the method are that all three groups of the multifunctional isocyanides were involved in the reaction with broad substituent scopes and mild reaction conditions, making the protocol a useful contribution to the synthesis of oxazolo[4,5-c]quinoline heterocycles.

16.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(4): 274-278, 2018 Apr.
Artigo em Zh | MEDLINE | ID: mdl-29658450

RESUMO

OBJECTIVE: To study the influence of acute pancreatitis in pregnancy (APIP) on pregnancy outcomes and neonates. METHODS: A retrospective analysis was performed for 33 APIP patients and 31 neonates born alive. RESULTS: Of the 33 APIP patients, 26 (79%) developed APIP in the late pregnancy. Fourteen (45%) patients had hyperlipidemic APIP, 13 (42%) had biliary APIP, and 4 (13%) had other types of APIP. According to the severity, 22 (67%) were mild APIP, 5 (15%) were moderate APIP, and 6 were severe APIP. None of the 33 APIP patients died. Among the 20 patients with term delivery, 11 underwent termination of pregnancy; among the 10 patients with preterm delivery, 9 underwent termination of pregnancy; two patients experienced intrauterine fetal death, and one experienced abortion during the second trimester. Among the 31 neonates born alive (two of them were twins), 1 (3%) died, 12 (39%) experienced neonatal hyperbilirubinemia, 8 (26%) had neonatal hypoglycemia, 6 (19%) had neonatal respiratory distress syndrome, 5 (16%) experienced infectious diseases, and 2 (6%) experienced intracranial hemorrhage. The hyperlipidemic APIP group had a higher percentage of patients undergoing termination of pregnancy than the biliary APIP and other types of APIP groups (P<0.05). The incidence rate of preterm infants in the moderate APIP was higher than in the mild and severe APIP groups (P<0.05). The mean birth weights of neonates were the lowest in the moderate APIP group. The incidence rates of neonatal respiratory distress syndrome, intracranial hemorrhage, and infectious disease were the lowest in the mild APIP group (P<0.05). CONCLUSIONS: APIP can lead to adverse pregnancy outcomes and neonatal diseases, which are associated with the severity of pancreatitis.


Assuntos
Pancreatite/complicações , Complicações na Gravidez , Doença Aguda , Peso ao Nascer , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Gravidez , Estudos Retrospectivos
17.
Cell Biol Int ; 41(2): 155-162, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27888557

RESUMO

To evaluate the effect of regulatory T cells (Tregs) on the inflammation resulting from lipopolysaccharide (LPS) challenge in prenatal brain tissue, Tregs isolated from pregnant mice were transferred into model mice, and the expression levels of fork head family transcription factor (Foxp3), interleukin-6 (IL-6), CD68 (a marker of microglia), and toll-like receptor 4 (TLR-4) were assessed in the fetal brain tissue. Foxp3, IL-6, and TLR-4 expression were detected by polymerase chain reaction and Western blot; CD68 expression level was detected using immunochemical analysis. Foxp3, IL-6, TLR-4, and CD68 expressions in fetal brain were significantly induced by maternal LPS administration, and the increased expression levels were markedly reduced by adoptive transfer of Tregs. Maternal LPS exposure significantly induced inflammation in perinatal brain tissue, and Tregs negatively regulated this LPS-induced inflammation.


Assuntos
Encéfalo/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Feminino , Feto/efeitos dos fármacos , Feto/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Inflamação/prevenção & controle , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Microglia/metabolismo , Gravidez , Nascimento Prematuro , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Regulação para Cima/efeitos dos fármacos
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(5): 567-571, 2017 May.
Artigo em Zh | MEDLINE | ID: mdl-28506351

RESUMO

OBJECTIVE: To investigate the risk factors, clinical features, and magnetic resonance imaging (MRI) changes of encephalopathy in high-risk late preterm infants. METHODS: Head MRI scan was performed for late preterm infants with high-risk factors for brain injury who were hospitalized between January 2009 and December 2014. The risk factors, clinical features, and head MRI features of encephalopathy in late preterm infants were analyzed. RESULTS: A total of 1 007 late preterm infants underwent MRI scan, among whom 313 (31.1%) had imaging features in accordance with the features of encephalopathy of prematurity. Of all infants, 76.7% had white matter damage. There was no association between the development of encephalopathy and gestational age in late preterm infants, but the detection rate of encephalopathy gradually increased with the increasing birth weight (P<0.05). The logistic regression analysis showed that a history of resuscitation was an independent risk factor for encephalopathy of prematurity (P<0.01). CONCLUSIONS: Encephalopathy of prematurity is commonly seen in high-risk late preterm infants, especially white matter damage. A history of resuscitation is an independent risk factor for encephalopathy in late preterm infants.


Assuntos
Encefalopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Modelos Logísticos , Masculino , Risco
19.
J Reprod Med ; 61(1-2): 39-46, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26995887

RESUMO

OBJECTIVE: To investigate the expression of heme oxygenase-1 (HO-1) and leukemia inhibitory factor (LIF) in maternal plasma and placental tissue in intrauterine infection-induced preterm birth. STUDY DESIGN: Using a mouse model of intrauterine infection in preterm birth, we used magnetic beads to extract normal pregnant mouse spleen Treg cells, injecting them into lipopolysaccharide (LPS)-treated pregnant mice. The subjects were divided into 4 groups: control group, LPS group, LPS+PBS group, and LPS+Treg group. RT-PCR and Western blot were used to evaluate HO-1, LIF mRNA, and protein levels in the placenta. ELISA was used to detect these parameters in the peripheral blood of pregnant mice. RESULTS: The expression of HO-1 and LIF in the placenta of the LPS group was significantly decreased when compared to that of the control group (p<0.05). Serum HO-1 and LIF levels were higher than in the control group (p<0.05). In the Treg cell-treated group placental tissue HO-1 and LIF expression were significantly higher than in the LPS group (p<0.05), and serum HO-1 and LIF expression were significantly lower than in the LPS group (p<0.05). CONCLUSION: HO-1 and LIF participate with Treg cells in the maternal-fetal interface, producing a unique immune microenvironment.


Assuntos
Heme Oxigenase-1/sangue , Fator Inibidor de Leucemia/sangue , Placenta/metabolismo , Nascimento Prematuro/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Heme Oxigenase-1/genética , Fator Inibidor de Leucemia/genética , Camundongos , Placenta/química , Gravidez , Nascimento Prematuro/sangue , Nascimento Prematuro/genética
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(5): 435-9, 2016 May.
Artigo em Zh | MEDLINE | ID: mdl-27165594

RESUMO

OBJECTIVE: To investigate the association between long non-coding RNAs (lncRNAs) and brain injury in inflammation-induced preterm mice, and to provide a reference for the prevention and treatment of brain injury. METHODS: An intraperitoneal injection of lipopolysaccharide in pregnant mice was performed to establish a model of inflammation-induced preterm mice with brain injury (preterm group). The full-term mice delivered by normal pregnant mice were used as controls (full-term group). The lncRNA chip assay was used to screen out the lncRNAs associated with brain injury in preterm mice. Quantitative real-time PCR was used to validate the lncRNAs identified by the above method. RESULTS: The preterm and full-term groups showed significant differences in the expression of 1 978 lncRNAs (P<0.05), consisting of 786 up-regulated lncRNAs and 1 192 down-regulated lncRNAs, and 29 lncRNAs were 1.5 or more times differentially expressed between the two groups. A further analysis was performed for the 10 most differentially expressed lncRNAs, and the results showed that these lncRNAs were involved in the biological processes including transcription, signal transduction, apoptosis, cell cycle, and inflammatory response, as well as G protein-coupled receptor signaling pathway and neuropeptide signaling pathway. Real-time PCR was performed to validate the expression of two lncRNAs in brain tissue in the preterm and full-term groups, and the results were consistent with those of the chip assay. CONCLUSIONS: The expression profiles of lncRNAs in brain tissue change significantly in inflammation-induced preterm mice, and the G protein-coupled receptor signaling pathway may be involved in the pathogenesis of preterm brain injury.


Assuntos
Encéfalo/metabolismo , Inflamação/complicações , RNA Longo não Codificante/análise , Animais , Feminino , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Receptores Acoplados a Proteínas G/fisiologia , Transdução de Sinais/fisiologia
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