UNASSIGNED: Diabetic retinopathy (DR) is one of the common chronic complications of diabetes mellitus, which has developed into the leading cause of irreversible visual impairment in adults worldwide. Compound Qilian tablets (CQLT) is a traditional Chinese medicine (TCM) developed for treating DR, but its mechanism is still unclear. This study explored the mechanism of action of CQLT in treating DR through metabolomics and intestinal microbiota.
UNASSIGNED: Histopathologic examination of the pancreas and retina of Zucker diabetic fatty (ZDF) rats and immunohistochemistry were used to determine the expression levels of retinal nerve damage indicators ionized calcium binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). Rat fecal samples were tested by LC-MS metabolomics to search for potential biomarkers and metabolic pathways for CQLT treatment of DR. Characteristic nucleic acid sequences of rat intestinal microbiota from each group were revealed using 16S rDNA technology to explore key microbes and related pathways for CQLT treatment of DR. At the same time, we investigated the effect of CQLT on the gluconeogenic pathway.
UNASSIGNED: After CQLT intervention, islet cell status was improved, Iba-1 and GFAP expression were significantly decreased, and abnormal retinal microvascular proliferation and exudation were ameliorated. Metabolomics results showed that CQLT reversed 20 differential metabolites that were abnormally altered in DR rats. Intestinal microbiota analysis showed that treatment with CQLT improved the abundance and diversity of intestinal flora. Functional annotation of metabolites and intestinal flora revealed that glycolysis/gluconeogenesis, alanine, aspartate and glutamate metabolism, starch and sucrose metabolism were the main pathways for CQLT in treating DR. According to the results of correlation analysis, there were significant correlations between Iba-1, GFAP, and intestinal microbiota and metabolites affected by CQLT. In addition, we found that CQLT effectively inhibited the gluconeogenesis process in diabetic mice.
UNASSIGNED: In conclusion, CQLT could potentially reshape intestinal microbiota composition and regulate metabolite profiles to protect retinal morphology and function, thereby ameliorating the progression of DR.

Pesticide residues in soil, especially multiple herbicide residues, cause a series of adverse effects on soil properties and microorganisms. In this work, the degradation of three herbicides and the effect on bacterial communities under combined pollution was investigated. The experimental results showed that the half-lives of acetochlor and prometryn significantly altered under combined exposure (5.02-11.17 d) as compared with those of individual exposure (4.70-6.87 d) in soil, suggesting that there was an antagonistic effect between the degradation of acetochlor and prometryn in soil. No remarkable variation in the degradation rate of atrazine with half-lives of 6.21-6.85 d was observed in different treatments, indicating that the degradation of atrazine was stable. 16S rRNA high-throughput sequencing results showed that the antagonistic effect of acetochlor and prometryn on the degradation rate under combined pollution was related to variation of the Sphingomonas and Nocardioide. Furthermore, the potential metabolic pathways of the three herbicides in soil were proposed and a new metabolite of acetochlor was preliminarily identified. The results of this work provide a guideline for the risk evaluation of combined pollution of the three herbicides with respect to their ecological effects in soil.

Hyperlipidemia is a lipid metabolism disorder that refers to increased levels of total triglycerides (TGs), cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) and decreased levels of high-density lipoprotein-cholesterol (HDL-C). It is a major public health issue with increased prevalence and incidence worldwide. The ability to identify individuals at risk of this disorder before symptoms manifest will facilitate timely intervention and management to avert potential complications. This can be achieved by employing metabolomics as an early detection method for the diagnostic biomarkers of hyperlipidemia. Metabolomics is an analytical approach used to detect and quantify metabolites. This provides the ability to explain the metabolic processes involved in the development and progression of certain diseases. In recent years, interest in the use of metabolomics to identify disease biomarkers has increased, and several biomarkers have been discovered, such as docosahexaenoic acid, glycocholic acid, citric acid, betaine, and carnitine. This review discusses the primary metabolic alterations in the context of hyperlipidemia. Furthermore, we provide an overview of recent studies on the application of metabolomics to the assessment of the efficacy of traditional herbal products and common lipid-lowering medications.

UNASSIGNED: Inflammatory bowel disease (IBD) is a common chronic inflammatory bowel disease characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases of the intestinal system, so we aimed to assess the causal relationship between human blood metabolites and susceptibility to IBD subtypes.
UNASSIGNED: We selected a genome-wide association study (GWAS) of 275 metabolites as the exposure factor, and the GWAS dataset of 10 IBD subtypes as the outcome, followed by univariate and multivariate analyses using a two-sample Mendelian randomization study (MR) to study the causal relationship between exposure and outcome, respectively. A series of sensitivity analyses were also performed to ensure the robustness of the results.
UNASSIGNED: A total of 107 metabolites were found to be causally associated on univariate analysis after correcting for false discovery rate (FDR), and a total of 9 metabolites were found to be significantly causally associated on subsequent multivariate and sensitivity analyses. In addition we found causal associations between 7 metabolite pathways and 6 IBD subtypes.
UNASSIGNED: Our study confirms that blood metabolites and certain metabolic pathways are causally associated with the development of IBD subtypes and their parenteral manifestations. The exploration of the mechanisms of novel blood metabolites on IBD may provide new therapeutic ideas for IBD patients.

Lonicera japonica Flos is a valuable herb in the Lonicerae family. While transcriptomic studies on L. japonica have focused on different tissues (stems, leaves, flowers) or flowering stages, few have investigated the molecular mechanisms underlying chemical composition synthesis influenced by exogenous factors, such as foliar fertilization. Moreover, most transcriptomic studies on L. Japonica have been conducted on chlorogenic acid and luteoloside, and the molecular synthesis mechanism of the overall chemical composition has not been analyzed. Methods: We conducted a single-factor, four-level foliar fertilization experiment using yeast polysaccharides. Different yeast polysaccharides concentrations were sprayed on L. japonica for six consecutive days with dynamic sampling. High-performance liquid chromatography determined the active ingredients in each group. The two groups exhibiting the most significant differences were selected for transcriptomic analysis to identify key synthetic genes responsible for L. japonica\'s active ingredients. Key results: Principal component analysis conducted on samples collected on September 8 revealed significant differences in the active ingredient amounts between the 0.1 g/L yeast polysaccharides treatment group and the control group. Transcriptome sequencing analysis identified 218 significantly differentially expressed genes, including 60 upregulated and 158 downregulated genes. Twelve differential genes involved in the chemical components synthesis pathway of L. japonica under yeast polysaccharides treatment were identified: PAL1, PAL2, PAL3, 4CL1, 4CL, CHS1, CHS2, CHS, CHI1, CHI2, F3H, and SOH. Conclusions: This study contributes to the theoretical understanding of essential synthetic genes associated with L. japonica\'s active ingredients. It offers data support for further gene exploration and sheds light on the molecular mechanisms underlying L. japonica quality formation. These findings hold significant implications for enhancing the content of secondary metabolites of L. japonica.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12298-024-01482-1.

The Brazilian Atlantic Forest, renowned for its exceptional species richness and high endemism, acts as a vital reservoir of terrestrial biodiversity, often referred to as a biodiversity hotspot. Consequently, there is an urgent need to restore this forest to safeguard certain species and to unravel the ecophysiological adaptations of others. This study aims to integrate some physiological parameters, including gas exchange and chlorophyll a fluorescence, with anatomical and metabolic techniques to elucidate how five different native species (Paubrasilia echinata, Chorisia glaziovii, Clusia nemorosa, Licania tomentosa, and Schinus terebinthifolius), each occupying distinct ecological niches, respond to seasonal variations in rainfall and their consequences. Our investigation has revealed that C. nemorosa and P. echinata exhibit robust mechanisms to mitigate the adverse effects of drought. In contrast, others demonstrate greater adaptability (e.g., S. terebinthifolia and C. glaziovii). In this context, exploring metabolic pathways has proven invaluable in comprehending the physiological strategies and their significance in species acclimatization. This study provides a comprehensive overview of the impact of water restrictions and their consequential effects on various species, defining the strategies each species uses to mitigate water privation during the dry season.

Fermentation-a process of compound degradation by microorganisms-is a traditional food processing method utilized worldwide for the long-term preservation of fresh foods. In recent years, fermented foods have gained attention as health foods. Fermentation increases the nutritional value of ingredients, producing complex flavors and aromas. To identify unknown components in fermented foods, it is necessary to analyze compounds and conditions nondestructively and comprehensively. We performed intact-state nuclear magnetic resonance (NMR) spectroscopy using intermolecular single quantum coherence (iSQC) to detect the degradation of vegetables directly and nondestructively. We used two types of vegetables and a rice bran bed (nukazuke), which is used for traditional vegetable fermentation in Japan. Major metabolites such as saccharides, organic acids, and amino acids were identified in iSQC-sliced spectra. Comparing NMR signal intensities during degradation revealed the transition of metabolites characteristic of lactic acid fermentation. A pathway-based network analysis showed pathways involved in amino acid metabolism and lactic acid fermentation. Our analytical approach with intact-state NMR spectroscopy using iSQC demonstrated that it may be effective in other experimental systems, allowing for the evaluation of phenomena that have been conventionally overlooked in their true state.

Sweet potato pulp water (SPPW) is a kind of sweet potato starch processing by-product with rich nutrition but low utilization. The impacts of different proportions of Coriolus versicolor (C. versicolor, CV) fermented sweet potato pulp water (CV-SPPW) on the physicochemical, structural and metabolic properties of yogurt were investigated. Compared with 0% group, the hardness index, elasticity index and cohesion of the 10% sample group increased by 1.9-fold, 55.7% and 1.39-fold, respectively. When CV-SPPW was added at an amount of 10%, the microstructure and sensory scores of yogurts were considered as the optimal. Metabolic pathway analysis indicated that the changes of yogurts were mainly involved in sugar metabolism and amino acid metabolism, and that the carbohydrate metabolites produced mainly included cellobiose, maltitol, d-trehalose and d-maltose. The CV-SPPW improved the structural characteristics of yogurts to varying degrees and the fermented yogurts exhibited better viscosity properties.

UNASSIGNED: Interest in the safety of herbal medicine is growing rapidly regarding knowledge and challenges in natural products. Hence, this study aimed to reveal the toxicological profile of Ardisia elliptica, a traditional medicinal plant used in the treatment of various illnesses.
UNASSIGNED: Acute toxicity study was performed on female and male Sprague Dawley rats with a single oral administration of 2000 mg/kg BW of 70% ethanolic A. elliptica leaf extract, using a combination of conventional investigations and 1H-NMR-based metabolomics approaches.
UNASSIGNED: Physical, hematological, biochemical, and histopathological assessments demonstrated the usual rat profile, with no mortality and delayed toxicity 14 days after administration. 1H NMR serum metabolomics depicted similar metabolites between normal and treated groups. Nevertheless, 1H NMR of urinary metabolomics revealed perturbation in carbohydrate, amino acid, and energy metabolism within 24h after extract administration, while no accumulation of toxic biomarkers in the collected biological fluids on Day 14. A minor gender-based difference revealed the influence of sex hormones and different energy expenditure on response to extract treatment.
UNASSIGNED: This study suggested that 2000 mg/kg BW of 70% ethanolic A. elliptica leaf extract is considered as safe for consumption and offered a comprehensive overview of the response of physiological and metabolic aspects applicable to food and herbal product development.

BACKGROUND: Metabolic pathways support the enzyme flux that converts input chemicals into energy and cellular building blocks. With a constant rate of input, steady-state flux is achieved when metabolite concentrations and reaction rates remain constant over time. Individual genes undergo mutation, while selection acts on higher level functions of the pathway, such as steady-state flux where applicable. Modeling the evolution of metabolic pathways through mechanistic sets of ordinary differential equations is a piece of the genotype-phenotype map model for interpreting genetic variation and inter-specific differences. Such models can generate distinct compensatory changes and adaptive changes from directional selection, indicating single nucleotide polymorphisms and fixed differences that could affect phenotype. If used for inference, this would ultimately enable detection of selection on metabolic pathways as well as inference of ancestral states for metabolic pathway function.
RESULTS: A software tool for simulating the evolution of metabolic pathways based upon underlying biochemistry, phylogenetics, and evolutionary considerations is presented. The Python program, Phylogenetic Evolution of Metabolic Pathway Simulator (PEMPS), implements a mutation-selection framework to simulate the evolution of the pathway over a phylogeny by interfacing with COPASI to calculate the steady-state flux of the metabolic network, introducing mutations as alterations in parameter values according to a model, and calculating a fitness score and corresponding probability of fixation based on the change in steady-state flux value(s). Results from simulations are consistent with a priori expectations of fixation probabilities and systematic change in model parameters.
CONCLUSIONS: The PEMPS program simulates the evolution of a metabolic pathway with a mutation-selection modeling framework based on criteria like steady-state flux that is designed to work with SBML-formatted kinetic models, and Newick-formatted phylogenetic trees. The Python software is run on the Linux command line and is available at https://github.com/nmccloskey/PEMPS .