Role of folic acid in regulating gut microbiota and short-chain fatty acids based on an in vitro fermentation model.

Folic acid deficiency is common worldwide and is linked to an imbalance in gut microbiota. However, based on model animals used to study the utilization of folic acid by gut microbes, there are challenges of reproducibility and individual differences. In this study, an in vitro fecal slurry culture model of folic acid deficiency was established to investigate the effects of supplementation with 5-methyltetrahydrofolate (MTHF) and non-reduced folic acid (FA) on the modulation of gut microbiota. 16S rRNA sequencing results revealed that both FA (29.7%) and MTHF (27.9%) supplementation significantly reduced the relative abundance of Bacteroidetes compared with control case (34.3%). MTHF supplementation significantly improved the relative abundance of Firmicutes by 4.49%. Notably, compared with the control case, FA and MTHF supplementation promoted an increase in fecal levels of Lactobacillus, Bifidobacterium, and Pediococcus. Short-chain fatty acid (SCFA) analysis showed that folic acid supplementation decreased acetate levels and increased fermentative production of isobutyric acid. The in vitro fecal slurry culture model developed in this study can be utilized as a model of folic acid deficiency in humans to study the gut microbiota and demonstrate that exogenous folic acid affects the composition of the gut microbiota and the level of SCFAs. KEY POINTS: • Establishment of folic acid deficiency in an in vitro culture model. • Folic acid supplementation regulates intestinal microbes and SCFAs. • Connections between microbes and SCFAs after adding folic acid are built.

Bacteriocins: Curial guardians of gastrointestinal tract.

The human gastrointestinal (GI) tract microbiome secretes various metabolites that play pivotal roles in maintaining host physiological balance and influencing disease progression. Among these metabolites, bacteriocins-small, heat-stable peptides synthesized by ribosomes-are notably prevalent in the GI region. Their multifaceted benefits have garnered significant interest in the scientific community. This review comprehensively explores the methods for mining bacteriocins (traditional separation and purification, bioinformatics, and artificial intelligence), their effects on the stomach and intestines, and their complex bioactive mechanisms. These mechanisms include flora regulation, biological barrier restoration, and intervention in epithelial cell pathways. By detailing each well-documented bacteriocin, we reveal the diverse ways in which bacteriocins interact with the GI environment. Moreover, the future research direction is prospected. By further studying the function and interaction of intestinal bacteriocins, we can discover new pharmacological targets and develop drugs targeting intestinal bacteriocins to regulate and improve human health. It provides innovative ideas and infinite possibilities for further exploration, development, and utilization of bacteriocins. The inevitable fact is that the continuously exploration of bacteriocins is sure to bring the promising future for demic GI health understanding and interference strategy.

Diverse Metabolic Effects of Cooking Oil Fume from Four Edible Oils on Human BEAS-2B Cells: Implications for Health Guidelines.

The 2021 WHO guidelines stress the importance of measuring ultrafine particles using particle number concentration (PNC) for health assessments. However, commonly used particle metrics such as aerodynamic diameter and number concentrations do not fully capture the diverse chemical makeup of complex particles. To address this issue, our study used high-throughput mass spectrometry to analyze the properties of cooking oil fumes (COFs) in real time and evaluate their impact on BEAS-2B cell metabolism. Results showed insignificant differences in COF number size distributions between soybean oil and olive oil (peak concentrations of 5.20 × 105/cm3), as well as between corn oil and peanut oil (peak concentrations of 4.35 × 105/cm3). Despite the similar major chemical components among the four COFs, variations in metabolic damage were observed, indicating that the relatively small amount of chemical components of COFs can also influence particle behavior within the respiratory system, thereby impacting biological responses. Additionally, interactions between accompanying gaseous COFs and particles may alter their chemical composition through various mechanisms, introducing additional chemicals and modifying existing proportions. Hence, the chemical composition and gaseous components of COFs hold equal importance to the particle number concentration (PNC) when assessing their impact on human health. The absence of these considerations in the current guidelines underscores a research gap. It is imperative to acknowledge that for a more comprehensive approach to safeguarding public health, guidelines must be regularly updated to reflect new scientific findings and robust epidemiological evidence.

Influence of Polycyclic Aromatic Compounds and Oxidation States of Soot Organics on the Metabolome of Human-Lung Cells (A549): Implications for Vehicle Fuel Selection.

Decades of research have established the toxicity of soot particles resulting from incomplete combustion. However, the unique chemical compounds responsible for adverse health effects have remained uncertain. This study utilized mass spectrometry to analyze the chemical composition of extracted soot organics at three oxidation states, aiming to establish quantitative relationships between potentially toxic chemicals and their impact on human alveolar basal epithelial cells (A549) through metabolomics-based evaluations. Targeted analysis using MS/MS indicated that particles with a medium oxidation state contained the highest total abundance of compounds, particularly oxygen-containing polycyclic aromatic hydrocarbons (OPAHs) composed of fused benzene rings and unsaturated carbonyls, which may cause oxidative stress, characterized by the upregulation of three specific metabolites. Further investigation focused on three specific OPAH standards: 1,4-naphthoquinone, 9-fluorenone, and anthranone. Pathway analysis indicated that exposure to these compounds affected transcriptional functions, the tricarboxylic acid cycle, cell proliferation, and the oxidative stress response. Biodiesel combustion emissions had higher concentrations of PAHs, OPAHs, and nitrogen-containing PAHs (NPAHs) compared with other fuels. Quinones and 9,10-anthraquinone were identified as the dominant compounds within the OPAH category. This knowledge enhances our understanding of the compounds contributing to adverse health effects observed in epidemiological studies and highlights the role of aerosol composition in toxicity.

Characterization of Biodiesel and Diesel Combustion Particles: Chemical Composition, Lipid Metabolism, and Implications for Health and Environment.

Biodiesel, derived from alkyl esters of vegetable oils or animal fats, has gained prominence as a greener alternative to diesel due to its reduced particle mass. However, it remains debatable whether biodiesel exposure has more severe health issues than diesel. This study performed high-resolution mass spectrometry to examine the detailed particle chemical compositions and lipidomics analysis of human lung epithelial cells treated with emissions from biodiesel and diesel fuels. Results show the presence of the peak substances of CHO compounds in biodiesel combustion that contain a phthalate ester (PAEs) structure (e.g., n-amyl isoamyl phthalate and diisobutyl phthalate). PAEs have emerged as persistent organic pollutants across various environmental media and are known to possess endocrine-disrupting properties in the environment. We further observed that biodiesel prevents triglyceride storage compared to diesel and inhibits triglycerides from becoming phospholipids, particularly with increased phosphatidylglycerols (PGs) and phosphatidylethanolamines (PEs), which potentially could lead to a higher probability of cancer metastasis.

bmVAE: a variational autoencoder method for clustering single-cell mutation data.

MOTIVATION: Genetic intra-tumor heterogeneity (ITH) characterizes the differences in genomic variations between tumor clones, and accurately unmasking ITH is important for personalized cancer therapy. Single-cell DNA sequencing now emerges as a powerful means for deciphering underlying ITH based on point mutations of single cells. However, detecting tumor clones from single-cell mutation data remains challenging due to the error-prone and discrete nature of the data. RESULTS: We introduce bmVAE, a bioinformatics tool for learning low-dimensional latent representation of single cell based on a variational autoencoder and then clustering cells into subpopulations in the latent space. bmVAE takes single-cell binary mutation data as inputs, and outputs inferred cell subpopulations as well as their genotypes. To achieve this, the bmVAE framework is designed to consist of three modules including dimensionality reduction, cell clustering and genotype estimation. We assess the method on various synthetic datasets where different factors including false negative rate, data size and data heterogeneity are considered in simulation, and further demonstrate its effectiveness on two real datasets. The results suggest bmVAE is highly effective in reasoning ITH, and performs competitive to existing methods. AVAILABILITY AND IMPLEMENTATION: bmVAE is freely available at https://github.com/zhyu-lab/bmvae. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Use of Lactiplantibacillus plantarum ZJ316 as a starter culture for nitrite degradation, foodborne pathogens inhibition and microbial community modulation in pickled mustard fermentation.

The potential of Lactiplantibacillus plantarum ZJ316 (ZJ316) as a starter culture for quality improvement and microbial community regulation in pickled mustard fermentation was elucidated in this study. Our results show that ZJ316 can deter the occurrence of nitrite peaks and maintain the nitrite content of pickled mustard at a low level (0.34 mg/kg). The headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry results indicate that ZJ316 gives a good flavor to pickled mustard. According to the 16S rDNA results, Firmicutes were the predominant microbiota after inoculation with ZJ316, and the abundances of Citrobacter, Enterobacter, and Proteus decreased simultaneously. In addition, antibacterial activity analysis showed that the supernatant of pickled mustard inoculated with ZJ316 had a significant inhibitory effect on Staphylococcus aureus D48, Escherichia coli DH5α, and Listeria monocytogenes LM1. In conclusion, L. plantarum ZJ316 has potential for use as an ideal starter in the process of vegetable fermentation.

Antibacterial Effects of Bacteriocin PLNC8 against Helicobacter pylori and Its Potential Mechanism of Action.

Helicobacter pylori (H. pylori) is a bacterium that can cause a variety of gastric diseases. Most bacteriocins have gained popularity due to their non-toxic effects on cells and antibacterial effects against a wide range of pathogenic bacteria. In this study, the chemical synthesis of the bipeptide bacteriocin PLNC8 was used to investigate its possible action mechanism against H. pylori ZJC03 in vitro. Results showed that PLNC8 had significant anti-H. pylori ZJC03 potential, which resulted in a significant reduction in urease activity and a minimum inhibitory concentration (MIC) of 80 µM. PLNC8 inhibited the growth of H. pylori ZJC03, disrupting its structure as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition, PLNC8 decreased the ATP level and hydrogen peroxide sensitivity of H. pylori ZJC03. In conclusion, PLNC8 disrupts the ability of H. pylori ZJC03 to alter the host environment, providing a new avenue for the prevention and control of H. pylori infection, providing a theoretical foundation for further elucidation of its regulatory mechanism.

Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma: a prospective phase II trial.

OBJECTIVE: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone (R-FPD) regimen followed by whole-brain radiotherapy (WBRT) for patients with primary central nervous system lymphoma (PCNSL). METHODS: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100 mg/m2 i.v. on D1), pemetrexed (600 mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1-5). Patients 60 years or younger who showed a complete response (CR) were treated with 23.4 Gy of WBRT after the end of chemotherapy; those older than 60 years with CR were treated with a wait-and-see approach; and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy + local tumor field irradiation up to 45 Gy, regardless of age. RESULTS: A total of 30 patients were included. After 2 cycles, the objective response rate (ORR) was 96.5% (28/29, 1 CR, 27 PR, 0 SD, and 1 PD). After 4 cycles, the ORR was 73.1% (19/26, 11 CR, 8 PR, 4 SD, and 3 PD). After WBRT, the ORR was 90.9% (10/11, 7 CR, 3 PR, and 1 SD). The grade III and IV toxicity responses were mainly leukopenia (20.0%), thrombocytopenia (23.3%), and anemia (10.0%). CONCLUSIONS: Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes, providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.