Genome-wide association study of maternal plasma metabolites during pregnancy.

Metabolites are key indicators of health and therapeutic targets, but their genetic underpinnings during pregnancy-a critical period for human reproduction-are largely unexplored. Using genetic data from non-invasive prenatal testing, we performed a genome-wide association study on 84 metabolites, including 37 amino acids, 24 elements, 13 hormones, and 10 vitamins, involving 34,394 pregnant Chinese women, with sample sizes ranging from 6,394 to 13,392 for specific metabolites. We identified 53 metabolite-gene associations, 23 of which are novel. Significant differences in genetic effects between pregnant and non-pregnant women were observed for 16.7%-100% of these associations, indicating gene-environment interactions. Additionally, 50.94% of genetic associations exhibited pleiotropy among metabolites and between six metabolites and eight pregnancy phenotypes. Mendelian randomization revealed potential causal relationships between seven maternal metabolites and 15 human traits and diseases. These findings provide new insights into the genetic basis of maternal plasma metabolites during pregnancy.

Multivariate HPLC system assessment and optimization for traditional Chinese medicine: a case study of Gastrodia elata.

The development of HPLC analytical methods for traditional Chinese medicine is intricate and time-consuming, influenced by factors such as column wear, solvent purity, and instrumental settings. A comprehensive evaluation of the HPLC system is crucial to mitigate potential variability and ensure the reliability of data. This is especially important given the complex and synergistic nature of the chemical components in traditional Chinese medicine, necessitating a multivariate measurement system analysis (MSA) to assess multiple correlated quality characteristics effectively. This study introduced a multivariate MSA method based on weighted principal components (WPC) to evaluate the HPLC system for the determination of metabolites in Gastrodia elata. By integrating multiple principal components and assigning weights according to their eigenvalues, the WPC method significantly enhanced both accuracy and robustness. It demonstrated a repeatability and reproducibility (% R&R) of 26.43% and a number of distinct categories (ndc) index of 5, confirming the system's acceptability. A full factorial experimental design was employed to identify key performance factors, leading to the recommendation to use five reference solutions for the standard curve and to triple sample preparations for improved precision and accuracy. Monte Carlo simulations confirmed the reliability of the system, showing % R&R and ndc values that follow a normal distribution, ranging from 19% to 22% and 6.07 to 7.38, respectively. Chromatographic conditions were optimized using a Box-Behnken experimental design. Subsequent validation experiments verified the method's high accuracy and reliability, with all relative standard deviation values for analytical precision, repeatability, and stability below 5%. The method also exhibited high recovery rates, exceeding 91% across three concentration levels, with RSD values under 4%. In conclusion, the application of a WPC-based multivariate MSA enabled a detailed evaluation of the HPLC system, ensuring accurate and reliable measurement of quality attributes. This method exemplified a scientifically rigorous approach for developing analytical methods in traditional Chinese medicine, enhancing both precision and reliability.

A nomogram with Ki-67 in the prediction of postoperative recurrence and death for glioma.

This study examined to evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients, a total of 76 patients diagnosed with glioma by pathology in Tengzhou Central People's Hospital were enrolled. The baseline data and follow ups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Ki-67 negative group showed of a longer OS survival time and a longer PFS survival time with log-rank test (x2 = 16.101, P < 0.001 and x2 = 16.961, P < 0.001). Age older than 50 years (HR = 2.074, 95% CI 1.097-3.923), abnormal treatment (HR = 2.932, 95% CI 1.343-6.403) and Ki-67 positive (HR = 2.722, 95% CI 1.097-6.755) were the independent predictive factors of death. High grade pathology (HR = 2.453, 95% CI 1.010-5.956) and Ki-67 positive (HR = 2.200, 95% CI 1.043-4.639) were the independent predictive factors of recurrence. The C-index for the nomogram of OS and PFS were 0.745 and 0.723, respectively. The calibration results showed that the nomogram could predict the overall and disease-free 1-year survival of glioma patients. In conclusion, the nomograms with Ki-67 as independent risk factor for OS and PFS could provide clinical consultation in the treatment and follow-up of malignant glioma.

Development and validation of a DLLME-HPLC-FLD method for determination of aflatoxins in Chrysanthemum morifolium based on quality by design principles.

INTRODUCTION: Aflatoxins, potent carcinogens produced by Aspergillus species, present significant health risks and commonly contaminate herbal products such as Chrysanthemum morifolium. Detecting these toxins in C. morifolium proves challenging due to the complex nature of the herbal matrix and the fluctuating levels of toxins found in different samples. OBJECTIVES: This study aimed to develop and optimize a novel method for the detection of aflatoxins in C. morifolium using dispersive liquid-liquid microextraction combined with high-performance liquid chromatography-fluorescence detection based on quality by design principles. METHODOLOGY: The method involved determining critical method attributes and parameters through the Plackett-Burman design, followed by optimization using the Box-Behnken design. Monte Carlo simulation was employed to establish a design space, which was experimentally verified. Method validation was performed to confirm accuracy, precision, and stability. RESULTS: The developed method exhibited excellent linearity (R2 > 0.9991) for aflatoxins B1, B2, G1, and G2 across a range of concentrations, with recovery rates between 85.52% and 102.01%. The validated method effectively quantified aflatoxins in C. morifolium under different storage conditions, highlighting the impact of temperature and storage time on aflatoxin production. CONCLUSION: This study successfully established a reliable and effective method for the detection of aflatoxins in C. morifolium, highlighting the importance of strict storage conditions to reduce aflatoxin contamination. Using a quality by design framework, the method demonstrated robustness and high analytical performance, making it suitable for routine quality control of herbal products.

CT-Guided Microwave Ablation with Vertebral Augmentation for Spinal Metastases with Posterior Wall Defects.

Purpose: To evaluate the efficacy and safety of combined microwave ablation (MWA) and vertebral augmentation (VA) in the treatment of spinal metastases with posterior wall defects. Patients and Methods: A retrospective review was conducted for 67 patients (42 men, 25 women) with painful spine metastases and posterior wall defects who underwent MWA combined with VA. Among these patients, 52 vertebrae had no epidural invasion and 33 had mild invasion but did not compress the spinal cord. Procedural effectiveness was determined by comparing visual analog scale (VAS) scores and Oswestry disability index (ODI) scores before the procedure and during the follow-up period. Results: The procedure was technically successful in all patients. The mean VAS score declined significantly from 6.85 ± 1.81 before the procedure to 3.27 ± 1.97 at 24 h, 1.96 ± 1.56 at 1 week, 1.84 ± 1.50 at 4 weeks, 1.73 ± 1.45 at 12 weeks, and 1.71 ± 1.52 at 24 weeks post-procedure (p < 0.01). The mean ODI score was lower post-procedure than before the procedure (p < 0.001). Transient nerve injury occurred in two patients (SIR classification D), and the incidence of asymptomatic bone cement (SIR classification A) was 43.5% (37/85). Conclusion: MWA combined with VA is an effective and safe treatment for painful spine metastases with posterior wall defects.

Schisandra chinensis lignans improve insulin resistance by targeting TLR4 and activating IRS-1/PI3K/AKT and NF-κB signaling pathways.

Schisandra chinensis, a traditional Chinese medicine, has been widely applied in China to treat diabetes and its complications. The aim of this study was to discover the active compounds and explain related molecular mechanism contributing to the anti-diabetic effect of Schisandra chinensis. Herein, the therapeutic effects of Schisandra chinensis extracts on type 2 diabetes mellitus (T2DM) were firstly confirmed in vivo. Subsequently, various lignans were isolated from Schisandra chinensis and tested for hypoglycemic activity in palmitic acid-induced insulin-resistant HepG2 (IR-HepG2) cells. Among these lignans, R-biar-(7S,8R)-6,7,8,9-tetrahydro-1,2,3,12,13,14-hexamethoxy-7,8-dimethyl-7-dibenzo [a, c] cyclooctenol (compound 2) and Gomisin A (compound 4) were identified significantly increased the glucose consumption in IR-HepG2 cells. Meanwhile, compounds 2 and 4 activated the insulin receptor substrate-1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/Ak strain transforming (AKT) pathway, which regulates glucose transporter 2 (GLUT2) and glucose-6-phosphatase (G6Pase), essential for gluconeogenesis and glucose uptake. These compounds also inhibited the nuclear factor-κB (NF-κB) signaling pathway, reducing interleukin-6 (IL-6) levels. Importantly, the hypoglycemic effects of compounds 2 and 4 were diminished after Toll-like receptor 4 (TLR4) knockdown. Cellular thermal shift assays confirmed increased TLR4 protein stability upon treatment with these compounds, indicating direct binding to TLR4. Furthermore, TLR4 knockdown reversed the effects of compounds 2 and 4 on the NF-κB and IRS-1/PI3K/AKT pathways. Taken together, compounds 2 and 4 alleviate IR by targeting TLR4, thereby modulating the NF-κB and IRS-1/PI3K/AKT pathways. These findings suggest that compounds 2 and 4 could be developed as therapeutic agents for T2DM.

Discovery of Novel Mcl-1 Inhibitors with a 3-Substituted-1H-indole-1-yl Moiety Binding to the P1-P3 Pockets to Induce Apoptosis in Acute Myeloid Leukemia Cells.

Mcl-1 is a main antiapoptotic protein in acute myeloid leukemia (AML) and is used as a target to develop inhibitors. Currently, potent Mcl-1 inhibitors primarily interact with the P2-P4 pockets of Mcl-1, but pharmacological modulation by targeting the P1 pocket is less explored. We designed a series of 1H-indole-2-carboxylic acid compounds as novel Mcl-1 inhibitors occupying the P1-P3 pockets and evaluated their Mcl-1 inhibition and apoptosis induction in AML cells. Two-dimensional 15N-HSQC spectroscopy indicated that 47 (Ki = 24 nM) bound to the BH3 binding groove, occupied the P1 pocket in Mcl-1, and formed interactions with Lys234 and Val249. 47 exhibited good microsomal stability and pharmacokinetic profiles, with low potential risk of cardiotoxicity. 47 inhibited tumor growth in HL-60 and THP-1 xenograft models with growth inhibition rate of 63.7% and 57.4%, respectively. Collectively, 47 represents a novel Mcl-1 inhibitor targeting the P1-P3 pockets with excellent antileukemia effects.

Nonactivated Aziridine Synthesis by Intermolecular Polarity-Mismatched Carboamination of Unactivated Alkenes with Unactivated Alkyl Halides.

A general intermolecular polarity-mismatched carboamination reaction of unactivated alkenes with unactivated alkyl halides has been developed. A series of nonactivated alkyl-substituted aziridines were constructed in exclusive regioselectivity. The dual polarity-mismatched mechanism might be involved.

Neuroprotective Mechanism of MOTS-c in TBI Mice: Insights from Integrated Transcriptomic and Metabolomic Analyses.

Background: Traumatic brain injury (TBI) is a condition characterized by structural and physiological disruptions in brain function caused by external forces. However, as the highly complex and heterogenous nature of TBI, effective treatments are currently lacking. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown notable antinociceptive and anti-inflammatory effects, yet its detailed neuroprotective effects and mode of action remain incompletely understood. This study investigated the neuroprotective effects and the underlying mechanisms of MOTS-c. Methods: Adult male C57BL/6 mice were randomly divided into three groups: control (CON) group, MOTS-c group and TBI group. Enzyme-linked immunosorbent assay (ELISA) kit method was used to measure the expression levels of MOTS-c in different groups. Behavioral tests were conducted to assess the effects of MOTS-c. Then, transcriptomics and metabolomics were performed to search Differentially Expressed Genes (DEGs) and Differentially Expressed Metabolites (DEMs), respectively. Moreover, the integrated transcriptomics and metabolomics analysis were employed using R packages and online Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: ELISA kit method showed that TBI resulted in a decrease in the expression of MOTS-c. and peripheral administration of MOTS-c could enter the brain tissue after TBI. Behavioral tests revealed that MOTS-c improved memory, learning, and motor function impairments in TBI mice. Additionally, transcriptomic analysis screened 159 differentially expressed genes. Metabolomic analysis identified 491 metabolites with significant differences. Integrated analysis found 14 KEGG pathways, primarily related to metabolic pathways. Besides, several signaling pathways were enriched, including neuroactive ligand-receptor interaction and retrograde endocannabinoid signaling. Conclusion: TBI reduced the expression of MOTS-c. MOTS-c reduced inflammatory responses, molecular damage, and cell death by down-regulating macrophage migration inhibitory factor (MIF) expression and activating the retrograde endocannabinoid signaling pathway. In addition, MOTS-c alleviated the response to hypoxic stress and enhanced lipid ß-oxidation to provide energy for the body following TBI. Overall, our study offered new insights into the neuroprotective mechanisms of MOTS-c in TBI mice.

Cell fate decision by a morphogen-transcription factor-chromatin modifier axis.

Cell fate decisions remain poorly understood at the molecular level. Embryogenesis provides a unique opportunity to analyze molecular details associated with cell fate decisions. Works based on model organisms have provided a conceptual framework of genes that specify cell fate control, for example, transcription factors (TFs) controlling processes from pluripotency to immunity1. How TFs specify cell fate remains poorly understood. Here we report that SALL4 relies on NuRD (nucleosome-remodeling and deacetylase complex) to interpret BMP4 signal and decide cell fate in a well-controlled in vitro system. While NuRD complex cooperates with SALL4 to convert mouse embryonic fibroblasts or MEFs to pluripotency, BMP4 diverts the same process to an alternative fate, PrE (primitive endoderm). Mechanistically, BMP4 signals the dissociation of SALL4 from NuRD physically to establish a gene regulatory network for PrE. Our results provide a conceptual framework to explore the rich landscapes of cell fate choices intrinsic to development in higher organisms involving morphogen-TF-chromatin modifier pathways.

Digitoxin inhibits ICC cell properties via the NF­κB/ST6GAL1 signaling pathway.

Intrahepatic cholangiocarcinoma (ICC) is a type of liver cancer associated with poor prognosis and increased mortality; the limited treatment strategy highlights the urgent need for investigation. Traditional Chinese Medicine (TCM), used alone or in combination with other treatments, can enhance therapeutic efficacy, improve life quality of patients and extend overall survival. In total, two rounds of screening of a TCM library of 2,538 active compounds were conducted using a Cell Counting Kit­8 assay and ICC cell lines. Cell proliferation and migration abilities were assessed through colony formation, 5­ethynyl­2'­deoxyuridine, would healing and Transwell assays. The impact of digitoxin (DT) on signaling pathways was initially investigated using RNA sequencing and further validated using reverse transcription­quantitative PCR, western blotting, lectin blotting and flow cytometry. ICC cells stably overexpressing ST6 ß­galactoside α­2,6­sialyltransferase 1 (ST6GAL1) were generated through lentiviral transfection. It was shown that DT emerged as a highly effective anti­ICC candidate from two rounds high­throughput library screening. DT could inhibit the proliferation and migration of ICC cells by suppressing NF­κB activation and reducing nuclear phosphorylated­NF­κB levels, along with diminishing ST6GAL1 mRNA and protein expression. The aforementioned biological effects and signal pathways of DT could be counteracted by overexpressing ST6GAL1 in ICC cells. In conclusion, DT suppressed ICC cell proliferation and migration by targeting the NF­κB/ST6GAL1 signaling axis. The findings of the present study indicated the promising therapeutic effects of DT in managing ICC, offering new avenues for treatment strategies.

Exploring the gut microbiota-hippocampus-metabolites axis dysregulation in sepsis mice.

Background: Sepsis is commonly associated with a sudden impairment of brain function, thus leading to significant rates of illness and mortality. The objective of this research was to integrate microbiome and metabolome to reveal the mechanism of microbiota-hippocampus-metabolites axis dysfunction in a mouse model of sepsis. Methods: A mouse model of sepsis was established via cecal ligation and puncture. The potential associations between the composition of the gut microbiota and metabolites in the hippocampus of mice with sepsis were investigated by combining 16S ribosomal RNA gene sequencing and ultra-high-performance liquid chromatography tandem mass spectrometry. Results: A total of 140 differential metabolites were identified in the hippocampal tissues of mice with sepsis when compared to those of control mice. These differential metabolites in mice with sepsis were not only associated with autophagy and serotonergic synapse, but also involved in the metabolism and synthesis of numerous amino acids. At the phylum level, the abundance of Bacteroidota was increased, while that of Firmicutes (Bacillota) was decreased in mice with sepsis. At the genus level, the abundance of Alistipes was increased, while that of Lachnospiraceae_NK4A136_group was decreased in mice with sepsis. The Firmicutes (Bacillota)/Bacteroidota (F/B) ratio was decreased in mice with sepsis when compared to that of control mice. Furthermore, the F/B ratio was positively correlated with 5'-methylthioadenosine, PC (18:3(9Z,12Z,15Z)/18:0) and curdione, and negatively correlated with indoxylsulfuric acid, corticosterone, kynurenine and ornithine. Conclusion: Analysis revealed a reduction in the F/B ratio in mice with sepsis, thus contributing to the disturbance of 5'-methylthioadenosine, curdione, PC (18:3(9Z,12Z,15Z)/18:0), corticosterone, ornithine, indoxylsulfuric acid and kynurenine; eventually, these changes led to hippocampus dysfunction. Our findings provide a new direction for the management of sepsis-induced hippocampus dysfunction.

Feasibility exploration of GSH in the treatment of acute hepatic encephalopathy from the aspects of pharmacokinetics, pharmacodynamics, and mechanism.

Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.

High-amylose starch-based gel as green adhesive for plywood: Adhesive property, water-resistance, and flame-retardancy.

The escalating demand for environmentally sustainable and cost-effective adhesives in the wood processing and manufacturing sector has prompted exploration into innovative solutions. This study introduces a novel gel adhesive composed of chemically unmodified high-amylose starch (G70, with 68 % amylose content) with a minimal proportion of urea-formaldehyde (UF) (UF/starch = 1:10, w/w). This G70/UF gel demonstrates remarkable adhesive capabilities for wooden boards under both dry conditions (with a shear stress of 4.13 ± 0.12 MPa) and wet conditions (with a shear strength of 0.93 ± 0.07 MPa after 2 h of water soaking). The study unveils that the elevated amylose content in the starch, coupled with a meticulously controlled isothermal process during bonding, is crucial for these enhancements. Specifically, the robust cohesion of amylose chains expedites phase separation between starch and UF, while the isothermal process facilitates the migration and enrichment of UF molecules at the gel-board and gel-air interfaces. Lacking these mechanisms, conventional amylopectin-rich starch/UF gels (27 % amylose content) show minimal improvement. Moreover, the G70/UF gel showcases exceptional fire retardancy. In all, the G70/UF gel presents a promising alternative for plywood production, reducing reliance on unhealthy UF resin while offering satisfactory bonding resistance in diverse conditions and superior flame retardancy.

Prevalence of placenta previa among deliveries: An update systematic review and meta-analysis after the introduction of the two-child policy in Mainland China.

Background: As birth policy can affect maternal and infant health, we sought to identify whether and how the introduction of the two-child policy might have affected the prevalence of placenta previa in pregnant women in mainland China. Methods: In this update meta-analysis and systematic review, we searched PubMed, Web of Science, the Cochrane Library, Weipu, Wanfang, and the China National Knowledge Infrastructure (CNKI) databases for studies evaluating the prevalence of placenta previa in China published between the inception of each database and March 2024, with no restrictions. Two investigators independently extracted the data from each included study. We then combined the prevalence of placenta previa using random-effects models. Results: We included 128 studies in our analysis, 48 more than in our previous review. The prevalence of placenta previa among Chinese pregnant women was 1.44% (95% confidence interval (CI) = 1.32, 1.56). After the implementation of the two-child policy, the prevalence increased significantly, from 1.25% (95% CI = 1.16, 1.34) to 4.12% (95% CI = 3.33, 4.91). Conclusions: The prevalence of placenta previa increased significantly from the one-child policy period to the two-child policy period among mainland Chinese pregnant women, with varying trends across regions. This change requires the attention of health officials and timely adjustment of resource allocation policies. Registration: PROSPERO: CRD42021262309.

Synthesis and Characterization of an All-Germanium Analogue of Cyclobutane-1,3-diyl.

A tetragermacyclobutane-1,3-diyl was prepared and structurally characterized via the reduction of chlorogermylene-coordinated germylgermylene with potassium graphite, which represents the first all-germanium analogue of cyclobutane-1,3-diyl. Single-crystal X-ray analysis of the tetragermacyclobutane-1,3-diyl disclosed that it adopts a planar-cis structure, which is different from those reported all-silicon cyclobutane-1,3-diyls. DFT calculations revealed that both the bulky substituents on the germanium atoms and the tethering of the amido groups are important for the planar cis-configuration of 5.

Identifying the association between depression and constipation: An observational study and Mendelian randomization analysis.

BACKGROUND: Both depression and constipation are universal disorders that seriously affect quality of life. But the phenotypic relationship and causality between depression and constipation are still unclear. METHODS: We first assessed phenotypic relationships by logistic regression analysis using large-scale data extracted from the National Health and Nutrition Examination Survey (N = 11,585). We then evaluated causality by bidirectional two-sample mendelian randomization (MR) analysis using Genome-wide association study (GWAS) data (depression: N = 807,553; constipation: N = 377,277). To investigate whether depression severity affects the causal relationship between depression and constipation, we conducted a further MR study on GWAS data of major depression (N = 480,359). RESULTS: About 11.31 % of the participants in the constipation group suffered from depression, which was significantly higher than the normal bowel group (6.09 %). The observational study showed a positive correlation between depression and constipation (OR = 1.968, 95%CI = 1.530-2.532). Besides, the risk of constipation was higher in participants with severe depression (OR = 2.294, 95%CI = 1.538-3.422) than in participants with mild depression (OR = 1.549, 95%CI = 1.242-1.932). Bidirectional MR analysis revealed an obviously causal effect of depression on constipation, but no causal effect of constipation on depression. In addition, the MR analysis also revealed a causal relationship between major depression and constipation. LIMITATION: The exact mechanism by which depression affects constipation is still unclear. CONCLUSION: This study reveals a positive correlation between depression and constipation and the causal effect of depression on constipation. Clinicians should keep the risk of constipation in mind when treating patients with depression.

A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F.

As a potential endocrine-disrupting chemical, bisphenol F (BPF) may cause nonalcoholic fatty liver disease (NAFLD)-like changes, but the mechanisms underpinning its pathogenesis as well as the intervention strategies remain poorly understood. Using the electron microscopy technology, along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays, we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells, accompanied by an increased total level of triglycerides. At the molecular level, the lipogenesis-associated mRNAs and proteins, including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase-1, peroxisome proliferator-activated receptor gamma, and CCAAT-enhancer-binding proteins, increased significantly via the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling regulation in both in vitro and in vivo studies. Furthermore, the immunofluorescence results also showed the robust lipogenesis induced by BPF, evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei. To investigate the intervention strategies for BPF-induced NAFLD-like changes, we demonstrated that bellidifolin, isolated and purified from Swertia chirayita, significantly attenuated BPF-induced lipid droplet deposition in HepG2 cell and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins. Therefore, the present study elucidates the mechanisms underlying BPF-induced lipid accumulation in HepG2 cells, while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.

Serum N-glycomic profiling identifies candidate biomarker panels for assessing coronary artery stenosis severity.

Stenosis severity may escalate over the course of coronary artery disease (CAD), increasing the risk of death for the patient. Conventionally, the assessment of stenosis degree relies on invasive coronary angiography (ICA), an invasive examination unsuitable for patients in poor physical condition or those with contrast allergies and one that imposes a psychological burden on patients. Although abnormal serum N-glycan profiles have exhibited robust associations with various cardiovascular diseases, including CAD, their potential in diagnosing CAD stenosis remains to be determined. In this study, we performed a comprehensive analysis of serum N-glycome from 132 patients who underwent ICA and 27 healthy controls using MALDI-TOF-mass spectrometry. The patients who underwent ICA examination were categorized into four groups based on stenosis severity: no/mild/moderate/severe stenosis. Twenty-seven N-glycans were directly quantified, and 47 derived glycan traits were obtained. Notably, among these 74 glycan features, 18 exhibited variations across the study groups. Using a combination of least absolute shrinkage and selection operator and logistic regression analyses, we developed five diagnostic models for recognizing stenosis degree. Our results suggested that alterations in serum N-glycosylation modifications might be valuable for identifying stenosis degree and monitoring disease progression in individuals with CAD. It is expected to offer a noninvasive alternative for those who could not undergo ICA because of various reasons. However, the diagnostic potential of serum N-glycan panels as biomarkers requires multicenter, large cohort validation in the future.