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INTRODUCTION: Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi'an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi'an, China METHODS: The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. RESULTS: Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1 week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. CONCLUSIONS: When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.
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New Delhi metallo-ß-lactamase-1 (NDM-1) is the most prevalent type of metallo-ß-lactamase and hydrolyzes almost all clinically used ß-lactam antibiotics. Here we show that the antimicrobial peptide thanatin disrupts the outer membrane of NDM-1-producing bacteria by competitively displacing divalent cations on the outer membrane and inducing the release of lipopolysaccharides. In addition, thanatin inhibits the enzymatic activity of NDM-1 by displacing zinc ions from the active site, and reverses carbapenem resistance in NDM-1-producing bacteria in vitro and in vivo. Thus, thanatin's dual mechanism of action may be useful for combating infections caused by NDM-1-producing pathogens.
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Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Parede Celular/efeitos dos fármacos , Resistência beta-Lactâmica/efeitos dos fármacos , beta-Lactamases/metabolismo , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Carbapenêmicos/farmacologia , Domínio Catalítico/efeitos dos fármacos , Modelos Animais de Doenças , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Concentração Inibidora 50 , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Zinco/metabolismoRESUMO
microRNA-290 (miR-290) clusters are highly expressed in mouse preimplantation embryos, but their specific role and regulatory mechanisms in the development of mouse preimplantation embryos remain unclear. Here, we found that miR-291a-5p and miR-291b-5p, as mature microRNA molecules of miR-290 clusters, were dynamically expressed in mouse preimplantation embryos. The expression of miR-291a-5p and miR-291b-5p in mouse embryos increased during the 2-4-cell stages and was accompanied by the decreasing expression of the autophagy-related genes Atg5 and Becn1 in mRNA. Immunofluorescence studies showed that the formation of autophagosomes and autophagic lysosomes increased in the 1-cell stage, decreased in the 2-cell stage, and rapidly decreased during the 4-8-cell stage. Transmission electron microscopy (TEM) also demonstrated that there were autophagosomes in the cytoplasm of fertilized eggs with a double-layer membrane structure, whereas this structure was not observed in the unfertilized oocyte cytoplasm. Moreover, miR-291a/b-5p inhibited the protein and mRNA expression of Atg5 and Becn1 in NIH/3T3 cells. A dual-luciferase reporter assay confirmed that miR-291a/b-5p directly targeted the Atg5 and Becn1 genes. MiR-291a/b-5p repressed rapamycin-induced autophagy-related LC3-I to LC3-II conversion, ultimately inhibiting the formation of autophagosomes. Furthermore, the microinjection of mouse zygote cytoplasm with miR-291a-5p inhibitors increased the mRNA expression of Atg5 and Becn1 in mouse embryos and facilitated the first cleavage of mouse embryos and blastocyst formation. Our results suggest the important role of miR-291a/b-5p during mouse preimplantation embryo development.
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The aim of the present study was to identify the differentially expressed microRNAs (miRNAs) in placenta from patients with preeclampsia, and examine their roles in the pathogenesis of preeclampsia in vivo and ex vivo. The placental expression levels of miRNAs were examined in tissue samples harvested from 20 patients with preeclampsia and 20 healthy control individuals. A total of 18 miRNAs were differentially expressed (12 upregulated and six downregulated) among the preeclampsia cases, compared with the controls. By further functional/pathway analysis, two significantly upregulated miRNAs, miR335 and miR584, were identified. These target endothelial nitric oxide synthase (eNOS), which has been repeatedly reported to be involved in the development of preeclampsia. The present study then verified eNOS as a target gene of miR335 and miR584 using a luceriferase assay, and confirmed the expression patterns of the two miRNAs and eNOS in preeclampsic and normal placentas. Additionally, to examine the function of miR584 and miR335 in human placenta, the present study transiently transfected the HTR8/Svneo cell line with miR584 and miR335 mimics or their inhibitors, and the results of a subsequent Transwell insert invasion assay revealed that miR584 and miR335 inhibited the migratory ability of the trophoblast cells, and that the effect was 'rescued' by overexpressed eNOS. These data revealed a negative regulatory role of miR584 and miR335 in the migration of HTR8/SVneo cells by targeting eNOS, and identified miR584 and miR335 as potential novel therapeutic targets in preeclampsia.
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Regulação da Expressão Gênica , MicroRNAs/genética , Óxido Nítrico Sintase Tipo III/genética , Pré-Eclâmpsia/genética , Interferência de RNA , Adulto , Pressão Sanguínea , Estudos de Casos e Controles , Linhagem Celular , Movimento Celular/genética , Proliferação de Células , Sobrevivência Celular , Feminino , Perfilação da Expressão Gênica , Humanos , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/metabolismo , Gravidez , RNA Mensageiro/genética , Fatores de Risco , Trofoblastos/metabolismo , Adulto JovemRESUMO
Preeclampsia (PE) is a pregnancy-induced disorder characterized by the overproliferation of trophoblasts. Hydatidiform moles, which are associated with a high risk of developing PE, are characterized by the excessive proliferation of trophoblastic tissue. H19 is highly expressed in placental tissue; however, its biological function remains unclear. A fundamental modification of the H19 gene is DNA methylation, which typically occurs in CG-rich regions at the promoter or the first exon region. In this study, in order to investigate the DNA methylation pattern of the H19 exon 1 region in placental tissues and trophoblast cells, placental specimens were collected from women in the first trimester of pregrancy (FTP) and the third trimester of pregnancy (TTP), as well as from from women with severe preeclampsia (sPE). We found that the DNA methylation levels of H19 exon 1 were significantly higher in the tissues obtained from women in TTP than from those obtained from women in FFP. The methylation status of CpG 1 sites within exon 1 of H19 was markedly higher in the placental tissues obtained from women with sPE than in the tissues obtained from women in TTP. In addition, we used the human choriocarcinoma cell line, JEG-3, and treated the cells with the methylation inhibitor, 5-aza-2'-deoxycytidine (5-AzaDc). Following treatment with 5-Aza-Dc, the methylation levels at this CpG site showed marked hypomethylation. In addtion, the cell proliferative, migratory and invasive capacities of the cells were remarkably inhibited. Our data suggest that hypermethylation at individual CpG sites within exon 1 of H19 may be involved in the dysfunction of trophoblasts and the pathogenesis of PE.
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Metilação de DNA/genética , Éxons/genética , Pré-Eclâmpsia/genética , RNA Longo não Codificante/genética , Trofoblastos/patologia , Adulto , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Decitabina , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Placenta/efeitos dos fármacos , Placenta/metabolismo , Gravidez , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Adulto JovemRESUMO
BACKGROUND: H19 is a paternally imprinted gene that has been shown to be highly expressed in the trophoblast tissue. Results from previous studies have initiated a debate as to whether noncoding RNA H19 acts as a tumor suppressor or as a tumor promotor in trophoblast tissue. In the present study, we developed lentiviral vectors expressing H19-specific small interfering RNA (siRNA) to specifically block the expression of H19 in the human choriocarcinoma cell line JAR. Using this approach, we investigated the impact of the H19 gene on the proliferation, invasion and apoptosis of JAR cells. Moreover, we examined the effect of H19 knockdown on the expression of insulin-like growth factor 2 (IGF2), hairy and enhancer of split homologue-1 (HES-1) and dual-specific phosphatase 5 (DUSP5) genes. RESULTS: H19 knockdown inhibited apoptosis and proliferation of JAR cells, but had no significant impact on cell invasion. In addition, H19 knockdown resulted in significant upregulation of HES-1 and DUSP5 expression, but not IGF2 expression in JAR cells. CONCLUSIONS: The finding that H19 downregulation could simultaneously inhibit proliferation and apoptosis of JAR cells highlights a putative dual function for H19 in choriocarcinoma and may explain the debate on whether H19 acts as a tumor suppressor or a tumor promotor in trophoblast tissue. Furthermore, upregulation of HES-1 and DUSP5 may mediate H19 downregulation-induced suppression of proliferation and apoptosis of JAR cells.
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Apoptose/fisiologia , Proliferação de Células , Coriocarcinoma/patologia , Lentivirus/genética , Proteínas Nucleares/genética , Interferência de RNA/fisiologia , Proteínas Supressoras de Tumor/genética , Neoplasias Uterinas/patologia , Apoptose/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Coriocarcinoma/metabolismo , Fosfatases de Especificidade Dupla/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Vetores Genéticos/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Fator de Crescimento Insulin-Like II/metabolismo , Proteínas Nucleares/fisiologia , Gravidez , Fatores de Transcrição HES-1 , Proteínas Supressoras de Tumor/fisiologia , Neoplasias Uterinas/metabolismoRESUMO
OBJECTIVE: To explore the role of H19 imprinting in etiology of pre-eclampsia. METHODS: Placentas of 24 women with pre-eclampsia (3 with mild pre-eclampsia and 21 with severe pre-eclampsia) and 50 healthy pregnant women at full term (control) were collected during selected cesarean delivery between August 2007 and March 2008. The statuses of H19 imprinting with placental tissues from normal pregnancy and patients with pre-eclampsia were identified upon polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The systolic and diastolic pressure were analyzed in H19 heterozygotic women. RESULTS: (1) There were 20 (40%) heterozygotes in 50 cases placenta tissues of the third trimesters, 11 (45%) heterozygotes in 24 cases placenta tissues of pre-eclampsia. There were no significant difference between two groups (P > 0.05). (2) All 20 heterozygotes in placenta tissues of the third trimesters are exclusively monoallelically expressed, while 5 cases (45%) in 11 heterozygotes of pre-eclampsia are biallelically expressed (loss of imprinting, LOI). There were significant difference between two groups (P < 0.01). (3) The values of systolic and diastolic pressure of patients with monoallelic expression of H19 were (171 +/- 9) mm Hg (1 mm Hg = 0.133 kPa) and (104 +/- 8) mm Hg, the values of systolic and diastolic pressure with biallelic expression were (194 +/- 21) mm Hg and (124 +/- 18) mm Hg. There were significant difference between two groups (P < 0.05). CONCLUSION: LOI of H19 can be identified in pre-eclamptic placentas and is associated with maternal blood pressures, which implies the involvement of H19 gene LOI in the pathogenesis of pre-eclampsia and its potential relationship with the severity of the disease.