ABSTRACT
BACKGROUND: The transcriptional repressor B-cell lymphoma 6 (BCL6) has been reported to inhibit inflammation. So far, experimental evidence for the role of BCL6 in bronchopulmonary dysplasia (BPD) is lacking. Our study investigated the roles of BCL6 in the progression of BPD and its downstream mechanisms. METHODS: Hyperoxia or lipopolysaccharide (LPS) was used to mimic the BPD mouse model. To investigate the effects of BCL6 on BPD, recombination adeno-associated virus serotype 9 expressing BCL6 (rAAV9-BCL6) and BCL6 inhibitor FX1 were administered in mice. The pulmonary pathological changes, inflammatory chemokines and NLRP3-related protein were observed. Meanwhile, BCL6 overexpression plasmid was used in human pulmonary microvascular endothelial cells (HPMECs). Cell proliferation, apoptosis, and NLRP3-related protein were detected. RESULTS: Either hyperoxia or LPS suppressed pulmonary BCL6 mRNA expression. rAAV9-BCL6 administration significantly inhibited hyperoxia-induced NLRP3 upregulation and inflammation, attenuated alveolar simplification and dysregulated angiogenesis in BPD mice, which were characterized by decreased mean linear intercept, increased radical alveolar count and alveoli numbers, and the upregulated CD31 expression. Meanwhile, BCL6 overexpression promoted proliferation and angiogenesis, inhibited apoptosis and inflammation in hyperoxia-stimulated HPMECs. Moreover, administration of BCL6 inhibitor FX1 arrested growth and development. FX1-treated BPD mice exhibited exacerbation of alveolar pathological changes and pulmonary vessel permeability, with upregulated mRNA levels of pro-inflammatory cytokines and pro-fibrogenic factors. Furthermore, both rAAV9-BCL6 and FX1 administration exerted a long-lasting effect on hyperoxia-induced lung injury (≥4 wk). CONCLUSIONS: BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.
Subject(s)
Bronchopulmonary Dysplasia , Hyperoxia , Lung Injury , Animals , Humans , Infant, Newborn , Mice , Animals, Newborn , Bronchopulmonary Dysplasia/etiology , Bronchopulmonary Dysplasia/metabolism , Disease Models, Animal , Endothelial Cells/pathology , Hyperoxia/metabolism , Inflammation/metabolism , Lipopolysaccharides/pharmacology , Lung/metabolism , Lung Injury/drug therapy , Lung Injury/etiology , Lung Injury/prevention & control , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Proto-Oncogene Proteins c-bcl-6/metabolism , RNA, Messenger/metabolismABSTRACT
BACKGROUND: Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations. However, preliminary studies have documented the pathophysiological changes in certain brain regions, such as the cerebellum, highlighting a need for further research to support the current understanding of this disease. AIM: To study brain changes in depressed adolescents. METHODS: This study enrolled 34 adolescents with depression and 34 age-, sex-, and education-level-matched healthy control (HC) individuals. Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow (CBF) analysis, respectively. Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses. RESULTS: The cerebellum, superior frontal gyrus, cingulate gyrus, pallidum, middle frontal gyrus, angular gyrus, thalamus, precentral gyrus, inferior temporal gyrus, superior temporal gyrus, inferior frontal gyrus, and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals. These patients with depression further presented with a pronounced drop in CBF in the left pallidum (group = 98, and peak t = - 4.4324), together with increased CBF in the right percental gyrus (PerCG) (group = 90, and peak t = 4.5382). In addition, 17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus (r = - 0.5231, P < 0.01). CONCLUSION: The right PerCG showed structural and CBF changes, indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.
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BACKGROUND: Electroconvulsive therapy (ECT) is a novel treatment strategy for adolescents with major depressive disorder (MDD). However, its related neurobiological changes associated with ECT remain undetermined. OBJECTIVE: To elucidate the impact of ECT on the regional cerebral blood flow (CBF), and to identify alterations in the CBF associated with clinical outcomes in adolescents with MDD. METHODS: Fifty-two treatment-naive adolescents who had experienced their first episode of MDD and 36 healthy controls (HCs) were recruited. To assess baseline parameters, all subjects were scanned with arterial spin labeling resting-state functional magnetic resonance imaging (ASL-fMRI) at the beginning of the study. Subsequently, 27 MDD adolescents were re-scanned after 2 weeks after ECT. CBF imaging was used for the prediction of specific clinical outcomes. Lastly, the associations between alterations seen on brain imaging alterations after ECT and ECT clinical efficacy (ΔHAMD scores) were determined. RESULTS: Relative to HCs, adolescents with MDD exhibited reduced CBF in the left medial superior frontal gyrus (SFGmed) (cluster = 243, peak t = -3.9373, and P < 0.001) and augmented CBF in the right percental gyrus (PerCG) (cluster = 321, peak t = 4.3332, and P < 0.001) at baseline. Following ECT, MDD adolescents exhibited reduced CBF in the right fusiform gyrus (FFG) (cluster = 309, peak t = -4.346, and P < 0.001) and left hippocampus (HIP) (cluster = 290, peak t = -4.706, and P < 0.001), and enhanced CBF in the left orbital part of the inferior frontal gyrus (ORBinf) (cluster = 214, peak t = 4.073, and P < 0.001). Correlation analysis suggested an inverse association between ΔHAMD scores and CBF values in the left ORBinf (R2 = 0.196, P = 0.021). CONCLUSIONS: It was found that ECT resulted in alterations in CBF in specific brain areas, highlighting the significance of ORBinf in ECT pathophysiology in MDD adolescents.
Subject(s)
Depressive Disorder, Major , Electroconvulsive Therapy , Humans , Adolescent , Electroconvulsive Therapy/methods , Brain , Neuroimaging , Magnetic Resonance Imaging/methods , Cerebrovascular CirculationABSTRACT
BACKGROUND: The use of antidepressant therapy alone has a limited efficacy in patients with childhood trauma-associated major depressive disorder (MDD). However, the effectiveness of antidepressant treatment combined with psychodrama in these patients is unclear. AIM: To evaluate the effectiveness of antidepressant treatment combined with psychodrama. METHODS: Patients with childhood trauma-associated MDD treated with antidepressants were randomly assigned to either the psychodrama intervention (observation group) or the general health education intervention (control group) and received combination treatment for 6 mo. The observation group received general health education given by the investigator together with the "semi-structured group intervention model" of Yi Shu psychodrama. A total of 46 patients were recruited, including 29 cases in the observation group and 17 cases in the control group. Symptoms of depression and anxiety as well as coping style and resting-state functional magnetic resonance imaging were assessed before and after the intervention. RESULTS: Symptoms of depression and anxiety, measured by the Hamilton Depression Scale, Beck Depression Inventory, and Beck Anxiety Inventory, were reduced after the intervention in both groups of patients. The coping style of the observation group improved significantly in contrast to the control group, which did not. In addition, an interaction between treatment and time in the right superior parietal gyrus node was found. Furthermore, functional connectivity between the right superior parietal gyrus and left inferior frontal gyrus in the observation group increased after the intervention, while in the control group the connectivity decreased. CONCLUSION: This study supports the use of combined treatment with antidepressants and psychodrama to improve the coping style of patients with childhood trauma-associated MDD. Functional connectivity between the superior parietal gyrus and inferior frontal gyrus was increased after this combined treatment. We speculate that psychodrama enhances the internal connectivity of the cognitive control network and corrects the negative attention bias of patients with childhood trauma-associated MDD. Elucidating the neurobiological features of patients with childhood trauma-associated MDD is important for the development of methods that can assist in early diagnosis and intervention.
ABSTRACT
Purpose: While electroconvulsive therapy (ECT) has been repeatedly been shown to effectively and efficiently treat the major depressive disorder (MDD), the mechanistic basis for such therapeutic efficacy remains to be firmly established. As such, further research exploring the ECT-based treatment of MDD in an adolescent population is warranted. Methods: This study included 30 treatment-naïve first-episode MDD patients and 30 healthy control (HC) individuals (aged 12-17 years). All participants were scanned using rs-fMRI, and the 30 MDD patients were scanned again after 2 weeks of the ECT treatment period. Intrinsic local activity in each voxel was assessed based on the fractional amplitude of low frequency fluctuation (fALFF) parameter, with all fALFF analyses being completed using the REST application. Correlations between ECT-related changes in fALFF and clinical parameters were additionally examined. Results: Relative to HCs, MDD patients exhibited increased fALFF values in the right inferior frontal gyrus (ORBinf), inferior occipital gyrus (IOG), and the left middle frontal gyrus (MFG) at baseline. Following ECT, these patients exhibited significant increases in fALFF values in the right medial superior frontal gyrus (SFGmed), dorsolateral superior frontal gyrus (SFGdor), anterior cingulate, and paracingulate gyrus (ACG), median cingulate and paracingulate gyrus (DCG), and left MFG. MDD patient HAMD scores were negatively correlated with fALFF values when analyzing pre-ECT vs. post-HCT ΔHAMD and fALFF values in the right SFGmed, SFGdor, and the left MFG. Conclusion: These data suggest that ECT induced altered fALFF in some regions of the brain, suggesting that these alterations may serve as a neurobiological indicator of ECT effectiveness in MDD adolescents.
ABSTRACT
Purpose: The major depressive disorder (MDD) can be a threat to the health of people all over the world. Although governments have developed and implemented evidence-based interventions and prevention programs to prevent MDD and maintain mental health in adolescents, the number of adolescents with this condition has been on the rise for the past 10 years. Methods: A total of 60 adolescents were recruited, including 32 drug-naive adolescents with first-episode MDD and 28 healthy controls (HCs). Alterations in the intrinsic cerebral activity of the adolescents with MDD were explored using arterial spin labeling (ASL) while differences in the regional cerebral blood flow (rCBF) of the two groups were assessed based on voxel-based whole-brain analysis. Finally, correlations between the regional functional abnormalities and clinical variables were investigated for adolescents with MDD. Results: Compared with HCs, MDD patients had a lower rCBF in the left triangular part of the inferior frontal gyrus (IFGtriang) but a higher one in the right Precental gyrus (PreCG). Negative correlations were also noted between the CBF in the left IFGtriang and the Hamilton depression scale (HAMD) scores of MDD patients. Conclusion: Elucidating the neurobiological features of adolescent patients with MDD is important to adequately develop methods that can assist in early diagnosis, precaution and intervention.
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Objective: To evaluate factors in predicting the treatment outcome of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids with a non-perfused volume ratio (NPVR) of at least 80%. Methods: One thousand patients with uterine fibroids who received USgHIFU were enrolled. Thirty-two independent variables of four dimensions of data set, including general information of patients, clinical symptoms, laboratory tests, and fibroid imaging characteristics, were used to investigate the potential predictors of the NPVR of at least 80% by multivariate logistic regression. NPVR was the gold standard for evaluating the efficiency of HIFU ablation, and a NPVR of at least 80% was considered sufficient ablation, while partial ablation was defined as having an NPVR of <80%. Results: Out of 1,000 fibroids, 758 obtained sufficient ablation and 242 obtained partial ablation, and the median NPVR was 88.3% (interquartile range: 80.3-94.8%). The probability of NPVR reaching 80% fibroids with a signal intensity of T2WI of hypointense, isointense, and hyperintense was 86.4, 76.5, and 62.6%, respectively; fibroids with an enhancement type of T1WI of slight, irregular, and regular was 81.5, 73.6, and 63.7%, respectively; and fibroids with uterine anteroposterior of 30-130 mm was 57.7-78.3%, respectively. In patients with a platelet count of 50 × 109/L-550 × 109/L, the probability of NPVR reaching 80% is from 53.4 to 80.1%, respectively. Conclusions: In predicting NPVR ≥ 80%, the signal intensity on T2WI was the most important factor affecting ablative efficiency, followed by enhancement type on T1WI, uterine anteroposterior, and platelet count.
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BACKGROUND: Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms. METHODS: WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested. RESULTS: The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs. CONCLUSION: SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.
ABSTRACT
Neonatal respiratory distress syndrome (NRDS) is a common disease that occurs in premature infants. However, the mechanisms underlying the disease remain unclear. microRNAs (miRNAs) have been indicated to play a crucial role in the development of NRDS. In this study, we aimed to explore the regulatory mechanisms of miR-296-5p in NRDS. The expression levels of miR-296-5p in preterm infants with NRDS were determined using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). A549 cells were transfected with lentiviral vectors encoding miR-296-5p, and the transfection efficiency was determined using RT-qPCR. Flow cytometry and CCK8 assay were performed to measure apoptosis and proliferation of A549 cells, respectively. The protein levels of pulmonary surfactant SP-A (SFTPA1), SP-B, Wnt7b, and ß-catenin were measured using western blotting. We demonstrated an upregulation of miR-296-5p in NRDS. The miR-296-5p was successfully overexpressed in A549 cells via lentivirus transfection, and the upregulation of miR-296-5p inhibited cell proliferation and secretion of SP-A and SP-B and also induced downregulation of the Wnt7b/ß-catenin in vitro. Therefore, miR-296-5p inhibits cell proliferation and secretion of pulmonary surfactants in A549 cells via downregulation of Wnt7b/ß-catenin signaling.
Subject(s)
MicroRNAs , Pulmonary Surfactants/metabolism , Respiratory Distress Syndrome, Newborn , Wnt Signaling Pathway/genetics , A549 Cells , Apoptosis/genetics , Cell Survival/genetics , Down-Regulation/genetics , Humans , Infant, Newborn , MicroRNAs/genetics , MicroRNAs/metabolism , Respiratory Distress Syndrome, Newborn/genetics , Respiratory Distress Syndrome, Newborn/metabolismABSTRACT
PURPOSE: This study aimed to compare the dose and effectiveness of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids with different sizes and explore the effect of uterine fibroid size on dose, which provided dose evaluation for clinicians in accordance with the size of uterine fibroids. MATERIALS AND METHODS: A total of 1,000 patients with symptomatic uterine fibroids who received a single-session USgHIFU treatment were enrolled in this study. The size of fibroids was divided into seven groups: 3-4 cm, 4-5 cm, 5-6 cm, 6-7 cm, 7-8 cm, 8-9 cm, and 9-11 cm. The dose was expressed on the basis of the energy efficiency factor (EEF) as the energy required for ablation per unit volume of tissue, and the non-perfused volume ratio (NPVR) was used to assess the effect of HIFU ablation. RESULTS: The median NPVR of 88.3% (IQR: 80.3%-94.8%) was obtained, and no significant difference was observed among the seven groups. The classification of T2-weighted image signal intensity fibroids in the 4-5 cm group was compared with that in the 6-7 cm and 8-9 cm groups, and the difference was significant (p < 0.05). However, the proportion of T2WI hyperintense signal fibroids had no significant difference among the seven groups (p > 0.05). The median EEF was 3.88 J/mm3, and a significant difference was observed among the seven groups of EEF (p < 0.05). The EEF of groups with a fibroid size less than 6 cm was more than double the EEF of groups with a fibroid size above 6 cm. In addition, the EEF of groups with a fibroid size of 4-5 cm and 3-4 cm was 3-4 times higher than those with a fibroid size above 7 cm (p < 0.05). CONCLUSIONS: A single-session HIFU ablation for uterine fibroids of 3-11 cm can obtain an NPVR of more than 80%. The EEF decreased with the increase of the size of uterine fibroids. A fibroid size of 6.5 cm was considered as a clinical meaningful point affecting EEF.
ABSTRACT
Necrotizing enterocolitis (NEC) is the leading cause of death due to gastrointestinal disease in preterm infants. The role of miRNAs in NEC is still unknown. The objective of this study was to identify differentially expressed (DE) miRNAs in rats with NEC and analyze their possible roles. In this study, a NEC rat model was established using Sprague-Dawley rat pups. Small RNA sequencing was used to analyze the miRNA expression profiles in the NEC and control rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to identify target mRNAs for the DE miRNAs and to explore their potential roles. The DE miRNAs were verified by real-time quantitative PCR (RT-qPCR). The status of intestinal injury and the elevated levels of inflammatory cytokines in the NEC group confirmed that the NEC model was successfully established. The 16 miRNAs were found to be differentially expressed between the NEC group and the control group of rats. Bioinformatics analysis indicated that the parental genes of the DE miRNAs were predominantly implicated in the phosphorylation, cell migration, and protein phosphorylation processes. Moreover, the DE miRNAs were mainly found to be involved in the pathways of axon guidance, endocytosis, and focal adhesion, as well as in the Wnt signaling pathway, which is related to colitis. The expression patterns of the candidate miRNAs (rno-miR-27a-5p and rno-miR-187-3p), as assessed by RT-qPCR, were in accordance with the expression patterns obtained by miRNA-sequencing. The miRNA/mRNA/pathway network revealed that rno-miR-27a-5p and rno-miR-187-3p might be involved in NEC via the Wnt signaling pathway. We found an altered miRNA expression pattern in rats with NEC. We hypothesize that rno-miR-27a-5p and rno-miR-187-3p might mediate the NEC pathophysiological processes via the Wnt signaling pathway.
Subject(s)
Enterocolitis, Necrotizing/genetics , MicroRNAs/genetics , Animals , Computational Biology , Disease Models, Animal , Enterocolitis, Necrotizing/pathology , Gene Expression Regulation/genetics , Humans , Infant, Premature , Rats , Rats, Sprague-Dawley , Sequence Analysis, RNA , Signal Transduction , Exome SequencingABSTRACT
BACKGROUND: Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis. METHODS: we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms. RESULTS: Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning. CONCLUSIONS: These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.
Subject(s)
Acute Lung Injury/metabolism , Drowning/metabolism , Ferroptosis/physiology , NF-E2-Related Factor 2/metabolism , Seawater/adverse effects , Acute Lung Injury/etiology , Acute Lung Injury/prevention & control , Animals , Cell Line , Drowning/etiology , Drowning/prevention & control , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Respiratory Mucosa/metabolismABSTRACT
Short-chain fatty acids (SCFAs), especially propionate, originate from the fermentation of dietary fiber in the gut and play a key role in inhibiting pulmonary inflammation. Chronic inflammation may induce an epithelial-mesenchymal transition (EMT) in alveolar epithelial cells and result in fibrotic disorders. This study was designed to investigate the beneficial effect of sodium propionate (SP) on lipopolysaccharide (LPS)-induced EMT. In cultured BEAS-2B cells, the protein expression levels of E-cadherin, α-smooth muscle actin (SMA), and vimentin were 0.66 ± 0.20, 1.44 ± 0.23, and 1.32 ± 0.21 in the LPS group vs 1.11 ± 0.36 (P < 0.05), 1.04 ± 0.30 (P < 0.05), and 0.96 ± 0.13 (P < 0.01) in the LPS + SP group (mean ± standard deviation), respectively. Meanwhile, LPS-triggered inflammatory cytokines and extracellular proteins were also reduced by SP administration in BEAS-2B cells. Moreover, SP treatment attenuated inflammation, EMT, extracellular matrix (ECM) deposition, and even fibrosis in a mouse EMT model. In terms of mechanism, LPS-treated BEAS-2B cells exhibited a higher level of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) phosphorylation, which was interrupted by SP treatment. It is worth noting that the blockade of the PI3K/Akt/mTOR signaling cascade reduced the LPS-evoked EMT process in BEAS-2B cells. These results suggest that SP can block LPS-induced EMT via inhibition of the PI3K/Akt/mTOR signaling cascade, which provides a basis for possible clinical use of SP in airway and lung diseases.
Subject(s)
Epithelial-Mesenchymal Transition/drug effects , Lipopolysaccharides/pharmacology , Lung Diseases/drug therapy , Phosphatidylinositol 3-Kinase/metabolism , Propionates/administration & dosage , Proto-Oncogene Proteins c-akt/metabolism , Actins/genetics , Actins/metabolism , Animals , Cadherins/genetics , Cadherins/metabolism , Humans , Lung Diseases/genetics , Lung Diseases/metabolism , Lung Diseases/physiopathology , Male , Mice , Phosphatidylinositol 3-Kinase/genetics , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Vimentin/genetics , Vimentin/metabolismABSTRACT
AIM: To demonstrate that specific bacteria might release bacterial extracellular DNA (eDNA) to exert immunomodulatory functions in the mouse small intestine. METHODS: Extracellular DNA was extracted using phosphate buffered saline with 0.5 mmol/L dithiothreitol combined with two phenol extractions. TOTO-1 iodide, a cell-impermeant and high-affinity nucleic acid stain, was used to confirm the existence of eDNA in the mucus layers of the small intestine and colon in healthy Male C57BL/6 mice. Composition difference of eDNA and intracellular DNA (iDNA) of the small intestinal mucus was studied by Illumina sequencing and terminal restriction fragment length polymorphism (T-RFLP). Stimulation of cytokine production by eDNA was studied in RAW264.7 cells in vitro. RESULTS: TOTO-1 iodide staining confirmed existence of eDNA in loose mucus layer of the mouse colon and thin surface mucus layer of the small intestine. Illumina sequencing analysis and T-RFLP revealed that the composition of the eDNA in the small intestinal mucus was significantly different from that of the iDNA of the small intestinal mucus bacteria. Illumina Miseq sequencing showed that the eDNA sequences came mainly from Gram-negative bacteria of Bacteroidales S24-7. By contrast, predominant bacteria of the small intestinal flora comprised Gram-positive bacteria. Both eDNA and iDNA were added to native or lipopolysaccharide-stimulated Raw267.4 macrophages, respectively. The eDNA induced significantly lower tumor necrosis factor-α/interleukin-10 (IL-10) and IL-6/IL-10 ratios than iDNA, suggesting the predominance for maintaining immune homeostasis of the gut. CONCLUSION: Our results indicated that degraded bacterial genomic DNA was mainly released by Gram-negative bacteria, especially Bacteroidales-S24-7 and Stenotrophomonas genus in gut mucus of mice. They decreased pro-inflammatory activity compared to total gut flora genomic DNA.
Subject(s)
Colon/microbiology , DNA, Bacterial/immunology , Gastrointestinal Microbiome/physiology , Gram-Negative Bacteria/physiology , Intestinal Mucosa/microbiology , Intestine, Small/microbiology , Animals , Colon/immunology , Colon/metabolism , Cytokines/immunology , Cytokines/metabolism , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , DNA, Bacterial/metabolism , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Intestine, Small/immunology , Intestine, Small/metabolism , Male , Mice , Mice, Inbred C57BL , Polymorphism, Restriction Fragment LengthABSTRACT
OBJECTIVE: To investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels at birth and respiratory distress syndrome (RDS) in preterm infants. METHODS: This retrospective study recruited preterm infants with gestational age of below 34 weeks who were born between January 2014 and December 2016. These preterm infants were divided into two groups: RDS (n=72) and control (n=40). Clinical data of the two groups were collected, including gestational age, birth weight, gender, delivery mode, Apgar scores at 1 minute and 5 minutes, incidence of maternal gestational diabetes mellitus, and use of prenatal steroid hormone. Peripheral blood samples were collected and 25(OH)D levels were measured by chemiluminescence immunoassay. The association between serum 25(OH)D levels at birth and RDS was analyzed by multivariate logistic regression. RESULTS: Apgar scores at 1 minute and 5 minutes and serum 25(OH)D levels in the RDS group were significantly lower than those in the control group (P<0.05), while the rates of neonatal asphyxia and vitamin D deficiency were significantly higher than those in the control group (P<0.05). Multivariate logistic regression analysis showed that neonatal asphyxia (OR=2.633, 95%CI: 1.139-6.085) and vitamin D deficiency (OR=4.064, 95%CI: 1.625-10.165) were risk factors for RDS in preterm infants. CONCLUSIONS: Vitamin D deficiency might be associated with increased risk of RDS in preterm infants. Reasonable vitamin D supplementation during pregnancy might reduce the incidence of RDS in preterm infants.
Subject(s)
Respiratory Distress Syndrome, Newborn/blood , Vitamin D/analogs & derivatives , Dietary Supplements , Female , Humans , Infant, Newborn , Infant, Premature , Male , Respiratory Distress Syndrome, Newborn/etiology , Vitamin D/blood , Vitamin D Deficiency/complicationsABSTRACT
OBJECTIVE: To assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels at birth and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: This study recruited preterm infants with gestational age of below 34 weeks who were born between January 2014 and December 2016. These preterm infants were classified into two groups: BPD and control. The association between serum 25(OH)D levels at birth and BPD was analyzed. RESULTS: Serum 25(OH)D levels in the BPD group was significantly lower than those in the control group [(37±17â nmol/L vs 47±20 nmol/L; P<0.05), and the rate of vitamin D deficiency was significantly higher than those in the control group (90.2% vs 74.0%; P<0.05). The level of serum 25(OH)D was negatively correlated with the incidence of BPD (r=-0.201, P=0.001). CONCLUSIONS: Vitamin D deficiency at birth may be associated with BPD in preterm infants, but need to be further studied by multivariate analysis.
Subject(s)
Bronchopulmonary Dysplasia/etiology , Infant, Premature/blood , Vitamin D/analogs & derivatives , Bronchopulmonary Dysplasia/blood , Female , Humans , Infant, Newborn , Male , Vitamin D/blood , Vitamin D Deficiency/complicationsABSTRACT
OBJECTIVE: To investigate vitamin D level at birth and possible influencing factors in preterm infants. METHODS: A total of 600 preterm infants were enrolled, and venous blood samples were collected within 24 hours after birth to measure the serum level of 25-hydroxyvitamin D [25(OH)D]. The effect of sex, birth weight, birth season, gestational age, mother's age, body mass index (BMI) in early pregnancy, delivery mode, and complications during pregnancy on serum 25(OH)D level was analyzed. RESULTS: The rates of vitamin D deficiency, insufficiency, and sufficiency were 42.0%, 38.7%, and 19.3% respectively. The preterm infants born in summer and autumn had a significantly higher serum 25(OH)D level than those born in winter (P<0.05) and a significantly lower incidence rate of vitamin D deficiency than those born in spring and winter (P<0.003). Compared with those whose mothers were aged <30 years, the infants whose mothers were aged ≥30 years had a significantly higher serum 25(OH)D level (P<0.05) and a significantly lower incidence rate of vitamin D deficiency (P<0.017). Compared with those whose mothers were overweight or had normal body weight, the infants whose mothers were obese had a significantly lower serum 25(OH)D level (P<0.05) and a significantly higher incidence rate of vitamin D deficiency (P<0.006). Compared with those whose mothers had no preeclampsia, the infants whose mothers had preeclampsia during pregnancy had a significantly lower serum 25(OH)D level (P<0.05) and a significantly higher incidence rate of vitamin D deficiency (P<0.017). The multivariate analysis showed that birth in winter and spring, mother's age <30 years, and early-pregnancy BMI ≥28 kg/m2 were risk factors for vitamin D deficiency (P<0.05). CONCLUSIONS: There is a high prevalence of vitamin D deficiency in preterm infants. Vitamin D supplementation should be given to the preterm infants with high-risk factors for vitamin D deficiency.
Subject(s)
Infant, Newborn/blood , Infant, Premature/blood , Vitamin D/analogs & derivatives , Dietary Supplements , Female , Humans , Incidence , Male , Seasons , Vitamin D/administration & dosage , Vitamin D/blood , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/etiologyABSTRACT
OBJECTIVE: Cyanidin-3-glucoside (C3G) is the main active ingredient of anthocyanidin. This study aimed to evaluate the effects of C3G on body weight gain, visceral adiposity, lipid profiles and insulin resistance in high-fat diet-induced obese rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into a control group (n=8) and a high fat diet group (n=22), and were fed with standard diet or high fat diet. Five weeks later, 17 high-fat diet-induced obese rats were randomly given C3G [100â mg/(kg·d)] or normal saline via intragastric administration for 5 weeks. Five weeks later, body weight, visceral adiposity and food intake were measured. Blood samples were collected for detecting fasting glucose, serum insulin, lipid profiles and adiponectin. Insulin resistance index, atherosclerosis index and average feed efficiency ratio were calculated. RESULTS: C3G supplementation markedly decreased body weight, visceral adiposity, average feed efficiency ratio, triglyceride, total cholesterol, low density lipoprotein cholesterol, fasting glucose, serum insulin, insulin resistance index and atherosclerosis index in high-fat diet-induced obese rats. C3G supplementation normalized serum adiponectin and high density lipoprotein cholesterol levels in high-fat diet-induced obese rats. CONCLUSIONS: Cyanidin-3-glucoside can reduce body weight gain, and attenuate obesity-associated dyslipidemia and insulin resistance in high-fat diet-fed rats via up-regulating serum adiponectin level.
Subject(s)
Anthocyanins/pharmacology , Glucosides/pharmacology , Insulin Resistance , Lipids/blood , Obesity/drug therapy , Weight Gain/drug effects , Animals , Blood Glucose/analysis , Diet, High-Fat , Male , Obesity/blood , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: To evaluate the effect of probiotics (bifidobacterium breve and lactobacillus acidophilus) on serum lipid, serum insulin and insulin resistance in high-fat diet (HFD)-induced obese rats. METHODS: Fifty male Sprague-Dawley rats were randomly assigned to a control (n=10) and a high fat diet groups (n=40) and were fed with standard diet and HFD respectively. Four weeks later, thirty-six HFD-induced obese rats were randomly administered with normal saline (NS), bifidobacterium breve and lactobacillus acidophilus daily (n=12 each). Four weeks later, body lengths, body weights and abdomen circumference of rats were measured, blood lipid, glucose and insulin levels were measured, and Lee's index and insulin resistance index were calculated. RESULTS: Body weight, abdomen circumference, Lee's index, fasting glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) in the NS-treated HFD group were significantly higher than the control group (P<0.05). The bifidobacterium breve and lactobacillus acidophilus-treated groups had significantly lower levels of body weight, abdomen circumference, Lee's index, fasting glucose, TC, TG and LDL than the NS-treated HFD group (P<0.05), but the levels of the parameters in the bifidobacterium breve and lactobacillus acidophilus-treated groups were significantly higher than the control group (P<0.05). High density lipoprotein (HDL) and insulin sensitivity index in the NS-treated HFD group were significantly lower than the control group (P<0.05). Bifidobacterium breve and lactobacillus acidophilus treatment dramatically increased HDL levels and insulin sensitivity index compared with the NS-treated HFD group (P<0.05), although the levels of the two parameters did not reach to the levels of the control group. There were significant differences in the levels of fasting insulin, insulin resistance index and insulin secretion index between the bifidobacterium breve and lactobacillus acidophilus groups (P<0.05). CONCLUSIONS: Lactobacillus acidophilus and bifidobacterium breve can decrease serum levels of lipid and glucose and improve insulin resistance in obese rats. Bifidobacterium breve seems to be more effective on attenuating insulin resistance than lactobacillus acidophilus.