Search

Wound healing involves a carefully regulated sequence of events, encompassing pro-inflammatory and anti-inflammatory stages, tissue regeneration, and remodeling. However, in individuals with diabetes, this process gets disrupted due to dysregulation caused by elevated glucose levels and pro-inflammatory cytokines in the bloodstream. Consequently, the pro-inflammatory stage is prolonged, while the anti-inflammatory phase is delayed, leading to impaired tissue regeneration and remodeling with extended healing time. Furthermore, the increased glucose levels in open wounds create an environment conducive to microbial growth and tissue sepsis, which can escalate to the point of limb amputation. Managing diabetic wounds requires meticulous care and monitoring due to the lack of widely available preventative and therapeutic measures. Existing clinical interventions have limitations, such as slow recovery rates, high costs, and inefficient drug delivery methods. Therefore, exploring alternative avenues to develop effective wound-healing treatments is essential. Nature offers a vast array of resources in the form of secondary metabolites, notably polyphenols, known for their antimicrobial, anti-inflammatory, antioxidant, glucose-regulating, and cell growth-promoting properties. Additionally, nanoparticles synthesized through environmentally friendly methods hold promise for wound healing applications in diabetic and non-diabetic conditions. This review provides a comprehensive discussion and summary of the potential wound-healing abilities of specific natural polyphenols and their nanoparticles. It explores the mechanisms of action underlying their efficacy and presents effective formulations for promoting wound-healing activity. [ABSTRACT FROM AUTHOR]

The gut microbiota and its secreted metabolites play a significant role in cardiovascular and musculoskeletal health and diseases. The dysregulation of the intestinal microbiota poses a significant threat to cardiovascular and skeletal muscle well-being. Nonetheless, the precise molecular mechanisms underlying these changes remain unclear. Furthermore, microgravity presents several challenges to cardiovascular and musculoskeletal health compromising muscle strength, endothelial dysfunction, and metabolic changes. The purpose of this review is to critically examine the role of gut microbiota metabolites on cardiovascular and skeletal muscle functions and dysfunctions. It also explores the molecular mechanisms that drive microgravity-induced deconditioning in both cardiovascular and skeletal muscle. Key findings in this review highlight that several alterations in gut microbiota and secreted metabolites in microgravity mirror characteristics seen in cardiovascular and skeletal muscle diseases. Those alterations include increased levels of Firmicutes/Bacteroidetes (F/B) ratio, elevated lipopolysaccharide levels (LPS), increased in para-cresol (p-cresol) and secondary metabolites, along with reduction in bile acids and Akkermansia muciniphila bacteria. Highlighting the potential, modulating gut microbiota in microgravity conditions could play a significant role in mitigating cardiovascular and skeletal muscle diseases not only during space flight but also in prolonged bed rest scenarios here on Earth. [ABSTRACT FROM AUTHOR]

The global COVID-19 pandemic, caused by SARS-CoV-2, has created an urgent need for novel antiviral agents, as it has led to a devastating loss of lives worldwide. In response, numerous vaccines were developed in 2022, with ongoing efforts for more candidates. Despite significant progress, reports of vaccine-related issues and side effects have emerged. The effectiveness of COVID-19 vaccines has been challenged by new viral variants, a lack of well-designed in vivo experiments, and randomised controlled trials. Currently, no clinically approved antiviral medications exist for treating COVID-19. However, a few broad-spectrum antiviral drugs have shown promising outcomes in clinical studies. Many scientists believe that natural compounds derived from herbal medicines and mushrooms could offer substantial benefits to COVID-19 patients. Ganoderma, known for its traditional use in promoting health and longevity, has a rich history of therapeutic applications and dietary supplementation. Numerous epidemiological and clinical studies have demonstrated that Ganoderma and its derivatives can enhance innate and adaptive immune responses against various pathogens, including viruses, in laboratory settings and living organisms. Therefore, the secondary metabolites in Ganoderma, such as triterpenoids, polysaccharides, and glycoproteins, hold significant potential for developing novel antiviral drugs. These compounds have demonstrated various antiviral mechanisms, including inhibition of viral replication, modulation of immune responses, and direct virucidal effects. Given the ongoing search for effective treatments against COVID-19, Ganoderma and its bioactive compounds stand out as promising candidates for further research and development. Their multifaceted antiviral mechanisms make them suitable for exploration as therapeutic agents against SARS-CoV-2, potentially contributing to developing novel antiviral drugs and enhancing the effectiveness of existing treatments. [ABSTRACT FROM AUTHOR]

Introduction: Biofouling poses a significant economic threat to various marine industries, leading to financial losses that can reach billions of euros annually. This study highlights the urgent need for effective alternatives to traditional antifouling agents, particularly following the global ban on organotin compounds. Material and methods: Streptomyces aculeolatus PTM-346 was isolated from sediment samples on the shores of the Madeira Archipelago, Portugal. The crude extract was fractionated using silica flash chromatography and preparative HPLC, resulting in two isolated marinone compounds: madeirone (1), a novel marinone derivative discovered in this study, and neomarinone (2). The antifouling activities of these compounds were tested against five marine bacterial species and the larvae of the mussel Mytilus galloprovincialis. Additionally, in silico and in vivo environmental toxicity evaluations of madeirone (1) and neomarinone (2) were conducted. Results: Madeirone (1) demonstrated significant antibiofilm efficacy, inhibiting Phaeobacter inhibens by up to 66%, Marinobacter hydrocarbonoclasticus by up to 60%, and Cobetia marina by up to 40%. Neomarinone (2) also exhibited substantial antibiofilm activity, with inhibition rates of up to 41% against P. inhibens, 40% against Pseudo-oceanicola batsensis, 56% against M. hydrocarbonoclasticus, 46% against C. marina, and 40% against Micrococcus luteus. The growth inhibition activity at the same concentrations of these compounds remained below 20% for the respective bacteria, highlighting their effectiveness as potent antibiofilm agents without significantly affecting bacterial viability. Additionally, both compounds showed potent effects against the settlement of Mytilus galloprovincialis larvae, with EC50 values of 1.76 μg/mL and 0.12 μg/mL for compounds (1) and (2), respectively, without impairing the viability of the targeted macrofouling species. In silico toxicity predictions and in vivo toxicity assays both support their potential for further development as antifouling agents. Conclusion: The newly discovered metabolite madeirone (1) and neomarinone (2) effectively inhibit both microand macrofouling. This distinct capability sets them apart from existing commercial antifouling agents and positions them as promising candidates for biofouling prevention. Consequently, these compounds represent a viable and environmentally friendly alternative for incorporation into paints, primers, varnishes, and sealants, offering significant advantages over traditional copper-based compounds. [ABSTRACT FROM AUTHOR]

Bacterial small molecule metabolites such as adenosine-diphosphate-d-glycero-β-d-manno-heptose (ADP-heptose) and their derivatives act as effective innate immune agonists in mammals. We show that functional nucleotide-diphosphate-heptose biosynthetic enzymes (HBEs) are distributed widely in bacteria, archaea, eukaryotes, and viruses. We identified a conserved STTR5 motif as a hallmark of heptose nucleotidyltransferases that can synthesize not only ADP-heptose but also cytidine-diphosphate (CDP)– and uridine-diphosphate (UDP)–heptose. Both CDP- and UDP-heptoses are agonists that trigger stronger alpha-protein kinase 1 (ALPK1)–dependent immune responses than ADP-heptose in human and mouse cells and mice. We also produced ADP-heptose in archaea and verified its innate immune agonist functions. Hence, the β-d-manno-heptoses are cross-kingdom, small-molecule, pathogen-associated molecular patterns that activate the ALPK1-dependent innate immune signaling cascade. [ABSTRACT FROM AUTHOR]

Solanum xanthocarpum fruits are used in the treatment of cough, fever, and heart disorders. It possesses antipyretic, hypotensive, antiasthmatic, aphrodisiac and antianaphylactic properties. In the present study, 24 elicitors (both biotic and abiotic) were used to enhance the production of glycoalkaloids in cell cultures of S. xanthocarpum. Four concentrations of elicitors were added into the MS culture medium. The maximum accumulation (5.56-fold higher than control) of demissidine was induced by sodium nitroprusside at 50 mM concentration whereas the highest growth of cell biomass (4.51-fold higher than control) stimulated by systemin at 30 mM concentration. A total of 17 genes of biosynthetic pathways of glycoalkaloids were characterized from the cells of S. xanthocarpum. The greater accumulation of demissidine was confirmed with the expression analysis of 11 key biosynthetic pathway enzymes e.g., acetoacetic-CoA thiolase, 3- hydroxy 3-methyl glutaryl synthase, β-hydroxy β-methylglutaryl CoA reductase, mevalonate kinase, farnesyl diphosphate synthase, squalene synthase, squalene epoxidase, squalene-2,3- epoxide cyclase, cycloartenol synthase, UDP-glucose: solanidine glucosyltransferase and UDP-rhamnose: solanidine rhamno-galactosyl transferase. The maximum expression levels of UDP-rhamnose: solanidine rhamno-galactosyl transferase gene was recorded in this study. • Solanum xanthocarpum fruits are used in the treatment of cough, and heart disorders. • It possesses antipyretic, hypotensive, and aphrodisiac properties. • Elicitation is used for increasing the production of secondary metabolites. • Four concentrations of elicitors were added into the MS culture medium. • The maximum accumulation of demissidine was induced by sodium nitroprusside. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Multidrug‐resistant bacteria in humans have prompted the search for alternative solutions derived from herbal medicines that can substitute antibiotics in livestock production. Thus, the goal of this study was to evaluate the phytogenic properties of Marrubium vulgare infusion (MVI) on weaned pigs. Thirty animals were randomly divided into five groups of six animals, each receiving a physiological solution, clenbuterol and the infusion extract at doses of 0.01 (MVI 1%), 0.1 (MVI 10%) and 0.2 (MVI 20%) mg kg−1 for 28 days. Biochemical parameters and the liquid chromatographic–electrospray ionization–mass spectrometric (LC‐ESI‐MS) chemical profiles of the infusion extract and animal serum were studied.The doses MVI 1 and 10% led to weight gain higher than the controls. No significant changes were noted in the biochemical parameters including erythrocytes, hemoglobin, hematocrit, mean corpuscular volume and others. Evaluation of enzymatic levels in blood revealed no significant changes. LC‐ESI‐MS data of MVI showed the presence of 34 secondary metabolites, and successive chromatographic purification of MVI yielded marrubiin and apigenin as major components. LC‐ESI‐MS data of animal serum showed the presence of a diterpene, a flavonoid and diverse cholic acid derivatives.Results indicated the doses MVI 1 and 10% promote weight gain with no significant alterations in blood biochemicals, and liver and kidney function. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

NMR (Nuclear Magnetic Resonance) spectroscopy is a well-established technique for elucidating the structure and composition of Natural Products (NP). However, while NMR spectra offer qualitative insights, there is often a growing demand within the NP research community for quantitative analysis using NMR techniques. Unfortunately, this demand is sometimes met with misconceptions and lacks the methodological rigor typically associated with analytical procedures, particularly concerning validation and mandatory adjustments of quantitative NMR (qNMR) parameters. Therefore, this minireview highlights the practical approaches concerning preparation and validation for qNMR analyses of plant extracts. Specifically, we provide a concise protocol detailing experimental settings crucial for ensuring the accuracy and reliability of quantitative measurements. It is noteworthy that such guidance is often absent in existing literature, and our minireview wants to bridge this gap by offering clear methodological recommendations. [ABSTRACT FROM AUTHOR]

Antibiotics resistance is a clear threat to the future of current tuberculosis treatments like rifampicin, prompting the need for new treatment options in this field. While plants can offer a plethora of chemical diversity in their constitutive natural products to tackle this issue, finding potentially bioactive compounds in them has not always proven to be that simple. Classical bioactivity-guided fractionation approaches are still trendy, but they bear significant shortfalls, like their time-consuming nature as well as the everincreasing risk of isolating known bioactive compounds. In this regard, we have developed an alternative method to the latter approach that allows for natural derivatives of a known bioactive scaffold to be efficiently targeted and isolated within a large library of plant extracts. Hence our approach allows for the anticipation of bioactive structure independently of preliminary bioassays. By relying on the chemical diversity of a set of 1,600 plant extracts analyzed by HRMS/MS, we were able to isolate and characterize several minor derivatives of a previously reported bioactive aza-anthraquinone compound from Cananga brandisiana, selected within the plant set. Assessment of bioactivity on these derivatives (especially onychine, with an IC50 value of 39 μM in infection) confirmed their expected activity on Mycobacterium marinum in our antiinfective assay. This proof-of-concept study has established an original path towards bioactive compounds isolation, with the advantage of potentially highlighting minor bioactive compounds, whose activity may not even be detectable at the extract level. [ABSTRACT FROM AUTHOR]

Peptide natural products have a wide range of useful applications as pesticides, veterinary agents, pharmaceuticals, and bioproducts. To discover new natural products, manipulate them for analog generation, and to harness the potential of these bioactive compounds for synthetic biology, it is necessary to develop robust methods for the expression of biosynthetic genes. Cell-free synthetic biology is emerging as an important complementary approach because it is highly desirable to express protein on a more rapid timescale and does not rely upon the genetic tractability of a strain thus improving the throughput of design-buildtest-learn cycles. Additionally, generating metabolites outside the cell can overcome issues such as cellular toxicity which can hamper applications like antibiotic development. In this review, we focus on the cell-free production of peptide natural products generated by non-ribosomal peptide synthetase. Nonribsomal peptides are biosynthesized by non-ribosomal peptide synthetases which are large "mega" enzymes that provide specific challenges to heterologous expression. First, we summarize NRPSs and their corresponding peptide metabolites that are expressed in cell-free systems. With that, we discuss the requirements and challenges to express such large proteins in cell-free protein synthesis as well as host machineries that have been developed for cell-free protein synthesis that could be particularly relevant to generating non-ribosomal peptide metabolites in the future. The development of cellfree systems can then be used for prototyping to accelerate efforts towards engineered biosynthesis of these complex pathways. [ABSTRACT FROM AUTHOR]

Brazil is one of the most biodiverse countries in the world, with a coastline that stretches over 7,000 km including various marine ecosystems, such as coral reefs, mangroves, and seagrass beds, among other habitats. These diverse environments provide a rich source of compounds, derived from primary or secondary metabolism, which may have countless biological activities. Research onmarine natural products (MNP) in Brazil has been ongoing for several decades and led to the discovery of numerous bioactive compounds with potential applications in medicine, agriculture, and cosmetics. These MNP are structurally complex, both from an architectural and stereochemical point of view. However, even with all the well-established techniques for the absolute configuration (AC) assignment, this stage of structural characterization of natural products is still under-explored and remains a challenge. This review presents an overview of natural product chemistry in Brazil, focusing on the stereochemical assignment of marine chiral compounds. The main goals are to describe the techniques employed in the assignments as well as to highlight the importance of choosing the appropriate methods for chiral natural products AC determinations. [ABSTRACT FROM AUTHOR]

Introduction: Cistanche salsa (C.A.Mey.) G. Beck is a perennial holoparasitic herb recognized for its medicinal properties, particularly in kidney-tonifying and laxative treatments. Despite its therapeutic potential, little is known about the endophyte communities inhabiting C. salsa and its host plants, and how these microorganisms may impact the production and accumulation of metabolites in C. salsa. Methods: We conducted a dual analysis focusing on metabolomics of wild C. salsa and microbiome characterization of both C. salsa and its host plant, Kalidium foliatum (Pall.) Moq. The metabolomics analysis revealed variations in metabolite composition across different parts of C. salsa. Additionally, the microbiome analysis involved studying endophytic bacteria and fungi, comparing their community structures between parasitic C. salsa and its host plant. Results: Significant variations in metabolite composition were observed through metabolomic profiling, which identified 93 secondary metabolites and 398 primary metabolites across various parts of C. salsa. Emphasis was placed on differences in metabolite composition within the flowers. Microbiome analysis revealed differential community compositions of endophytic bacteria between the parasitic and host plants, whereas differences in endophytic fungi were less pronounced. Certain endophytes, such as Bacteroidota, Proteobacteria, Ascomycota, and Basidiomycota, were associated with the production of specific secondary metabolites in C. salsa, including the plant-specific compound salsaside. Discussion: Our findings highlight the intricate relationship between C. salsa and its endophytic microbiota, suggesting a potential role of these microorganisms in modulating the biosynthesis of bioactive compounds. The differential preferences of endophytic bacteria and fungi across various microenvironments within the parasitic plant system underscore the complexity of these interactions. Further elucidation of these dynamics could enhance our understanding of C. salsa's medicinal properties and its ecological adaptations as a holoparasitic herb. [ABSTRACT FROM AUTHOR]

Macrobrachium nipponense is an important commercial freshwater species in China. However, the ability of alkali tolerance of M. nipponense is insufficient to culture in the major saline-alkali water source in China. Thus, it is urgently needed to perform the genetic improvement of alkali tolerance in this species. In the present study, we aimed to analyse the effects of alkali treatment on gills in this species after 96 h alkalinity exposure under the alkali concentrations of 0 mmol/L, 4 mmol/L, 8 mmol/L, and 12 mmol/L through performing the histological observations, measurement of antioxidant enzymes, metabolic profiling analysis, and transcriptome profiling analysis. The results of the present study revealed that alkali treatment stimulated the contents of malondialdehyde, glutathione, glutathione peroxidase in gills, indicating these antioxidant enzymes plays essential roles in the protection of body from the damage, caused by the alkali treatment. In addition, high concentration of alkali treatment (> 8 mmol/L) resulted in the damage of gill membrane and haemolymph vessel, affecting the normal respiratory function of gill. Metabolic profiling analysis revealed that Metabolic pathways, Biosynthesis of secondary metabolites, Biosynthesis of plant secondary metabolites, Microbial metabolism in diverse environments, Biosynthesis of amino acids were identified as the main enriched metabolic pathways of differentially expressed metabolites, which are consistent with the previous publications, treated by the various environmental factors. Transcriptome profiling analyses revealed that the alkali concentration of 12 mmol/L has more regulatory effects on the changes of gene expression than the other alkali concentrations. KEGG analysis revealed that Phagosome, Lysosome, Glycolysis/Gluconeogenesis, Purine Metabolism, Amino sugar and nucleotide sugar metabolism, and Endocytosis were identified as the main enriched metabolic pathways in the present study, predicting these metabolic pathways may be involved in the adaption of alkali treatment in M. nipponense. Phagosome, Lysosome, Purine Metabolism, and Endocytosis are immune-related metabolic pathways, while Glycolysis/Gluconeogenesis, and Amino sugar and nucleotide sugar metabolism are energy metabolism-related metabolic pathways. Quantitative PCR analyses of differentially expressed genes (DEGs) verified the accuracy of the RNA-Seq. Alkali treatment significantly stimulated the expressions of DEGs from the metabolic pathways of Phagosome and Lysosome, suggesting Phagosome and Lysosome play essential roles in the regulation of alkali tolerance in this species, as well as the genes from these metabolic pathways. The present study identified the effects of alkali treatment on gills, providing valuable evidences for the genetic improvement of alkali tolerance in M. nipponense. [ABSTRACT FROM AUTHOR]

Over the past two decades, numerous techniques have been developed for analysing microRNAs in body fluids and tissues. However, these techniques still face technical challenges, particularly when compared to well-established techniques for proteins and metabolites. Recently, the ODG platform was introduced, which is an innovative technology that allows for the direct detection and quantification of microRNAs in liquid biopsies without requiring extraction or amplification. This study presents the implementation of the ODG platform within a semi-automated protocol to create the "SA-ODG" platform, enhancing the efficiency and precision of microRNA testing while reducing hands-on time required by laboratory staff. For the first time, the SA-ODG platform has been used to directly quantify microRNAs in solid tissues. The results demonstrate precise analysis of miR-122-5p in mouse liver tissues using SA-ODG. These developments represent a crucial step forward in advancing the field of extraction and amplification-free microRNA detection and quantification. [ABSTRACT FROM AUTHOR]

As a plant classified under the “medicine food homology” concept, garlic offers various health benefits and comes in many different varieties. In this study, the metabolite composition of different garlic varieties were analyzed using LC–MS/MS quadrupole‐Orbitrap mass spectrometry and ICP‐MS. A total of 30 chemical elements and 1256 metabolites were identified. Significant differences in chemical elements and metabolomics profiles were observed among the five garlic groups (VIP > 1.5). Compared to WG, PG contained 5 unique compounds, HG had 15 unique compounds, SCG had 18 unique compounds, and SBG had 26 unique compounds. Furthermore, the results showed that WG had smaller differences with PG and HG, but significant differences with SBG and SCG. KEGG analysis revealed metabolic pathways associated with the formation of differential metabolites. These findings uncover the differences and mechanisms in the composition of various garlic varieties, providing a theoretical foundation for distinguishing the nutritional components of different garlic types. [ABSTRACT FROM AUTHOR]

A novel dual PI3K α/δ inhibitor, TQ‐B3525, has been developed for the targeted treatment of lymphoma and solid tumors. TQ‐B3525 is primarily metabolized by CYP3A4 and FOM3, while also serving as a substrate for the P‐glycoprotein transporter. The aim of this study was to anticipate the drug–drug interaction (DDI) of TQ‐B3525 and its two metabolites with CYP3A4 enzyme potent inducer (rifampicin) and CYP3A4/P‐gp inhibitor (itraconazole) utilizing a physiologically based pharmacokinetic (PBPK) modeling approach. Clinical data from healthy and cancer patient adults were employed to construct and evaluate the PBPK model for TQ‐B3525, M3, and M8‐3. Models involving rifampicin combined with midazolam, itraconazole combined with midazolam or digoxin were utilized to showcase the robustness of evaluating DDI effects. The simulated drug exposure of TQ‐B3525, M3, and M8‐3 in healthy and patient adults were consistent with clinical data, and the mean fold error values were within the acceptable ranges. The simulated results of positive substrates correspond to those reported in the literature. Co‐administration with rifampicin reduces Cmax and AUC of TQ‐B3525 to 76.1% and 46.0%, while increasing the levels of M3 and M8‐3. With itraconazole, Cmax and AUC of TQ‐B3525 rise to 131% and 204%, but decrease substantially for M3 and M8‐3. PBPK model simulation results showed that the systemic exposure of TQ‐B3525 was significantly affected when co‐administered with CYP3A4/P‐gp inducers and inhibitors. This indicates that the combination with strong inducers and inhibitors should be carefully avoided or adjust the dosage of TQ‐B3525 in clinic. [ABSTRACT FROM AUTHOR]

Viral diseases pose a serious global health threat due to their rapid transmission and widespread impact. The RNA-dependent RNA polymerase (RdRp) participates in the synthesis, transcription, and replication of viral RNA in host. The current study investigates the antiviral potential of secondary metabolites particularly those derived from bacteria, fungi, and plants to develop novel medicines. Using a virtual screening approach that combines molecular docking and molecular dynamics (MD) simulations, we aimed to discover compounds with strong interactions with RdRp of five different retroviruses. The top five compounds were selected for each viral RdRp based on their docking scores, binding patterns, molecular interactions, and drug-likeness properties. The molecular docking study uncovered several metabolites with antiviral activity against RdRp. For instance, cytochalasin Z8 had the lowest docking score of –8.9 (kcal/mol) against RdRp of SARS-CoV-2, aspulvinone D (–9.2 kcal/mol) against HIV-1, talaromyolide D (–9.9 kcal/mol) for hepatitis C, aspulvinone D (–9.9 kcal/mol) against Ebola and talaromyolide D also maintained the lowest docking score of –9.2 kcal/mol against RdRp enzyme of dengue virus. These compounds showed remarkable antiviral potential comparable to standard drug (remdesivir –7.4 kcal/mol) approved to target RdRp and possess no significant toxicity. The molecular dynamics simulation confirmed that the best selected ligands were firmly bound to their respective target proteins for a simulation time of 200 ns. The identified lead compounds possess distinctive pharmacological characteristics, making them potential candidates for repurposing as antiviral drugs against SARS-CoV-2. Further experimental evaluation and investigation are recommended to ascertain their efficacy and potential. [ABSTRACT FROM AUTHOR]

Engineered nanoparticles (NPs) pose a broad spectrum of interesting properties that make them useful for many applications. However, continuous exposure to NPs requires the need to deeply understand the outcomes when these NPs interact with different biological environments. After exposure within (to) these environments, the pristine surfaces of NPs strongly interact with the molecules from the surrounding medium, including metabolites, lipids, glycan, and proteins, forming the so-called protein corona (PC). It is well established that the NP-PC strongly influences the biological fate of various NPs types, including cellular uptake, toxicity, and biodistribution. Thus, for a proper assessment of potential hazards associated with engineered NPs, it is mandatory to study and evaluate the PC that forms around NPs. Herein, we describe protocols in detail for the isolation and characterization of NP-PC complexes and cover the following aspects: 1) isolation protocols for different nanomaterials in a range of exposing media, including magnetic isolation methods for superparamagnetic NPs, 2) NP physicochemical characterization using advanced and standard techniques available in regular laboratories, and 3) NP-PC characterization of the protein and glycan components. [ABSTRACT FROM AUTHOR]

The antiviral agent amantadine is frequently detected in seawater and marine organisms. Because of increasing concentrations, amantadine has become a contaminant of emerging concern. This compound has toxic effects on the brown algae Laminaria japonica. The effects of amantadine on the biological processes of L. japonica and the corresponding toxic mechanisms remain unclear. In this study, amantadine toxicity on L. japonica was investigated using histopathological and physiological characteristics combined with metabolomics analysis. Changes in metabolites were determined by untargeted metabolomics after exposure to 107 ng/L amantadine for 72 h. The catalase activity in the exposure group slightly increased, whereas the superoxide dismutase activity greatly decreased. An increase in the malondialdehyde concentration was observed after amantadine exposure, which suggested that lipid peroxidation and cell damage occurred. Metabolomics analysis showed that there were 406 differentially expressed metabolites after amantadine exposure. These were mainly phospholipids, amino acids, purines, and their derivatives. Inhibition of the glycerophospholipid metabolism affected the lipid bilayer and cell structure, which was aligned with changes in histological observation. Changes in amino acids led to perturbation of protein synthesis and induced oxidative stress through interference with glutathione metabolism and tyrosine metabolism. Amantadine also interfered with energymetabolismin L. japonica by disturbing the tricarboxylic acid cycle and purine metabolism. The results of this study provide new insights into the mechanism of amantadine toxicity on L. japonica. [ABSTRACT FROM AUTHOR]

In plants due to their sessile nature, secondary metabolites are important components against different abiotic and biotic stress, such as extended darkness. For this reason, the variation of secondary metabolite content of the Arabidopsis thaliana HapMap natural population following 0-and 6-d darkness treatment were detected and the raw data of different accessions at two timepoints were deposited in the Zenodo database. Moreover, the annotated secondary metabolites of these samples are presented in this data descriptor, which we believe will be a usefully re-usable resource for future integrative analysis with dark-treated transcripts, proteins or other phenotypic data in order to comprehensively illustrate the multiomic landscape of Arabidopsis in response to the stresses exerted by extended darkness. [ABSTRACT FROM AUTHOR]

Saponins are plant secondary metabolites comprising glycosylated triterpenoids, steroids or steroidal alkaloids with a broad spectrum of toxicity to microbial pathogens and pest organisms that contribute to basal plant defense to biotic attack. Secretion of glycosyl hydrolases that enzymatically convert saponins into less toxic products was thus far the only mechanism reported to enable fungal pathogens to colonize their saponin-containing host plant(s). We studied the mechanisms that the fungus Botrytis cinerea utilizes to be tolerant to well-characterized, structurally related saponins from tomato and Digitalis purpurea. By gene expression studies, comparative genomics, enzyme assays and testing a large panel of fungal (knockout and complemented) mutants, we unraveled four distinct cellular mechanisms that participate in the mitigation of the toxic activity of these saponins and in virulence on saponin-producing host plants. The enzymatic deglycosylation that we identified is novel and unique to this fungus-saponin combination. The other three tolerance mechanisms operate in the fungal membrane and are mediated by protein families that are widely distributed in the fungal kingdom. We present a spatial and temporal model on how these mechanisms jointly confer tolerance to saponins and discuss the repercussions of these findings for other plant pathogenic fungi, as well as human pathogens. Plant saponins are secondary metabolites with broad antimicrobial toxicity. Here, You et al. characterize the mechanisms by which the fungus Botrytis cinerea establishes tolerance to saponins. [ABSTRACT FROM AUTHOR]

The best environment for plant growth and development contains certain essential metabolites. A broad category of metabolites known as "plant biostimulants" (PBs) includes biomolecules such as proteins, carbohydrates, lipids, and other secondary metabolites related to groups of terpenes, specific nitrogen-containing compounds, and benzene ring-conjugated compounds. The formation of biomolecules depends on both biotic and abiotic factors, such as the release of PB by plants, animals, and microorganisms, or it can result from the control of temperature, humidity, and pressure in the atmosphere, in the case of humic substances (HSs). Understanding the genomic outputs of the concerned organism (may be plants or others than them) becomes crucial for identifying the underlying behaviors that lead to the synthesis of these complex compounds. For the purposes of achieving the objectives of sustainable agriculture, detailed research on PBs is essential because they aid in increasing yield and other growth patterns of agro-economic crops. The regulation of homeostasis in the plant-soil-microbe system for the survival of humans and other animals is mediated by the action of plant biostimulants, as considered essential for the growth of plants. The genomic size and gene operons for functional and regulation control have so far been revealed through technological implementations, but important gene annotations are still lacking, causing a delay in revealing the information. Next-generation sequencing techniques, such as nanopore, nanoball, and Illumina, are essential in troubleshooting the information gaps. These technical advancements have greatly expanded the candidate gene openings. The secondary metabolites being important precursors need to be studied in a much wider scale for accurate calculations of biochemical reactions, taking place inside and outside the synthesized living cell. The present review highlights the sequencing techniques to provide a foundation of opportunity generation for agricultural sustainability. [ABSTRACT FROM AUTHOR]

This work reports on the validation of a liquid chromatography–tandem mass spectrometric method for the simultaneous quantification of more than 700 mycotoxins and other secondary fungal metabolites and plant toxins in pasta, biscuits, crackers and musli. The "dilute and shoot" approach was found to be fully applicable to these complex matrices, as only 7–14% of the analytes exhibited significant matrix effects while recoveries of the extraction were outside the target range of 70–120% for only 26 compounds. Data on repeatability (based on 7 brands per matrix) and on intermediate precision was compliant to the related < 20% criterion for 95–98% and 99% of all analytes, respectively. The limits of quantification were much lower than the related regulatory limits set for mycotoxins in cereal products. Application of the method to 157 samples from the European market revealed the presence of enniatins and deoxynivalenol in the majority of the samples. No regulatory limits were exceeded except the sum of ergot alkaloids being higher in a few samples than the 50–150 µg/kg to be implemented as of July 2024. [ABSTRACT FROM AUTHOR]

Biliary atresia (BA) is a progressive fibroinflammatory disease affecting both the extrahepatic and intrahepatic bile ducts, potentially leading to chronic cholestasis and biliary cirrhosis. Despite its prevalence, the exact mechanisms behind BA development remain incompletely understood. Recent research suggests that the gut microbiota and its metabolites may play significant roles in BA development. This paper offers a comprehensive review of the changing characteristics of gut microbiota and their metabolites at different stages of BA in children. It discusses their influence on the host's inflammatory response, immune system, and bile acid metabolism. The review also explores the potential of gut microbiota and metabolites as a therapeutic target for BA, with interventions like butyrate and gut microbiota preparations showing promise in alleviating BA symptoms. While progress has been made, further research is necessary to untangle the complex interactions between gut microbiota and BA, paving the way for more effective prevention and treatment strategies for this challenging condition. [ABSTRACT FROM AUTHOR]

The gut microbiota is a complex ecosystem composed of many bacteria and their metabolites.It plays an irreplaceable role in human digestion, nutrient absorption, energy supply, fat metabolism, immune regulation, and many other aspects. Exploring the structure and function of the gut microbiota, as well as their key genes and metabolites, will enable the early diagnosis and auxiliary diagnosis of diseases, new treatment methods, better effects of drug treatments, and better guidance in the use of antibiotics. The identification of gut microbiota plays an important role in clinical diagnosis and treatment, as well as in drug research and development. Therefore, it is necessary to conduct a comprehensive review of this rapidly evolving topic. Traditional identification methods cannot comprehensively capture the diversity of gut microbiota. Currently, with the rapid development of molecular biology, the classification and identification methods for gut microbiota have evolved from the initial phenotypic and chemical identification to identification at the molecular level. This review integrates the main methods of gut microbiota identification and evaluates their application. We pay special attention to the research progress on molecular biological methods and focus on the application of high-throughput sequencing technology in the identification of gut microbiota. This revolutionary method for intestinal flora identification heralds a new chapter in our understanding of the microbial world. [ABSTRACT FROM AUTHOR]

Objective: To investigate effect of Yiqi Huoxue Huazhuo Jiedu Prescription （YHHJP） on inflammatory factors of brain tissues, tight junction between brain and colon tissues, intestinal flora and bacterial metabolites in cerebral ischemia reperfusion injury （CIRI） rats based on brain-gut axis. Methods: Fifty male SD rats of SPF grade were randomly divided into sham-operation group （Sham）, model group （MCAO）, low, medium, high doses YHHJP groups （TCM-L/TCM-M/TCM-H）. Middle cerebral artery occlusion model was established according to Zea Longa methods. Neurological function defects were detected 3 days after administration. TTC staining was used to calculate infarct size of brain tissue. Pathological changes of brain tissue were observed by Nissl staining, and pathological changes of brain and colon tissues were observed by HE staining. IL-1β, IL-6, TNF-α in brain tissue and LPS content in serum were detected by ELISA, and D-LA content in serum was detected by biochemical method. Gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1, Claudin-1 in colon tissue were studied by Real-time fluorescent quantitative PCR. Intestinal flora were detected by 16S rDNA high-throughput sequencing. Results: Compared with Sham group, pathological damage of brain and colon tissue were serious in MCAO group, intestinal flora structure was significantly different, neural function impairment was aggravated, infarct size was increased, IL-1β, IL-6, TNF-α contents in brain tissue, and LPS, D-LA contents in serum were increased, gene expressions of ZO-1 and Claudin-5 in brain tissue and gene expressions of ZO-1 and Claudin-1 in colon tissue were decreased significantly （P<0.05）. Compared with MCAO group, pathological damage of brain and colon tissue of rats were relieved in TCM-L, TCM-M, TCM-H groups, disturbance of intestinal microflora microecology was improved, neurological function impairment and infarct size were markedly decreased, IL-1β, IL-6, TNF-α contents in brain tissue were decreased, gene expressions of ZO-1 and Claudin-1 in colon tissue were increased significantly （P<0.05）; LPS and D-LA contents in serum were decreased in YHHJP medium and high doses groups, while gene expressions of ZO-1 and Claudin-5 in brain tissue were increased significantly （P< 0.05）. Conclusion: YHHJP has a good effect on improving CIRI, whose mechanism may be related to regulating diversity of intestinal flora, reducing release of intestinal bacterial metabolites LPS and D-LA, increasing gene expressions of tight junction proteins ZO-1, Claudin-5 and Claudin-1, and down-regulating secretion of proinflammatory cytokine. [ABSTRACT FROM AUTHOR]

Plants and insects have co-existed for almost 400 million years and their interactions can be beneficial or harmful, thus reflecting their intricate co-evolutionary dynamics. Many herbivorous arthropods cause tremendous crop loss, impacting the agro-economy worldwide. Plants possess an arsenal of chemical defenses that comprise diverse secondary metabolites that help protect against harmful herbivorous arthropods. In response, the strategies that herbivores use to cope with plant defenses can be behavioral, or molecular and/or biochemical of which salivary secretions are a key determinant. Insect salivary secretions/oral secretions (OSs) play a crucial role in plant immunity as they contain several biologically active elicitors and effector proteins that modulate plants' defense responses. Using this oral secretion cocktail, insects overcome plant natural defenses to allow successful feeding. However, a lack of knowledge of the nature of the signals present in oral secretion cocktails has resulted in reduced mechanistic knowledge of their cellular perception. In this review, we discuss the latest knowledge on herbivore oral secretion derived elicitors and effectors and various mechanisms involved in plant defense modulation. Identification of novel herbivore-released molecules and their plant targets should pave the way for understanding the intricate strategies employed by both herbivorous arthropods and plants in their interactions. [ABSTRACT FROM AUTHOR]

Sesquiterpene lactones (SL) represent a class of secondary metabolites found in the Asteraceae family, notable for their unique structures. The SL α‐santonin (1) and its derivatives are worthy of mention due to their diverse biological properties. Additionally, 4H‐chromenes and 4H‐chromones are appealing frameworks holding the capability to be used as structural motifs for new drugs. Furthermore, unambiguous structural elucidation is crucial for developing novel compounds for diverse applications. In this context, it is common to find in the literature molecules erroneously assigned. Therefore, the use of quantum mechanical calculations to simulate NMR chemical shifts has emerged as a valuable strategy. In this work, we conceived the synthesis of two halogenated 4H‐chromenediones derived from photosantonic acid (2), a photoproduct arising from irradiation of α‐santonin (1) in the ultraviolet region. The structure of the chlorinated and brominated products was determined by NMR analysis, with the aid of quantum mechanical calculations at the B3LYP/6‐311 + G(2d,p)//M062x/6‐31 + G(d,p) level of theory. All analyses were in agreement and led to the assignment of the brominated 4H‐chromene‐2,7‐dione as (3S,3aS,5aR,9bS)‐5a‐(2‐bromopropan‐2‐yl)‐3‐methyl‐3,3a,5,5a,8,9b‐hexahydro‐4H‐furo[2,3‐f]chromene‐2,7‐dione (11b) and of the chlorinated 4H‐chromene‐2,7‐dione as (3S,3aS,5aR,9bS)‐5a‐(2‐chloropropan‐2‐yl)‐3‐methyl‐3,3a,5,5a,8,9b‐hexahydro‐4H‐furo[2,3‐f]chromene‐2,7‐dione (12b). The diastereoselectivities of the reactions were explained based on products and intermediates formation energy calculated using B3LYP/6‐31 + G(d,p) as the level of theory. Structures 11b and 12b were identified as the thermodynamic and kinetic products of the reaction among all candidates. Consequently, the strategy utilized in this study is robust and successfully illustrates the use of quantum mechanical calculations in the structural elucidation of new compounds with potential applications as novel drugs or products. [ABSTRACT FROM AUTHOR]

Several natural compounds have been found to act as PPARγ agonists, thus regulating numerous biological processes, including the metabolism of carbohydrates and lipids, cell proliferation and differentiation, angiogenesis, and inflammation. Recently, Cladosporols, secondary metabolites purified from the fungus Cladosporium tenuissimum, have been demonstrated to display an efficient ability to control cell proliferation in human colorectal and prostate cancer cells through a PPARγ-mediated modulation of gene expression. In addition, Cladosporols exhibited a strong anti-adipogenetic activity in 3T3-L1 murine preadipocytes, preventing their in vitro differentiation into mature adipocytes. These data interestingly point out that the interaction between Cladosporols and PPARγ, in the milieu of different cells or tissues, might generate a wide range of beneficial effects for the entire organism affected by diabetes, obesity, inflammation, and cancer. This review explores the molecular mechanisms by which the Cladosporol/PPARγ complex may simultaneously interfere with a dysregulated lipid metabolism and cancer promotion and progression, highlighting the potential therapeutic benefits of Cladosporols for human health. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we screened a MYB transcription factor controlling the synthesis of linanol in Freesia hybrida. This transcription factor is functionally conservative and can play a role in regulating the expression of the linanol synthase gene in the model plant Arabidopsis, but the interaction with another bHLH type transcription factor eventually leads to different regulatory effects of the MYB regulator in Freesia hybrida and Arabidopsis. Acting as the most abundant and widely distributed volatile secondary metabolites in plants, terpenoids play crucial roles in diverse physiological regulations and metabolic processes. Terpene synthases play a decisive role in determining the composition and diversity of terpenoids. Though the regulation of terpene synthases has been extensively investigated across various plant species, limited studies have focused on the upstream transcriptional regulation of terpene synthases. In this study, we have identified linalool as the predominant volatile compound that is released gradually from Freesia hybrida flowers throughout flower blooming. In the context of the transcriptome, a typical MYB transcription factor, FhMYB108, was screened based on homologous gene comparison. FhMYB108 is capable of regulating the expression of FhTPS1, and both their expression levels showed gradual increase during flower opening. Moreover, FhMYB108 exerts a stimulatory effect on the transcription of Arabidopsis thaliana AtTPS14, while no significant increase in AtTPS14 expression is observed upon the stabilization of FhMYB108 in A. thaliana. The highly expressed AtMYC2 in A. thaliana could interact with FhMYB108 to suppress the activation of AtTPS14 by FhMYB108. The present study not only elucidates the regulatory mechanism underlying linalool synthesis but also discovers the synergistic effect of MYB and bHLH transcription factors in governing the biosynthesis of volatile terpenoids. [ABSTRACT FROM AUTHOR]

Simple Summary: Anise seeds offer nutritional and therapeutic benefits that are valuable to both animal and human health. This study investigated the ability of the endophytic Actinomycetota sp. JW0824 strain to biofortify anise seeds from Egypt, Tunisia, Syria, and Morocco. In this study, significant increases in the dry weight of seeds and oil yields were observed, along with enhancements in the levels of primary and secondary metabolites such as sugars, flavonoids, alkaloids, phenols, vitamins, and essential oils. The number of essential oil metabolic enzymes (PAL and DAHPS) was also consistently increased. The findings suggest that Actinomycetota sp. JW0824 could be used to enhance the yield and quality of anise seeds. Anise (Pimpinella anisum L.) seeds have various nutritional and therapeutic benefits and are thus considered a valuable addition to animal and human health. Hence, in this study, we aimed to induce the nutritive and biological value of anise seeds. To this end, the potential biofortification effect of the endophytic Actinomycetota sp. JW0824 strain, isolated during the fall of 2023 from the medicinal plant Achyranthes aspera, exhibiting natural distribution in the Jazan region of Saudi Arabia, was investigated in four varieties of anise seeds from Egypt, Tunisia, Syria, and Morocco. Results revealed significant increments (p < 0.05) in the seed dry weight percentage (DW%) and oil yields. In line with increased biomass accumulation, the metabolism of the primary and secondary metabolites was increased. There were differential increases in proteins, sugars, flavonoids, alkaloids, phenols, vitamins (e.g., β-carotene, ascorbic acid), and essential oil components (e.g., phenylpropanoids and monoterpenes), along with their precursor phenylalanine. Consistently, the activity of L-phenylalanine aminolyase (PAL) was increased in the Egyptian and Tunisian varieties at 83.88% and 77.19%, respectively, while 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) activity increased in all varieties, with a significant 179.31% rise in the Egyptian variety. These findings highlight the beneficial effects of Actinomycetota sp. JW0824 as a bioinoculant for anise seeds, suggesting its potential application in agricultural practices to improve seed yield and quality. Further field trials are recommended to assess the commercial viability of this endophyte for enhancing anise seed production and potentially benefiting other plant species. [ABSTRACT FROM AUTHOR]

Purpose: The impact of dietary nutrients on body growth performance and the composition of gut microbes and metabolites is well-established. In this study, we aimed to determine whether dietary protein can regulate the physiological indexes and changes the intestinal tissue morphology in rats, and if dietary protein was a crucial regulatory factor for the composition, function, and metabolic pathways of the gut microbiota. Method: A total of thirty male Sprague Dawley (SD) rats (inbred strain, weighted 110 ± 10 g) were randomly assigned to receive diets containing animal-based protein (whey protein, WP), plant-based protein (soybean protein, SP), or a blended protein (soybean-whey proteins, S-WP) for a duration of 8 weeks. To investigate the effects of various protein supplement sources on gut microbiota and metabolites, we performed a high throughput 16S rDNA sequencing association study and fecal metabolomics profiling on the SD rats. Additionally, we performed analyses of growth indexes, serum biochemical indexes, and intestinal morphology. Results: The rats in S-WP and WP group exhibited a significantly higher body weight and digestibility of dietary protein compared to the SP group (P < 0.05). The serum total protein content of rats in the WP and S-WP groups was significantly higher (P < 0.05) than that in SP group, and the SP group exhibited significantly lower (P < 0.05) serum blood glucose levels compared to the other two groups. The morphological data showed the rats in the S-WP group exhibited significantly longer villus height and shallower crypt depth (P < 0.05) than the SP group. The gut microbial diversity of the SP and S-WP groups exhibited a higher level than that of the WP group, and the microbiomes of the WP and S-WP groups are more similar compared to those of the SP group. The Arachidonic acid metabolism pathway is the most significant KEGG pathway when comparing the WP group and the SP group, as well as when comparing the SP group and the S-WP group. Conclusion: The type of dietary proteins exerted a significant impact on the physiological indices of SD rats. Intake of S-WP diet can enhance energy provision, improve the body's digestion and absorption of nutrients, as well as promote intestinal tissue morphology. In addition, dietary protein plays a crucial role in modulating fecal metabolites by regulating the composition of the gut microbiota. Metabolomics analysis revealed that the changes in the levels of arachidonic acid metabolites and secondary bile acid metabolite induced by Clostridium_sensu_stricto_1 and [Eubacterium]_coprostanoligenes_group maybe the primarily causes of intestinal morphological differences. [ABSTRACT FROM AUTHOR]

Importance and objective: Self-reported caffeine consumption has been widely used in research while it may be subject to bias. We sought to investigate the associations between self-reported caffeine consumption and plasma levels of caffeine and its two main metabolites (paraxanthine and theophylline) in the community. Methods: Data from two population-based studies (SKIPOGH1 and 2 (N = 1246) and CoLaus|PsyCoLaus (N = 4461)) conducted in Switzerland were used. Self-reported caffeine consumption was assessed using questionnaires. Plasma levels of caffeine and its metabolites were quantified by ultra-high performance liquid chromatography coupled to a tandem quadrupole mass spectrometer. Results: In both studies, mean log plasma levels of caffeine and its two metabolites were over 6.48 (plasma levels = 652 ng/ml) when no caffeine consumption was reported. Subsequently, nonlinear associations between log plasma levels and self-reported caffeine consumption were observed in SKIPOGH, with a change of the slope at 3–5 cups of espresso per day in SKIPOGH1 but not SKIPOGH2. In CoLaus|PsyCoLaus, increased daily consumption of caffeinated beverages was associated with increased log plasma levels with a change of the slope at 3 cups. In both studies, declared caffeine consumption higher than 3–5 cups per day was not associated with higher plasma levels of caffeine and its metabolites. Conclusion: Self-reports of no or low caffeine consumption and consumption of more than 3–5 cups of coffee should be interpreted with caution, with possible under- or over-estimation. Quantifying plasma levels of caffeine and its metabolites may contribute to a better estimation of caffeine intake. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the most lethal gynecological malignancy and is often associated with both DNA repair deficiency and extensive metabolic reprogramming. While still emerging, the interplay between these pathways can affect ovarian cancer phenotypes, including therapeutic resistance to the DNA damaging agents that are standard‐of‐care for this tumor type. In this review, we will discuss what is currently known about cellular metabolic rewiring in ovarian cancer that may impact DNA damage and repair in addition to highlighting how specific DNA repair proteins also promote metabolic changes. We will also discuss relevant data from other cancers that could be used to inform ovarian cancer therapeutic strategies. Changes in the choice of DNA repair mechanism adopted by ovarian cancer are a major factor in promoting therapeutic resistance. Therefore, the impact of metabolic reprogramming on DNA repair mechanisms in ovarian cancer has major clinical implications for targeted combination therapies for the treatment of this devastating disease. [ABSTRACT FROM AUTHOR]

A host of metabolic enzymes reversibly self‐assemble to form membrane‐less, intracellular filaments under normal physiological conditions and in response to stress. Often, these enzymes reside at metabolic control points, suggesting that filament formation affords an additional regulatory mechanism. Examples include cytidine‐5′‐triphosphate (CTP) synthase (CTPS), which catalyzes the rate‐limiting step for the de novo biosynthesis of CTP; inosine‐5′‐monophosphate dehydrogenase (IMPDH), which controls biosynthetic access to guanosine‐5′‐triphosphate (GTP); and ∆1‐pyrroline‐5‐carboxylate (P5C) synthase (P5CS) that catalyzes the formation of P5C, which links the Krebs cycle, urea cycle, and proline metabolism. Intriguingly, CTPS can exist in co‐assemblies with IMPDH or P5CS. Since GTP is an allosteric activator of CTPS, the association of CTPS and IMPDH filaments accords with the need to coordinate pyrimidine and purine biosynthesis. Herein, a hypothesis is presented furnishing a biochemical connection underlying co‐assembly of CTPS and P5CS filaments – potent inhibition of CTPS by glutamate γ‐semialdehyde, the open‐chain form of P5C. [ABSTRACT FROM AUTHOR]

Pastoral agriculture underpins the New Zealand economy. Its success in generating export income is due to a mild and moist temperate climate, productive soils, innovative farmers supported by an effective research and development system, and an energy efficient production system based on year-round grazing. However, pastoral agriculture is entirely reliant on introduced pasture and forage species and their ability to withstand both endemic and introduced pasture pests. Critical to this is the mutualistic relationship between ryegrass and Epichloë fungal endophytes which provide a range of secondary metabolites that deter herbivory by both ruminants and insect pests. The challenge has been to identify and commercialise Epichloë strains which while providing protection against insect pests, ensuring ryegrass persistence, do not cause animal health and welfare issues. The critical role that Epichloë fungal endophytes play in maintaining pasture persistence and as a result the pastoral economy of New Zealand will be reviewed. [ABSTRACT FROM AUTHOR]

In this paper, the first complete phytochemical analysis of an Italian specimen of Araucaria cunninghamii Mudie led to the identification of six secondary metabolites, one of which was identified in the species for the first time. The chemophenetic and ethnobotanical evaluations of this specimen are widely discussed. [ABSTRACT FROM AUTHOR]

Growth years are important factors that affect the accumulation of secondary metabolites in Eurycoma longifolia roots. This study aimed to investigate the effect of different growth years on the metabolites and gene expression of E. longifolia roots and hairy root cultures. To achieve this, metabolite profiles and candidate transcripts of terpenoid backbone biosynthesis and sesquiterpenoid and triterpenoid pathways of 1- and 11-year old E. longifolia roots and hairy root cultures were obtained and integrated using partial least squares (PLS). Integration of eighty-two metabolites and forty-five selected candidate genes using PLS successfully differentiated 1-, 11-year-old E. longifolia roots and hairy root cultures, indicating significant metabolite-gene expression differences in response to different growth years and root types. Amino acids, 2-C-methyl-D-erythritol-4-phosphate cytidylyl-transferase (MCT) and acetyl-CoA C-acetyltransferase (AACT) were responsible for the discrimination of 1-year-old E. longifolia root. Quassinoids of eurycomanone and eurycomalactone and genes linked to the upstream synthesis in mevalonate (MVA) pathway contributed to the discrimination of the11-year-old E. longifolia root. 11-hydroxycanthin-6-one and genes that participate in the methylerythritol phosphate (MEP) pathway upstream of terpenoid biosynthesis were responsible for the discrimination of E. longifolia hairy root cultures. [ABSTRACT FROM AUTHOR]

Purpose: Saliva is often used as a tool for identifying systemic diseases because of the noninvasive nature of its collection. Moreover, salivary metabolites can be potential predictive factors for postoperative survival. We conducted the present study to establish whether salivary metabolites can function as predictive biomarkers for lung surgery complications. Methods: Unstimulated salivary samples were collected from 412 patients before lung surgery. Salivary metabolites were analyzed comprehensively by capillary electrophoresis mass spectrometry. Clinical data with the discriminatory ability of biomarkers were assessed to predict lung surgery complications using multivariate logistic regression analysis. The primary endpoint was the risk factors for postoperative complications of Clavien–Dindo grade ≥ III. Results: Postoperative complications of Clavien–Dindo grade ≥ III developed in 36 patients (8.7%). There was no postoperative 30-day mortality. Male sex (odds ratio [OR], 3.852; 95% confidence interval CI 1.455–10.199; p = 0.007) and salivary gamma-butyrobetaine (OR, 0.809; 95% CI 0.694–0.943; p = 0.007) were identified as significant risk factors for postoperative complications of Clavien–Dindo grade ≥ III. Conclusion: Salivary metabolites are potential noninvasive biomarkers for predicting postoperative complications of lung surgery. [ABSTRACT FROM AUTHOR]

Plant secondary metabolism is profoundly influenced by environmental stress. Low-temperature stress can induce the production of NO and ROS. The root of Astragalus membranaceus Bge. var. mongolicus Hsiao is commonly used as a medicinal herb in Asia. This study aimed to regulate the secondary metabolism and improve the quality of cultivated A. membranaceus var. mongolicus by subjecting it to different temperatures (5, 20, and 5/20°C). The activities and gene expressions of enzymes catalyzing the synthesis of secondary metabolites, including PAL, CHS, HMGR, SQS, were determined. Nitric oxide synthase (NOS) activity and the contents of NO, superoxide radical (), hydrogen peroxide (H2O2), and malondialdehyde (MDA) and five secondary metabolites were measured. Low-temperature stress of 5°C significantly increased NOS activities and NO contents, which led to a considerable surge in the levels of , H2O2, and MDA. Furthermore, the activities of SOD, CAT, and POD, increased rapidly and peaked on the 2nd and 3rd days. The gene expressions and activities of PAL, CHS, HMGR, and SQS were also markedly enhanced, which led to a substantial increase in all secondary metabolites. In the 5°C treatment group, calyculin-7-glucoside, ononin, calycosin, formononetin, and astragaloside IV were increased by 45.6, 36.6, 97.9, 123.4, and 74.9%, respectively, compared with the 20°C treatment group. Thus, low-temperature stress can significantly improve the secondary metabolism of A. membranaceus var. mongolicus, enhance the accumulation of medicinal chemical components, and augment the quality of the herb. [ABSTRACT FROM AUTHOR]

The problem of drug abuse is one of the most important scourges of society in our modern era, as its spread increases day after day in many countries of the world, and what makes matters worse is the emergence of new types of drugs whose chemical composition and source are unknown. There are many types of drugs, all of which pose serious health risks, the most important of which is addiction, which is represented by many behavioral and physiological phenomena and practices that develop upon repeated use of these narcotic substances. Mostly, it leads to a strong and urgent desire and need for continuous consumption and dependence on it in daily life, despite the harmful consequences that the addict suffers from, as well as the appearance of its withdrawal symptoms. Drugs include many types, some of which are extracted naturally from plants and some of which are chemically manufactured in laboratories. Without exception, all of them pose a real danger to physical and psychological health and may often lead to death. Narcotic substances are divided according to several factors, including their effect. On humans, the severity of addiction to it, as well as its chemical composition, etc. Plants produce a wide range of secondary metabolites as a defense as they strive to survive. These secondary metabolites include many alkaloids, most of which are used as narcotic substances. These chemicals often serve to deter plant-harming herbivores or to protect against pathogens and bush damage near plant roots, as well as to mitigate the effects of plantharming radiation. Interestingly, many of these chemical compounds have the ability to interact with the human body in specific ways, from organ failure and death to reactions that lead to useful and life-saving medications. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) encompass a diverse array of membrane-bound organelles released outside cells in response to developmental and physiological cell needs. EVs play important roles in remodeling the shape and content of differentiating cells and can rescue damaged cells from toxic or dysfunctional content. EVs can send signals and transfer metabolites between tissues and organisms to regulate development, respond to stress or tissue damage, or alter mating behaviors. While many EV functions have been uncovered by characterizing ex vivo EVs isolated from body fluids and cultured cells, research using the nematode Caenorhabditis elegans has provided insights into the in vivo functions, biogenesis, and uptake pathways. The C. elegans EV field has also developed methods to analyze endogenous EVs within the organismal context of development and adult physiology in free-living, behaving animals. In this review, we summarize major themes that have emerged for C. elegans EVs and their relevance to human health and disease. We also highlight the diversity of biogenesis mechanisms, locations, and functions of worm EVs and discuss open questions and unexplored topics tenable in C. elegans , given the nematode model is ideal for light and electron microscopy, genetic screens, genome engineering, and high-throughput omics. [ABSTRACT FROM AUTHOR]

Microbial metabolism has been deeply studied over decades and it is considered to be understood to a great extent. Annotated genome sequences of many microbial species have contributed a lot to generating biochemical knowledge on metabolism. However, researchers still discover novel pathways, unforeseen reactions or unexpected metabolites which contradict to the expected canon of biochemical reactions in living organisms. Here, we highlight a few examples of such non‐canonical pathways, how they were found, and what their importance in microbial biotechnology may be. The predictive power of metabolic modelling, well‐founded on biochemical knowledge and genomic information is discussed in the light of both discovery of yet unknown existing metabolic routes and the prediction of others, new to Nature. [ABSTRACT FROM AUTHOR]

Chassis strains, derived from Streptomyces coelicolor M145, deleted for one or more of its four main specialized metabolites biosynthetic pathways (CPK, CDA, RED and ACT), in various combinations, were constructed for the heterologous expression of specialized metabolites biosynthetic pathways of various types and origins. To determine consequences of these deletions on the metabolism of the deleted strains comparative lipidomic and metabolomic analyses of these strains and of the original strain were carried out. These studies unexpectedly revealed that the deletion of the peptidic clusters, RED and/or CDA, in a strain deleted for the ACT cluster, resulted into a great increase in the triacylglycerol (TAG) content, whereas the deletion of polyketide clusters, ACT and CPK had no impact on TAG content. Low or high TAG content of the deleted strains was correlated with abundance or paucity in amino acids, respectively, reflecting high or low activity of oxidative metabolism. Hypotheses based on what is known on the bio‐activity and the nature of the precursors of these specialized metabolites are proposed to explain the unexpected consequences of the deletion of these pathways on the metabolism of the bacteria and on the efficiency of the deleted strains as chassis strains. [ABSTRACT FROM AUTHOR]

Marine microorganisms are increasingly recognized as primary producers of marine secondary metabolites, drawing growing research interest. Many of these organisms are unculturable, posing challenges for study. Metagenomic techniques enable research on these unculturable microorganisms, identifying various biosynthetic gene clusters (BGCs) related to marine microbial secondary metabolites, thereby unveiling their secrets. This review comprehensively analyses metagenomic methods used in discovering marine microbial secondary metabolites, highlighting tools commonly employed in BGC identification, and discussing the potential and challenges in this field. It emphasizes the key role of metagenomics in unveiling secondary metabolites, particularly in marine sponges and tunicates. The review also explores current limitations in studying these metabolites through metagenomics, noting how long‐read sequencing technologies and the evolution of computational biology tools offer more possibilities for BGC discovery. Furthermore, the development of synthetic biology allows experimental validation of computationally identified BGCs, showcasing the vast potential of metagenomics in mining marine microbial secondary metabolites. [ABSTRACT FROM AUTHOR]

Cyanobacteria are important targets for biotechnological applications due to their ability to grow in a wide variety of environments, rapid growth rates, and tractable genetic systems. They and their bioproducts can be used as bioplastics, biofertilizers, and in carbon capture and produce important secondary metabolites that can be used as pharmaceuticals. However, the photosynthetic process in cyanobacteria can be limited by a wide variety of environmental factors such as light intensity and wavelength, exposure to UV light, nutrient limitation, temperature, and salinity. Carefully considering these limitations, modifying the environment, and/or selecting cyanobacterial species will allow cyanobacteria to be used in biotechnological applications. [ABSTRACT FROM AUTHOR]

• Exposure of medicinal plant samples to ambient air in the environmental conditions of Lubumbashi leads to mineral and microbial contamination. • The level of solar irradiation in Lubumbashi city leads to quantitative variations in phenolic compounds and terpenoids in fresh and dry samples of exposed medicinal plants. • Phytochemical variations caused by the studied drying conditions do not have a proportional impact on the studied biological activities. The quality of medicinal plant products is highly dependent on drying conditions, which can lead to contaminated drugs, and/or with considerable phytochemical and pharmacological variations. In Lubumbashi (a very sunny city with polluted air), the used medicinal plants are exposed to the sun and ambient air for drying or on the sales premises, but the real impact of solar energy and ambient air on the quality and pharmacological value of exposed medicinal plant samples has never been studied. This study seeks to determine the impact of solar irradiation and ambient air in Lubumbashi on the quality, and biological activities of samples from the most used medicinal plants in Lubumbashi/DR Congo. The root barks of single-plant samples from Terminalia mollis M.A.Lawson, Securidaca longepedunculata Fresen, Oldfieldia dactylophylla (Welw. ex Oliv.) J.Léonard. and Phyllanthus muellerianus (Kuntze) Exell. were dried in the sun, oven, and shade respectively. Mineral and microbial contamination were assessed. In addition, phytochemical and pharmacological analyses were also done. Samples exposure to ambient air led to mineral contamination, with the appearance of highly toxic elements such as As, and a significant increase in others such as Al, Co, Cr, Cu, Ni, and Pb. Microbial contamination exceeded admissible limits in some samples and varied according to drying conditions and species, of which S. longepedunculata was the most contaminated. The levels of total phenols, flavonoids, and terpenoids varied significantly according to drying conditions and species. For example, in T. mollis , total phenols increased from 457.6 ± 2.33 to 536.4 ± 1.56 mg GAEq/g in fresh samples exposed to the sun for 10 days, total flavonoids increased from 455.2 ± 16.49 to 617.1 ± 14.29 mg QEq/g when dry samples were exposed to the sun for 10 days; total terpenoids decreased significantly compared to the shade-dried sample. Biological activity also varied according to species and experimental conditions. For example, an increase in activity against S. aureus (from 11.00 ± 1.00 to 17.33 ± 0.58 mm) was observed in the fresh sample of P. muellerianus exposed to sunlight for 10 days, while increases in hemozoin synthesis inhibitory (from 44.6 ± 3.9 to 52.7 ± 2.4 %) and antiradical activity (from 23.7 ± 0.7 to 29.5 ± 0.1 %) were observed in the fresh S. longepedunculata sample exposed to the sun for 5 days. Exposure of the studied medicinal plant samples to ambient air in the environmental conditions of Lubumbashi would result in worrying mineral contamination and drying of these samples in the sun in the above-mentioned region, in the oven, or the shade would result in variations, some of which are negative, in certain secondary metabolites and biological activities. [ABSTRACT FROM AUTHOR]

• The optimum flower bud differentiation conditions were selected. • The changes of carbohydrate and hormone during flower bud differentiation were measured. • The change trend of GA 3 and IAA was consistent. Using the Phalaenopsis pulcherrima (P. pulcherrima) as the test material, the optimal conditions for flower bud differentiation were selected by setting different photoperiods and temperatures. The process of flower bud differentiation was observed, and changes in the content of carbohydrates, hormones, and other metabolites during flower bud differentiation were studied. The results showed that the optimum time of illumination was 16 h. d−1 and the temperature was 30 ℃ / 25 ℃. According to the characteristics of the flower bud development of P. pulcherrima , the differentiation process can be divided into six periods: the initial differentiation phase, inflorescence primordium differentiation phase, flower primordium differentiation phase, sepal primordium differentiation phase, petal primordium differentiation phase, and column and pollinia differentiation phase. The soluble sugar content in the leaves showed a trend of first increasing and then decreasing. The soluble sugar content was highest 30 days after the treatment, when the differentiation of the inflorescence primordium was completed. The starch content first decreased, then increased, and finally decreased. The starch content was lowest at 30 days of treatment and highest at 35 days. The soluble protein content in the leaves reached a maximum after 30 days of treatment. With the continuous differentiation of flower buds, the soluble protein content showed an overall decreasing trend. The zeatin (ZT) content reached a maximum at day 35, showing an overall decreasing trend from days 35 to 50 and reaching a minimum at day 50. The gibberellin (GA 3) and auxin (IAA) content first decreased and then increased during the process of flower bud differentiation. The changes in soluble sugar and soluble protein content during flower bud differentiation are consistent, while the changes in GA 3 and IAA are consistent. [ABSTRACT FROM AUTHOR]

• Equisetum diffusum modulates fatty acid metabolism to adapt at high altitudes. • PUFA content and unsaturation index of glycolipids enhance with increase in altitude. • Arachidonic acid contributes significantly to the change in PUFA content. • Antioxidant enzyme activity enhances at higher altitudes in response to combined stress. • Accumulation of osmolytes and secondary metabolites augments stress responsive effects. Equisetum diffusum D. Don, a perennial herb of Equisetaceae, is considered as native to the Himalayan mountain range. This plant has prolific distribution along different altitudes of Eastern Himalayan region. Generally, mountain flora, like E. diffusum, experience a combination of contrasting abiotic stresses and may represent a unique natural model for investigating physiological resilience to address climate change. So, the present study has been framed to compare the metabolic responses in E. diffusum growing at different elevation belts with an aim to understand the underlying basis for their high-altitude adjustment ability. The biochemical profiles of this plant, collected from three different altitudinal transects of Darjeeling hills, were compared. The fatty acid profiles of neutral lipids, membrane phospholipids and glycolipids demonstrated palmitic acid and oleic acid as the predominant fatty acids. The major outcome was the substantial increase of polyunsaturated fatty acids (PUFAs) and unsaturation index in glycolipids of the samples collected from higher altitudes. Major proportion of changes in PUFA content was contributed by arachidonic acid. Therefore, the plants homeostatically control the membrane fluidity by enhancing the unsaturation of glycolipid fatty acids. Moreover, significantly higher antioxidant enzyme activities in higher altitude samples reflect the involvement of these enzymes in coping with the oxidative stress condition and membrane damage. The stress responsive effects may be further augmented by enhanced content of secondary metabolites. Therefore, a combination of biochemical responses along with the changes in membrane plasticity can be predicted as the metabolic adjustment strategies for high-altitude adaptation of E. diffusum. [ABSTRACT FROM AUTHOR]

• A literature survey revealed that information about antidiabetic activities of Typha domingensis is not available. • For the first time, in-vitro, in-silico , and in-vivo antidiabetic activities were performed. • Chemical profiling was done with UHPLC-MS and HPLC-PDA. • The study provides scientific evidence that n-butanol fraction of T. domingensis has strong antidiabetic effects and after evaluation it can be used for treating diabetes. Typha is one of the valuable plant genera in folklore use in diabetes, and it can be a good source of bioactive chemicals. The current project was planned to investigate the pharmaceutical potential of n -butanol fraction of Typha domingensis Pers. (TDBF), a less explored medicinal plant. The phytochemical composition of the TDBF was assessed through a comprehensive analysis, encompassing the quantification of total bioactive contents (including total tannins and HPLC-PDA quantification) and a thorough exploration of secondary metabolites through scanning with UHPLC-MS. The pharmacological assessment included the determination of antioxidant activity (Total Antioxidant Capacity and Metal Chelating Assay), hemolytic potential, in-vitro antidiabetic effects (α-glucosidase and α-amylase inhibition, and antiglycation activity), as well as in-vivo antidiabetic activities. Molecular docking and ADMET studies were also performed for UHPLC-MS identified compounds. The TDBF showed 134.76 ± 8.23 mg TAE/g total tannin contents. With HPLC-PDA, p -Hydroxy benzoic acid and p -Coumaric acid were quantified. During UHPLC-MS scanning, a total of five bioactive metabolites were identified in the negative mode, while 54 were detected in the positive mode. The in-vivo assessment of antidiabetic activity revealed a notable reduction in blood glucose levels in diabetic rats following treatment with the extract, demonstrating its efficacy compared to the control groups. Furthermore, the extract exhibited a positive impact on renal and liver function, evidenced by lowered levels of serum urea, ALT, ALP, creatinine, and a decrease in serum cholesterol levels. The results of this study showed that Typha domingensis Pers. possesses a variety of bioactive compounds and demonstrates notable potential in regulating diabetes. The study recommends further investigation into isolating these bioactive phytochemicals for their potential therapeutic applications across various diseases. [ABSTRACT FROM AUTHOR]