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Polychlorinated biphenyls (PCBs) and their metabolites are linked to developmental neurotoxicity, but their levels in the gestational and lactational environment remain unexplored. This study investigated the effects of dietary exposure to the Fox River Mixture (FRM) on serum levels of PCBs and their metabolites in female C57BL/6 J mice. Mice were exposed to 0.1, 1.0, or 6.0 mg/kg body weight/day of FRM beginning two weeks before mating and throughout gestation and lactation. Serum samples collected from the dams at weaning were analyzed using gas chromatograph-tandem mass spectrometry and nontarget liquid chromatography-high resolution mass spectrometry. Results showed complex and dose-dependent differences in PCB and metabolite profiles. Untargeted metabolomics revealed alterations in metabolites involved in glucuronidation. Network analysis suggested disturbances in heme and amino acid metabolism associated with higher chlorinated PCBs. These findings suggested that PCBs and metabolites present in the gestational and lactation environment of mice may contribute to developmental neurotoxicity in rodents.

Caffeine is an ergogenic substance that is consumed globally in many forms. The use of buccally absorbable formulations instead of gastrointestinal uptake has become increasingly popular over the years, especially when accelerated absorption with minimal gastrointestinal stress is desired. This study investigated the impact of five different formulations and administration routes of caffeine on the whole blood concentrations of caffeine, paraxanthine, and theobromine: caffeinated capsules, tablets, shots, pouches, and chewing gums. A uniform dose of caffeine (200 mg) was administered to 16 healthy recreational athletes (26.0 ± 2.1 years) using a randomized crossover design. Samples were taken in the form of dried blood spots at 16 different time points in a 2-hr timeframe after drug administration. The samples were analyzed using a validated liquid chromatography–tandem mass spectrometry method. The results for caffeine showed no significant differences in the overall bioavailability (area under the concentration–time curve), maximal concentration, and time to maximum concentration. However, when analyzing the bioavailability of caffeine in the first 5, 10, and 15 min, the liquid caffeine formulation was superior to other administered forms (p <.05). This indicates that caffeine solubility has a major influence on its absorption rate. In sports, the rate of caffeine absorption must be considered, not only when ingesting anhydrous caffeine, but also when choosing buccal absorption. These findings imply that general guidelines for ergogenic caffeine use should consider the formulation used and, accordingly, the corresponding route of absorption. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effect of exercise intensity on the proportion and rate of carbohydrate oxidation and glucoregulatory hormone responses during recovery from exercise. Six physically active participants completed 1 hr of low-intensity (LI; 50% lactate threshold) or moderate-intensity (MI; 100% lactate threshold) exercise on separate days following a randomized counterbalanced design. During exercise and for 6 hr of recovery, samples of expired air were collected to determine oxygen consumption, respiratory exchange ratio, energy expenditure, and substrate oxidation rates. Blood samples were also collected to measure glucoregulatory hormones (catecholamines, GH) and metabolites (glucose, free fatty acids, lactate, pH, and bicarbonate). During exercise, respiratory exchange ratio, energy expenditure, and the proportion and rate of carbohydrate (CHO) oxidation were higher during MI compared with LI. However, during recovery from MI, respiratory exchange ratio and the proportion and rate of CHO oxidation were lower than preexercise levels and corresponding LI. During exercise and early recovery, catecholamines and growth hormone were higher in MI than LI, and there was a trend for higher levels of free fatty acids in the early recovery from MI compared with LI. In summary, CHO oxidation during exercise increases with exercise intensity but there is a preference for CHO sparing (and fat oxidation) during recovery from MI exercise compared with LI exercise. This exercise intensity-dependent shift in substrate oxidation during recovery is explained, in part, by the pattern of change of key glucoregulatory hormones including catecholamines and growth hormone and plasma fatty acid concentrations. [ABSTRACT FROM AUTHOR]

Today, colorectal cancer (CRC) diagnosis is performed using colonoscopy, which is the current, most effective screening method. However, colonoscopy poses risks of harm to the patient and is an invasive process. Recent research has proven metabolomics as a potential, non-invasive detection method, which can use identified biomarkers to detect potential cancer in a patients body. The aim of this study is to develop a machine-learning (ML) model based on chemical descriptors that will recognize CRC-associated metabolites. We selected a set of metabolites found as the biomarkers of CRC, confirmed that they participate in cancer-related pathways, and used them for training a machine-learning model for the diagnostics of CRC. Using a set of selective metabolites and random compounds, we developed a range of ML models. The best performing ML model trained on Stage 0-2 CRC metabolite data predicted a metabolite class with 89.55% accuracy. The best performing ML model trained on Stage 3-4 CRC metabolite data predicted a metabolite class with 95.21% accuracy. Lastly, the best-performing ML model trained on Stage 0-4 CRC metabolite data predicted a metabolite class with 93.04% accuracy. These models were then tested on independent datasets, including random and unrelated-disease metabolites. In addition, six pathways related to these CRC metabolites were also distinguished: aminoacyl-tRNA biosynthesis; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; arginine biosynthesis; and alanine, aspartate, and glutamate metabolism. Thus, in this research study, we created machine-learning models based on metabolite-related descriptors that may be helpful in developing a non-invasive diagnosis method for CRC.

Oxylipins are a group of bioactive fatty acid metabolites generated via enzymatic oxygenation. They are notably involved in inflammation, pain, vascular tone, hemostasis, thrombosis, immunity, and coagulation. Oxylipins have become the focus of therapeutic intervention since they are implicated in many conditions, such as nonalcoholic fatty liver disease, cardiovascular disease, and aging. The liver plays a crucial role in lipid metabolism and distribution throughout the organism. Long-term exposure to pesticides is suspected to contribute to hepatic carcinogenesis via notable disruption of lipid metabolism. Prometryn is a methylthio-s-triazine herbicide used to control the growth of annual broadleaf and grass weeds in many cultivated plants. The amounts of prometryn documented in the environment, mainly waters, soil and plants used for human and domestic consumption are significantly high. Previous research revealed that prometryn decreased liver development during zebrafish embryogenesis. To understand the mechanisms by which prometryn could induce hepatotoxicity, the effect of prometryn (185 mg/kg every 48 h for seven days) was investigated on hepatic and plasma oxylipin levels in mice. Using an unbiased LC-MS/MS-based lipidomics approach, prometryn was found to alter oxylipins metabolites that are mainly derived from cytochrome P450 (CYP) and lipoxygenase (LOX) in both mice liver and plasma. Lipidomic analysis revealed that the hepatotoxic effects of prometryn are associated with increased epoxide hydrolase (EH) products, increased sEH and mEH enzymatic activities, and induction of oxidative stress. Furthermore, 9-HODE and 13-HODE levels were significantly increased in prometryn treated mice liver, suggesting increased levels of oxidation products. Together, these results support that sEH may be an important component of pesticide-induced liver toxicity.

Aflatoxins are secondary metabolites produced by certain filamentous fungi such as Aspergillus flavus and may pose severe risks to human health. The presence of aflatoxins in commercial food products such as pistachio can bring severe economic drawbacks during harvest, production, and exportation. This study aimed to reduce aflatoxin levels in raw pistachio by active food packaging film enriched with silver nanoparticles and quinoa peptides and extend the shelf-life. The pistachios contaminated with Aspergillus flavus were packaged in a nanocomposite film enriched with silver nanoparticles, quinoa peptide with antifungal properties, and low-density polyethylene at varying percentages. Then, all samples were stored at 25°C for 30 days. The amount of Aflatoxin B1 and total aflatoxin (B1, B2, G1, and G2) were measured with high-performance liquid chromatography. The results showed that the percentage of film composition and time significantly affected aflatoxin values during storage (P < 0.05). The control sample had the highest amount of aflatoxins, while the sample was packaged with a film containing 35% silver nanoparticles, and the quinoa peptide had the lowest amount of aflatoxin at the end of the storage period. Based on the results obtained, the combined use of silver nanoparticles and quinoa peptides in pistachio packaging reduced aflatoxins and increased the shelf life of raw pistachio. [ABSTRACT FROM AUTHOR]

The residue and dissipation studies of diafenthiuron, its metabolites and cyantraniliprole were carried out on okra under field conditions after two applications of Cyantraniliprole 7.3% w/w + Diafenthiuron 36.4% w/w SC @ 60 + 300 g a.i./ha. Okra fruit samples were collected at 0 (2 hr), 1, 3, 5, 7, 10 and 15 days after second spray. The samples were processed using QuEChERS methodology and analysed on LCMS/MS. The total initial residues of diafenthiuron (diafenthiuron + CGA 177960, CGA 227352, CGA 140408) in okra fruit were 0.28 and 0.55 mg kg−1 at single and double dose, respectively. The total residues of diafenthiuron dissipated below limit of quantification (LOQ) of 0.01 mg kg−1 at 10 days of application at both the doses. The initial residues of cyantraniliprole in okra were 0.23 and 0.42 mg kg−1 at single and double dose, respectively. The residues dissipated below

Liquid crystal monomers (LCMs), prized for their unique optical properties, are ubiquitous in a range of electronic products. However, their growing use and disposal have led to a continuous influx of LCMs into the environment as contaminants. This review synthesizes information on the sources, environmental distribution, migration, transformation, toxicity, and risks associated with LCMs. It also introduces predictions of adverse outcomes related to protein binding potential, grounded in the Adverse Outcome Pathway framework. It was pointed out for the first time that the fundamental causes of LCM contamination were informal recycling and dismantling patterns, coupled with obsolete liquid crystal processing technologies. The significant variability among different types of LCMs in distribution patterns, environmental persistence, bioaccumulation, mobility, and toxicity were emphasized. Notably, fluorinated LCMs, especially fluorobiphenyls, which posed the greatest comprehensive risk, were prone to accumulate in atmospheric dust. Our molecular docking results showed that monomers containing cyano groups, which had greater direct toxicity, carcinogenic, and mutagenic risk, also exhibited strong binding affinity, underscoring the need for priority control strategies. Additionally, this review delved into LCM exposure pathways and the heightened toxicity during degradation and metabolism. It emphasizes the importance of risk assessments for LCMs and identifies key scientific questions that require further investigation. The insights provided a scientific foundation for preventing environmental risks and promoting green chemical alternatives related to LCMs. [ABSTRACT FROM AUTHOR]

This article reviews the geographical distribution, ethnomedicinal applications, and phytochemistry of the genus Monanthotaxis Baill, tribe Uvariae of the family Annonaceae. The reviewed works of literature were collected from various electronic databases including Google Scholar, PubMed, Science Direct, The International Plant Names Index (IPNI), and Research Gate. During this review, ninety-eight species of the genus Monanthotaxis were found to be widely distributed in tropical Africa. Some of those species are used in folkloric medicine by various communities to manage diseases and disease conditions such as fever, vomiting, headache, stomach-ache, malaria, helminthiasis, and hysteria. In the past 44 years (1979 to 2023), one hundred and nineteen secondary metabolites with different biomedical potentials have been reported from this genus. The reported compounds are categorised into flavonoids, alkaloids, terpenoids, polyoxygenated cyclohexane, and cyclohexene derivatives, benzyl derivatives, cinnamic acid derivatives, and stilbenoids. Most of the reported compounds showed an array of bioactivities corroborating the use of some members of the genus in folkloric medicine. [ABSTRACT FROM AUTHOR]

Metabolic dysregulation in the ischemic region has been increasingly recognized as a contributing factor to ischemic stroke pathogenesis. Taohong Siwu decoction (THSWD), a traditional Chinese medicine preparation used to enhance blood circulation, is frequently employed in treating ischemic stroke. However, the metabolic regulatory mechanism underlying the therapeutic effects of THSWD in ischemic stroke remains largely unexplored. In this study, we employed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate the metabolic changes in the brain tissue of ischemic stroke rat model. Our investigation revealed that 30 metabolites exhibited significant dysregulation in the ischemic brain regions, specifically the cortex and striatum, following ischemic injury. Following the treatment of THSWD, almost all the dysregulated metabolites got different degrees of callback. Further pathway analysis indicated that THSWD might exert its therapeutic effects by restoring energy metabolism, improving neurotransmitter metabolism, recovering polyamine metabolism, and so on. DESI-MSI offers a favorable methodology for investigating the alterations in the spatial distribution and level within the ischemic brain region following treatment with THSWD in ischemic stroke. These findings provide a novel perspective on the underlying mechanisms of the efficacy of THSWD in ischemic stroke treatment. [ABSTRACT FROM AUTHOR]

Saponins encompass a diverse group of naturally occurring glycoside molecules exhibiting amphiphilic properties and a broad range of biological activities. There is a resurgence of interest in those saponins produced by marine organisms based on their potential therapeutic benefits, application in food products and most recently their potential involvement in intra- and inter-species chemical communication. The continual advancements in liquid chromatography techniques and mass spectrometry technologies have allowed for greater detection rates, as well as improved isolation and elucidation of saponins. These factors have significantly contributed to the expansion in the catalogue of known saponin structures isolated from marine invertebrates; however, there currently exists no specific chemical library resource to accelerate the discovery process. In this study, a Marine Animal Saponin Database (MASD v1.0) has been developed to serve as a valuable chemical repository for known marine saponin-related data, including chemical formula, molecular mass and biological origin of nearly 1000 secondary metabolites associated with saponins produced by marine invertebrates. We demonstrate its application with an exemplar asteroid extract (Acanthaster cf. solaris, also known as crown-of-thorns starfish; COTS), identifying saponins from the MASD v1.0 that have been previously reported from COTS, as well as 21 saponins isolated from multiple other related asteroid species. This database will help facilitate future research endeavours, aiding researchers in exploring the vast chemical diversity of saponins produced by marine organisms and providing ecological insights, and the realisation of their potential for various applications, including as pharmaceuticals. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) antiviral administration and adherence are essential to reach the World Health Organization's 2030 hepatitis elimination goals. As HBV treatment guidelines are now simplified and expanded, adherence to treatment will be critical, but challenges to adherence are poorly studied. After introducing tenofovir disoproxil fumarate (TDF) monotherapy to expectant mothers with high-risk HBV in Kinshasa, DRC, we conducted semi-structured interviews to understand medication adherence behaviors, to complement pill counts and measurement of TDF metabolite levels. Key facilitators of adherence identified included trust in healthcare workers, a better understanding of HBV, and family support. Identified barriers included fear of stigma and low health literacy. Knowledge about HBV disease remains low, underscoring the importance of ongoing education of clinic staff and patients alike. [ABSTRACT FROM AUTHOR]

Background: Oral lichen planus (OLP) is a chronic oral mucosal inflammatory disease with a risk of becoming malignant. Emerging evidence suggests that microbial imbalance plays an important role in the development of OLP. However, the association between the oral microbiota and the metabolic features in OLP is still unclear. Methods: We conducted 16S rRNA sequencing and metabolomics profiling on 95 OLP patients and 105 healthy controls (HC).To study oral microbes and metabolic changes in OLP, we applied differential analysis, Spearman correlation analysis and four machine learning algoeithms Results: The alpha and beta diversity both differed between OLP and HC. After adjustment for gender and age, we found an increase in the relative abundance of Pseudomonas, Aggregatibacter, Campylobacter, and Lautropia in OLP, while 18 genera decreased in OLP. A total of 153 saliva metabolites distinguishing OLP from HC were identified. Notably, correlations were found between Oribacterium, specific lipid and amino acid metabolites, and OLP's clinical phenotype. Additionally, the combination of Pseudomonas, Rhodococcus and (±)10-HDoHE effectively distinguished OLP from HC. Conclusions: Based on multi-omics data, this study provides comprehensive evidence of a novel interplay between oral microbiome and metabolome in OLP pathogenesis using the oral microbiota and metabolites of OLP patients. [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]

Occupational exposure to 4,4′-methylenebis(2-chloroaniline) (MOCA) has been linked to an increased risk of bladder cancer among employees in Japanese plants, indicating its significance as a risk factor for urinary bladder cancer. To investigate the role of MOCA metabolism in bladder carcinogenesis, we administered MOCA to non-humanized (F1-TKm30 mice) and humanized-liver mice for 4 and 28 wk. We compared MOCA-induced changes in metabolic enzyme expression, metabolite formation, and effects on the urinary bladder epithelium in the 2 models. At week 4, MOCA exposure induced simple hyperplasia, cell proliferation, and DNA damage in the urothelium of the humanized-liver mice, whereas in the non-humanized mice, these effects were not observed. Notably, the concentration of 4-amino-4′-hydroxylamino-3,3′-dichlorodiphenylmethane (N -OH-MOCA) in the urine of humanized-liver mice was more than 10 times higher than that in non-humanized mice at the 4-wk mark. Additionally, we observed distinct differences in the expression of cytochrome P450 isoforms between the 2 models. Although no bladder tumors were detected after 28 wk of treatment in either group, these findings suggest that N -OH-MOCA significantly contributes to the carcinogenic potential of MOCA in humans. [ABSTRACT FROM AUTHOR]

Objective: The observational association between blood metabolites and asthma has been extensively studied. However, it is still unclear whether this association is causal. In this study, we aimed to investigate the causal relationship between blood metabolites and asthma using a bidirectional Mendelian randomization (MR) analysis. Additionally, we aimed to explore the potential mechanisms underlying this relationship. Methods: The study design involved the use of genetic instruments as instrumental variables (IVs) to fulfill the assumptions of MR analysis. The data on 1,091 metabolites and 309 metabolite ratios were obtained from the Canadian Longitudinal Study on Aging (CLSA), while the data on asthma were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS Project. Utilizing the inverse variance-weighted (IVW) method as the primary MR analysis approach, sensitivity tests were conducted to assess the reliability of the findings, which involved employing Cochran's Q and the MR-Egger intercept. Furthermore, Bayesian weighted MR was used to further test the robustness of the results. Additionally, pathway analysis was conducted to explore the metabolic explanations underlying asthma. Result: In our study, a comprehensive MR Analysis identified 10 metabolites and 6 metabolite ratios significantly associated with the development of asthma (FDR < 0.05). The metabolites included glycerophosphocholines(GPCs), glycerophosphoethanolamines(GPEs), and an unknown metabolite. Of these, 1-arachidonoyl-GPC, 1-myristoyl-2-arachidonoyl-GPC, 1-palmitoyl-2-arachidonoyl-GPC, and 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC were associated with an increased risk of asthma, whereas 1,2-dilinoleoyl-GPC, 1-palmitoyl-2-linoleoyl-GPC, 1,2-dilinoleoyl-GPE, 1 − oleoyl − 2 − linoleoyl − GPE, 1-palmitoyl-2-linoleoyl-GPE, and X-21470 were found to have a protective effect. No heterogeneity and pleiotropy were observed in the significant metabolites (p > 0.05), and each metabolite exhibited a consistent effect direction across all five methods. BWMR analysis results confirmed the significance and direction of effects across exposures, except for Cholesterol to linoleoyl-arachidonoyl-glycerol ratio(p = 0.673). Pathway analysis suggests that glycerophospholipid metabolism may potentially be a mechanism underlying the development of asthma. Conclusion: Our MR findings suggest that the identified metabolites and pathways can serve as biomarkers for clinical asthma screening and prevention, while also providing new insights for future mechanistic exploration and drug target selection. [ABSTRACT FROM AUTHOR]

The influence of epigenetic factors on plant defense responses and the balance between growth and defense is becoming a central area in plant biology. It is believed that the biosynthesis of secondary metabolites can be regulated by epigenetic factors, but this is not associated with the formation of a "memory" to the previous biosynthetic status. This review shows that some epigenetic effects can result in epigenetic memory, which opens up new areas of research in secondary metabolites, in particular flavonoids. Plant-controlled chromatin modifications can lead to the generation of stress memory, a phenomenon through which information regarding past stress cues is retained, resulting in a modified response to recurring stress. How deeply are the mechanisms of chromatin modification and memory generation involved in the control of flavonoid biosynthesis? This article collects available information from the literature and interactome databases to address this issue. Visualization of the interaction of chromatin-modifying proteins with the flavonoid biosynthetic machinery is presented. Chromatin modifiers and "bookmarks" that may be involved in the regulation of flavonoid biosynthesis through memory have been identified. Through different mechanisms of chromatin modification, plants can harmonize flavonoid metabolism with: stress responses, developmental programs, light-dependent processes, flowering, and longevity programs. The available information points to the possibility of developing chromatin-modifying technologies to control flavonoid biosynthesis. [ABSTRACT FROM AUTHOR]

The genus Pseudomonas is one of the most varied and widespread bacterial genera, with species found in most environment. They are known to degrade organic and inorganic compounds, produce secondary metabolites, and enhance plant growth. The genome of Pseudomonas koreensis AB36, a heavy metal resistant organism isolated from a gold mine was sequenced to unveil the versatile metabolic potential of the organism. The genome is a single circular chromosome of 5,902,614 bp, with G + C content of 60.1%. There are 4154 similar orthologous gene clusters shared among strain AB36 and other sequenced P. koreensis strains with 7 clusters found alone in the genome of strain AB36. Genome mining of the organism predicted 8 biosynthetic gene clusters using antiSMASH including three non-ribosomal peptide synthethase (NRPS) clusters, arylpolyene and bacteriocin. The genome contains putative genes for heavy metal transport/resistance. These results show the heavy metal resistance ability and degradation of xenobiotic compounds of strain AB36 as well as its potential to adapt to various environments. [ABSTRACT FROM AUTHOR]

Carissa carandas L. is a wild food plant, however, is cultivated for its fruits to be utilized to make pickles, jams, and other similar products. Fruit of this plant has been intensively investigated for its bioactive potential; however, a scanty study is reported on the leaf, which is usually wasted. In the present study, ethanolic extract of the leaf of C. carandas was analyzed for its total bioactive contents and found rich in phenolics and flavonoids (26.67 ± 0.33 mg GAE/g extract and 18.42 ± 0.05 mg RE/g extract, respectively). These findings were substantiated due to UHPLCMS/MS analysis, which disclosed the presence of about 110 secondary metabolites, mostly lignans, flavonoids, and terpenoids. In DPPH and ABTS free radical inhibition assays, the extract showed inhibitory values as 47.51 ± 0.09 and 93.09 ± 2.8 mg TE/g extract, respectively. Its further antioxidant potential was observed in CUPRAC and FRAP assays, wherein the metal reducing power was recorded as 102.05 ± 1.03 and 67.24 ± 0.9 mg TE/g extract, respectively, while in phosphomolybdenum and metal chelating assays, the extract also disclosed potential activity (0.92 ± 0.02 mmol TE/g extract and 21.42 ± 0.34 mg EDTAE/g extract). The extract was also significantly active against tyrosinase (45.69 ± 0.7 mg KAE/g extract) and showed mild activities against AChE (3.61 ± 0.16 mg GALAE/g extract), BChE (1.43 ± 0.2 mg GALAE/g extract), α-amylase (0.46 ± 0.01 mmol ACAE/g extract) and α-glucosidase (1.05 ± 0.02 mmol ACAE/g extract). In computational studies, binding affinities for AChE and BChE enzymes were from −4.21 to −12.70 and −7.58 to −12.53 kcal/mol, respectively, confirming the results of the invitro tests and ADME studies. The current finding suggested that C. carandas may be considered as a source for several nutraceutical formulations. [ABSTRACT FROM AUTHOR]

The objective of this ongoing research is to investigate and assess the aqueous extracts, vegetable oil, and residual plant components derived from O. dillenii by use of HPLC, and GC-MS. Subsequent investigations employed colorimetric techniques to identify reducing and soluble sugars. We developed and validated an energy-dispersive X-ray fluorescence (EDXRF) method for determining the concentrations of essential chemical elements (O, C, Ca, Mg, K, S, P) in seeds, juice, and peel, as well as their residues. HPLC analysis yielded results indicating that extracts from O. dillenii seeds, juice, and peel from distinct regions (Oujda, Nador, and Essaouira) contained elevated concentrations of metabolites. Specifically, peel and juice extracts exhibited the highest levels of organic acids and betanin compared to O. dillenii seeds. Conversely, seed oils displayed a noteworthy tocopherol content, predominantly δ-tocopherol. Similarly, an examination of organic acid composition in juice, peel, and seeds from three different regions revealed their elevated levels. Citric acid and oxalic acid emerged as predominant components in the juice. Overall, Opuntia dillenii's physicochemical and phytochemical characterization improves in understanding its potential as a bioactive chemical promoter, which could lead to the creation of new medicinal medicines or functional food ingredients. [ABSTRACT FROM AUTHOR]

This study presents an initial exploration of the phytochemical composition and biological properties of Salsola foetida, a wild plant native to southeastern Algeria. The investigation encompassed an analysis of the biochemical content, phytochemical profile, and bioactivity of the plant's aerial parts. The biomass of S. foetida was found to comprise 51.2 ± 0.4% ash, with elemental analysis revealing the presence of carbon, oxygen, calcium, sodium, chlorine, magnesium, potassium, and sulfur. Carbohydrates were identified as the predominant constituents, surpassing the levels of proteins and lipids. Phytochemical screening, coupled with Fourier Transform Infrared (FT-IR) analysis, confirmed the presence of various secondary metabolites, including alkaloids and phenols. Reversed-phase high-performance liquid chromatography (RP-HPLC) analysis further delineated a spectrum of phenolic compounds, with rutin emerging as the predominant compound at 1.59 µg/ml. Quantification revealed a noteworthy phenolic content of 67.1 ± 0.2 µg GE/mg ED. The extract exhibited robust radical scavenging effects, with the radical 50% inhibitory concentration (IC50) being 61.8 ± 0.2 μg/ml, along with protective effects against H2O2-induced hemolysis and the ability to reduce ferric ions. Additionally, the extract demonstrated anti-inflammatory, antibacterial, and antidiabetic activities. Notably, it exhibited considerable sunscreen properties, boasting a sun protected factor (SPF) value of 21 ± 1. Overall, S. foetida presents promising antioxidant activity and a spectrum of potential biological activities, underscoring its significance as a novel antioxidant candidate for applications in animal nutrition, medicine, and natural product research. [ABSTRACT FROM AUTHOR]

Background: Inflammatory cytokines and migraines have been associated in previous research, but the underlying mechanisms of action are still elusive. The biological functions of metabolites are crucial in the onset of migraine. Our goals were to clarify the cause‐and‐effect connection between inflammatory cytokines and migraines and explore the potential mediating function of metabolites. Methods: Utilizing summary‐level data from genome‐wide association studies (GWAS), we conducted two‐sample Mendelian randomization (MR) analyses to evaluate the possible causal connection between inflammatory cytokines and migraines. A two‐step MR analysis was employed to further investigate the potential mediating pathways of metabolites. Results: MR analysis identified a total of 9 inflammatory cytokines that were genetically associated with migraines, and we subsequently identified 21 mediated relationships, with 20 metabolites (13 metabolites, 7 ratios) acting as potential mediators between 8 inflammatory cytokines and migraine. The 9 inflammatory cytokines were beta‐nerve growth factor levels (β‐NGF), T‐cell surface glycoprotein CD5 levels (CD5), T‐cell surface glycoprotein CD6 isoform levels (CD6), C‐X‐C motif chemokine 11 levels (CXCL11), interleukin‐4 levels (IL‐4), oncostatin‐M levels (OSM), signalling lymphocytic activation molecule levels (SLAM), C‐C motif chemokine 25 levels (CCL25) and monocyte chemoattractant protein‐1 levels (MCP‐1). Conclusion: Our research findings provide evidence for both a causal connection between inflammatory cytokines and migraines, as well as a metabolite‐mediated pathway. These biomarkers facilitate the detection, diagnosis and treatment of migraines while offering fresh perspectives on their underlying mechanisms. [ABSTRACT FROM AUTHOR]

The low‐molecular‐weight (LMW) reduced sulfur substances (RSS) composition of dissolved organic matter (DOM) was examined along the GEOTRACES US‐GP15 section in the Pacific Ocean. We demonstrate that LMW RSS constitutes a significant fraction of nonvolatile dissolved organic sulfur (DOS). While thiols such as glutathione were below our detection limit (300 pM), RSS containing two carbon (C) sulfur (S) bonds were present at concentrations in the hundreds of nM range. RSS accumulation was observed in subtropical waters. The most likely source of these RSS is microbial alteration of sulfurized DOM with production of secondary thioamidated metabolites. RSS are initially produced by cyanobacteria to mitigate copper and oxidative stress induced by UV‐B irradiance. A preferential remineralization of RSS over dissolved organic carbon (DOC) in the upper 350 m suggests a partial lability of LMW DOS. Deeper, homogeneous concentrations and C : S ratio indicate increasing stability of this LMW DOS. [ABSTRACT FROM AUTHOR]

Dittrichia viscosa (L.) Greuter, a perennial plant in the Asteraceae, has strong allelopathic activity due to the high content of various secondary metabolites. The bicyclic sesquiterpenoid α‐costic acid is the most abundant secondary metabolite of D. viscosa. Its remarkable insecticidal, antiparasitic, and phytotoxic activities point to its potential use as a natural herbicide, but information on its mode of action is lacking.To shed light on the mechanism of action of α‐costic acid in plant cells, we investigated the phytotoxicity of α‐costic acid in tomato plants (Solanum lycopersicum L.) through in vivo assays, the underlying cellular effects using biochemical assays, and the effect on subcellular organelles using confocal microscopy on tomato protoplasts incubated with organelle‐specific fluorescent probes.In vivo tests showed that α‐costic acid inhibited the growth of tomato seedlings and induced chlorosis and spot lesions in leaves. Biochemical assays demonstrated that α‐costic acid caused ion leakage, chlorophyll depletion, H2O2 overproduction, callose deposition, and membrane lipid peroxidation. Confocal microscopy demonstrated that α‐costic acid determined ROS overproduction and network disruption in mitochondria, singlet oxygen overproduction in chloroplasts, vacuole disintegration, and autophagosome formation.Overall, our data are consistent with a model according to which α‐costic acid phytotoxicity is related to oxidative stress in mitochondria and chloroplasts that induces extensive membrane damage, ultimately resulting in cell death associated with autophagy [ABSTRACT FROM AUTHOR]

The endophytic fungus Setosphaeria rostrata K.J. Leonard, 1976, was isolated from Datura innoxia Mill. and characterized by analysis of nucleotide sequences of the Internal Transcribed Spacer (ITS) region. To diversify the secondary metabolites in the fungus, valproic acid (a histone deacetylase inhibitor) was supplemented and subsequently evaluated for the antibacterial, total phenolic content and antioxidant activity. A significant difference in the antioxidant activity and phenolic content was observed among the extracts. The ethyl acetate extract obtained from the experimental part has shown almost two fold increase in the antioxidant activity. The total phenolic content was higher in ethyl acetate extract of the control than experimental sample. The control and experimental extracts were found to have mild activity against Pseudomonas aeruginosa (NCIM 5029). To support the difference in antioxidant activity, the extracts were analyzed via Gas Chromatography and Mass Spectroscopy (GCMS) and the profile of volatile metabolites was obtained. The outcome obtained from GCMS profile has supported the differences observed between the extracts. This study remarkably depicts that the valproic acid can be used to diversify the secondary metabolites in fungi. [ABSTRACT FROM AUTHOR]

Tomato is the most important horticultural crop, and India is its second largest producer; however, the plant‐pathogenic nematode Meloidogyne incognita is a serious pest of tomato, causing detrimental losses in its production. This study is focused on the use of multistress‐tolerant Pseudomonas aeruginosa SSVP3 to control this devastating nematode and attempts to decipher the roles of its metabolites and volatile organic compounds (VOCs) during this interaction. The supernatant of P. aeruginosa SSVP3 caused 58% mortality in M. incognita J2 juveniles. The major nematicidal metabolites, identified using liquid chromatography‐mass spectrometry, were pyocyanin, pyoluteorin, pyochelin, benthocyanin and phenazines. The VOCs secreted by P. aeruginosa SSVP3, which were identified via gas chromatography–mass spectrometry (HS‐SPME‐GC–MS) in a mixture, caused 98% mortality in M. incognita J2 juveniles. In a pot experiment, seedling root treatment with P. aeruginosa SSVP3 activated the induced systemic response in tomato plants to M. incognita by increasing the activity of defence and antioxidant enzymes as well as the proline and phenolic contents. The malondialdehyde content in P. aeruginosa SSVP3‐treated plants decreased as compared to those in the other treatment groups. The number of galls formed and the number of endoparasitic stages of M. incognita in the untreated nematode control plants were much greater (19 and 35) than those in the P. aeruginosa SSVP3‐treated (0.33 and 1) and chemically treated groups (0.67 and 1.33). These results indicate that P. aeruginosa and its secreted metabolites and VOCs have a high potential for controlling nematodes. [ABSTRACT FROM AUTHOR]

Among the most important aquaculture resources for our country, salmon and trout stand out. Their production has increased significantly in recent decades, making them two of the most valuable resources in economic terms. However, high aquaculture production has allowed many pathogens to proliferate, causing infectious diseases and significant production losses. Piscirickettsia salmonis is a gram‐negative, facultative intracellular bacterium that is responsible for causing severe disease in a variety of salmonid fish species. Despite the significant impact of P. salmonis on aquaculture, effective treatments for this disease remain limited. Current prevention and control strategies often include antibiotics and vaccines. However, these treatments have shown varying degrees of efficacy. A promising approach involves synthesizing bioactive analog compounds with antibacterial properties. Quinones, secondary metabolites that are abundant in nature, have become a focal point of interest due to their diverse physiological activities, including antibiotic, insecticidal, antifungal, and anticancer properties. In this study, it is shown the synthesis of series 6‐bromo‐7‐arylaminoisoquinoline‐5,8‐quinones, the characterization of these compounds using classical spectroscopic methods such as one‐dimensional nuclear magnetic resonance (NMR), FT‐IR (infrared), mass spectrometry, and the biological activity against Piscirickettsia salmonis. The brominated derivative compounds showed no cytotoxicity at any concentration evaluated. Furthermore, the infectivity of P. salmonis after treatment with the analog compounds indicated that derivatives methyl 6‐bromo‐7‐((4‐methoxyphenyl)amino)‐1,3‐dimethy‐5,8‐dioxo‐5,8‐dihydroisoquinoline‐4‐carboxylate (4b) and methyl 7‐((4′‐amino‐[1,1′‐biphenyl]‐4‐yl)amino)‐6‐bromo‐1,3‐dimethy‐5,8‐dioxo‐5,8‐dihydroisoquinoline‐4‐carboxylate (4g) reduced the bacterial load at 25 μg/mL concentration. [ABSTRACT FROM AUTHOR]

Aim: Diabetic cognitive impairment (DCI), considered one of the most severe and commonly overlooked complications of diabetes, has shown inconsistent findings regarding the metabolic profiles in DCI patients. This systematic review and meta‐analysis aimed to identify dysregulated metabolites as potential biomarkers for early DCI, providing valuable insights into the underlying pathophysiological mechanisms. Materials and Methods: A systematic search of four databases, namely PubMed, Embase, Web of Science and Cochrane, was conducted up to March 2024. Subsequently, a qualitative review of clinical studies was performed followed by a meta‐analysis of metabolite markers. Finally, the sources of heterogeneity were explored through subgroup and sensitivity analyses. Results: A total of 774 unique publications involving 4357 participants and the identification of multiple metabolites were retrieved. Of these, 13 clinical studies reported metabolite differences between the DCI and control groups. Meta‐analysis was conducted for six brain metabolites and two metabolite ratios. The results revealed a significant increase in myo‐inositol (MI) concentration and decreases in glutamate (Glu), Glx (glutamate and glutamine) and N‐acetylaspartate/creatine (NAA/Cr) ratios in DCI, which have been identified as the most sensitive metabolic biomarkers for evaluating DCI progression. Notably, brain metabolic changes associated with cognitive impairment are more pronounced in type 2 diabetes mellitus than in type 1 diabetes mellitus, and the hippocampus emerged as the most sensitive brain region regarding metabolic changes associated with DCI. Conclusions: Our results suggest that MI, Glu, and Glx concentrations and NAA/Cr ratios within the hippocampus may serve as metabolic biomarkers for patients with early‐stage DCI. [ABSTRACT FROM AUTHOR]

The influence of the initial pH on the morphology and secondary metabolite production in cocultures and axenic cultures of Aspergillus terreus and Streptomyces rimosus was investigated. The detected secondary metabolites (6 of bacterial and 4 of fungal origin) were not found in the cultures initiated at pH values less than or equal to 4.0. The highest mean levels of oxytetracycline were recorded in S. rimosus axenic culture at pH 5.0. Initiating the axenic culture at pH 5.9 led to visibly lower product levels, yet the presence of A. terreus reduced the negative effect of non-optimal pH and led to higher oxytetracycline titer than in the corresponding S. rimosus axenic culture. The cocultivation initiated at pH 5.0 or 5.9 triggered the formation of oxidized rimocidin. The products of A. terreus were absent in the cocultures. At pH 4.0, the striking morphological differences between the coculture and the axenic cultures were recorded. [ABSTRACT FROM AUTHOR]

The aim of this review was to evaluate the feasibility of treating sleep disorders using novel gut microbiota intervention strategies. Multiple factors can cause sleep disorders, including an imbalance in the gut microbiota. Studies of the microbiome-gut-brain axis have revealed bidirectional communication between the central nervous system and gut microbes, providing a more comprehensive understanding of mood and behavioral regulatory patterns. Changes in the gut microbiota and its metabolites can stimulate the endocrine, nervous, and immune systems, which regulate the release of neurotransmitters and alter the activity of the central nervous system, ultimately leading to sleep disorders. Here, we review the main factors affecting sleep, discuss possible pathways and molecular mechanisms of the interaction between sleep and the gut microbiota, and compare common gut microbiota intervention strategies aimed at improving sleep physiology. [ABSTRACT FROM AUTHOR]

Mycotoxins, secondary metabolites produced by mycotoxigenic fungi, are a major problem affecting food safety and security, because of their adverse health effects, their socio-economic impact and the difficulty of degradation or removal by conventional food processing methods. Plant-sourced natural products are a novel and effective control method for fungal infestation and mycotoxin production, with the advantages of biodegradability and acceptability for food use. However, development of resistance, low and inconsistent efficacy, and a limited range of antifungal activities hinder the effective application of single plant natural products for controlling mycotoxin contamination. To overcome these limitations, combinations of plant natural products have been tested extensively and found to increase efficacy, often synergistically. However, this extensive and promising research area has seen little development of practical applications. This review aims to provide up-to-date information on the antifungal, anti-mycotoxigenic and synergistic effects of combinations of plant natural products, as well as their mechanisms of action, to provide a reference source for future research and encourage application development. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the potential causal association between Sleep Apnea Syndrome (SAS) and Depression, focusing on the roles of gut microbiota, serum metabolites, and inflammatory factors in these conditions. Mendelian Randomization (MR) analysis was performed using data from genome-wide association studies to assess 211 types of gut microbiota, 1400 serum metabolites, and 91 inflammatory factors as potential contributing factors. Causal inference was conducted using the Inverse Variance Weighted (IVW) method, with additional robustness checks through Cochran's Q test, MR-Egger regression intercept test, MR-PRESSO global test, and leave-one-out analysis. The MR analysis indicated a positive correlation between the risk of SAS and Depression (OR = 1.12, 95 % CI: 1.05–1.19, P < 0.001), with a reciprocal analysis showing a similar positive correlation between Depression and the risk of SAS (OR = 1.19, 95 % CI: 1.07–1.31, P = 0.001). Additionally, causal associations were identified between 15 types of gut microbiota, 36 serum metabolites, and 2 inflammatory factors with SAS, and between 11 types of gut microbiota, 23 serum metabolites, and 3 inflammatory factors with Depression (IVW, all P < 0.05). The robustness of these findings was confirmed through the MR-Egger regression intercept test and MR-PRESSO global test. This study provides epidemiological evidence of a bidirectional causal association between SAS and Depression, emphasizing the potential roles of gut microbiota, serum metabolites, and inflammatory factors in the pathogenesis of these disorders. These findings may inform the development of new therapeutic strategies. • Unveils a bidirectional causal link between SAS and depression. • Highlights the role of gut microbiota, serum metabolites, and inflammatory factors in SAS and depression. • Offers new treatment insights, emphasizing the value of targeted interventions in prevention and therapy. [ABSTRACT FROM AUTHOR]

Context: cervicitis is a common gynecological inflammatory disease. the chinese herbal prescription Kang-Gong-Yan (KGY) is clinically effective against cervicitis; however, the chemical constituents and therapeutic mechanism of KGY remain elusive. Objective: to analyze the chemical constituents of KGY and explore the potential mechanism of KGY in treating cervicitis. Materials and methods: UHPLC-Q-exactive Plus Orbitrap MS was used to identify the active compounds of KGY; Sprague-Dawley (SD) female rats were randomly divided into the control, model, and KGY groups. Phenol mucilage (25%) was slowly injected into the vagina and cervix of the rats to establish the cervicitis model. then, rats in the KGY groups (low dose: 1 g/kg/d; medium dose: 5 g/kg/d; high dose: 10 g/kg/d) were continuously gavaged KGY for one week. he staining was used to observe the cervical tissues of rats; elisa was used to detect inflammatory factors in plasma; non-targeted metabolomics was used to analyze metabolites; 16s rRNA sequencing was used to analyze intestinal microorganisms. Results: KGY exerted anti-cervicitis effects and decreased the levels of IL-6, IL-1β, AND TNF-α. the mechanism of KGY in treating cervicitis is mainly associated with betaine, amino acid, pyrimidine, and phospholipid metabolism by regulating fifteen metabolites. Moreover, KGY reversed cervicitis-induced gut dysbiosis by mediating five bacteria. Discussion and conclusions: the chinese herbal prescription KGY may alleviate cervicitis by modulating metabolites and gut microbiota disorders. these findings provide a scientific basis for the clinical application of KGY and a new strategy for treating cervicitis in chinese medicine. [ABSTRACT FROM AUTHOR]

Epidemiological evidence on ultra-processed food (UPF) and cause-specific mortality remains limited and mixed. Molecular mechanisms underlying UPF intake and mortality remain unexplored. This study aimed to evaluate the associations between UPF consumption, metabolic signatures, and all-cause, premature, and cause-specific mortality. This study included 27670 participants (mean age 58.1 years) from the Malmö Diet and Cancer (MDC) cohort study. Consumption of UPF was assessed using a food frequency questionnaire and a 7-day food diary. In a subset of the MDC (n = 879), the associations of UPF with 991 plasma metabolites were investigated. An elastic net regression model was used to establish the metabolic signature of UPF. Cox proportional hazards regression model was used to determine the association between UPF intake, metabolic signature, and mortality risk. During a median follow-up of 23.3 years, a total of 11333 participants died. UPF intake showed a nonlinear positive association with all-cause mortality, with more pronounced associations found in females (P interaction = 0.044); in females, UPF was linked to a higher mortality risk in a linear manner, while the association was J-shaped in males. Each standard deviation (SD) increment in UPF intake was associated with an increased risk of premature mortality (HR, 1.06; 95 % CI, 1.03–1.09), cardiovascular disease (CVD) mortality (HR, 1.05; 95 % CI, 1.01–1.08) or respiratory disease mortality (HR, 1.08; 95 % CI, 1.01–1.15), but not cancer mortality. The metabolic signature for UPF consumption (with 93 metabolites) was positively associated with all-cause mortality risk (HR per 1 SD, 1.23; 95 % CI, 1.06–1.42). Our results suggest that higher UPF intake is associated with increased risk of all-cause, premature, CVD, and respiratory disease mortality, with the association varying across sex for all-cause mortality. The plasma metabolic signature of UPF showed a positive association with all-cause mortality. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) has emerged as a promising immunotherapeutic approach for the treatment of various tumors. However, the efficacy of this therapy is limited in a subset of patients, and it is important to develop strategies to enhance immune responses. Studies have demonstrated a critical role of gut microbiota in regulating the therapeutic response to ICB. Gut microbiota composition, diversity, and function are mediated by metabolites, such as short-chain fatty acids and secondary bile acids, that interact with host immune cells through specific receptors. In addition, gut bacteria may translocate to the tumor site and stimulate antitumor immune responses. Therefore, maintaining a healthy gut microbiota composition, for instance through avoiding the use of antibiotics or probiotic interventions, can be an effective approach to optimize ICB therapy. This review summarizes the current understanding of the microbiota-immunity interactions in the context of ICB therapy, and discusses potential clinical implications of these findings. [ABSTRACT FROM AUTHOR]

Chronic constipation is a prevalent clinical condition. Its etiology and pathogenesis have not yet been fully understood. In recent years, mounting evidence suggests a close association between chronic constipation and intestinal dysbiosis, including alterations in the colony structure and metabolites, as well as the modulation of bowel movements via the brain–gut–microbiota axis. With the deepening of related research, probiotic-related therapies are expected to become a potential first-line treatment for chronic constipation in the future. In this review, we summarize the current research insights into the intricate relationships between chronic constipation and the gut microbiota and briefly discuss several different approaches for treating chronic constipation. The findings from this review may advance our understanding of the pathological mechanisms underlying chronic constipation and, ultimately, translate them into improvements in patient care. [ABSTRACT FROM AUTHOR]

Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., two nootropics, are recognized in Indian Ayurvedic texts. Studies have attempted to understand their action as memory enhancers and neuroprotectants, but many molecular aspects remain unknown. We propose that Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb. share common neuroprotective mechanisms. Mass spectrometry–based untargeted metabolomics and network pharmacology approach were used to identify potential protein targets for the metabolites from each extract. Phytochemical analyses and cell culture validation studies were also used to assess apoptosis and ROS activity using aqueous extracts prepared from both herbal powders. Further, docking studies were also performed using the LibDock protocol. Untargeted metabolomics and network pharmacology approach unveiled 2751 shared metabolites and 3439 and 2928 non-redundant metabolites from Bacopa monnieri and Centella asiatica extracts, respectively, suggesting a potential common neuroprotective mechanism among these extracts. Protein-target prediction highlighted 92.4% similarity among the proteins interacting with metabolites for these extracts. Among them, kinases mapped to MAPK, mTOR, and PI3K-AKT signaling pathways represented a predominant population. Our results highlight a significant similarity in the metabolome of Bacopa monnieri (L.) Wettst and Centella asiatica (L.) Urb., and their potential protein targets may be attributed to their common neuroprotective functions. Workflow employed for phytochemical assays, mass spectrometry-based metabolomics, protein-target identification, cell culture validations, and docking studies. Comparison of Bacopa monnieri and Centella asiatica non-redundant metabolite identification at MS level,as well as at MS/MS level [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is a well-established potent food mycotoxin. We previously evidenced that laccase could restrain AFB1's genetic and oxidative toxicity in vitro conditions; nevertheless, there is no report about the in vivo toxicity of the laccase-mediated metabolites of aflatoxin B1 (LM-AFB1). In this investigation, we evaluated the in vivo safety of LM-AFB1 in comparison with the parent toxin using serum liver function tests (LFTs), oxidative stress biomarkers, histopathological examinations, and CYP1A2 and GSTA3 gene expression. Adult male mice were divided into four groups: (1) Control; (2) 4 mg/kg AFB1; (3) 4 mg/kg LM-AFB1; (4) 4 mg/kg intermediate transformational metabolites of AFB1 (CA-AFB1). In this study, AFB1's liver toxicity was confirmed but LM-AFB1 did not significantly change the values. Gene expression analysis indicates that the utilization of laccase for bioremediation does not result in the suppression of glutathione S-transferase, in contrast to AFB1. Our research findings demonstrate that laccase has the potential to mitigate AFB1-induced liver toxicity in mice by averting oxidative stress caused by AFB1. [ABSTRACT FROM AUTHOR]

Common buckwheat (Fagopyrum esculentum Moench) is a gluten-free underutilized pseudocereal with excellent therapeutic and nutraceutical potential. Sprouts and microgreens produced from this plant species can be consumed regularly owing to a rich nutritional profile that can be improved by regulating the abiotic factors during their growth. Therefore, this study explores the responses of common buckwheat sprouts and microgreens in terms of growth and phytochemicals accumulation under temperature (16, and 25 ºC) and photoperiodic (16/8 h and 20/4 h, light/dark intervals) variations. Some analyses were also performed at 4 and 8 ºC. The findings highlight the beneficial effects of mild stress induced by extended photoperiod and moderate temperature like enhanced yield and phytochemical content. Extending the photoperiodic duration from 16/8 h to 20/4 h significantly triggered the biosynthesis of pigments such as carotenoids and chlorophyll in 12-day-old microgreen leaves. Likewise, a moderate temperature i.e., 16 ºC was proved more effective in inducing the accumulation of secondary metabolites including phenolics and flavonoids. However, extreme cold conditions hindered the sprouting and growth rate underscoring common buckwheat sensitivity to low temperature. These findings are crucial for refining the production strategies, ensuring the nutritional values, and optimizing the potential of common buckwheat sprouts and microgreens as "superfoods". [ABSTRACT FROM AUTHOR]

The present study examined the synergistic impact of exogenous hydrogen sulfide (H2S) and nitric oxide (NO) in mitigating nickel (Ni; 1 µM) induced toxicity in two paddy field cyanobacteria, namely Nostoc muscorum ATCC 27893 and Anabaena sp. PCC 7120. The evaluation encompasses growth, photosynthetic pigments (chlorophyll a, carotenoids and phycocyanin), oxidative biomarkers, and enzymes and metabolites involved in the ascorbate–glutathione (AsA-GSH) cycle. Cellular Ni accumulation resulted in elevated reactive oxygen species (ROS) production, reduced pigment levels, and impeded growth. The augmented activities of AsA-GSH cycle enzymes (ascorbate peroxidase, glutathione reductase, and dehydroascorbate reductase) were unable to counteract these toxic effects. However, exogenous supplementation of 8 µM H2S and 10 µM NO significantly reduced Ni-induced toxicity. This amelioration involved decreasing ROS levels, minimizing cellular Ni accumulation, enhancing photosynthetic pigments level, and elevating the AsA-GSH cycle's potential, thereby functioning as promoters of the metal detoxification system. The SEM analysis depicted Ni-accumulation on the surface of both cyanobacterial cells. Furthermore, introducing scavengers (PTIO for NO and HT for H2S) and inhibitors (L-NAME for NO and PAG for H2S) reversed the positive effects of H2S and NO, exacerbating damages under Ni-induced stress. This study proposed a cross-talk mechanism between H2S and NO, wherein H2S downregulates signaling on NO-mediated alleviation under Ni stress in both cyanobacteria. Additionally, the present work suggests that utilizing a lower dose of H2S and NO (cost-effective) in paddy fields could enhance the growth of cyanobacteria (as a significant biofertilizer), even under existing stressful conditions. This approach aims to support sustainable agriculture and uphold rice crop productivity. [ABSTRACT FROM AUTHOR]

Main conclusion: The metabolomic of the Italian endemic species Stachys italica was investigated and potential positive metabolites for human’s health were detected, quantified and discussed in relation to its synecology. Stachys italica is a species endemic to central-southern Italy, traditionally used for human consumption. The present research reports the results of a phytosociological study of this species in two southern regions of Italy (Apulia and Calabria). The collected plant material was used to make two types of extracts: hot water infusion to evaluate the use of this plant as tea and hydroalcoholic extraction to evaluate the use of it in herbal liqueur preparation. The extracts obtained by the hot water infusion had a values of total polyphenols and antioxidant capacity similar to values found in black tea. The analysis of non-volatiles compounds revealed the presence of biologically active substances like lavandulifolioside, verbascoside, and methoxyflavones. The analysis of volatiles fraction of metabolites demonstrated fifty-three volatiles compounds in the plant aerial part, 19 of which belonging to monoterpenoids, and 17 to the class of sesquiterpenoids. Among them, α-pinene, β-pinene, cis-ocimene, limonene and t-caryophyllene, were the most abundant compounds. The results were compared with already published results and referred to other similar species (such as Sideritis syriaca) which represent herbal mixtures usually collected and used as “mountain tea” in the Balkans and Eastern European countries. [ABSTRACT FROM AUTHOR]

Background: Non‐invasive evaluation of phosphomonoesters (PMEs) and phosphodiesters (PDEs) by 31‐phosphorus MR spectroscopy (31P MRS) may have potential for early therapy (non‐)response assessment in cancer. However, 31P MRS has not yet been applied to investigate the human pancreas in vivo. Purpose: To assess the technical feasibility and repeatability of 31P MR spectroscopic imaging (MRSI) of the pancreas, compare 31P metabolite levels between pancreas and liver, and determine the feasibility of 31P MRSI in pancreatic cancer. Study Type: Prospective cohort study. Population: 10 healthy subjects (age 34 ± 12 years, four females) and one patient (73‐year‐old female) with pancreatic ductal adenocarcinoma. Field Strength/Sequence: 7‐T, 31P FID‐MRSI, 1H gradient‐echo MRI. Assessment: 31P FID‐MRSI of the abdomen (including the pancreas and liver) was performed with a nominal voxel size of 20 mm (isotropic). For repeatability measurements, healthy subjects were scanned twice on the same day. The patient was only scanned once. Test–retest 31P MRSI data of pancreas and liver voxels (segmented on 1H MRI) of healthy subjects were quantified by fitting in the time domain and signal amplitudes were normalized to γ‐adenosine triphosphate. In addition, the PME/PDE ratio was calculated. Metabolite levels were averaged over all voxels within the pancreas, right liver lobe and left liver lobe, respectively. Statistical Tests: Repeatability of test–retest data from healthy pancreas was assessed by paired t‐tests, Bland–Altman analyses, and calculation of the intrasubject coefficients of variation (CoVs). Significant differences between healthy pancreas and right and left liver lobes were assessed with a two‐way analysis of variance (ANOVA) for repeated measures. A P‐value <0.05 was considered statistically significant. Results: The intrasubject CoVs for PME, PDE, and PME/PDE in healthy pancreas were below 20%. Furthermore, PME and PME/PDE were significantly higher in pancreas compared to liver. In the patient with pancreatic cancer, qualitatively, elevated relative PME signals were observed in comparison with healthy pancreas. Data Conclusion: In vivo31P MRSI of the human healthy pancreas and in pancreatic cancer may be feasible at 7 T. Evidence Level: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

An actinobacterium newly isolated from soil during a screening study was identified as Streptomyces sp. MC12 (GenBank accession number: PP757795) based on 16S rRNA analysis. For secondary metabolite production, fermentation was carried out in ISP 2 broth at 30°C, pH 7.3, for seven days under shaking conditions at 180 rpm. As a result of fermentation studies, the antagonistic effect of the crude extract, obtained through ethyl acetate extraction, against various microorganisms was determined. The MIC values of the extract against Staphylococcus aureus and Escherichia coli were 101.3 µg/mL and 153.6 µg/mL, respectively. It was also found to exhibit strong antifungal activity against Penicillium spp. Streptomyces sp. MC12, which displays both antifungal and antibacterial properties, is considered a potential secondary metabolite producer for future studies, particularly in pharmacology and the biocontrol of fungal pathogens. [ABSTRACT FROM AUTHOR]

Red apricot (Prunus spp.) and Black Fig (Ficus carica L.) are two of the most commonly grown summer fruits in the Nakhchivan region. In this preliminary study, ethanol fruit extracts were compared based on their total phenolic content (TPC) and antioxidant properties. According to the Folin-Ciocalteu method, the TPC was found to be 176.20 mg GAE/100 g in red apricot and 45.30 mg GAE/100 g in fig. Their antioxidant capacities were assessed using 2,2-Diphenyl-1- picrylhydrazyl (DPPH) radical scavenging activity. The scavenging activity, identified as the concentration of ethanol extract needed to scavenge half of the radicals (SC50), was determined to be 3.52 mg/mL for red apricot and 6.46 mg/mL for fig. Based on these two biological activity assays, red apricot exhibited higher phenolic composition and radical scavenging activity. However, further studies are required to understand whether these differences are attributed to secondary metabolites in these fruits. [ABSTRACT FROM AUTHOR]

Bleeding from a wound as a result of physical injury is a life-threatening condition. In pursuing new drug structures, the effect of crude fungal extracts fungal isolated from Jatropha multifida on wound healing and coagulation of mouse whole blood was investigated. Jatropha multifida leaves were sterilized, cut into small segments, and then incubated in Potato Dextrose Agar for seven days. Four isolates were purified and their morphologies were characterized. Identification of isolates was confirmed by a molecular protocol. Two crude extracts from Phlebiopsis gigantea (OK021602) and Phyllosticta sp (OK021603), which exhibited higher phytochemicals composition, were selected and evaluated using wound excision and coagulation of mouse whole blood, by administering 30 µg/mL, 50 µg/mL and 70 µg/mL crude extracts respectively. The percentage of wound healing in mice was higher (p<0.05) for the crude extracts of Phlebiopsis gigantea (OK021602) as compared to that of Phyllosticta sp (OK021603). The highest percentages of wound contraction were 99% at 70 µg/mL, and 53% at 70 µg/mL for Phlebiopsis gigantea (OK021602) and Phyllosticta sp (OK021603), respectively as compared to the control group which had 42% wound contraction at day 15 post-treatment. The results of the present study clearly indicate that Jatropha multifida leaves harbor endophytic fungi that produce pharmacologically important bioactive secondary metabolites with wound and hemostatic effects; therefore, further exploration is inevitable, particularly for the purification and identification of specific chemical structures of bioactive compounds. [ABSTRACT FROM AUTHOR]

Leptadenia reticulata is a vital Ayurvedic medicinal herb, commonly known as Jivanti or Jiv, and contains revitalising, rejuvenating, and lactogenic activities. It has been used in traditional medicine for treating respiratory disorders, wounds, inflammation, cough, dehydration, tuberculosis, colitis, chickenpox, dysentery, eye diseases, night blindness, fever, and snake bites. It is a perennial herb of Indian origin belonging to the Asclepiadaceae family and has been utilised for its therapeutic properties since ancient times. It is a key ingredient in several marketed herbal drugs, including chyawanprash, speman, and leptaden. Several potent compounds, including β-sitosterol, γ-sitosterol, phytol, α-amyrin, β-amyrin, apigenin, reticulin, deniculatin, leptaculatin, diosmetin, and rutin are present in this herb and attributed various pharmacological activities, including antidiabetic, antimicrobial, antioxidant, anti-abortifacient, anticancer, antipyretic, analgesic, anti-inflammatory, and antiulcer properties. This review provides an in-depth analysis of the distribution, ethnobotanical use, botanical description, phytocompounds, and pharmacological activities of Leptadenia reticulata. HIGHLIGHTS: Leptadenia reticulata is a vital Ayurvedic herb containing revitalising, rejuvenating, and lactogenic activities. It is present in polyherbal formulations chyawanprash, speman, and leptaden. Its secondary metabolites have anticancer, anticholesterol, antidiabetic, antiabortifacient, and anti-inflammatory potential. This review shows the distribution, morphology, and therapeutic potential of Leptadenia reticulata. A summary of the phytochemicals present in Leptadenia reticulata will also be provided. [ABSTRACT FROM AUTHOR]

Two previously undescribed natural cyathane diterpenoids Me-dentifragilin A (1) and Epi-neocyathin O (2), and three known cyathane diterpenoids 3–5, cyathin O, neocyathin P, and cyathin I, were isolated from the rice medium of the Cyathus striatus CBPFE A06. Their structures were established by NMR spectra, and HR-ESI-MS. Compounds 1–5 displayed encouraging neurotrophic activity in PC-12 cells at doses of 5 µM. Meanwhile, 1–5 significantly inhibited LPS-induced NO generation in BV2 cells with the IC50 values ranging from 2.44 ± 0.16 to 4.33 ± 0.32 μM. Western blot analysis showed that 2 and 4 inhibited the expression of genes involved in nitric oxide (NO) production. Molecular docking revealed that five residues of inducible NO synthase (iNOS) are key residues affecting the interaction of 2 and 4 with iNOS. This study enriches the structural diversity of cyathane diterpenes and adds to the evidence that cyathane diterpenes prevent and treat neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The global yield of wheat is limited by Fusarium head blight (FHB), the most damaging disease of wheat accompanied by mycotoxin contamination. Use of resistant cultivars, from an economical point of view, is the most effective control method for plant diseases. Many naturally occurring secondary metabolites in plants are involved in resistance mechanisms against FHB, especially phenolic compounds with antioxidant properties which caused various colouration of the grain in wheat. The objective of this paper was to evaluate the resistance of wheat with different grain colour on the base of accumulation of deoxynivalenol (DON) in grain and other important FHB traits after inoculation with Fusarium culmorum. Visual symptom score (VSS), Fusarium damaged kernels (FDK) and reduction of grain weight per spike (GWS-R) were determined. This study compared current conventional red wheat cultivars and coloured-grain wheat cultivars or lines with blue aleurone, purple pericarp, red grain and white grain. It was found that the cultivars with a purple pericarp (e.g. Rufia) had the lowest DON content and FDK. Statistically significant interactions between grain colour and year were found for all the variables: DON, VSS, FDK, GWS-R. Red grain materials had the lowest DON levels of all the groups studied in 2016 and 2017, but not in 2018. The most constant and second lowest DON levels in all three years were found in the cultivars/lines with purple pericarp. [ABSTRACT FROM AUTHOR]