PubMed

Int J Biol Macromol. 2025 Jan 4:139533. doi: 10.1016/j.ijbiomac.2025.139533. Online ahead of print.ABSTRACTMyostatin (MSTN) is a protein that plays a crucial role in regulating skeletal muscle development. Despite the known benefits of MSTN mutant cattle for increasing beef production, their potential impact on CH4 emissions has not been quantified. The study comparing wild-type (WT) cattle to MSTN-knockout (MSTN-KO) cattle revealed that CH4 production was lower. Macrogenomic analysis revealed a significant decrease in rumen archaea, with reduced Richness indices (P = 0.036). The MSTN-KO cattle also showed altered archaea distribution and composition at different taxonomic levels. LEfSe results showed changes in 21 methanogenic archaea clades, with obligately hydrogen (H2)-dependent methylotrophs Candidatus Methanoplasma termitum species belonging to Methanomassiliicoccales order demonstrating the most significant decrease. Rumen metabolites revealed a decrease in the ratio of acetate to propionate, indicating a shift in rumen fermentation pattern towards propionate fermentation. Additionally, the changing trend of methanogenic archaea is consistent with the evolution of methanogens, and this is correlated with the higher levels of linoleic acid in the rumen of MSTN-KO cattle. Linoleic acid affects the utilization of H2 by methanogenic archaea, leading to a reduction in obligately H2-dependent methylotrophs. Our study suggests that MSTN-KO cattle have potential as an economically and ecologically benign breed for reducing methane emissions.PMID:39761884 | DOI:10.1016/j.ijbiomac.2025.139533

Int J Biol Macromol. 2025 Jan 4:139514. doi: 10.1016/j.ijbiomac.2025.139514. Online ahead of print.ABSTRACTNumerous studies indicate that Schisandra chinensis (Turcz.) Baill (SC) has anti-type 2 diabetes mellitus (T2DM) effects, and its processed products are commonly used in clinical practice. However, limited reports exist on the mechanisms of polysaccharides from its vinegar products and their role in T2DM. We purified a novel polysaccharide from vinegar-processed Schisandra chinensis (VSC) and used intestinal microbiota 16S rRNA analysis and metabolomics to study changes in T2DM mice after vinegar-processed Schisandra chinensis polysaccharide (VSP) intervention, aiming to elucidate how VSP alleviates T2DM. VSP has shown significant therapeutic effects in T2DM mice, which can regulate the imbalance of glucose and lipid metabolism, alleviate pancreatic and liver damage, restore the integrity of the intestinal barrier, and inhibit the inflammatory response. Serum metabolomics and microbiological analysis showed that VSP could significantly regulate 104 endogenous metabolites and rectify gut microbiota disorders in T2DM mice. Additionally, VSP enhanced the levels of short-chain fatty acids (SCFAs) and the expression of GPR41/43 in the colon of T2DM mice. Correlation analysis revealed significant correlations among specific gut microbiota, serum metabolites, and fecal SCFAs. Overall, these findings will provide a basis for further VSP development.PMID:39761882 | DOI:10.1016/j.ijbiomac.2025.139514

J Adv Res. 2025 Jan 4:S2090-1232(25)00003-7. doi: 10.1016/j.jare.2025.01.003. Online ahead of print.ABSTRACTINTRODUCTION: Hyperglycemia and hyperlipidemia are the hallmarks of type 2 diabetes mellitus (T2DM). T2DM is a systemic metabolic disease caused by insulin resistance and malfunctioning pancreatic β-cells. Although ginseng (the roots of Panax ginseng C.A. Meyer) can be used to treat T2DM, the underlying mechanism is unclear.OBJECTIVES: To assess the role and mechanism of, γ-aminobutyric acid-fructosyl-glucose (GABAFG), a maillard reaction product of ginseng, in T2DM treatment.METHODS: The metabolism of GABAFG in serum and tissues was analyzed via ultra-high performance liquid chromatography-Q exactive-mass spectrometry (UHPLC-QE-MS). The molecular mechanisms of GABAFG in pancreatic β-cells (in vivo and in vitro) were investigated via Western blotting, qPCR and immunofluorescence. In addition, the results were validated via high-throughput sequencing and serum metabolomics.RESULTS: GABAFG alleviated the elevation of blood glucose and blood lipids in HFD/STZ-induced T2DM mice. Also, GABAFG reduced the insulin resistance-associated IRS-1 signaling axis in pancreatic β-cells in vitro. Mechanistically, GABAFG targeted the nuclear translocation of TFEB inhibited apoptosis of pancreatic β-cells by enhancing autophagolysosome function. In addition, GABAFG remodeled the gut microbiota. Specifically, GABAFG increased Akkermansia, decreased Romboutsia abundance, and decreased serum glycerophospholipid metabolism, thus alleviating T2DM-induced dyslipidemia.CONCLUSION: This is the first study to assess the pharmacological effects of ginseng-derived GABAFG in T2DM. Therefore, this study provides a new theoretical basis for understanding ginseng effect in metabolic diseases.PMID:39761869 | DOI:10.1016/j.jare.2025.01.003

J Ethnopharmacol. 2025 Jan 4:119327. doi: 10.1016/j.jep.2025.119327. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Ardisia is a large genus of Primulaceae, 734 accepted species worldwide, and most species are used as ethnomedicines for the treatment of bruises, rheumatism, tuberculosis, and various inflammatory diseases. According to our previous ethnobotanical survey, Ardisia gigantifolia Stapf, Ardisia hanceana Mez (Da-luo-san), and Ardisia crenata Sims (Xiao-luo-san) are commonly used in folk medicine for the treatment of rheumatism. Among them, A. hanceana and A. crenata in folklore has "Use Da-luo-san and Xiao-luo-san together for better rheumatism treatment". These three plants can be referred to as the characteristic herbs of Ardisia.AIM OF THE STUDY: To characterize the metabolites of three plants of Ardisia, clarify the metabolites differences, validate the traditional folk applications, and identify potential biomarkers.MATERIALS AND METHODS: UPLC-QTOF-MS and UPLC-QTRAP-MS metabolomics analysis techniques were utilized to reveal the metabolites of three plants of Ardisia. Combined with multivariate statistical analysis, differentially accumulated metabolites (DAMs) and biomarkers were screened. The inhibition of NO production was measured, and the p_value was determined using one-way ANOVA with Fisher's LSD test, to validate folk traditional application.RESULTS: A total of 328 metabolites were identified from the three plants' roots using UPLC-QTOF-MS, and 86 DAMs were screened by OPLS-DA. Among them, flavonoids are the main DAMs, especially between Zou-ma-tai group (A. gigantifolia) and the Luo-san group (A. hanceana and A. crenata). UPLC-QTRAP-MS was used to quantify the three DAMs, and it was found that the contents of (+/-)-catechin and gallic acid were higher in the Luo-san group. To verify the traditional application of the three plants, it was found that the activity of the three plants was better at 0.2 mg/mL, and the activity of the Luo-san group was significantly stronger than that of the Zou-ma-tai (p < 0.001). Further, 16 potential anti-inflammatory active biomarkers were screened by the two groups, and the relative contents of flavonoids was significantly higher in the Luo-san group, which was inferred to be a possible key active ingredient in the Luo-san group for the treatment of rheumatic diseases. Further network pharmacological methods verified that these flavonoid components may exert their therapeutic effects on rheumatic diseases by modulating multiple signaling pathways such as TNF, 1L-17, NF-κB, and T-cell receptor through key targets such as PTGS2, ESR1, ALOX5, CA2, XDH, and AKR1B1.CONCLUSION: This study identified the main active metabolites of the three plants of Ardisia, verified the local folklore that "Use Da-luo-san and Xiao-luo-san together for better rheumatism treatment", and spread the folk traditional knowledge. It is indicated that the Luo-san group have important potential medicinal value and development prospects. It further provides a scientific basis for the conservation and utilization of Ardisia resources as well as sustainable development.PMID:39761835 | DOI:10.1016/j.jep.2025.119327

Environ Pollut. 2025 Jan 4:125646. doi: 10.1016/j.envpol.2025.125646. Online ahead of print.ABSTRACTThe biological pathways connecting ambient fine particulate matter (PM2.5)-induced initial adverse effects to the development of atherosclerotic cardiovascular diseases are not fully understood. We hypothesize that lysoglycerophospholipids (LysoGPLs) are pivotal mediators of atherosclerosis induced by exposure to PM2.5. This study investigated the changes of LysoGPLs in response to PM2.5 exposure and the mediation role of LysoGPLs in the pro-atherosclerotic effects of PM2.5 exposure. In this longitudinal panel study, 110 adults aged 50-65 years from Beijing, China, were followed between 2013 and 2015. Targeted metabolomics analyses were utilized to quantify 18 LysoGPLs from five subclasses in 579 plasma samples. Daily PM2.5 mass concentration was monitored at a station. We used linear mixed-effect models to estimate the responses of LysoGPLs to PM2.5 exposure. Subsequently, mediation analyses were conducted to investigate the mediating role of LysoGPLs in PM2.5-associated changes in non-high density lipoprotein-cholesterol (Non-HDL-C), a biomarker for pro-atherosclerotic apolipoprotein B-containing lipoproteins, and various inflammatory biomarkers, including interleukin (IL)-8, monocyte chemoattractant protein-1 (MCP-1), soluble CD40 ligand, and interferon (IFN)-γ. Short- to medium-term (1-30 days) PM2.5 exposure was associated with significant increases in six lysophosphatidic acids (LPAs), three lysoalkylphosphatidylcholines [LPC(O)s], and three lysophosphatidylglycerols (LPGs), as well as decreases in two LPAs and one lysophosphatidylserine (LysoPS), with maximus changes of 0.5-2.1%, 0.8-2.1%, 1.9-3.0%, -1.4--3.7%, and -8.0%, respectively. Furthermore, the elevated levels of LPA 18:1/18:2, LPC(O) 18:0/18:1, and LPG 16:0/16:1/18:0 significantly mediated the PM2.5-associated increase in Non-HDL-C (18-49%), IL-8 (9-24%), MCP-1 (12-26%), and IFN-γ (4-12%) over 30 days. In conclusion, short- to medium-term PM2.5 exposure was associated with altered metabolism of LysoGPLs, which mediated the PM2.5-associated pro-atherosclerotic response.PMID:39761719 | DOI:10.1016/j.envpol.2025.125646

Plant Physiol. 2025 Jan 6:kiaf005. doi: 10.1093/plphys/kiaf005. Online ahead of print.ABSTRACTStylo (Stylosanthes guianensis) is a tropical legume that exhibits considerable tolerance to manganese (Mn) toxicity, which severely constrains plant growth in acidic soils. To elucidate the Mn detoxification mechanisms in stylo, this study investigated the excess Mn-regulated metabolic profile of stylo roots and examined the role of metabolic enzymes in Mn tolerance. Excess Mn triggered oxidative stress in the two stylo genotypes tested. However, Mn-stimulated activation of antioxidant defense systems was observed in the Mn-tolerant genotype RY5 but not in the Mn-sensitive genotype TF0317. Metabolomic analysis of the Mn-tolerant RY5 roots revealed numerous excess Mn-responsive metabolites, mainly related to flavonoids and phenolic acids. Furthermore, a set of genes involved in the phenylpropanoid/flavonoid pathway were upregulated by excess Mn in stylo roots, especially in RY5. We characterized the excess Mn-inducible gene SgPAL2, encoding phenylalanine ammonia-lyase. SgPAL2 localized to the endoplasmic reticulum. Compared to control plants, SgPAL2 overexpression led to increases in shoot and root dry weights under Mn-excess conditions, whereas SgPAL2 suppression had the opposite effect. Moreover, SgPAL2 overexpression dramatically altered secondary metabolism, particularly flavonoid metabolism. In a bioassay, the inhibition of root elongation caused by excess Mn was alleviated by treatment with exogenous calycosin, an SgPAL2-regulated isoflavonoid, suggesting calycosin can detoxify Mn. Taken together, these findings indicate that SgPAL2 plays a critical role in enhancing Mn tolerance in stylo through metabolic regulation.PMID:39761536 | DOI:10.1093/plphys/kiaf005

Tree Physiol. 2025 Jan 6:tpaf003. doi: 10.1093/treephys/tpaf003. Online ahead of print.ABSTRACTNorway maple and sycamore belong to the Acer genus and produce desiccation-tolerant and desiccation-sensitive seeds, respectively. We investigated the seed germination process at the imbibed and germinated stages using metabolomic and proteomic approaches to determine why sycamore seeds germinate earlier and are more successful at establishing seedlings than Norway maple seeds under controlled conditions. Embryonic axes and embryonic axes with protruded radicles were analyzed at the imbibed and germinated stages, respectively. Among the 212 identified metabolites, 44 and 67 differentially abundant metabolites were found at the imbibed and germinated stages, respectively, in both Acer species. Higher levels of amines, growth and defense stimulants, including B vitamins, were found in sycamore. We identified 611 and 447 proteins specific to the imbibed and germinated stages, respectively, in addition to groups of proteins expressed at different levels. Functional analysis of significantly regulated proteins revealed that proteins with catalytic and binding activity were enriched during germination, and proteins possibly implicated in nitrogen metabolism and metabolite interconversion enzymes were the predominant classes. Proteins associated with the control of plant growth regulation and seed defense were observed in both species at both germination stages. Sycamore proteins possibly involved in abscisic acid signal transduction pathway, stress tolerance and alleviation, ion binding and oxygenase activities appeared to accompany germination in sycamore. We identified peptides containing methionine (Met) oxidized to methionine sulfoxide (MetO), and functional analyses of proteins with significantly regulated MetO sites revealed that translation, plant growth and development, and metabolism of nitrogen compounds were the main processes under Met/MetO redox control. We propose that higher levels of storage proteins and amines together with higher levels of B vitamins supported more efficient nitrogen utilization in sycamore, resulting in faster seedling growth. In conclusion, omic signatures identified in sycamore seem to predispose germinated sycamore seeds to better postgerminative growth.PMID:39761348 | DOI:10.1093/treephys/tpaf003

PLoS One. 2025 Jan 6;20(1):e0313337. doi: 10.1371/journal.pone.0313337. eCollection 2025.ABSTRACTAdonis amurensis Regel et Radde is a remarkable and important spring ephemeral plant and gained considerable attention because of its remarkable medicinal properties. Extensive research has been conducted on its therapeutic applications, physical characteristics, flowering patterns, reproductive, cultural and molecular biology. However, there is a lack of comprehensive understanding regarding the metabolic changes associated with flower developmental stages. This study was designed to investigate the changes in metabolites and their interrelationships at five distinct developmental stages of A. amurensis flower: Flower Primordium (FP), Sepal Stage (SE), Perianth Primordium (PE), Stamens Stage (SE), and Pistil Stage (PI). High-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) was utilized to investigate and characterize the metabolites associated with specific flower developmental stages. The various stages of flower development exerted a substantial influence on both the quantity and composition of metabolites present, signifying significant changes in the types and quantities of metabolites throughout the developmental progression of the flower. Metabolite Set Enrichment Analysis (MSEA) and annotation via the KEGG database highlighted enriched pathways such as flavonoid biosynthesis and plant hormone signal transduction, which are crucial for flower maturation. The highest number of differentially expressed metabolites was identified between the SE and PI stages, emphasizing a marked appreciation in metabolite expression linked to the development of reproductive organs. Key pathways such as flavonoid biosynthesis and plant hormone signal transduction were markedly enriched, underscoring their roles in flower maturation and potential pharmacological applications. Our research not only helps us in understanding the metabolomic dynamics during the flower development of A. amurensis but also emphasizes the potential pharmacological implication of stage-specific metabolites. Identifying these metabolites can help targeted bioprospecting and optimization of extraction methods to tackle the plant's full therapeutic potential, particularly in the development of treatments for cardiac insufficiency, edema, and possibly cancer.PMID:39761237 | DOI:10.1371/journal.pone.0313337

Chronobiol Int. 2025 Jan 6:1-14. doi: 10.1080/07420528.2024.2449015. Online ahead of print.ABSTRACTSeven-day actigraphy was performed within 1 month in 122 community-dwelling adults (mean age 24.40 y, 31 (25.4%) men) in the same city of Tyumen, Russia. Groups with different COVID-19 status (present, COVID-19(+), n = 79 vs absent, COVID-19(-), n = 43) did not differ in mean age, gender distribution, or body mass index. Vaccination status was equally represented in the COVID groups. We found that COVID-19 status, a history of SARS-CoV-2 infection, was differentially associated with daylight susceptibility. Daylight exposure was estimated using parametric and non-parametric indices: 24-h Amplitude, MESOR or M10 of white and blue light exposure (BLE) and compared between the groups. Distinctively in COVID-19(+) individuals, a smaller normalized 24-h amplitude of BLE (NAbl) was associated with lower circadian robustness, assessed by a smaller relative non-parametric amplitude (RA), a lower circadian function index (CFI), later bedtime, later onset of least active 5 h (L5), shorter total sleep duration, later phase and smaller circadian amplitude of physical motor activity. Such associations were absent in the overall COVID-19(-) population or in the vaccinated COVID(-) group. Considering COVID-status and light hygiene, defined as NAbl ≥ 1 versus NAbl < 1, only those with COVID(+) and NAbl < 1 (poorer light hygiene) had a statistically significantly delayed phase of activity and sleep, reduced circadian amplitude of physical activity, and lower circadian robustness. Accounting for gender and BMI, participants diagnosed with COVID-19 at an earlier date were older and had poorer circadian light hygiene. Altogether, our data suggest that those with COVID-19 were more vulnerable to circadian disruption due to poor circadian light hygiene, manifested as phase delay, small amplitude, a less robust circadian pattern of activity, and as delayed sleep. Our data suggest that the need for optimal circadian light hygiene is greater in individuals with a history of SARS-CoV-2 infection.PMID:39761104 | DOI:10.1080/07420528.2024.2449015

Biol Trace Elem Res. 2025 Jan 6. doi: 10.1007/s12011-024-04505-w. Online ahead of print.ABSTRACTCadmium is a heavy metal contaminant known to cause various health issues. However, limited research exists on the serum metabolomic effects of cadmium exposure in children. In this study, we recruited 42 children to analyze their serum metabolomic profiles, along with measuring urinary cadmium and creatinine concentrations, to evaluate the impact of environmental cadmium exposure on serum metabolism. We also screened for potential biomarkers. The findings revealed that environmental cadmium exposure led to disruptions in amino acid metabolism, biosynthesis of secondary metabolites, endocrine function, lipid metabolism, nervous system function, sensory processes, and the metabolism of cofactors and vitamins in children. Lansioside C, Hydroxytanshinone, and 1-Methylinosine were identified as potential biomarkers. In conclusion, environmental cadmium exposure negatively impacts children's neurological development by inducing metabolic disturbances and increasing the risk of oxidative stress-related disorders. This study provides a valuable theoretical foundation for future efforts to prevent the harmful effects of cadmium exposure in children and mitigate associated health risks.PMID:39760993 | DOI:10.1007/s12011-024-04505-w

Metab Brain Dis. 2025 Jan 6;40(1):89. doi: 10.1007/s11011-024-01513-6.ABSTRACTSerious neurological disorders were associated with cadmium toxicity. Hence, this research aimed to investigate the potential neuroprotective impacts of the ethanolic extracts of Citrus aurantium unripe fruits and leaves (CAF and CAL, respectively) at doses 100 and 200 mg/kg against cadmium chloride-provoked brain dysfunction in rats for 30 consecutive days. HPLC for natural pigment content revealed that CAF implied higher contents of Chlorophyll B, while the CAL has a high yield of chlorophyll A and total carotenoid. Fifty-seven chromatographic peaks were identified by UPLC/MS/MS; 49 and 29 were recognized from CAF or CAL, respectively. Four compounds were isolated from CAF: 3',4',7 -trihydroxyflavone, isorhainetin, vitexin, and apigenin. In vitro studies outlined the antioxidant capacity of studied extracts where CAF showed better scavenging radical DPPH activity. Results clarified that both extracts with a superior function of CAF at the high adopted dose significantly ameliorated CdCl2-induced neuro-oxidative stress and neuro-inflammatory response via restoring antioxidant status and hindering nuclear factor kappa B (NF-κB) stimulation. Moreover, it up-regulated the levels of phospho-protein kinase B (p-Akt), phospho- cAMP-response element binding protein (p-CREB), and brain-derived neurotropic factor (BDNF) levels, and elicited a marked decrease in the content of glycogen synthase kinase 3 beta (GSK3β), besides amending Caspase-3 and hyperphosphorylation of tau protein in brain tissues. Moreover, a significant improvement in the rats' behavioral tasks of the CAL and CAF-treated groups has been recorded, as indicated by marked preservation in locomotion, exploratory, and memory functions of the experimental rats. In conclusion, the reported neuroprotective impacts of C. aurantium extracts may be through modulating p-AKT/p-CREB/BDNF and / or p-Akt/ GSK3β/NF-κB signaling pathways.PMID:39760898 | DOI:10.1007/s11011-024-01513-6

Arch Toxicol. 2025 Jan 6. doi: 10.1007/s00204-024-03947-4. Online ahead of print.ABSTRACTSnake envenomation presents a significant global health challenge, especially in rural areas of tropical and subtropical regions. Traditional antivenom therapies face limitations related to efficacy, availability, and specificity, prompting a need for novel approaches. Recent advancements in omics technologies, particularly metabolomics and proteomics, have enhanced our understanding of snake venom composition, toxicity, and potential therapeutic strategies. Metabolomics allows for the study of metabolic changes induced by venom, providing insights into disrupted pathways and possible inhibitors. Proteomics facilitates the identification and characterization of venom proteins, unveiling their interactions with therapeutic agents. Integrative databases such as the Snake Venom Database (SVDB) and STAB Profiles enhance this research by cataloging venom components and aiding in the analysis of venom-antivenom interactions. The combined application of metabolomics and proteomics has led to the identification of crucial metabolic pathways and protein targets essential for effective venom inhibition. This review explores current advances in these fields, emphasizing the role of omics in identifying novel inhibitors and developing next-generation antivenoms. The integrated approach of metabolomics and proteomics offers a comprehensive understanding of snake venom biology, paving the way for more effective and tailored therapeutic solutions for envenomation.PMID:39760869 | DOI:10.1007/s00204-024-03947-4

AIDS. 2025 Jan 3. doi: 10.1097/QAD.0000000000004103. Online ahead of print.ABSTRACTHIV-1 remains a global challenge, especially in high-prevalence areas like South Africa. This study explores the relationship between inflammation and metabolism in people with HIV, focusing on immune markers and the tryptophan-kynurenine (Trp-Kyn) pathway. We examined immune markers (hsCRP, suPAR, IL-6, NGAL, and sCD163) and Trp-Kyn metabolites (QUIN, Trp, Kyn, Trp/Kyn ratio, and kynurenic acid) in n = 69 treatment-naive South African people with HIV. Using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics and various assays, we observed significant associations between immune markers and Trp-Kyn metabolites. IL-6 was negatively associated with Trp (P < 0.001) and positively with the Kyn/Trp ratio (P = 0.005). hsCRP was positively associated with QUIN (P = 0.036). suPAR showed significant negative associations with Trp (P = 0.036), positive associations with the Kyn/Trp ratio (P < 0.001), and QUIN (P = 0.007). sCD163 negatively associated with Trp (P < 0.001) and positively with the Kyn/Trp ratio (P < 0.001). When participants were stratified by inflammation levels (based on CRP), IL-6 (P = 0.002), QUIN (P = 0.009), and Kyn (P = 0.032) were significantly higher in the high inflammation group. Specific associations were observed only in certain groups, such as IL-6 negatively associating with Trp and kynurenic acid in the high inflammation group, and suPAR associating negatively with Trp in the low inflammation group. These exploratory findings provide further insight into how peripheral inflammation and metabolism are interrelated in South African people with HIV, potentially guiding future therapeutic strategies.PMID:39760690 | DOI:10.1097/QAD.0000000000004103

J Sep Sci. 2025 Jan;48(1):e70072. doi: 10.1002/jssc.70072.ABSTRACTEvaluating the practical utility of endangered plant species is crucial for their conservation. Nevertheless, numerous endangered plants, including Sinocalycanthus chinensis, lack historical usage data, leading to a paucity of guidance in traditional pharmacological research. This gap impedes their development and potential utilization. Ultra-high-performance liquid chromatography and Orbitrap high-resolution mass spectrometry were employed to analyze the S. chinensis leaves collected at different harvesting times. Then, the metabolites were automatically annotated by a self-built R script in conjunction with characteristic fragment ions, neutral loss filtering, and feature-based molecular networking. By integrating metabolomics with network medicine analysis, the potential usage and optimal harvest times for S. chinensis were unlocked. A total of 305 metabolites were identified, with 66.8% annotated by self-built R script. A progressive increase in metabolite disparities was observed from May to August, followed by a relatively minor distinction from August to October. Notably diverse metabolites were detected in S. chinensis harvested during different periods, implying potential variations in efficacy. Network medicine analysis indicated possible therapeutic implications of S. chinensis for lung cancer, diabetes, bladder cancer, and Alzheimer's disease. Samples collected in May and September demonstrated exceptional efficacy. Harvesting was strategically conducted during these months based on variations in sample characteristics and metabolite content, tailored to their intended applications for dietary or medicinal purposes. This study developed an efficient methodology for investigating metabolites and exploring the potential applications of S. chinensis in food and herbal medicine. Consequently, it provides technical support for the sustainable conservation of endangered plants with limited clinical application experience.PMID:39760617 | DOI:10.1002/jssc.70072

Clin Chem Lab Med. 2025 Jan 7. doi: 10.1515/cclm-2024-1337. Online ahead of print.ABSTRACTOBJECTIVES: Urinary steroid profiling after hydrolysis of conjugates is an emerging tool to differentiate aggressive adrenocortical carcinomas (ACC) from benign adrenocortical adenomas (ACA). However, the shortcomings of deconjugation are the lack of standardized and fully validated hydrolysis protocols and the loss of information about the originally conjugated form of the steroids. This study aimed to evaluate the quality of the deconjugation process and investigate novel diagnostic biomarkers in urine without enzymatic hydrolysis.METHODS: 24 h urine samples from 40 patients with ACC and 40 patients with ACA were analyzed by untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry both unmodified and after hydrolysis with arylsulfatase/glucuronidase from Helix pomatia. Both approaches were compared regarding the differentiation of ACC vs. ACA via ROC analyses and to evaluate the hydrolyzation efficiency of steroid conjugates.RESULTS: Steroid glucuronides were fully deconjugated, while some disulfates and all monosulfates were still largely detectable after enzymatic hydrolysis, suggesting incomplete and variable deconjugation. In unhydrolyzed urine, steroid monosulfates showed the best differentiation between ACC and ACA (highest AUC=0.983 for C21H32O6S, followed by its isomer and two isomers with the molecular formula C21H32O7S). Moreover, several disulfates were highly abundant and increased in ACC compared to ACA.CONCLUSIONS: This work highlights the limitations of hydrolyzing steroid conjugates before analysis and shows a possible superiority of a direct analysis approach compared to a hydrolysis approach from a methodological point of view and regarding diagnostic accuracy. Several steroid conjugates were found as promising diagnostic biomarkers for differentiation between ACC and ACA.PMID:39760337 | DOI:10.1515/cclm-2024-1337

Glia. 2025 Jan 6. doi: 10.1002/glia.24666. Online ahead of print.ABSTRACTHuman genetics studies lent firm evidence that microglia are key to Alzheimer's disease (AD) pathogenesis over a decade ago following the identification of AD-associated genes that are expressed in a microglia-specific manner. However, while alterations in microglial morphology and gene expression are observed in human postmortem brain tissue, the mechanisms by which microglia drive and contribute to AD pathology remain ill-defined. Numerous mouse models have been developed to facilitate the disambiguation of the biological mechanisms underlying AD, incorporating amyloidosis, phosphorylated tau, or both. Over time, the use of multiple technologies including bulk tissue and single cell transcriptomics, epigenomics, spatial transcriptomics, proteomics, lipidomics, and metabolomics have shed light on the heterogeneity of microglial phenotypes and molecular patterns altered in AD mouse models. Each of these 'omics technologies provide unique information and biological insight. Here, we review the literature on the approaches and findings of these methods and provide a synthesis of the knowledge generated by applying these technologies to mouse models of AD.PMID:39760224 | DOI:10.1002/glia.24666

Front Microbiol. 2024 Dec 20;15:1528258. doi: 10.3389/fmicb.2024.1528258. eCollection 2024.ABSTRACTBACKGROUND/AIM: The purpose of this study was to examine the hepatic bacterial composition and metabolome characteristics of patients with NAFLD using 16S rDNA sequencing and metabolomics. The results of the study revealed substantial differences in hepatic bacterial composition and metabolites between the NAFLD group and the control group. These differences were used to identify potential biomarkers that could be employed to diagnose NAFLD.SUBJECTS/METHODS: Liver tissues from 13 patients in the NAFLD group and 12 patients in the control group were collected for microbiota examination.RESULTS: The bacterial DNA profiles of the liver were significantly different between NAFLD patients and controls. NAFLD patients exhibited an enrichment of Enterobacterales, Mycobacteriales, Pseudomonadales, Flavobacteriales and Xanthomonadales, Sphingomonadales, Lysobact, which was characterised by a lack of erales. At the genus level, the abundance values of Escherichia-Shigella, Rhodococcus, and Chryseobacterium in the NAFLD group were significantly elevated, while the abundance values of Stenotrophomonas, Lawsonella and Sphingobium were significantly reduced. A total of 402 distinct metabolites were identified between the two groups, with 78 metabolites that were up-regulated and 14 metabolites that were down-regulated. The enrichment of metabolic pathways indicated that linoleic acid metabolism was the most significant contributor to the metabolic differences, and lipid metabolism was substantially differentiated. The hepatic metabolite levels were substantially correlated with the changes in hepatic microflora, as demonstrated by the correlation analysis.CONCLUSION: Differences in pathogenesis and host physiological function of NAFLD may be attributed to the hepatic flora and metabolomic characteristics. In the future, this presents new opportunities for the investigation of prospective diagnostic and therapeutic targets for NAFLD.PMID:39760085 | PMC:PMC11697427 | DOI:10.3389/fmicb.2024.1528258

Front Microbiol. 2024 Dec 20;15:1493272. doi: 10.3389/fmicb.2024.1493272. eCollection 2024.ABSTRACTThe Western Ghats of India is recognized as one of the world's eight "hottest hotspots" of biological diversity. Trichoderma-a well-known biocontrol agent, was explored from this hotspot. A total of 260 Trichoderma spp. isolates were studied, with 9% exhibiting strong biocontrol potential and crop growth-promoting activity. Furthermore, this study identified three novel isolates-Trichoderma caribbaeum var. caribbaeum, Trichoderma lixii, and Trichoderma brevicompactum-which are reported for the first time from the Western Ghats making a significant contribution to the field. Based on internal transcribed spacer ribosomal RNA (ITS-rRNA) and translation elongation factor 1-α (tef-1α) gene sequence analysis, molecular characterization, identified major isolates as Trichoderma koningiopsis, Trichoderma asperellum, T. caribbaeum var. caribbaeum, T. lixii, T. brevicompactum, Trichoderma atroviride, and Trichoderma erinaceum. Seed biopriming with the effective Trichoderma strain TR11 reduced the maydis leaf blight (MLB) disease index to 32.92% and improved plant growth-promoting attributes in maize. Defensive enzyme activities were increased 2.5-4.2-fold in various treatments with the TR11 isolate, along with enhanced lignification postpathogen inoculation, indicating strengthened plant defense mechanisms. The promising strain T. brevicompactum-TR11 produces secondary metabolites; among them, 5% were found to have a role in biocontrol activity such as octadecanoic acid, palmitic acid-TMS, 5-(4-nitrophenoxymethyl), furane-2-carboxaldehyde, and stearic acid-TMS, phosphoric acid-3TMS, galactopyranose, 5TMS. This study explored Trichoderma diversity in the Western Ghats of India with phylogenetic relationship, metabolomics insights, and biocontrol efficacy against MLB disease.PMID:39760082 | PMC:PMC11695376 | DOI:10.3389/fmicb.2024.1493272

Rep Pract Oncol Radiother. 2024 Dec 4;29(5):649-650. doi: 10.5603/rpor.102823. eCollection 2024.ABSTRACTMulti-omics approaches are revolutionizing cancer research and treatment by integrating single-modality omics methods, such as the transcriptome, genome, epigenome, epi-transcriptome, proteome, metabolome, and developing omics (single-cell omics). These technologies enable a deeper understanding of cancer and provide personalized treatment strategies. However, challenges such as standardization and appropriate methods for funneling complex information into clinical consequences remain. The tumor microenvironment (TME) is a complex system containing cancer cells, immune cells, stromal cells, and secreted molecules. To overcome these challenges, researchers can establish standardized protocols for data collection, analysis, and interpretation. Collaborations and data sharing among research groups and institutions can create a comprehensive and standardized multi-omics database, facilitating cross-validation and comparison of results. Multi-omics profiling enables in-depth characterization of diversified tumor types and better reveal their function in cancer immune escape. Datasets play a fundamental role in multi-omics approaches, with artificial intelligence and machine learning (AI) rapidly advancing in multi-omics for cancer.PMID:39759552 | PMC:PMC11698559 | DOI:10.5603/rpor.102823

Front Immunol. 2024 Dec 11;15:1473895. doi: 10.3389/fimmu.2024.1473895. eCollection 2024.ABSTRACTINTRODUCTION: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, notably delta and omicron, has significantly accelerated the global pandemic, worsening conditions worldwide. However, there is a lack of research concerning the molecular mechanisms related to immune responses and metabolism induced by these variants.METHODS: Here, metabolomics combined with transcriptomics was performed to elucidate the immunometabolic changes in the lung of hamsters infected with delta and omicron variants.RESULTS: Both variants caused acute inflammation and lung pathology in intranasally infected hamsters. Principal component analysis uncovered the delta variant significantly altered lung metabolite levels between the pre- and post-infection states. Additionally, metabolic pathways determined by assessment of metabolites and genes in lung revealed significant alterations in arginine biosynthesis, glutathione metabolism, and tryptophan metabolism upon infection with both variants and closely linked to inflammatory cytokines, indicating immune activation and oxidative stress in response to both variants. These metabolic changes were also evident in the serum, validating the presence of systemic alterations corresponding to those identified in lung. Notably, the delta variant induced a more robust metabolic regulation than the omicron variant.DISCUSSION: The study suggests that multi-omics is a valuable approach for understanding immunometabolic responses to infectious diseases, and providing insights for effective treatment strategies.PMID:39759510 | PMC:PMC11697598 | DOI:10.3389/fimmu.2024.1473895