Nontargeted metabolomics reveals the potential mechanism underlying the association between birthweight and metabolic disturbances.

AIMS: The aim of this study was to characterize the metabolites associated with small- and large-gestational-age newborns in maternal and cord blood, and to investigate potential mechanisms underlying the association between birthweight and metabolic disturbances. RESEARCH DESIGN AND METHODS: We recorded detailed anthropometric data of mother-offspring dyads. Untargeted metabolomic assays were performed on 67 pairs of cord blood and maternal fasting plasma samples including 16 pairs of small-for-gestational (SGA, < 10th percentile) dyads, 28 pairs of appropriate-for-gestational (AGA, approximate 50 percentile) dyads, and 23 pairs of large-for-gestational (LGA, > 90th percentile) dyads. The association of metabolites with newborn birthweight was conducted to screen for metabolites with U-shaped and line-shaped distributions. The association of metabolites with maternal and fetal phenotypes was also performed. RESULTS: We found 2 types of metabolites that changed in different patterns according to newborn birthweight. One type of metabolite exhibited a "U-shaped" trend of abundance fluctuation in the SGA-AGA-LGA groups. The results demonstrated that cuminaldehyde level was lower in the SGA and LGA groups, and its abundance in cord blood was negatively correlated with maternal BMI (r = -0.352 p = 0.009) and weight gain (r = -0.267 p = 0.043). 2-Methoxy-estradiol-17b 3-glucuronide, which showed enrichment in the SGA and LGA groups, was positively correlated with homocysteine (r = 0.44, p < 0.001) and free fatty acid (r = 0.42, p < 0.001) in maternal blood. Serotonin and 13(S)-HODE were the second type of metabolites, denoted as "line-shaped", which both showed increasing trends in the SGA-AGA-LGA groups in both maternal and cord blood and were both significantly positively correlated with maternal BMI before pregnancy. Moreover, cuminaldehyde, serotonin, 13(S)-HODE and some lipid metabolites showed a strong correlation between maternal and cord blood. CONCLUSIONS: These investigations demonstrate broad-scale metabolomic differences associated with newborn birthweight in both pregnant women and their newborns. The U-shaped metabolites associated with both the SGA and LGA groups might explain the U-shaped association between birthweight and metabolic dysregulation. The line-shaped metabolites might participate in intrauterine growth regulation. These observations might help to provide new insights into the insulin resistance and the risk of metabolic disturbance of SGA and LGA babies in adulthood and might identify potential new markers for adverse newborn outcomes in pregnant women.

Molecular analysis of dominant species in Listeria monocytogenes-positive biofilms in the drains of food processing facilities.

Listeria monocytogenes exhibits symbiotic codependence with the dominant commensal bacteria, which may help it avoid being removed or inactivated by disinfectants in local environments. In this study, we investigated L. monocytogenes-positive biofilms at food production facilities, and the dominant bacterial species of the biofilms were identified to determine the properties of the microbiological background. For this purpose, the ISO 11290 method was used for the detection and isolation of L. monocytogenes, and the species were further identified based on 16S rRNA and hly genes. 16S rRNA gene-based cloning, terminal restriction fragment length polymorphism, and denaturing gradient gel electrophoresis were combined to evaluate the dominant bacteria of the drain biofilms. Out of 100 drain samples, 8 were naturally contaminated with L. monocytogenes. Three molecular methods consistently showed that Pseudomonas psychrophila, Pseudomonas sp., and Klebsiella oxytoca were dominant species in 3Q, 5Q, and 6Q samples; Aeromonas hydrophila and Klebsiella sp. were significantly dominant in 1-2, 1-3, and 3-2 samples; A. hydrophila and K. oxytoca were dominant in the 2-3 sample; and A. hydrophila and Pseudomonas sp. were prominent in the 3-3 sample. Different biofilms from the same plant shared common bands, suggesting that similar bacteria can be found and can be dominant in different biofilms. This study provides a better understanding of the dominant compositions in these bacterial communities. Further studies to determine the mechanism of co-culture with L. monocytogenes will be of critical importance in predicting effective disinfection strategies.

Elevated LDL-c may warn of the risk of gallbladder stones in the patients with metabolic dysfunction-associated steatotic liver disease: A case-control study.

PURPOSE: This study aimed to explore the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and the development of new-onset gallbladder stone disease (GSD) and to identify factors that influence the occurrence of new-onset GSD in patients with MASLD. METHODS: In this retrospective case-control study, patients who underwent asymptomatic GSD screening during annual routine health check-ups at two hospitals in China between August 2017 and July 2022 were included. Patients with new-onset GSD and controls without GSD were matched 1:1 based on age, sex, race, occupation, diet, drinking habits, systolic blood pressure, diastolic blood pressure, and fasting blood glucose levels. RESULTS: The study comprised 1200 patients with new-onset GSD and 1200 controls without GSD. Patients with new-onset GSD had higher rates of MASLD (33.8% vs. 22.2 %, P < 0.001) and hypercholesterolemia (12.6% vs. 7.2 %, P < 0.001) compared to controls. Waist circumference (WC) (OR = 1.042, 95 % CI: 1.022-1.063, P < 0.001), high-density lipoprotein cholesterol (HDL-c) (OR = 0.048, 95 % CI: 0.037-0.062, P < 0.001), triglycerides (OR = 0.819, 95 % CI: 0.699-0.958, P = 0.013), and hypercholesterolemia (OR = 5.023, 95 % CI: 2.735-9.225, P < 0.001) were independently associated with new-onset GSD. Among patients with MASLD, WC (OR = 1.075, 95 % CI: 1.026-1.127, P = 0.003), total cholesterol (TC) (OR = 2.094, 95 % CI: 1.259-3.484, P = 0.004), HDL-c (OR = 0.088, 95 % CI: 0.054-0.142, P < 0.001), and low-density lipoprotein cholesterol (LDL-c) (OR = 4.056, 95 % CI: 2.669-6.163, P < 0.001) were independently associated with new-onset GSD. CONCLUSIONS: The findings indicate that hypercholesterolemia is independently associated with GSD. Among patients with MASLD, hypercholesterolemia also showed an independent association with GSD. Notably, this study is the first to identify serum LDL-c levels as potentially the most significant risk factor for GSD, highlighting that elevated LDL-c could serve as an important indicator for individuals with MASLD.

Effect of Qingyitang on activity of intracellular Ca2+-Mg2+-ATPase in rats with acute pancreatitis.

AIM: To study the change of intracellular calcium-magnesium ATPase (Ca(2+)-Mg(2+)-ATPase) activity in pancreas, liver and kidney tissues of rats with acute pancreatitis (AP), and to investigate the effects of Qingyitang (QYT) (Decoction for clearing the pancreas) and tetrandrine (Tet) and vitamin E (VitE) on the activity of Ca(2+)-Mg(2+)-ATPase. METHODS: One hundred and five Sprague-Dawley rats were randomly divided into: normal control group, AP group, treatment group with QYT (1 ml/100 g) or Tet (0.4 ml/100 g) or VitE (100 mg/kg). AP model was prepared by a retrograde injection of sodium taurocholate into the pancreatic duct. Tissues of pancreas, liver and kidney of the animals were taken at 1 h, 5 h, 10 h respectively after AP induction, and the activity of Ca(2+)-Mg(2+)-ATPase was studied using enzyme-histochemistry staining. Meanwhile, the expression of Ca(2+)-Mg(2+)-ATPase of the tissues was studied by RT-PCR. RESULTS: The results showed that the positive rate of Ca(2+)-Mg(2+)-ATPase in AP group (8.3%, 25%, 29.2%) was lower than that in normal control group (100%) in all tissues (P<0.01), the positive rate of Ca(2+)-Mg(2+)-ATPase in treatment group with QYT (58.3%, 83.3%, 83.3%), Tet (50.0%, 70.8%, 75.0%) and VitE (54.2%, 75.0%, 79.2%) was higher than that in AP group (8.3%, 25.0%, 29.2%) in all tissues (P<0.01). RT-PCR results demonstrated that in treatment groups Ca(2+)-Mg(2+)-ATPase gene expression in pancreas tissue was higher than that in AP group at the observing time points, and the expression at 5 h was higher than that at 1 h. The expression of Ca(2+)-Mg(2+)-ATPase in liver tissue was positive, but without significant difference between different groups. CONCLUSION: The activity and expression of intracellular Ca(2+)-Mg(2+)-ATPase decreased in rats with AP, suggesting that Ca(2+)-Mg(2+)-ATPase may contribute to the occurrence and development of cellular calcium overload in AP. QYT, Tet and VitE can increase the activity and expression of Ca(2+)-Mg(2+)-ATPase and may relieve intracellular calcium overload to protect the tissue and cells from injuries.

Expression level of Pre B cell leukemia homeobox 2 correlates with poor prognosis of gastric adenocarcinoma and esophageal squamous cell carcinoma.

Pre B cell leukemia homeobox 2 (PBX2), a member of PBX family, acts as a co-factor of homeobox proteins to regulate proliferation and differentiation of tumor cells. Our recent study revealed prognostic significance of PBX2 expression in non-small cell lung carcinoma. The significance of PBX2 expression was examined in cases with gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC), and the role of PBX2 in tumor behavior was evaluated in GC and ESCC cell lines of knocked-down PBX2 expression. Expression level of PBX2 was immunohistochemically examined in 94 patients of GC and 64 patients of ESCC. Staining intensity for PBX2 was categorized as equal to or stronger (level 1) and weaker (level 2) than that of endothelial cells. Cases with level 1 expression in more than 20% of tumor were defined as high and others low expression. Patients with low PBX2 expression showed a better prognosis than those with high expression in both GC and ESCC. Multivariate analysis revealed PBX2 expression to be an independent prognosticator for both GC and ESCC. Knocked-down expression of PBX2 in GC and ESCC cell lines resulted in decrease of in vitro colony formation and in vivo tumorigenic activities, but proliferative and invasive activities did not change. Under serum depletion, apoptotic cell proportion was higher in PBX2 knocked-down cells than in control cells. The knock-down of PBX2 reduced Bcl-2 expression. Taken together, the high expression level of PBX2 was an independent negative prognosticator for both GC and ESCC, and PBX2 might promote tumor growth through suppression of apoptosis.