Essential Metabolites Research Articles

Inflammatory Bowel Disease and Gut Microbiota Dysbiosis: Current understanding and Future Direction

Inflammatory Bowel Disease (IBD) represents a group of chronic, relapsing inflammatory disorders primarily affecting the gastrointestinal tract. The pathogenesis of IBD is multifaceted, involving genetic predisposition, environmental triggers, and dysregulation of the immune response. Recent research has illuminated the pivotal role of gut microbiota dysbiosis in the development and perpetuation of IBD. The human gut harbors a complex and dynamic ecosystem of microorganisms that profoundly influences host health and disease. Alterations in the composition, diversity, and function of the gut microbiota, termed dysbiosis, have been consistently linked to IBD. Shifts in microbial composition, reduction in microbial diversity, and imbalances in beneficial versus pathogenic microorganisms characterize the dysbiotic state associated with IBD.The intricate interplay between the host immune system and the gut microbiota is a key determinant in IBD pathogenesis. Dysbiosis triggers aberrant immune responses, leading to chronic mucosal inflammation and tissue damage. Furthermore, dysbiotic alterations disrupt essential microbial-derived metabolites and signaling molecules crucial for gut homeostasis, further exacerbating the disease. Advancements in high-throughput sequencing technologies and metagenomic analysis have enabled comprehensive characterization of microbial communities in IBD, uncovering microbial signatures and functional pathways associated with disease phenotypes and treatment responses. Therapeutic interventions targeting the gut microbiota, such as probiotics, prebiotics, fecal microbiota transplantation, and microbial-based therapies, have shown promise in preclinical and clinical studies for modulating dysbiosis and ameliorating IBD symptoms.
 Keywords: Inflammatory Bowel Disease, Dysbiosis, Fecal microbiota, Probiotics

The follicle-stimulating hormone triggers rapid changes in mitochondrial structure and function in porcine cumulus cells

Oocyte maturation is a key process during which the female germ cell undergoes resumption of meiosis and completes its preparation for embryonic development including cytoplasmic and epigenetic maturation. The cumulus cells directly surrounding the oocyte are involved in this process by transferring essential metabolites, such as pyruvate, to the oocyte. This process is controlled by cyclic adenosine monophosphate (cAMP)-dependent mechanisms recruited downstream of follicle-stimulating hormone (FSH) signaling in cumulus cells. As mitochondria have a critical but poorly understood contribution to this process, we defined the effects of FSH and high cAMP concentrations on mitochondrial dynamics and function in porcine cumulus cells. During in vitro maturation (IVM) of cumulus-oocyte complexes (COCs), we observed an FSH-dependent mitochondrial elongation shortly after stimulation that led to mitochondrial fragmentation 24 h later. Importantly, mitochondrial elongation was accompanied by decreased mitochondrial activity and a switch to glycolysis. During a pre-IVM culture step increasing intracellular cAMP, mitochondrial fragmentation was prevented. Altogether, the results demonstrate that FSH triggers rapid changes in mitochondrial structure and function in COCs involving cAMP.

Absolute quantification of nicotinamide mononucleotide in biological samples by double isotope-mediated liquid chromatography-tandem mass spectrometry (dimeLC-MS/MS)

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite for fundamental biological phenomena, including aging. Nicotinamide mononucleotide (NMN) is a key NAD+ intermediate that has been extensively tested as an effective NAD+-boosting compound in mice and humans. However, the accurate measurement of NMN in biological samples has long been a challenge in the field. Here, we have established an accurate, quantitative methodology for measuring NMN by using liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) with double isotopic NMN standards. In this new methodology, the matrix effects of biological samples were properly adjusted, and the fate of NMN could be traced during sample processing. We have demonstrated that this methodology can accurately quantitate NMN levels in mouse plasma and confirmed quick, direct NMN uptake into blood circulation and cells. This double isotope-mediated LC-MS/MS (dimeLC-MS/MS) can easily be expanded to other NAD+-related metabolites as a reliable standard methodology for NAD+ biology.

Citraconate promotes the malignant progression of colorectal cancer by inhibiting ferroptosis.

Metastasis is a principal factor in the poor prognosis of colorectal cancer. Recent studies have found microbial metabolites regulate colorectal cancer metastasis. By analyzing metabolomics data, we identified an essential fecal metabolite citraconate that potentially promotes colorectal cancer metastasis. Next, we tried to reveal its effect on colorectal cancer and the underlying mechanism. Firstly, the response of colorectal cancer cells (HCT116 and MC38 cells) to citraconate was assessed by Cell Counting Kit-8 assay, clonogenic assay, transwell migration and invasion assay. Moreover, we utilized an intra-splenic injection model to evaluate the effect of citraconate on colorectal cancer liver metastasis in vivo. Then molecular approaches were employed, including RNA sequencing, mass spectrometry-based metabolomics, western blot, quantitative real-time PCR, cell ferrous iron colorimetric assay and intracellular malondialdehyde measurement. In vitro, citraconate promotes the growth of colorectal cancer cells. In vivo, citraconate aggravated liver metastasis of colorectal cancer. Mechanistically, downstream genes of NRF2, NQO1, GCLC, and GCLM high expression induced by citraconate resulted in resistance to ferroptosis of colorectal cancer cells. In summary, citraconate promotes the malignant progression of colorectal cancer through NRF2-mediated ferroptosis resistance in colorectal cancer cells. Furthermore, our study indicates that fecal metabolite may be crucial in colorectal cancer development.

How has the evolution of our understanding of the compartmentalization of sphingolipid biosynthesis over the past 30 years altered our view of the evolution of the pathway?

Sphingolipids are unique among cellular lipids inasmuch as their biosynthesis is compartmentalized between the endoplasmic reticulum (ER) and the Golgi apparatus. This compartmentalization was first recognized about thirty years ago, and the current review not only updates studies on the compartmentalization of sphingolipid biosynthesis, but also discusses the ramifications of this feature for our understanding of how the pathway could have evolved. Thus, we augment some of our recent studies by inclusion of two further molecular pathways that need to be considered when analyzing the evolutionary requirements for generation of sphingolipids, namely contact sites between the ER and the Golgi apparatus, and the mechanism(s) of vesicular transport between these two organelles. Along with evolution of the individual enzymes of the pathway, their subcellular localization, and the supply of essential metabolites via the anteome, it becomes apparent that current models to describe evolution of the sphingolipid biosynthetic pathway may need substantial refinement.

Engineering of a Substrate Affinity Reduced S-Adenosyl-methionine Synthetase as a Novel Biosensor for Growth-Coupling Selection of L-Methionine Overproducers.

Biosensors are powerful tools for monitoring specific metabolites or controlling metabolic flux towards the products in a single cell, which play important roles in microbial cell factory construction. Despite their potential role in metabolic flux monitoring, the development of biosensors for small molecules is still limited. Reported biosensors often exhibit bottlenecks of poor specificity and a narrow dynamic range. Moreover, fine-tuning the substrate binding affinity of a crucial enzyme can decrease its catalytic activity, which ultimately results in the repression of the corresponding essential metabolite biosynthesis and impairs cell growth. However, increasing intracellular substrate concentration can elevate the availability of the essential metabolite and may lead to restore cellular growth. Herein, a new strategy was proposed for constructing whole-cell biosensors based on enzyme encoded by essential gene that offer inherent specificity and universality. Specifically, S-adenosyl-methionine synthetase (MetK) in E. coli was chosen as the crucial enzyme, and a series of MetK variants were identified that were sensitive to L-methionine concentration. This occurrence enabled the engineered cell to sense L-methionine and exhibit L-methionine dose-dependent cell growth. To improve the biosensor's dynamic range, an S-adenosyl-methionine catabolic enzyme was overexpressed to reduce the intracellular availability of S-adenosyl-methionine. The resulting whole-cell biosensor effectively coupled the intracellular concentration of L-methionine with growth and was successfully applied to select strains with enhanced L-methionine biosynthesis from random mutagenesis libraries. Overall, our study presents a universal strategy for designing and constructing growth-coupled biosensors based on crucial enzyme, which can be applied to select strains overproducing high value-added metabolites in cellular metabolism.

Engineering a Novel Acetyl-CoA Pathway for Efficient Biosynthesis of Acetyl-CoA-Derived Compounds.

Acetyl-CoA is an essential central metabolite in living organisms and a key precursor for various value-added products as well. However, the intracellular availability of acetyl-CoA limits the efficient production of these target products due to complex and strict regulation. Here, we proposed a new acetyl-CoA pathway, relying on two enzymes, threonine aldolase and acetaldehyde dehydrogenase (acetylating), which can convert one l-threonine into one acetyl-CoA, one glycine, and generate one NADH, without carbon loss. Introducing the acetyl-CoA pathway could increase the intracellular concentration of acetyl-CoA by 8.6-fold compared with the wild-type strain. To develop a cost-competitive and genetically stable acetyl-CoA platform strain, the new acetyl-CoA pathway, driven by the constitutive strong promoter, was integrated into the chromosome of Escherichia coli. We demonstrated the practical application of this new acetyl-CoA pathway by high titer production of β-alanine, mevalonate, and N-acetylglucosamine. At the same time, this pathway achieved a high-yield production of glycine, a value-added commodity chemical for the synthesis of glyphosate and thiamphenicol. This work shows the potential of this new acetyl-CoA pathway for the industrial production of acetyl-CoA-derived compounds.

Permeation of gabapentin through LAT1: A comparative study between graphene and cell membrane

LAT1 (SLC7A5) is a membrane transporter that permits the uptake of essential amino acids, metabolites, and drugs into the cell, and is found to be overexpressed in a broad range of cancers and neurological disorders. It has been hypothesized that LAT1 transporters tend to share a general mechanism of action—alternative access transport. Nevertheless, little information is available on the real-time permeability of metabolites and drugs through LAT1 in the presence of graphene or the endothelial cell membrane. This work analyzed the interactions at the interface of LAT1 and a neurological drug, gabapentin, comparing graphene and membrane as substrates for LAT1. RMSD analysis on the molecular dynamics trajectories indicated that both graphene and membrane systems effectively allowed LAT1 to adsorb and stabilize gabapentin. However, from energetics, secondary structure analysis, and interfacial water molecules, graphene is found to be more suitable to act as a scaffold for in vitro analysis of LAT1.

2P-FLIM unveils time-dependent metabolic shifts during osteogenic differentiation with a key role of lactate to fuel osteogenesis via glutaminolysis identified

BackgroundHuman mesenchymal stem cells (hMSCs) utilize discrete biosynthetic pathways to self-renew and differentiate into specific cell lineages, with undifferentiated hMSCs harbouring reliance on glycolysis and hMSCs differentiating towards an osteogenic phenotype relying on oxidative phosphorylation as an energy source.MethodsIn this study, the osteogenic differentiation of hMSCs was assessed and classified over 14 days using a non-invasive live-cell imaging modality—two-photon fluorescence lifetime imaging microscopy (2P-FLIM). This technique images and measures NADH fluorescence from which cellular metabolism is inferred.ResultsDuring osteogenesis, we observe a higher dependence on oxidative phosphorylation (OxPhos) for cellular energy, concomitant with an increased reliance on anabolic pathways. Guided by these non-invasive observations, we validated this metabolic profile using qPCR and extracellular metabolite analysis and observed a higher reliance on glutaminolysis in the earlier time points of osteogenic differentiation. Based on the results obtained, we sought to promote glutaminolysis further by using lactate, to improve the osteogenic potential of hMSCs. Higher levels of mineral deposition and osteogenic gene expression were achieved when treating hMSCs with lactate, in addition to an upregulation of lactate metabolism and transmembrane cellular lactate transporters. To further clarify the interplay between glutaminolysis and lactate metabolism in osteogenic differentiation, we blocked these pathways using BPTES and α-CHC respectively. A reduction in mineralization was found after treatment with BPTES and α-CHC, demonstrating the reliance of hMSC osteogenesis on glutaminolysis and lactate metabolism.ConclusionIn summary, we demonstrate that the osteogenic differentiation of hMSCs has a temporal metabolic profile and shift that is observed as early as day 3 of cell culture using 2P-FLIM. Furthermore, extracellular lactate is shown as an essential metabolite and metabolic fuel to ensure efficient osteogenic differentiation and as a signalling molecule to promote glutaminolysis. These findings have significant impact in the use of 2P-FLIM to discover potent approaches towards bone tissue engineering in vitro and in vivo by engaging directly with metabolite-driven osteogenesis.Graphical

Experimental and Computational Analysis of Newly Identified Pathogenic Mutations in the Creatine Transporter SLC6A8

Creatine is an essential metabolite for the storage and rapid supply of energy in muscle and nerve cells. In humans, impaired metabolism, transport, and distribution of creatine throughout tissues can cause varying forms of mental disability, also known as creatine deficiency syndrome (CDS). So far, 80 mutations in the creatine transporter (SLC6A8) have been associated to CDS. To better understand the effect of human genetic variants on the physiology of SLC6A8 and their possible impact on CDS, we studied 30 missense variants including 15 variants of unknown significance, two of which are reported here for the first time. We expressed these variants in HEK293 cells and explored their subcellular localization and transport activity. We also applied computational methods to predict variant effect and estimate site-specific changes in thermodynamic stability. To explore variants that might have a differential effect on the transporter’s conformers along the transport cycle, we constructed homology models of the inward facing, and outward facing conformations. In addition, we used mass-spectrometry to study proteins that interact with wild type SLC6A8 and five selected variants in HEK293 cells. In silico models of the protein complexes revealed how two variants impact the interaction interface of SLC6A8 with other proteins and how pathogenic variants lead to an enrichment of ER protein partners. Overall, our integrated analysis disambiguates the pathogenicity of 15 variants of unknown significance revealing diverse mechanisms of pathogenicity, including two previously unreported variants obtained from patients suffering from the creatine deficiency syndrome.

Electronic cigarette vapor disrupts key metabolic pathways in human lung epithelial cells

The steady increase in the use of electronic cigarettes (ECs) has reached an epidemic level, increasing mortality and morbidity, mainly due to pulmonary toxicity. Several mechanisms are involved in EC-induced toxicity, including oxidative stress and increased inflammation. Concurrently, the integrity of cellular metabolism is essential for cellular homeostasis and mitigation of toxic insults. However, the effects of EC on cellular metabolism remain largely unknown. In this study, we investigated the metabolic changes induced by EC in human lung epithelial cells (A549) using an untargeted metabolomics approach. A549 cells were exposed to increasing EC vapor extract concentrations, and cell viability, oxidative stress, and metabolomic changes were assessed. Our findings show that ECs induce cell death and increase oxidative stress in a concentration-dependent manner. Metabolomic studies demonstrated that ECs induce unique metabolic changes in key cellular metabolic pathways. Our results revealed that exposure to ECs induced clear segregation in metabolic responses which is driven significantly by number of essential metabolites such as aminoacids, fatty acids, glutathione, and pyruvate. Interstingly, our metabolomics results showed that each concentration of ECs induced unqiues pattern of metabolic changes, suggesting the complexity of ECs induced cytotoxcity. Disrupted metabolites were linked to essential cellular pathways, such as fatty acid biosynthesis, as well as glutathione, pyruvate, nicotinate and nicotinamide, and amino acid metabolisms. These results highlight the potential adverse effects of ECs on cellular metabolism and emphasize the need for further research to fully understand the long-term consequences of EC use. Overall, this study demonstrates that ECs not only induce cell death and oxidative stress but also disrupt cellular metabolism in A549 lung epithelial cells.

Petunia bZIP transcription factor PhbZIP3 is involved in floral volatile benzenoid/phenylpropanoid biosynthesis through regulating the expression of PhPAL2 and PhBSMT

Floral volatile benzenoid/phenylpropanoid compounds (FVBPs) are essential plant secondary metabolites and play a pivotal role in plant reproduction and development. However, the knowledge of transcriptional regulation of its biosynthesis pathway remains limited. Although extensively implicated in the regulation of plant secondary metabolisms, the basic leucine zipper (bZIP) family has not been reported to regulate FVBP biosynthesis. This study aimed to screen out important bZIP transcription factor members in the transcriptional regulation of FVBP biosynthesis in petunia. The entirety of bZIP genes throughout the petunia genome was ascertained and in-depth investigations into their phylogenetic relationships, structural characteristics, expression patterns, and potential interactions with structural genes related to FVBP biosynthesis were conducted. Outcomes showed that 77 bZIP genes of petunia could be categorized into 11 groups. The significant quantitative differences of introns and conserved motifs among the petunia bZIP members, along with the variety of cis-acting elements, reflected the structure diversity of petunia bZIPs. Seven candidate bZIP genes for regulating FVBP biosynthesis were selected because of their up-regulated expression level after flower opening according to RNA sequencing data. Based on the qPCR and the subcellular localization analysis, one nuclear-localized member, PhbZIP3 was screened out. PhbZIP3 was mainly expressed in the corolla, and its expression level increased significantly during the anthesis period. Dual luciferase assay revealed that PhbZIP3 could enhance the expression of PhPAL2 and PhBSMT. The findings from the yeast one-hybrid assay further corroborated the interaction between PhbZIP3 and the promoters of PhPAL2 and PhBSMT. Taken together, these results suggest that PhbZIP3 play a pivotal role in the regulatory mechanism of FVBP biosynthesis in petunia.

Sodium butyrate ameliorates sepsis-associated lung injury by enhancing gut and lung barrier function in combination with modulation of CD4+Foxp3+ regulatory T cells

Sepsis-associated lung injury often coexists with intestinal dysfunction. Butyrate, an essential gut microbiota metabolite, participates in gut-lung crosstalk and has immunoregulatory effects. This study aims to investigate the effect and mechanism of sodium butyrate (NaB) on lung injury. Sepsis-associated lung injury was established in mice by cecal ligation and puncture (CLP). Mice in treatment groups received NaB gavage after surgery. The survival rate, the oxygenation index and the lung wet-to-dry weight (W/D) ratio were calculated respectively. Pulmonary and intestinal histologic changes were observed. The total protein concentration in bronchoalveolar lavage fluid (BALF) was measured, and inflammatory factors in serum and BALF were examined. Diamine oxidase (DAO), lipopolysaccharide (LPS), and surfactant-associated protein D (SP-D) levels in serum and amphiregulin in lung tissue were assessed. Intercellular junction protein expression in the lung and intestinal tissues were examined. Changes in immune cells were analyzed. NaB treatment improved the survival rate, the oxygenation index and the histologic changes. NaB decreased the W/D ratio, total protein concentration, and the levels of proinflammatory cytokines, as well as SP-D, DAO and LPS, while increased the levels of anti-inflammatory cytokines and amphiregulin. The intercellular junction protein expression were improved by NaB. Furthermore, the CD4+/CD8+ T-cell ratio and the proportion of CD4+Foxp3+ regulatory T cells (Tregs) were increased by NaB. Our data suggested that NaB gavage effectively improved the survival rate and mitigated lung injury in CLP mice. The possible mechanism was that NaB augmented CD4+Foxp3+ Tregs and enhanced the barrier function of the gut and the lung.

Metabolic exchanges are ubiquitous in natural microbial communities.

Microbial communities drive global biogeochemical cycles and shape the health of plants and animals-including humans. Their structure and function are determined by ecological and environmental interactions that govern the assembly, stability and evolution of microbial communities. A widely held view is that antagonistic interactions such as competition predominate in microbial communities and are ecologically more important than synergistic interactions-for example, mutualism or commensalism. Over the past decade, however, a more nuanced picture has emerged, wherein bacteria, archaea and fungi exist within interactive networks in which they exchange essential and non-essential metabolites. These metabolic interactions profoundly impact not only the physiology, ecology and evolution of the strains involved, but are also central to the functioning of many, if not all, microbiomes. Therefore, we advocate for a balanced view of microbiome ecology that encompasses both synergistic and antagonistic interactions as key forces driving the structure and dynamics within microbial communities.

Improving the Quality and Safety of Pu-erh Tea by Inoculation of Saccharomyces cerevisiae and Lactobacillus plantarum

The sensory quality and health benefits of Pu-erh tea are mainly determined by microbial fermentation processing. The directed exogenous inoculation of specific microorganisms is an effective method to improve the quality and flavor of Pu-erh tea. In this study, Lactobacillus plantarum and Saccharomyces cerevisiae were introduced into the fermentation processes of Pu-erh tea, as they are the main contributors to enzyme secretion, to change the tea’s functional components. The raw tea materials, spontaneous fermentation tea and microbiological fermentation tea were analyzed by microbiomics and metabolomics. A total of 248 metabolites were characterized, 71 of which were identified as essential metabolites involved in the metabolic changes. These essential metabolites were produced by specific dominant microbial species with multivariate analysis methods. Metabolites essential to the sensory quality and health benefits of Pu-erh tea, such as flavonoids and free amino acids, were increased in tea samples inoculated with Lactobacillus plantarum and Saccharomyces cerevisiae following fermentation. Fungal diversity decreased after fermentation, and both the diversity and richness of bacteria were significantly decreased. In conclusion, our results demonstrate the advantages of Lactobacillus plantarum and Saccharomyces cerevisiae in forming the unique sensory characteristics of Pu-erh tea, and they indicate that the microbial composition is a key factor in altering the tea’s metabolic profile. Our work establishes a theoretical foundation for the promotion of the safety and quality of Pu-erh tea through exogenous inoculation with Lactobacillus plantarum and Saccharomyces cerevisiae.

Comparative taxonomical, biological and pharmacological potential of healthy and geminivirus infected leaves of Hibiscus rosa-sinensis L.: First report

In the present research project, the first report on comparative analysis of the taxonomical, biological and pharmacological potential of healthy and geminivirus infected Hibiscus rosa sinensis (L.) leaves of the family Malvaceae was done by using different micro and macroscopic techniques. First of all, leaves were characterized for Cotton leaf curl Multan virus (CLCuMuV) and its associated betasatellite (Cotton leaf curl Multan Betasatellite; CLCuMB). Different morphological parameters like shape and size of stem, leaves, seeds and roots, presence and absence of ligule, distance between nodes and internodes and type of inflorescence etc. were analyzed. CLCuMuV infected H. rosa-sinensis revealed systematic symptoms of infection like chlorosis of leaves, stunted growth, decrease in size of roots, shoots and distortion etc. Anatomical investigation was performed under light ad scanning electron microscope. Different anatomical features like length and shape of guard cells, subsidiary cells, presence or absence of stomata, secretory ducts and trichomes were examined. In both plant samples anomocytic types of stomata and elongated, non-glandular and pointed tip trichomes were present, but the size (especially length and width) of trichomes and other cells like epidermal, subsidiary, and guard cells were highest in virus infected plants likened to healthy one. In the antibacterial activity, the maximum antibacterial potentail was seen in methanolic extract of K. pneumonea while antifungal activity was shown by methanolic extract of A. solani. Plants interact with different biological entities according to environmental conditions continuously and evolved. These types of interactions induce changes positively and negatively on plant metabolism and metabolites production. Many plant viruses also attacked various host plants consequently alter their secondary metabolism. To overcome such virus infected plants produces many important and different types of secondary plant metabolites as a defense response. Subsequent analysis of this n-hexane plant extract using Gas chromatography mass spectroscopy technique revealed that Hibiscus eluted contained 10 main compounds in Healthy sample and 13 compounds in infected one. Presence of essential secondary metabolites were also analyzed by FTIR analysis. The present study provides a comprehensive and novel review on taxonomy (morphology, anatomy) and antimicrobial potential of both healthy and geminivirus infected H. rosa-sinensis.

Ozonated water soaking improves the flower growth, antioxidant activity, and bioactive compound accumulation in Agastache rugosa

Ozonated water (OW) is now being recognized as an innovative and eco-friendly solution for managing plant growth while also promoting the production of bioactive compounds and essential plant metabolites. This study aimed to identify the most effective duration of OW treatment to promote plant growth and accumulation of antioxidant activity and bioactive compounds in Agastache rugosa in a plant factory. Whole plants were subjected to OW soaking treatments for varying durations (0, 1, 10, 20, 40, and 80 s) at a concentration of 1 µmol·mol−1, once per week, at 0, 1, 2, 3, and 4 weeks after transplantation. Five weeks after transplantation, plant samples were collected for the analysis of their plant growth parameters, photosynthetic pigments and parameters, total flavonoid, antioxidant activity, and bioactive compounds. Stem length was decreased in all OW treatments, while the number of flower branches, the flower fresh and dry weights were significantly increased under 20, 40, and 80 s OW treatments than in the control group. The net photosynthetic rate decreased significantly in 20, 40, and 80 s OW treatments compared with the control. Chlorophyll a concentration was the highest in the 20-s OW treatment, and chlorophyll b concentration was the highest in the 10-s OW treatment. Total flavonoid levels in plants increased significantly under 20-, 40-, and 80-s OW treatments, and their antioxidant activity (superoxide dismutase, catalase, and peroxidase) were significantly higher under 40- and 80-s OW treatments than in the control. Rosmarinic acid content increased significantly under the 10- and 40-s OW treatments, whereas the tilianin and acacetin contents increased significantly under the 20-, 40-, and 80-s OW treatments compared to those in the control. Our results suggest that soaking whole plants in OW for 20–80 s enhances the flower growth and bioactive compounds in A. rugosa for medicinal use.Graphical

Plasma essential fatty acid on hospital admission is a marker of COVID-19 disease severity

It is important for allocation of resources to predict those COVID patients at high risk of dying or organ failure. Early signals to initiate cellular events of host immunity can be derived from essential fatty acid metabolites preceding the cascade of proinflammatory signals. Much research has focused on understanding later proinflammatory responses. We assessed if remodelling of plasma phospholipid content of essential fatty acids by the COVID-19 virus provides early markers for potential death and disease severity. Here we show that, at hospital admission, COVID-19 infected subjects who survive exhibit higher proportions of C20:4n-6 in plasma phospholipids concurrent with marked proinflammatory cytokine elevation in plasma compared to healthy subjects. In contrast, more than half of subjects who die of this virus exhibit very low C18:2n-6 and C20:4n-6 content in plasma phospholipids on hospital admission compared with healthy control subjects. Moreover, in these subjects who die, the low level of primary inflammatory signals indicates limited or aberrant stimulation of host immunity. We conclude that COVID-19 infection results in early fundamental remodelling of essential fatty acid metabolism. In subjects with high mortality, it appears that plasma n-6 fatty acid content is too low to stimulate cellular events of host immunity.

The trehalose 6-phosphate phosphatase family in plants.

Trehalose 6-phosphate (Tre6P), the intermediate of trehalose biosynthesis, is an essential signalling metabolite linking plant growth and development to carbon metabolism. While recent work has focused predominantly on the enzymes that produce Tre6P, little is known about the proteins that catalyse its degradation, the trehalose 6-phosphate phosphatases (TPPs). Often occurring in large protein families, TPPs exhibit cell-, tissue- and developmental stage-specific expression patterns, suggesting important regulatory functions in controlling local levels of Tre6P and trehalose as well as Tre6P signalling. Furthermore, growing evidence through gene expression studies and transgenic approaches shows that TPPs play an important role in integrating environmental signals with plant metabolism. This review highlights the large diversity of TPP isoforms in model and crop plants and identifies how modulating Tre6P metabolism in certain cell types, tissues, and at different developmental stages may promote stress tolerance, resilience and increased crop yield.

Microbiota-derived tryptophan metabolism: Impacts on health, aging, and disease

The intricate interplay between gut microbiota and the host is pivotal in maintaining homeostasis and health. Dietary tryptophan (TRP) metabolism initiates a cascade of essential endogenous metabolites, including kynurenine, kynurenic acid, serotonin, and melatonin, as well as microbiota-derived Trp metabolites like tryptamine, indole propionic acid (IPA), and other indole derivatives. Notably, tryptamine and IPA, among the indole metabolites, exert crucial roles in modulating immune, metabolic, and neuronal responses at both local and distant sites. Additionally, these metabolites demonstrate potent antioxidant and anti-inflammatory activities. The levels of microbiota-derived TRP metabolites are intricately linked to the gut microbiota's health, which, in turn, can be influenced by age-related changes. This review aims to comprehensively summarize the cellular and molecular impacts of tryptamine and IPA on health and aging-related complications. Furthermore, we explore the levels of tryptamine and IPA and their corresponding bacteria in select diseased conditions, shedding light on their potential significance as biomarkers and therapeutic targets.