The association of insufficient gestational weight gain in women with gestational diabetes mellitus with adverse infant outcomes: A case-control study.

Background: To investigate the association between insufficient maternal gestational weight gain (GWG) during dietary treatment, and neonatal complications of small-for-gestational-age (SGA) infants born to mothers with Gestational diabetes mellitus (GDM). Methods: A retrospective case-control study was conducted, involving 1,651 infants born to mothers with GDM. The prevalence of a perinatal outcome and maternal GWG were compared among SGA, adequate- (AGA), and large-for-gestational-age (LGA); association with birth weight and GWG was identified using Pearson's correlation analysis; binary logistic regression was performed to determine the odds ratio (OR) associated with SGA. Results: In total, 343 SGA, 1025 AGA, and 283 LGA infants met inclusion criteria. The frequency of SGA infants who were siblings (41.7 vs. 4.3 vs. 1.9%) and composite of complications (19.2 vs. 12.0 vs. 11.7%) were higher in SGA infants than in those in AGA or LGA infants group (both P < 0.01). GWG and pre-partum BMI were lower among the SGA mothers with GDM group (11.7 ± 4.5 kg, 25.2 ± 3.1 kg/m2) than AGA (12.3 ± 4.6 kg, 26.3 ± 3.4 kg/m2) or LGA (14.0 ± 5.1 kg, 28.7 ± 3.9 kg/m2) mothers with GDM group. Binary logistic regression showed that siblings who were SGA (AOR 18.06, 95% CI [10.83-30.13]) and preeclampsia (AOR 3.12, 95% CI [1.34-7.30]) were associated with SGA, but not GWG below guidelines (P > 0.05). The risk of SGA (25.7 vs. 19.1 vs. 14.2%) and FGR (15.3 vs. 10.9 vs. 7.8%) was higher in GWG below guidelines group than those in GWG above and within guidelines group, the risk of low Apgar score (6.4 vs. 3.0 vs. 2.8%) was higher in GWG above guidelines group than that in GWG below and within guidelines group (P < 0.05). Conclusion: Our findings demonstrated that GWG above and below guidelines, compared with GWG within guidelines, had a higher risk of adverse infant outcomes. Our findings also suggested that GWG below guidelines did not increase the risk for SGA, though SGA infants had more adverse outcomes among neonates born to mothers with GDM.

Corrigendum: The association of insufficient gestational weight gain in women with gestational diabetes mellitus with adverse infant outcomes: a case-control study.

[This corrects the article DOI: 10.3389/fpubh.2023.1054626.].

Effects of rapamycin and OSI-027 on α-SMA in lung tissue of SD rat pups with hyperoxic lung injury.

OBJECTIVE: To investigate the effect and significance of mammalian target of rapamycin (mTOR) inhibitors on the expression of α-SMA in lung injury induced by high volume fraction of inspired oxygen (hyperoxygen) in SD rat pups. METHODS: Seventy-two Sprague-Dawley rat pups (age: 3 weeks) were randomly divided into air + saline, hyperoxia + saline, hyperoxia + OSI-027, and hyperoxia + rapamycin groups. Animal models were constructed (n = 18). Hyperoxia was induced by continuous administration of 90% oxygen. Normal saline, OSI-027, and rapamycin are administered by intraperitoneal injection on 1d, 3d, 6d, 8d, 10d, 13d of the observation period, respectively. Following assessments were made on the 3rd, 7th, and 14th day of modeling: pathological changes in lung tissues, lung injury score, Western Blot to assess the distribution and expressions of mTOR, pS6K1, and α-SMA protein in lung tissues. RESULTS: In terms of time factors, the protein expressions of mTOR, pS6K1, and α-SMA increased with time. Except for the air group, the lung injury scores of the other groups increased with time, In terms of grouping factors, lung injury score in the air group was significantly lower than that in the other groups. In the hyperoxia group, the protein expressions of mTOR, PS6K1, and α-SMA were significantly higher than those in the other groups. The lung injury score in the hyperoxia group was significantly higher than that in the other groups. The lung injury score in the hyperoxia OSI group was significantly lower than that in the hyperoxia rapamycin group. CONCLUSION: In hyperoxia lung injury, inhibiting the activation of mTOR signaling pathway can effectively reduce the expression of α-SMA; however, only mTORC1/2 dual inhibitor OSI-027 exhibited an anti-proliferative effect, and alleviated hyperoxia-induced lung injury and fibrosis in SD rat pups.

[Proteome analysis of type II alveolar epithelial cell in hyperoxia induced lung injury].

OBJECTIVE: To investigate the damage mechanism of type II alveolar epithelial cells (AEC II) after hyperoxia exposure by proteomics. METHODS: The primary AEC II of preterm Sprague-Dawley (SD) rats were divided into normoxia and hyperoxia groups, and cultured in room air (21% O2) or hyperoxia (95% O2) condition, respectively. The cell morphology change was observed under an inverted contrast microscope; the protein expressions of Bcl-2 and caspase-3 were detected by Western Blot to ensure a successful model. Total protein in AEC II was collected, and mass spectrometry-based tandem mass tag (TMT)-labeled quantitative proteomics were used to detect the change of protein profile. Proteins with changes greater than 1.5-fold and P < 0.05 were considered differentially expressed, and bioinformatics analysis was performed. According to the proteomic results, AEC II were divided into three groups: normoxia group, hyperoxia group and hyperoxia+MW167 group (γ-secretase inhibitor MW167 was added to culture medium 30 minutes before they were placed into the chamber). The cell viability was detected by the cell proliferation and toxicity kit (CCK-8), and the expressions of Hes1, Bax mRNA were detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: (1) The cells in the normoxia group proliferated and prolonged significantly, and the cytoplasmic particulate matter was abundant. In the hyperoxia group, nucleus pyknosis and cytoplasmic particulate matter decreased significantly. Compared with the normoxia group, the expression of caspase-3 in the hyperoxia group was significantly increased, and the expression of Bcl-2 was significantly decreased (caspase-3/GAPDH: 1.352±0.086 vs. 0.769±0.080, Bcl-2/GAPDH: 0.614±0.060 vs. 1.361±0.078, both P < 0.01). (2) A total of 162 differentially expressed proteins were identified between normoxia and hyperoxia groups, the proteins up-regulated by hyperoxia were commonly associated with response processes to various stimuli, and located in the extracellular region; the proteins down-regulated by hyperoxia were commonly associated with synthesis of substances, and located in the cellular matrix. KEGG Pathway analyses suggested that metabolism by cytochrome P450, oxidative phosphorylation, and Notch signaling pathway were associated with the mechanism of hyperoxia injury on AEC II. (3) Compared with the normoxia group, the viability of cells in the hyperoxia group was significantly decreased, and the expressions of Hes1 and Bax mRNA were significantly increased [cell viability (A value): 0.060±0.003 vs. 1.058± 0.017, Hes1 mRNA (2-ΔΔCt): 2.235±0.606 vs. 1.144±0.107, Bax mRNA (2-ΔΔCt): 2.210±0.240 vs. 1.084±0.096, all P < 0.05]. Compared with the hyperoxia group, the viability of cells in the hyperoxia+MW167 group was significantly increased, and the expressions of Hes1 and Bax mRNA were significantly decreased [cell viability (A value): 0.271±0.025 vs. 0.060±0.003, Hes1 mRNA (2-ΔΔCt): 0.489±0.046 vs. 2.235±0.606, Bax mRNA (2-ΔΔCt): 1.289±0.041 vs. 2.210±0.240, all P < 0.05]. CONCLUSIONS: The mechanism of hyperoxia injury on AECII may be related to the metabolism by cytochrome P450, oxidative phosphorylation and activation of Notch signaling pathway.

Hydrogen protects against hyperoxia-induced apoptosis in type II alveolar epithelial cells via activation of PI3K/Akt/Foxo3a signaling pathway.

Oxidative stress is regarded as a key regulator in the pathogenesis of prolonged hyperoxia-induced lung injury, which causes injury to alveolar epithelial cells and eventually leads to development of bronchopulmonary dysplasia (BPD). Many studies have shown that hydrogen has a protective effect in a variety of cells. However, the mechanisms by which hydrogen rescues cells from damage due to oxidative stress in BPD remains to be fully elucidated. This study sought to evaluate the effects of hydrogen on hyperoxia-induced lung injury and to investigate the underlying mechanism. Primary type II alveolar epithelial cells (AECIIs) were divided into four groups: control (21% oxygen), hyperoxia (95% oxygen), hyperoxia + hydrogen, and hyperoxia + hydrogen + LY294002 (a PI3K/Akt inhibitor). Proliferation and apoptosis of AECIIs were assessed using MTS assay and flow cytometry (FCM), respectively. Gene and protein expression were detected by quantitative polymerase chain reaction (q-PCR) and western blot analysis. Stimulation with hyperoxia decreased the expression of P-Akt, P- FoxO3a, cyclinD1 and Bcl-2. Hyperoxic conditions increased levels of Bim, Bax, and Foxo3a, which induced proliferation restriction and apoptosis of AECIIs. These effects of hyperoxia were reversed with hydrogen pretreatment. Furthermore, the protective effects of hydrogen were abrogated by PI3K/Akt inhibitor LY294002. The results indicate that hydrogen protects AECIIs from hyperoxia-induced apoptosis by inhibiting apoptosis factors and promoting the expression of anti-apoptosis factors. These effects were associated with activation of the PI3K/Akt/FoxO3a pathway.