Elevated alanine transaminase is nonlinearly associated with in-hospital death in ICU-admitted diabetic ketoacidosis patients

Aims: To investigate the association between alanine transaminase (ALT) and in-hospital death in patients admitted to the intensive care unit for diabetic ketoacidosis (DKA). Methods: A cohort of 2,684 patients was constructed from the eICU Collaborative Research Database. Baseline demographic and clinical characteristics were summarized. Cox regression with restricted cubic spline functions was modelled to explore the nonlinear association between alanine transaminase and in-hospital death. Subgroup analyses were conducted between sexes, age groups, and people with/without obesity. Results: After adjusting multiple confounders, a nonlinear, S-shaped association between ALT and in-hospital death was found. Compared to patients at median ALT, patients at the 90th percentile of ALT have a 1.88 (95% CI: 1.34–2.62) times higher hazard of in-hospital death in the unstratified cohort. Similar results were found in males (hazard ratio (HR)=1.69, 95% confidence interval (CI): 1.24–2.30); patients aged under 65 years (HR=1.65, 95% CI: 1.09–2.49); patients aged 65 years or above (HR=3.45, 95% CI: 1.67–7.14); non-obese patients (HR=1.52, 95% CI: 1.00–2.32); and obese patients (HR=2.76, 95% CI: 1.38–5.54). Conclusions: Elevated ALT is robustly associated with in-hospital death in ICU-admitted DKA patients across several subgroups. Close monitoring of ALT in these patients is recommended

Target profiling analyses of bile acids in the evaluation of hepatoprotective effect of gentiopicroside on ANIT-induced cholestatic liver injury in mice

AbstractEthnopharmacological relevanceGentiopicroside (GPS), one of iridoid glucoside representatives, is the most potential active component in Gentiana rigescens Franch. ex Hemsl and Gentiana macrophylla Pall. These two herbs have been used to treat jaundice and other hepatic and billiary diseases in traditional Chinese medicine for thousands of years.Aim of the studyThis study aimed to investigate the protective effects and mechanisms of GPS on α-naphthylisothiocyanate (ANIT) induced cholestatic liver injury in mice.Materials and methodsMice were treated with GPS (130mg/kg, ig) for 5 consecutive days. On the third day, mice were given a single dose of Alpha-naphthylisothiocyanate (75mg/kg, ig). Serum biochemical markers and individual bile acids in serum, liver, urine and feces were measured at different time points after ANIT administration. The expression of hepatic bile acid synthesis, uptake and transporter genes as well as ileum bile acid transporter genes were assayed.ResultsIn this study, ANIT exposure resulted in serious cholestasis with liver injury, which was demonstrated by dramatically increased serum levels of ALT, ALP, TBA and TBIL along with TCA CA, MCAs and TMCAs accumulation in both liver and serum. Furthermore, ANIT significantly decreased bile acid synthesis related gene expressions, and increased expression of bile acid transporters in liver. Continuous treatment with GPS attenuated ANIT-induced acute cholestasis as well as liver injury and correct the dyshomeostasis of bile acids induced by ANIT. Our data showed that GPS significantly upregulated the hepatic mRNA levels of synthesis enzymes (Cyp8b1 and Cyp27a1) and transporters (Mrp4 Mdr1 and Ost-β) as well as ileal bile acid circulation mediators (Asbt and Fgf15), accompanied by serum and hepatic bile acid levels decrease and further urinary and fecal bile acid levels increase.ConclusionGPS can change bile acids metabolism which highlights its importance in mitigating cholestasis, resulting in the marked decrease of intracellular bile acid pool back toward basal levels. And the protective mechanism was associated with regulation of bile acids-related transporters, but the potential mechanism warrants further investigation

Growth Differentiation Factor 15 Is Induced by Hepatitis C Virus Infection and Regulates Hepatocellular Carcinoma-Related Genes

Liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) are commonly induced by chronic hepatitis C virus (HCV) infection. We aimed to identify and characterize the involvement of previously screened cytokine GDF15 in HCV pathogenesis. We examined the GDF15 expression after HCV infection both in vitro and in vivo. Cultured JFH-1 HCV was used to determine the GDF15 function on virus propagation. GDF15 overexpression and RNA interference were employed to profile the GDF15-regulated genes, signaling pathways and cell biology phenotypes. The mRNA expression and protein secretion of GDF15 was dramatically increased in HCV-infected hepatoma cells, which maybe a host response to viral proteins or infection-induced cell stress. Patients infected with HCV had an average 15-fold higher blood GDF15 level than that of healthy volunteers. Three HCC individuals in the HCV cohort showed extremely high GDF15 concentrations. Transfection or exogenously supplied GDF15 enhanced HCV propagation, whereas knockdown of endogenous GDF15 resulted in inhibition of virus replication. Overexpressed GDF15 led to Akt activation and the phosphorylation of Akt downstream targeted GSK-3β and Raf. Several HCC-related molecules, such as E-cadherin, β-catenin, Cyclin A2/B1/D1, were up-regulated by GDF15 stimulation in vitro. Overexpression of GDF15 in hepatoma cells resulted in increased DNA synthesis, promoted cell proliferation, and importantly enhanced invasiveness of the cells. In conclusion, these results suggest that an elevated serum GDF15 level is a potential diagnostic marker for viral hepatitis, and GDF15 may contribute to HCV pathogenesis by altering the signaling and growth of host cells

Development of a necroptosis-related gene signature and the immune landscape in ovarian cancer

Abstract Background Necroptosis is a novel type of programmed cell death distinct from apoptosis. However, the role of necroptosis in ovarian cancer (OC) remains unclear. The present study investigated the prognostic value of necroptosis-related genes (NRGs) and the immune landscape in OC. Methods The gene expression profiling and clinical information were downloaded from the TCGA and GTEx databases. Differentially expressed NRGs (DE-NRGs) between OC and normal tissueswere identified. The regression analyses were conducted to screen the prognostic NRGs and construct the predictive risk model. Patients were then divided into high- and low-risk groups, and the GO and KEGG analyses were performed to explore bioinformatics functions between the two groups. Subsequently, the risk level and immune status correlations were assessed through the ESTIMATE and CIBERSORT algorithms. The tumor mutation burden (TMB) and the drug sensitivity were also analyzed based on the two-NRG signature in OC. Results Totally 42 DE-NRGs were identified in OC. The regression analyses screened out two NRGs (MAPK10 and STAT4) with prognostic values for overall survival. The ROC curve showed a better predictive ability in five-year OS using the risk score. Immune-related functions were significantly enriched in the high- and low-risk group. Macrophages M1, T cells CD4 memory activated, T cells CD8, and T cells regulatory infiltration immune cells were associated with the low-risk score. The lower tumor microenvironment score was demonstrated in the high-risk group. Patients with lower TMB in the low-risk group showed a better prognosis, and a lower TIDE score suggested a better immune checkpoint inhibitor response in the high-risk group. Besides, cisplatin and paclitaxel were found to be more sensitive in the low-risk group. Conclusions MAPK10 and STAT4 can be important prognosis factors in OC, and the two-gene signature performs well in predicting survival outcomes. Our study provided novel ways of OC prognosis estimation and potential treatment strategy

Metabolomic Profiling of Aqueous Humor from Pathological Myopia Patients with Choroidal Neovascularization

Choroidal neovascularization (CNV) is a severe complication observed in individuals with pathological myopia (PM). Our hypothesis is that specific metabolic alterations occur during the development of CNV in patients with PM. To investigate this, an untargeted metabolomics analysis was conducted using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) on aqueous humor (AH) samples obtained from meticulously matched PM patients, including those with CNV (n = 11) and without CNV (n = 11). The analysis aimed to identify differentially expressed metabolites between the two groups. Furthermore, the discriminative ability of each metabolite was evaluated using the area under the receiver operating characteristic curve (AUC). Enriched metabolic pathways were determined using the KEGG and MetaboAnalyst databases. Our results revealed the detection of 272 metabolites using GC–MS and 1457 metabolites using LC–MS in AH samples. Among them, 97 metabolites exhibited significant differential expression between the CNV and non-CNV groups. Noteworthy candidates, including D-citramalic acid, biphenyl, and isoleucylproline, demonstrated high AUC values ranging from 0.801 to 1, indicating their potential as disease biomarkers. Additionally, all three metabolites showed a strong association with retinal cystoid edema in CNV patients. Furthermore, the study identified 12 altered metabolic pathways, with five of them related to carbohydrate metabolism, suggesting their involvement in the occurrence of myopic CNV. These findings provide possible disease-specific biomarkers of CNV in PM and suggest the role of disturbed carbohydrate metabolism in its pathogenesis. Larger studies are needed to validate these findings

Detection of antibodies against porcine epidemic diarrhea virus in serum and colostrum by indirect ELISA

An indirect porcine epidemic diarrhea virus (PEDV) anti-immunoglobulin (Ig) G ELISA based on the S1 portion of the spike protein was validated and compared with an indirect immunofluorescence assay. On field serum samples the diagnostic sensitivity of the S1 ELISA was 100%, the diagnostic specificity was 94% and the S1 ELISA showed no cross-reactivity with antibodies against other porcine coronaviruses. Colostrum samples (n = 133) were also tested for anti-PEDV IgG and IgA. The diagnostic sensitivity was 92% for IgG and 100% for IgA, and the diagnostic specificity was 90% for IgG and 99.4% for IgA. These data suggest that the S1 ELISA is a sensitive and specific test that could also be used to evaluate PEDV colostral immunity

Rapid Antibiotic Adsorption from Water Using MCM-41-Based Material

The contamination of antibiotics in the environment has raised serious concerns, impacting both human life and ecosystems. This has led to a growing focus on the development of cost-effective and environmentally friendly adsorbent materials. Mesoporous molecular sieve MCM-41, known for its strong adsorption capacity, low cost, and efficient regenerative properties, holds significant promise for addressing this issue. In this study, we investigated the adsorption behavior of demolded MCM-41 materials in relation to tetracycline, doxycycline, and levofloxacin at different temperatures and pH levels. Our experiments encompassed the adsorption of these three common antibiotics, revealing that a neutral or weakly acidic pH environment promoted adsorption, whereas alkaline conditions hindered it. Utilizing the equilibrium isotherm model, we determined the theoretical maximum adsorption capacities for tetracycline (TC), doxycycline (DOX), and levofloxacin (LFX) as 73.41, 144.83, and 33.67 mg g−1, respectively. These findings underscore the significant potential of MCM-41 in mitigating antibiotic wastewater contamination

Table_1_Early enteral nutrition with exclusive donor milk instead of formula milk affects the time of full enteral feeding for very low birth weight infants.DOCX

This study investigated the effects of exclusive donor milk or formula in the first 7 days after birth, on the time to full enteral feeding, growth, and morbidity of adverse events related to premature infants. This was a retrospective study carried out from July 2014 to December 2019 at the Department of Neonatology of Shanghai Children’s Hospital. All infants with a birth weight < 1,500 g and a gestational age ≤ 32 who received exclusive donor milk or formula in the first 7 days after birth were included in this study. The time to full enteral feeding (defined as 150 mL/kg) in the donor milk group was significantly shorter than in the formula group (18 vs. 22 days, p = 0.01). Donated breast milk was also associated with a lower incidence of NEC (4.4 vs. 7%, p < 0.01), ROP (3.8 vs. 13.2%, p < 0.01), and culture-confirmed sepsis (11 vs. 22.6%, p < 0.01). Using donated breast milk instead of current formula milk for early enteral nutrition can shorten the time to full enteral feeding and reduce the incidence of NEC, ROP, and sepsis.</p