RÉSUMÉ
Gut microbiota are associated with adverse neurodevelopmental outcomes in preterm infants; however, the precise causal relationship remains unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to comprehensively study the relationship between gut microbiota and adverse neurodevelopmental outcomes in preterm infants and identify specific causal bacteria that may be associated with the occurrence and development of adverse neurodevelopmental outcomes in preterm infants. The genome-wide association analysis (GWAS) of the MiBioGen biogroup was used as the exposure data. The GWAS of six common adverse neurodevelopmental outcomes in premature infants from the FinnGen consortium R9 was used as the outcome data. Genetic variations, namely, single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10-5) and genome-wide statistical significance threshold (5 × 10-8) were selected as instrumental variables (IVs). MR studies use inverse variance weighting (IVW) as the main method. To supplement this, we also applied three additional MR methods: MR-Egger, weighted median, and weighted mode. In addition, the Cochrane's Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out methods were used for sensitivity analysis. Our study shows a causal relationship between specific gut microbiota and neurodevelopmental outcomes in preterm infants. These findings provide new insights into the mechanism by which gut microbiota may mediate adverse neurodevelopmental outcomes in preterm infants.
RÉSUMÉ
BACKGROUND: Shenmai injection is frequently utilized in China to clinically treat granulocytopenia in oncology patients following chemotherapy. Despite this, the drug's therapeutic benefits remain a topic of contention, and its active components and potential treatment targets have yet to be established. The present study utilizes a network pharmacology approach to investigate the drug's active ingredients and possible therapeutic targets, and to evaluate the effectiveness of Shenmai injection in treating granulocytopenia through meta-analysis. METHODS: In our subject paper, we utilized the TCMID database to investigate the active ingredients present in red ginseng and ophiopogon japonicus. To further identify molecular targets, we employed SuperPred, as well as OMIM, Genecards, and DisGeNET databases. Our focus was on targets associated with granulocytopenia. The DAVID 6.8 database was utilized to perform gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Additionally, a protein-protein interaction network was established. The resulting "drug-key component-potential target-core pathway" network was used to predict the mechanism of action of Shenmai injection in the treatment of granulocytopenia. In order to evaluate the quality of the studies included in our analysis, we utilized the Cochrane Reviewers' Handbook. We then conducted a meta-analysis of the clinical curative effect of Shenmai injection for granulocytopenia, utilizing the Cochrane Collaboration's RevMan 5.3 software. RESULTS: After conducting a thorough screening, the study identified 5 primary ingredients of Shenmai injection - ophiopogonoside a, ß-patchoulene, ginsenoside rf, ginsenoside re, and ginsenoside rg1-that can potentially target 5 essential proteins: STAT3, TLR4, PIK3CA, PIK3R1, and GRB2. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that Shenmai injection can be beneficial in treating granulocytopenia by interacting with pathways such as HIF-1 signaling, T-cell receptor signaling, PI3K-Akt signaling, chemokine signaling, and FoxO signaling. The results of meta-analysis indicate that the treatment group exhibited superior performance in terms of both efficiency and post-treatment leukocyte count when compared to the control group. CONCLUSION: In summary, studies in network pharmacology demonstrate that Shenmai injection exerts an impact on granulocytopenia via various components, targets, and mechanisms. Additionally, evidence-based studies provide strong support for the effectiveness of Shenmai injection in preventing and treating granulocytopenia.
Sujet(s)
Agranulocytose , Médicaments issus de plantes chinoises , Leucopénie , Humains , Phosphatidylinositol 3-kinases , Médicaments issus de plantes chinoises/pharmacologie , Médicaments issus de plantes chinoises/usage thérapeutiqueRÉSUMÉ
Biotin film was prepared by low-energy electron beam deposition (LEBD). The molecular structure, chemical composition and micromorphology of the biotin film were investigated by 1HNMR, FTIR, XPS, AFM and SEM. The results showed the molecular structure of a monolayer of biotin film is fully consistent with the molecular structure of the initial biotin powders. The contact angle test showed that the biotin film exhibit good hydrophilicity. The release kinetics of biotin film was tested by UV-Vis method. It was found that the film was almost completely released in about two weeks. The cell viability of MC3T3-E1 cells on the surface of the biotin film was attaining 100.54 ± 1.7% (P < 0.05), showing excellent biocompatibility and biosafety. Titanium implant with surface of biotin film was implanted into the femoral head of rabbits as experimental group. The animals were euthanized after four weeks. Compared with the control group, mature lamellar bone formation was observed with dense trabecular bone, and the expression of Coll-I, Runx2 and BMP-2 was better. The results showed that the repair effect of bone defect in the experimental group was excellent.
Sujet(s)
Biotine , Électrons , Animaux , Biotine/pharmacologie , Ostéogenèse , Lapins , Titane/pharmacologieRÉSUMÉ
OLIG1 is an oligodendrocyte (OL) transcription factor, which can contribute to the proliferation and differentiation of OLs, and the maturation of myelin. The aim of this study was to clarify the role of OLIG1 in neonatal Sprague Dawley rats with periventricular leukomalacia (PVL), induced by hypoxiaischemia (HI). Newborn rats in the HI group were subjected to ligation of the right carotid artery, followed by 8% oxygen delivery for 2 h, while rats in the normoxia group were only subjected to isolation of the right carotid artery, without exposure to hypoxia. Samples of brain tissue from rats in both groups were collected at 1, 3, 7, 14 and 21 days. In the HI group, observation by transmission electron microscopy (TEM) revealed OLs with a damaged nuclear membrane, cellular atrophy, deformation and necrosis, and cells in myelin with a high number of small vacuoles. A doublelabel immunofluorescence assay revealed the translocation of OLIG1 from the cytoplasm to the nucleus, while western blot and reverse transcriptionquantitative polymerase chain reaction assays showed that there is a significant decrease, followed by an increase, in the gene and protein expression levels of OLIG1 and myelin basic protein (MBP). Despite the increase at the late stages of HI, the final levels of these proteins remained lower than the corresponding levels in the normoxia group. In conclusion, the decreased protein expression of OLIG1 following HI plays an important role in inhibiting the development and maturation of OLs and myelin. Although OLIG1 may, via its nuclear translocation, promote the growth and development of myelin to a certain extent, this factor fails to fully repair injured myelin.