Background Per- and poly-fluoroalkyl substances (PFAS) can influence gestational diabetes mellitus (GDM); however, current studies on their association are limited and have yielded inconsistent findings. Objective To investigate the association between maternal exposure to PFAS, as measured by urinary concentrations in early pregnancy, and the risk of developing GDM. Methods Based on the Wuhu Birth Cohort in Anhui Province conducted between 2020 and 2023, this study included 1910 pregnant women. Urine samples were collected during the first trimester, and a 75 g oral glucose tolerance test (OGTT) was completed at 24–28 gestational weeks. The concentrations of six PFAS in urine were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Participants were categorized into low, medium, and high exposure groups according to tertiles of individual PFAS concentrations. Logistic regression analysis was employed to assess the potential impact of early-pregnancy PFAS exposure levels on the risk of GDM, with stratified analyses by maternal age and fetal sex. A generalized weighted quantile sum regression (gWQS) model was applied to evaluate the relative weight distribution of the six PFAS in their mixture effect. Results The logistic regression results revealed that both medium exposure to perfluorohexane sulfonate (PFHxS) (OR=1.475, 95%CI: 1.040, 2.093) and high exposure to perfluorononanoic acid (PFNA) (OR=1.430, 95%CI: 1.013, 2.018) were positively associated with diagnosed GDM. This association was more pronounced among women older than 28 years. Among pregnant women carrying male fetuses, high-level exposures to per fluorohexanoic acid (PFHxA) (OR=1.708, 95%CI: 1.006, 2.899) and PFHxS (OR=2.116, 95%CI: 1.247, 3.584) showed positive associations with diagnosed GDM. In contrast, among those carrying female fetuses, moderate perfluorooctanesulfonic acid (PFOS) exposure was associated with a lower risk of GDM (OR=0.542, 95%CI: 0.311, 0.946). The gWQS results demonstrated that PFOS (0.48) and perfluorobutane sulfonate (PFBS) (0.34) contributed the most to the mixture effect. Conclusion Early-pregnancy exposure to PFAS (particularly PFHxS and PFNA) may be an etiological factor for GDM, with maternal age and fetal sex potentially acting as effect modifiers in this association.

Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

OBJECTIVES: To evaluate the impact of HBV infection on pre- and postpartum health-related quality of life (HRQoL) in pregnant women. METHODS: A prospective matched cohort consisting of 70 HBV-infected and 70 healthy pregnant women was recruited from the Fifth Affiliated Hospital of Guangzhou Medical University between April 17 and September 25, 2023. HRQoL of the participants was assessed at 16-24 weeks of gestation, between 32 weeks and delivery, and 5-13 weeks postpartum. Mixed linear models were used for evaluating temporal trends of HRQoL changes, and univariate ANOVA with multiple linear regression was used to identify the predictors of HRQoL. RESULTS: Compared with healthy pregnant women, HBV-infected pregnant women had consistently lower total HRQoL scores across all the 3 intervals, with the lowest scores observed between 32 weeks of gestation and delivery, during which these women had significantly reduced mental component scores (74.27±13.43 vs 80.21±12.9, P=0.009) and postpartum mental (76.52±16.19 vs 85.02±6.51, P<0.001) and physical component scale scores (77.17±14.71 vs 83.09±10.1, P=0.009). HBV infection was identified as an independent risk factor affecting HRQoL during late pregnancy and postpartum periods. Additional independent risk factors for postpartum HRQoL reduction included self-pay medical expenses, spouse's neutral attitude toward the current pregnancy, and preexisting comorbidities (all P<0.05). CONCLUSIONS HRQoL of pregnant women deteriorates progressively in late pregnancy, and HBV infection exacerbates reductions of physical function and role emotion in late pregnancy and after delivery, suggesting the importance of targeted interventions for financial burdens, partner support and comorbid conditions to improve HRQoL of pregnant women with HBV infection.
Humans ; Female ; Pregnancy ; Quality of Life ; Prospective Studies ; Postpartum Period ; Hepatitis B, Chronic/psychology* ; Adult ; Pregnancy Trimester, Third ; Pregnancy Trimester, Second ; Pregnancy Complications, Infectious

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

OBJECTIVE: To investigate the association between fluid balance trajectories within the first 3 days of intensive care unit (ICU) admission and 28-day mortality as well as the incidence of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients were extracted from the Medical Information Mart of Intensive Care-IV (MIMIC-IV). Group-based trajectory modeling (GBTM) was used to analyze the daily fluid balance of patients within 3 days of ICU admission, and grouping them accordingly. Univariate and multivariate Logistic regression analyses were performed to assess the association between fluid balance trajectory and 28-day mortality and ICU CRRT in SAP patients. RESULTS: A total of 251 SAP patients were included, with 33 deaths within 28 days, and a 28-day mortality of 13.15%; 49 patients (19.52%) continued to receive bedside CRRT after 3 days of ICU admission. The fluid balance on the 3rd day, cumulative fluid balance within 3 days of ICU admission, and incidence of CRRT in the death group were significantly higher than those in the survival group. According to GBTM groups, there were 127 cases in the moderate fluid resuscitation with rapid reduction (MF group), 44 cases in the large fluid resuscitation with rapid reduction (LF group), 20 cases in the moderate fluid resuscitation with slow reduction (MS group), and 60 cases in the small fluid resuscitation with slow reduction (SS group). The cumulative fluid balance within 3 days of ICU admission of the MF group, LF group, MS group, and SS group were 8.60% (5.15%, 11.70%), 16.70% (13.00%, 21.02%), 23.40% (19.38%, 25.45%), and 0.65% (-2.35%, 2.20%), respectively, and the incidence of CRRT during ICU hospitalization were 11.02%, 29.55%, 85.00%, and 8.33%, respectively, with statistically significant differences among the groups (both P < 0.05); the 28-day mortality were 11.02%, 18.18%, 20.00%, and 11.67%, respectively, with no statistically significant difference among the groups (P > 0.05). Kaplan-Meier survival curve analysis showed there was no statistically significant difference in 28-day cumulative survival rate among groups with different fluid balance trajectories (Log-rank test: χ ² = 2.31, P = 0.509). Multivariate Logistic regression analysis showed that cumulative fluid balance within 3 days of ICU admission was an independent risk factor for 28-day mortality [odds ratio (OR) = 1.071, 95% confidence interval (95%CI) was 1.005-1.144, P = 0.040] and CRRT requirement (OR = 1.233, 95%CI was 1.125-1.372, P < 0.001); early aggressive fluid resuscitation on day 1 reduced CRRT risk (OR = 0.866, 95%CI was 0.756-0.978, P = 0.030). CONCLUSIONS Dynamic fluid management is essential in SAP patients. While early aggressive fluid resuscitation may reduce CRRT demand, excessive cumulative fluid balance is associated with increased 28-day mortality and CRRT incidence.
Humans ; Male ; Female ; Middle Aged ; Water-Electrolyte Balance ; Continuous Renal Replacement Therapy ; Intensive Care Units ; Aged ; Adult ; Pancreatitis/mortality* ; Logistic Models ; Retrospective Studies ; Renal Replacement Therapy

OBJECTIVES: To investigate the protective effects and underlying mechanisms of Gynostemma pentaphyllum (GP)ethanol extract on motor dysfunction in a mouse model of Parkinson's disease (PD). METHODS: Eighty C57BL/6 male mice were randomly divided into five groups: control group, model group, levodopa group (positive control group), low-dose GP group, and high-dose GP group, with 16 mice per group. The PD model was induced by injection of 6-hydroxydopamine into the substantia nigra pars reticulata of the mice. Two weeks after 6-hydroxydopamine, positive control group received intraperitoneal injection of levodopa 10 mg·kg^－1·d^－1, while low-dose GP and high-dose GP groups received GP extract 100 or 200 mg·kg^－1·d^－1 orally for three weeks. After a 3-week-treatment, the effects of GP on motor dysfunction in 6-hydroxydopamine-induced PD were assessed using open field and CatWalk gait tests, while the effects on muscle strength were evaluated by forelimb grip strength. Immunofluorescence staining was used to detect the number of tyrosine hydroxylase (TH) positive neurons. The levels of dopamine and serotonin in the midbrain were determined by enzyme-linked immunosorbent assay. In addition, Western blotting was performed to detect the expression of mitogen-activated protein kinase (MAPK) family proteins such as p-extracellular signal-regulated kinase (ERK)1/2, p-p38 and p-c-Jun N-terminal kinase (JNK)1/2, and mitochondrial apoptosis pathway proteins such as B-cell lymphoma (Bcl)-2, Bcl-2 associated X protein (Bax), and cleaved-cysteine aspartic acid specific protease (caspase)-3. RESULTS: Behavioral experiments showed that GP significantly improved the spontaneous activity and motor coordination of PD mice (P<0.05). The forelimb grip strength was also increased by GP treatment (P<0.05), compared to the PD model group. In addition, compared with the model group, the number of TH-positive neurons in substantia nigra pars reticulata region, the levels of dopamine and serotonin in midbrain and the expression of p-ERK1/2 were significantly increased by GP treatment (all P<0.05), whereas the expression of p-p38 and p-JNK1/2, the ratio of Bax/Bcl-2 and cleaved-caspase-3/caspase-3 were significantly decreased (all P<0.05). CONCLUSIONS The results indicate that GP might increase dopamine and serotonin levels in the midbrain and promote the survival of dopaminergic neurons in substantia nigra pars reticulata by regulating the expression of phosphorylation of MAPK family proteins and the expression of mitochondrial apoptosis-related proteins, thereby ameliorating motor deficits in PD mice.
Animals ; Mice ; Male ; Gynostemma/chemistry* ; Mice, Inbred C57BL ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Parkinson Disease/metabolism* ; Disease Models, Animal ; Neurons/pathology*

Objective To investigate the levels of serum neuregulin-4(NRG4)and serum fatty acid binding protein 4(FABP4)in patients with diabetes retinopathy(DR)and their diagnostic value.Methods From A-pril 2020 to April 2023,a total of 84 DR patients admitted to Endocrine and Metabolic Disease Hospital Affili-ated to Shandong First Medical University were regarded as the observation group.Based on the type of retinal lesions,they were grouped into proliferative lesion group(35 cases)and non proliferative lesion group(49 ca-ses).In addition,84 patients with simple diabetes in the same period were regarded as the NDR group,and 84 healthy people who underwent physical examination in the same period were regarded as the control group.Enzyme linked immunosorbent assay was applied to detect serum levels of NRG4 and FABP4.Multivariate Logistic regression was applied to analyze the influencing factors of DR occurrence.Receiver operating charac-teristic(ROC)curve was applied to analyze the diagnostic value of serum NRG4 and FABP4 levels for DR.Results The levels of C-reactive protein(CRP),fasting plasma glucose(FPG),fasting insulin(FINS)and FABP4 in the observation group were higher than those in the NDR group and the control group(P<0.05),and the serum NRG4 level was lower than those in the NDR group and the control group(P<0.05).The ser-um NRG4 level in the proliferative lesion group was lower than that in the non proliferative lesion group(P<0.05),and the FABP4 level was higher than that in the non proliferative lesion group(P<0.05).NRG4 was a protective factor for the occurrence of DR(P<0.05),while FABP4 was a risk factor for the occurrence of DR(P<0.05).The area under the curve(AUC)of serum NRG4 and FABP4 for diagnosing DR was 0.850 and 0.866,and the AUC of combined diagnosis was 0.930.The efficacy of the combination of the two was su-perior to that of the individual diagnosis of serum NRG4 and FABP4(Zcombination-NRG4=3.467,Zcombination-FABP4=2.987,P=0.001,0.002).Conclusion The serum FABP4 level in DR patients is greatly increased,while the NRG4 level is greatly decreased.The combination of the two has high diagnostic value for DR.

Objective:To investigate the mechanism of microRNA-597-3p ( miR-579-3p) in improving hypoxic-ischemic encephalopathy (HIE) by regulating the interleukin-1 receptor-associated kinase 1 (IRAK1)/tumor necrosis factor receptor-associated factor 6 (TRAF6)/transforming growth factor-β-activated kinase 1 (TAK1)/nuclear factor-κB (NF-κB) signaling pathway. Methods:Peripheral blood of healthy neonates ( n=5) and HIE newborns ( n=5) from June 2023 to June 2024 in the No.215 Hospital of Shaanxi Nuclear Industry were collected. The differential expression of miRNA in peripheral blood of neonates with HIE was analyzed by next-generation sequencing. The oxygen-glucose deprivation (OGD) method was used to establish the HIE cell model, which was designated as the OGD group, while cells without OGD treatment served as the control group. Rat adrenal pheochromocytoma PC12 cells were transfected with miR-579-3p mimic (mimic), mimic negative control (mimic-NC), miR-579-3p inhibitor (inhibitor), inhibitor negative control (inhibitor-NC), respectively, and divided into the mimic group, mimic-NC group, inhibitor group, inhibitor-NC group. On the basis of mimic group and inhibitor group, IRAK1 overexpression plasmid ( oeIRAK1) and IRAK1 small interfering RNA plasmid ( siIRAK1) were transfected respectively, which were divided into oeIRAK1 group and siIRAK1 group. The relative expression level of mRNA was detected by real-time reverse transcription-PCR. The absorbance ( A) value was detected by cell counting kit-8 assay. The apoptosis rate was detected by Annexin Ⅴ-fluorescein isothiocyanate/propidium iodide double staining. The relative expression of protein was detected by Western blotting. The levels of pro-inflammatory factors and anti-oxidative stress factors were detected by enzyme-linked immunosorbent assay. Bioinformatics analysis was used to predict the binding site between miR-579-3p and IRAK1, and the dual-luciferase reporter assay was performed to validate their targeting relationship. A total of 12 7-day-old SD rats were selected and randomly divided into the HIE group and the sham group by the random number table method. In the HIE group, the right common carotid artery of rats was permanently occluded, followed by hypoxia exposure, whereas rats in the sham group only underwent common carotid artery exposure without ligation or hypoxia treatment. Immunohistochemical staining was used to detect the expression of protein in brain tissue of HIE rats. The least significant difference t-test was used for comparison between the two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:Compared with the healthy neonates, a total of 278 differentially expressed miRNAs were detected in the peripheral blood of neonates with HIE, among which miR-579-3p showed the most significant downregulation. The relative expression level of miR-579-3p in the mimic group (15.78±1.93) was significantly higher than that in the mimic-NC group (1.00±0.14) ( P<0.01), and in the inhibitor group (0.29±0.14) was significantly lower than that in inhibitor-NC group (1.00±0.14) ( P<0.01). The A value in the mimic group (0.89±0.09) was significantly higher than that in the mimic-NC group (0.52±0.08) ( P<0.01), and in the inhibitor group (0.30±0.05 ) was significantly lower than that in the inhibitor-NC group (0.56±0.07) ( P<0.05). The apoptosis rate of mimic group [(7.47±1.53)%] was significantly lower than that in the mimic-NC group [(30.97±3.47)%] ( P<0.05), and in the inhibitor group [(49.05±4.21)%] was significantly lower than that in the inhibitor-NC group [(35.51±3.64)%] ( P<0.01). The relative expression level of cysteine aspartic acid specific protease-3 ( Caspase-3) and B-cell lymphoma-2 (Bcl-2) associated X protein ( Bax) (1.21±0.10, 1.40±0.13), the relative expression of cleaved Caspase-3 and Bax (1.00±0.13, 1.13±0.09), the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α [(45.15±5.14, 38.34±5.69) pg/mg] in the mimic group were significantly lower than those in the mimic-NC group [2.10±0.14, 2.37±0.16, 2.29±0.09, 2.27±0.12, (95.67±9.05, 63.99±5.24) pg/mg] (all P<0.01). The relative expression level of Bcl-2 and Claspin (1.03±0.09, 1.00±0.04), the relative expression of Bcl-2 and Claspin (1.21±0.06, 0.94±0.09), the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) [(67.65±6.86, 58.07±5.20) U/mg] in the mimic group were significantly higher than those in the mimic-NC group [(0.51±0.05, 0.52±0.02, 0.58±0.05, 0.46±0.07, 42.08±5.86, 29.80±4.85) U/mg] ( P<0.05, 0.01). The relative expression level of Caspase-3 and Bax (2.72±0.16, 2.97±0.10), the relative expression of cleaved Caspase-3 and Bax (3.25±0.17, 2.76±0.16), the levels of IL-6 and TNF-α [(122.80±11.59, 92.58±7.56) pg/mg] in the inhibitor group were significantly higher than those in the inhibitor-NC group [(1.86±0.14, 2.12±0.10, 2.35±0.15, 1.82±0.15, (88.13±8.59, 68.61±6.17) pg/mg] ( P<0.05, 0.01). The relative expression levels of Bcl-2 and Claspin mRNA (0.17±0.04, 0.20±0.06), the relative expression of Bcl-2 and Claspin proteins (0.11±0.03, 0.13±0.05), the levels of SOD and GSH-Px [(16.62±3.19, 12.01±1.92) U/mg] in the inhibitor group were significantly lower than those in the inhibitor-NC group [0.54±0.05, 0.54±0.05, 0.53±0.10, 0.45±0.07, (38.09±5.47, 30.90±3.87) U/mg] ( P<0.05, 0.01). IRAK1 was identified as a putative target of miR-579-3p. The relative luciferase activity of wild-type IRAK1 in the mimic group (0.45±0.05) was significantly lower than that in the mimic-NC group (1.00±0.08) ( P<0.01). The relative expression levels of IRAK1, TRAF6, TAK1 and NF-κB mRNA in the mimic group (0.96±0.09, 0.96±0.11, 1.34±0.16, 1.74±0.20), the relative expression of IRAK1, TRAF6, TAK1, and phosphorylated NF-κB (p-NF-κB) proteins (0.96±0.20, 1.27±0.19, 1.34±0.18, 1.16±0.19) were all lower than those in the mimic-NC group (1.96±0.17, 1.88±0.24, 2.39±0.23, 2.44±0.20, 2.33±0.22, 2.17±0.24, 2.25±0.28, 2.06±0.28) (all P<0.01). The relative expression levels of IRAK1, TRAF6, TAK1 and NF-κB mRNA in the inhibitor group (2.54±0.15, 2.61±0.13, 2.97±0.15, 2.99±0.20), the relative expression of IRAK1, TRAF6, TAK1 and p-NF-κB proteins (3.73±0.34, 3.17±0.25, 3.68±0.22, 3.29±0.20) were all higher than those in the inhibitor-NC group (1.87±0.18, 1.84±0.19, 2.15±0.24, 2.24±0.26, 2.35±0.23, 1.94±0.25, 2.05±0.27, 2.17±0.29) (all P<0.01). The A value in the oeIRAK1 group (0.66±0.07) was significantly lower than that in the mimic group (0.94±0.10) ( P<0.05), and in the siIRAK1 group (0.51±0.08) was significantly higher than that in the inhibitor group (0.23±0.05) ( P<0.05). The apoptosis rate in the oeIRAK1 group [(23.32±2.40)%] was significantly higher than that in the mimic group [(9.02±1.23)%] ( P<0.05), and in the siIRAK1 group [(28.27±2.57)%] was significantly lower than that in the inhibitor group [(48.96±4.60)%] ( P<0.01). The levels of IL-6 and TNF-α in the oeIRAK1 group [(85.10±6.98, 59.49±5.78) pg/mg] were significantly higher than those in the mimic group [(47.51±8.87, 23.65±3.75) pg/mg], and the levels of SOD and GSH-Px [(49.58±5.63, 41.31±6.21) U/mg] were significantly lower than those in the mimic group [(81.22±6.94, 62.26±5.44) U/mg] ( P<0.05, 0.01). The levels of IL-6 and TNF-α in the siIRAK1 group [(108.25±9.47, 74.87±8.71) pg/mg] were significantly lower than those in the inhibitor group [(142.65±13.88, 104.49±9.18) pg/mg], and the levels of SOD and GSH-Px [(35.87±3.69, 34.89±4.96) U/mg] were significantly higher than those in the inhibitor group [(15.55±3.70, 15.62±3.30) U/mg] ( P<0.05, 0.01). The relative expression level of miR-579-3p in the HIE group (0.47±0.11) was significantly lower than that in the sham group (1.00±0.09) ( P<0.01). The levels of IL-6 and TNF-α in the HIE group [(62.18±6.42, 68.42±4.91) pg/mg] were significantly higher than those in the sham group [(20.77±4.68, 31.16±4.95) pg/mg], and the levels of SOD and GSH-Px [(22.63±3.33, 19.07±2.86) U/mg] were significantly lower than those in the sham group [(47.89±4.58, 56.55±4.45) U/mg] (all P<0.01). The relative levels of TLR4, IRAK1, TRAF6, TAK1, NF-κB, and Caspase-3 mRNA, TLR4, IRAK1, TRAF6, TAK1, p-NF-κB, and cleaved Caspase-3 proteins in the HIE group (1.87±0.24, 2.03±0.21, 2.23±0.20, 1.85±0.18, 1.91±0.20, 2.36±0.20, 2.36±0.28, 2.16±0.28, 1.95±0.27, 2.05±0.26, 2.34±0.24, and 2.72±0.23) were all higher than those in the sham group (1.00±0.15, 1.00±0.11, 1.00±0.09, 1.00±0.05, 1.00±0.12, 1.00±0.15, 1.00±0.15, 1.00±0.21, 1.00±0.10, 1.00±0.14, 1.00±0.19, 1.00±0.16) (all P<0.01), which were consistent with the immunohistochemical staining results. Conclusions:miR-579-3p might alleviate HIE-induced neuronal damage by regulating the IRAK1/TRAF6/TAK1/NF-κB signaling pathway.