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1.
Front Immunol ; 12: 667781, 2021.
Article in English | MEDLINE | ID: mdl-34093564

ABSTRACT

Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that especially plays an important role in innate immune. However, the roles of LECT2 in the immune response of the economically important fish Nile tilapia (Oreochromis niloticus) against bacterial infection remains unclear. In this study, a lect2 gene from Nile tilapia (On-lect2) was identified, and its roles in the fish's immune response against bacterial infection were determined and characterised. On-lect2 contains an open reading frame of 456 bp that encodes a peptide of 151 amino acids, as well as the conservative peptidase M23 domain. On-LECT2 is 62%-84% identical to other fish species and about 50% identical to mammals. The highest transcriptional level of On-lect2 was detected in the liver, whereas the lowest levels were detected in the other tissues. Moreover, the On-LECT2 protein is located mainly in the brain and head kidney. The transcriptional levels of On-lect2 substantially increased in the head kidney, brain, liver and spleen after Streptococcus agalactiae infection. Knockdown On-lect2 led to higher mortality due to liver necrosis or haemorrhage and splenomegaly. In vitro analysis indicated that the recombinant protein of On-LECT2 improved phagocytic activity of head kidney-derived macrophages. In vivo challenge experiments revealed several functions of On-LECT2 in the immune response of Nile tilapia against bacterial infection, including promotion of inflammation, reduction of tissue damages and improvement of survival rate.


Subject(s)
Cichlids/microbiology , Fish Diseases/prevention & control , Fish Proteins/metabolism , Immunity, Innate , Intercellular Signaling Peptides and Proteins/metabolism , Macrophages/microbiology , Streptococcal Infections/veterinary , Streptococcus agalactiae/pathogenicity , Animals , Cichlids/genetics , Cichlids/immunology , Cichlids/metabolism , Fish Diseases/immunology , Fish Diseases/metabolism , Fish Diseases/microbiology , Fish Proteins/genetics , Host-Pathogen Interactions , Intercellular Signaling Peptides and Proteins/genetics , Macrophages/immunology , Macrophages/metabolism , Streptococcal Infections/metabolism , Streptococcal Infections/microbiology , Streptococcal Infections/prevention & control , Streptococcus agalactiae/immunology , Transcription, Genetic
2.
N Engl J Med ; 380(21): 2031-2040, 2019 05 23.
Article in English | MEDLINE | ID: mdl-31116919

ABSTRACT

BACKGROUND: Nasal high-flow therapy is an alternative to nasal continuous positive airway pressure (CPAP) as a means of respiratory support for newborn infants. The efficacy of high-flow therapy in nontertiary special care nurseries is unknown. METHODS: We performed a multicenter, randomized, noninferiority trial involving newborn infants (<24 hours of age; gestational age, ≥31 weeks) in special care nurseries in Australia. Newborn infants with respiratory distress and a birth weight of at least 1200 g were assigned to treatment with either high-flow therapy or CPAP. The primary outcome was treatment failure within 72 hours after randomization. Infants in whom high-flow therapy failed could receive CPAP. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome, with a noninferiority margin of 10 percentage points. RESULTS: A total of 754 infants (mean gestational age, 36.9 weeks, and mean birth weight, 2909 g) were included in the primary intention-to-treat analysis. Treatment failure occurred in 78 of 381 infants (20.5%) in the high-flow group and in 38 of 373 infants (10.2%) in the CPAP group (risk difference, 10.3 percentage points; 95% confidence interval [CI], 5.2 to 15.4). In a secondary per-protocol analysis, treatment failure occurred in 49 of 339 infants (14.5%) in the high-flow group and in 27 of 338 infants (8.0%) in the CPAP group (risk difference, 6.5 percentage points; 95% CI, 1.7 to 11.2). The incidences of mechanical ventilation, transfer to a tertiary neonatal intensive care unit, and adverse events did not differ significantly between the groups. CONCLUSIONS: Nasal high-flow therapy was not shown to be noninferior to CPAP and resulted in a significantly higher incidence of treatment failure than CPAP when used in nontertiary special care nurseries as early respiratory support for newborn infants with respiratory distress. (Funded by the Australian National Health and Medical Research Council and Monash University; HUNTER Australian and New Zealand Clinical Trials Registry number, ACTRN12614001203640.).


Subject(s)
Continuous Positive Airway Pressure , Noninvasive Ventilation , Oxygen Inhalation Therapy/methods , Respiratory Distress Syndrome, Newborn/therapy , Continuous Positive Airway Pressure/adverse effects , Female , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Male , Noninvasive Ventilation/adverse effects , Treatment Failure
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