JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2023
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IF 3
Dan Xiao,Ying Jin,Mengyu Zhang,Xiangjie Di,Lisha Fu,Changke Jiang,Zhuoli Lai,Yating Ge,Shanmian Ji,Yuming Zhang,Li Zheng,Zhenlei Wang,Fang Gong
Persistent patent ductus arteriosus (PDA) is generally observed in preterm neonates. Oral ibuprofen is the standard treatment for closing PDA in China. To investigate the chiral pharmacokinetics of ibuprofen enantiomers in Chinese premature infants with PDA, a simple, fast, and sensitive analytical enantioselective technology was developed with ultra-performance liquid chromatography (UPLC) – tandem mass spectrometry (MS/MS). Chromatographic separation of (R)-ibuprofen and (S)-ibuprofen was accomplished on a Lux® 3 µm Cellulose-3 (150 mm × 2.0 mm, 3 μm) at a flow rate of 0.2 mL/min within 6 min. UPLC separation was achieved by isocratic elution with a mobile phase consisting of formic acid:water (75:1000000, v/v) and acetonitrile:methanol (1:1, v/v). Only 50 µL of plasma samples were pre-treated with acetonitrile precipitation. Ibuprofen-d 3 was used as an internal standard. The standard curves of both enantiomers were linear over a concentration range of 0.0500 μg/mL to 50.00 μg/mL. The method has been validated for selectivity, carryover effect, lower limit of quantification, precision, accuracy, matrix effect, extraction recovery, dilution integrity, and stability based on the existing guidelines of the National Medical Products Administration, the United States Food and Drug Administration, and the European Medicines Agency. This method has been successfully applied to investigate the pharmacokinetics of ibuprofen enantiomers in 9 preterm infants with PDA. Our results showed that a high chiral inversion ratio of (R)- to (S)-ibuprofen exists in Chinese preterm neonates. Further studies should be conducted to monitor drug concentration following oral administration of ibuprofen and to consider the effect of individual variations and ethnic differences in metabolizing enantiomers of ibuprofen in premature neonates with PDA.
研究领域:
药理学
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新生儿医学
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分析化学
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DOI
PubMed
高影响因子
Heliyon
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2024
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IF 3.4
Maomao Sun,Congrong Wu,Jie Jiang,Yue He,Sha Zhu,Yonghui Yu
Background Maternal hypertensive disorders of pregnancy (HDP) was associated with increased risk of congenital hypothyroidism in preterm infants, but its underlying mechanisms remain unclear. Objective To investigate the possible mechanisms by which intrauterine exposure to HDP affects thyroid hormone synthesis in preterm infant rats. Methods preterm infant rats were obtained by Caesarean section delivery from the L-NAME group and Control groups which was induced by L-NAME and saline, respectively. Thyroid hormone levels of preterm infant rats were detected by ELISA, and morphology structure were observed by H&E staining and electron microscopy, and the expression of key factors of thyroid hormone synthesis and endoplasmic reticulum stress indicators were analyzed by RT-qPCR and Western blotting. Results Compared with the Control group, significantly higher serum TSH concentration was observed in the L-NAME group (p < 0.05), while T3 and T4 levels showed no noticeable change. The L-NAME group revealed a reduction in the size and number of thyroid follicles, with the emergence of thyroid follicular epithelial hyperplasia. While electron microscopy revealed that the endoplasmic reticulum of thyroid follicular epithelial cells was marked swollen within L-NAME group. Additionally, the mRNA expression of Ttf1 , Pax8 and Tshr was down-regulated in thyroid tissues of L-NAME group. Furthermore, the protein levels of Tg, NIS and TSHR were reduced, while the protein level of p-IRE1α, ATF6α, XBP1s and Bip were increased in the L-NAME group. Conclusion The results indicated that HDP may reduce the expression of key molecules involved in thyroid synthesis through endoplasmic reticulum stress which could ultimately result in the development of congenital hypothyroidism.
研究领域:
医学
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内分泌学
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DOI
高影响因子
Frontiers in Pharmacology
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2023
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IF 5.6
Hao Liu,Jing-Kun Miao,Meng Cai,Lin Gan,Hui-Qing Zhao,Xiao-Feng Lei,Jin Yu
Objective: This study aims to determine the drug concentration of etomidate, remifentanil, and rocuronium bromide for general anesthesia in fetus as well as the placental transport rate between term and preterm delivery, twins, and singleton. Study design: Sixty parturients with 72 fetuses undergoing cesarean section under general anesthesia were included. According to whether the fetus was a twin or premature, parturients were divided into Group I (term singleton), Group II (premature singleton), Group III (term twins), and Group IV (premature twins). The preoperative demographic characteristics and laboratory examination of parturients, hemodynamic indicators, the Apgar score of neonates at 1, 5, and 10 min after delivery and at specific assigned values, umbilical artery blood gas analysis results, neonatal weight, and resuscitative measures were recorded. Anesthetic drug concentrations in maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood were detected by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). Result: No significant differences were observed in the concentrations of etomidate, remifentanil, and rocuronium bromide in MA, UV, and UA blood, or in the UV/MA and UA/UV ratios between term and preterm infants, twins, and singletons. Moreover, there was no variation in the anesthetic drug concentration among each pair of twins. Additionally, no correlation was found between the neonatal weight and the plasma concentrations of anesthetic drugs in UV and UA blood, except for remifentanil in UA blood. Conclusion: Preterm or twin deliveries do not affect the neonatal concentration of etomidate, remifentanil, and rocuronium bromide used in general anesthesia for cesarean sections. Clinical Trial Registration: www.chictr.org.cn , identifier ChiCTR2100046547
研究领域:
妇产科学
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麻醉学
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药理学
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DOI
PubMed
高影响因子
Gut Microbes
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2024
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IF 12.2
Zhenhui Chen,Huijuan Chen,Wanwen Huang,Xiaotong Guo,Lu Yu,Jiamin Shan,Xiaoshi Deng,Jiaxin Liu,Wendan Li,Wei Shen,Hongying Fan
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants with no specific treatments available. We aimed to identify the molecular mechanisms underlying NEC and investigate the therapeutic effects of Bacteroides fragilis on NEC. Clinical samples of infant feces, bile acid-targeted metabolomics, pathological staining, bioinformatics analysis, NEC rat model, and co-immunoprecipitation were used to explore the pathogenesis of NEC. Taxonomic characterization of the bile salt hydrolase (bsh) gene, enzyme activity assays, 16S rRNA sequencing, and organoids were used to explore the therapeutic effects of B. fragilis on NEC-related intestinal damage. Clinical samples, NEC rat models, and in vitro experiments revealed that total bile acid increased in the blood but decreased in feces. Moreover, the levels of FXR and other bile acid metabolism-related genes were abnormal, resulting in disordered bile acid metabolism in NEC. Taurochenodeoxycholic acid accelerated NEC pathogenesis and taurodeoxycholate alleviated NEC. B. fragilis displayed bsh genes and enzyme activity and alleviated intestinal damage by restoring gut microbiota dysbiosis and bile acid metabolism abnormalities by inhibiting the FXR-NLRP3 signaling pathway. Our results provide valuable insights into the therapeutic role of B. fragilis in NEC. Administering B. fragilis may substantially alleviate intestinal damage in NEC.
研究领域:
微生物学
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胃肠病学
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儿科
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代谢组学
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分子生物学
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DOI
PubMed
高影响因子
Translational Pediatrics
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2021
·Vol. 10
·期 9
·2313
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IF 2.488
Wei Shen,Wen Qiu,Yuting Liu,Weihua Liao,Yiyi Ma,Yan He,Zhang Wang,Hongwei Zhou
Background The gut microbiome plays a potential role in clinical events in preterm infants and may affect their lateral development. Understanding the initial colonization of microbes in the gut, their early dynamic changes, and the major factors correlated with these changes would provide crucial information about the developmental process in early life. Methods The present study enrolled 151 preterm infants and examined the longitudinal dynamics of their fecal microbiome profiles during the period of hospitalization using 16S ribosomal RNA gene sequencing. Random forest modeling was used to predict postnatal age (Age), postmenstrual age (PMA), and gestational age (GA), using gut microbiome features. Results Principal coordinate analysis revealed that the gut microbiome of the preterm infants displayed an obvious time-dependent change pattern, which showed the strongest association with Age, followed by PMA, and a much weaker association with (GA). Random forest modeling further evidenced the time-dependent change pattern, with the Pearson’s correlation coefficients between the actual values and the gut microbiome-predicted values being 0.68, 0.53, and 0.38 for postnatal, postmenstrual, and gestational age, respectively. The microbiome dynamism could be further divided into four Age stages, each with its own characteristic microbial taxa. The first 1–4 days (T1 stage) represented the meconium microbiome, with colonization of a high diversity of microbes before or during delivery. During 5–15 days (T2 stage), the gut microbiome of the preterm infants underwent a rapid turnover, in which microbial diversity declined, and stabilized afterward. Enterobacteriaceae , Enterococcaceae , Streptococcaceae , Staphylococcaceae , and Clostridiaceae were the major classes in the gut microbiome in the lateral stages of development (T3–T4 stage). Conclusions Postnatal age, rather than the gestational age, is significantly correlated with the gut microbiome of preterm infants, suggesting that clinical interventions contribute more to the early dynamics of gut microbiome in preterm infants than the natural development of the gut.
研究领域:
微生物组学
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新生儿科学
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发育生物学
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临床微生物学
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生物信息学
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2025
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IF 8
Yanchen Liu,Guangqing Mu,Xiaoyan Yang,Xian Cheng,Jingjing Kang,Xuemei Zhu
To advance precision nutrition and optimize feeding strategies for preterm infants, it is essential to further clarify the differences and interrelations in protein composition and digestive behavior between infant formulas (IFs) and human milk (HM). In this study, an integrated approach combining protein compositional analysis, protein digestion profiling, and targeted amino acid metabolomics was employed to systematically investigate these differences from the perspective of “protein composition– in vitro digestion behavior–amino acid release patterns.” Our findings revealed that β-lactoglobulin (4–11 % of total protein in IFs, absent in HM) exhibited pronounced aggregation during digestion, markedly enhancing its resistance to peptic hydrolysis. Caseins, present at higher levels and in more mineralized forms in IFs (37–48 % vs. 9.5–11 % in HM), further impeded enzymatic cleavage. In contrast, HM samples—particularly colostrum without human milk fortifier (HMF)—underwent a more gradual proteolytic process and displayed a more balanced amino acid release profile. Excessive release of certain amino acids (e.g., lysine, histidine, phenylalanine) in specific IFs may induce acute nitrogen metabolic imbalance in preterm infants. Glutamine and glutamic acid emerged as major contributors to the divergent amino acid release patterns between IF and HM, with their reduced liberation potentially linked to calcium soap formation and peptide masking. Additionally, the incorporation of full-strength HMF into HM appeared to obscure arginine-rich cleavage sites, which may partially account for the increased lactoferrin excretion observed in mixed feeding low-weight infants. Enhancing casein phosphopeptide content or aligning protein composition more closely with that of HM in IFs may represent promising strategies to reduce the nutritional outcome disparities between formula-fed and breastfed preterm infants.
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2025
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IF 8
Yanchen Liu,Ning Wang,Guangqing Mu,Yajuan Zhou,De Qiong,Yongzhu Cuomu,Baima Ciren,Xuemei Zhu
Preterm birth (<37 weeks) is a major global health challenge, and optimal nutrition is critical for reducing growth restriction, metabolic disorders, and impaired neurodevelopment. Human milk (HM) provides unique lipid structures, notably sn-2 palmitic acid-enriched triacylglycerols (TAGs), which promote efficient fat absorption and physiological development. However, most commercial preterm infant formulas (IFs) lack these structural features due to reliance on vegetable oils. This study compared lipidomic profiles of commercial IFs with preterm HM, focusing on fatty acid composition, sn-2 fatty acid distribution, TAG species, and phospholipids. A linear programming model was applied to coordinately optimize multiple lipid dimensions and design an optimized formula (DF), enriched in OPO and OPL, with higher sn-2 palmitic acid and lower OOO and OPP compared with IFs. Validation in a preterm rat model showed that DF improved body growth, intestinal villus development, and liver–kidney maturation relative to IF. DF also reduced visceral fat accumulation, improved lipid distribution, and alleviated hepatic burden. Serum analysis indicated lower triglycerides and low-density lipoprotein cholesterol (LDL-C), elevated insulin-like growth factor (IGF-1) and growth hormone, and preserved liver function. Digestive product analysis further revealed enhanced retention of polyunsaturated fatty acids at the sn-2 position as 2-monoacylglycerols, promoting absorption while reducing fecal saturated fatty acid–calcium soaps. These findings demonstrate that multidimensional structural lipid optimization, particularly enrichment of sn-2 palmitic acid and HM-like TAGs, represents a promising approach for next-generation preterm formulas to better align with HM and support metabolic health in preterm infants.
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DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2022
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IF 11.467
Keke Huang,Zhiqing Lin,Yuanyuan Ge,Xuhao Chen,Yining Pan,Ziru Lv,Xiaoting Sun,Hao Yu,Jiangfan Chen,Qingqing Yao
Retinopathy of prematurity (ROP) is characterized by pathological angiogenesis and associated inflammation in the retina and is the leading cause of childhood blindness. MiRNA-223 (miR-223) drives microglial polarization toward the anti-inflammatory phenotype and offers a therapeutic approach to suppress inflammation and consequently pathological neovascularization . However, miRNA-based therapy is hindered by the low stability and non-specific cell-targeting ability of delivery systems. In the present study, we developed folic acid–chitosan (FA–CS)-modified mesoporous silica nanoparticles (PMSN) loaded with miR-223 to regulate retinal microglial polarization. The FA–CS/PMSN/miR-223 nanoparticles exhibited high stability and loading efficiency, achieved targeted delivery, and successfully escaped from lysosomes. In cultured microglial cells, treatment with FA–CS/PMSN/miR-223 nanoparticles upregulated the anti-inflammatory gene YM1/2 and IL-4RA, and downregulated the proinflammatory genes iNOS , IL-1β , and IL-6 . Notably, in a mouse oxygen-induced retinopathy model of ROP, intravitreally injected FA–CS/PMSN/miR-223 nanoparticles (1 μg) decreased the retinal neovascular area by 52.6%. This protective effect was associated with the reduced and increased levels of pro-inflammatory (M1) and anti-inflammatory (M2) cytokines, respectively. Collectively, these findings demonstrate that FA–CS/PMSN/miR-223 nanoparticles provide an effective therapeutic strategy for the treatment of ROP by modulating the miR-223-mediated microglial polarization to the M2 phenotype.
研究领域:
眼科学
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纳米技术
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分子生物学
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炎症
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治疗学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
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2022
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IF 6.832
Mingming Ma,Qiao Luo,Lijing Fan,Weilong Li,Qiang Li,Yu Meng,Chen Yun,Hongwei Wu,Yongping Lu,Shuang Cui,Fanna Liu,Bo Hu,Baozhang Guan,Huanhuan Liu,Shengling Huang,Wenxue Liang,Stanislao Morgera,Bernhard Krämer,Shaodong Luan,Lianghong Yin,Berthold Hocher
Acute kidney injury (AKI) is a susceptible factor for chronic kidney disease (CKD). There is still a lack of effective prevention methods in clinical practice. This study investigated the protective effect of the urinary exosomes from premature infants on cisplatin-induced acute kidney injury. Here we isolated exosomes from the fresh urine of premature infants. A C57BL/6 mice model of cisplatin-induced acute kidney injury was given 100 ug urinary exosomes 24 hours after model establishment. The kidneys were collected for pathological examination and the evaluation of renal tubular damage and apoptosis. In the in vitro experiment, human renal cortex/proximal tubular cells (HK-2) were induced by cisplatin to assess the effect of the urine exosomes from premature infants. Exosome microRNA (miRNA) sequencing technology was applied to investigate the miRNAs enriched in exosomes and the dual-luciferase gene reporter system to examine the targeting relationship of the miRNA with target genes. The results indicated that the urinary exosomes could decrease the serum creatinine level and the apoptosis of renal tubular cells, and reduce mice mortality. In addition, miR-30a-5p was the most abundant miRNA in the exosomes. It protected HK-2 cells from cisplatin-induced apoptosis by targeting and down-regulating the mitogen-activated protein kinase 8 (MAPK8). Together, our findings identified that the urinary exosomes derived from premature infants alleviated cisplatin-induced acute kidney injury and inhibited the apoptosis of HK-2 via miR-30a-5p, which could target MAPK8. These findings implied that urinary exosomes from premature infants riched in miR-30a-5p might become a potential treatment for AKI.
研究领域:
肾病学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2020
·Vol. 11
·期 2
·1869-1880
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IF 4.171
Xinyue Dai,Tinglan Yuan,Xinghe Zhang,Qin Zhou,Huiya Bi,Renqiang Yu,Wei Wei,Xingguo Wang
This study aimed to quantify the short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) in human milk triacylglycerols (TAGs) and investigate their concentrations in human milk consumed during lactation by infants born at different gestational ages. One hundred and eighty milk samples from the mothers of 30 full-term, 10 early-preterm (≤32 weeks), 10 mild-preterm (32–34 weeks), and 10 near-term (34–37 weeks) infants were collected from the colostrum, transitional, and mature milk. The human milk TAGs were transferred into fatty-acid methyl esters via potassium methoxide in methanol and determined using gas chromatography (GC). The total SCFA (4:0) and MCFA concentrations (6:0 and 8:0) were highest in the mature milk (1.47 ± 0.66 mg g−1 fat from full-term infant milk), approximately 42.18% higher than those in transitional milk. Significantly higher SCFA and MCFA concentrations were found in full-term milk than in preterm milk (p = 0.001). The milk TAGs were analyzed using ultra-high-performance supercritical fluid chromatography with quadrupole-time-of-flight mass spectrometry (UHPSFC-Q-TOF-MS), which showed that the SCFAs and MCFAs were mainly esterified with long-chain fatty-acid groups (16:0, 18:1 n-9, and 18:2 n-6) at the glycerol backbone. The infants’ daily SCFA intake from human milk was estimated; this was highest from mature milk for full-term infants (∼14 mg d−1) which was significantly different from that of preterm infants from colostrum and transitional milk (p < 0.001). The correlation between dietary SCFAs and MCFAs in human milk and nutrition in newborns, especially in the gut microbiotas of preterm infants, requires further study.
研究领域:
营养学
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儿科
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分析化学
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婴儿健康
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DOI
PubMed
高影响因子
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