Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Molecular Networking-Based Metabolome, In Vitro Antidiabetic and Anti-Inflammatory Effects of Breonadia salicina (Vahl) Hepper & J.R.I. Wood

Wed, 26/06/2024 - 12:00
Metabolites. 2024 May 21;14(6):291. doi: 10.3390/metabo14060291.ABSTRACTBreonadia salicina (Vahl) Hepper & J.R.I. Wood is widely distributed throughout Africa. It is used ethnobotanically to treat various diseases. However, the metabolic profile of the Breonadia species is not well characterized and the metabolites that are responsible for the bioactivity of this plant remain unknown. Therefore, there is a need to determine the phytochemical and bioactivity profile to identify metabolites that contribute to the antidiabetic, anti-inflammatory and antiproliferation activity, including the genotoxicity and cytotoxic effects, of Breonadia salicina. The study is aimed at exploring the metabolomic profile antidiabetic, anti-inflammatory and antiproliferation activity, as well as the genotoxicity and cytotoxicity effects, of constituents of B. salicina. The compounds in the B. salicina extract were analyzed by ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS), and the resultant data were further analyzed using a molecular networking approach. The crude stem bark and root extracts showed the highest antidiabetic activity against α-amylase at the lowest test concentration of 62.5 µg/mL, with 74.53 ± 0.74% and 79.1 ± 1.5% inhibition, respectively. However, the crude stem bark and root extracts showed the highest antidiabetic activity against α-glucosidase at the lowest test concentration of 31.3 µg/mL, with 98.20 ± 0.15% and 97.98 ± 0.22% inhibition, respectively. The crude methanol leaf extract showed a decrease in the nitrite concentration at the highest concentration of 200 µg/mL, with cell viability of 90.34 ± 2.21%, thus showing anti-inflammatory activity. No samples showed significant cytotoxic effects at a concentration of 10 µg/mL against HeLa cells. Furthermore, a molecular network of Breonadia species using UPLC-QTOF-MS with negative mode electrospray ionization showed the presence of organic oxygen compounds, lipids, benzenoids, phenylpropanoids and polyketides. These compound classes were differentially distributed in the three different plant parts, indicating the chemical differences between the stem bark, root and leaf extracts of B. salicina. Therefore, the identified compounds may contribute to the antidiabetic and anti-inflammatory activity of Breonadia salicina. The stem bark, root and leaf extracts of B. salicina yielded thirteen compounds identified for the first time in this plant, offering a promising avenue for the discovery of new lead drugs for the treatment of diabetes and inflammation. The use of molecular networking produced a detailed phytochemical overview of this Breonadia species. The results reported in this study show the importance of searching for bioactive compounds from Breonadia salicina and provide new insights into the phytochemical characterization and bioactivity of different plant parts of Breonadia salicina.PMID:38921427 | DOI:10.3390/metabo14060291

Volatile Semiochemicals Emitted by <em>Beauveria bassiana</em> Modulate Larval Feeding Behavior and Food Choice Preference in <em>Spodoptera frugiperda</em> (Lepidoptera: Noctuidae)

Wed, 26/06/2024 - 12:00
J Fungi (Basel). 2024 Jun 20;10(6):438. doi: 10.3390/jof10060438.ABSTRACTBeauveria bassiana is an entomopathogenic fungus that parasitizes and kills insects. The role of volatile organic compounds (VOCs) emitted by B. bassiana acting as semiochemicals during its interaction with lepidopterans is poorly explored. Here, we studied the effect of VOCs from B. bassiana and 3-methylbutanol (as a single compound) on the feeding behavior of L2 larvae of Spodoptera frugiperda in sorghum plants. Additionally, we assessed whether fungal VOCs induce chemical modifications in the plants that affect larval food preferences. Metabolomic profiling of plant tissues was performed by mass spectrometry and bioassays in a dual-choice olfactometer. The results showed that the larval feeding behavior was affected by the B. bassiana strain AI2, showing that the insect response is strain-specific. Furthermore, 80 µg of 3-methylbutanol affected the number of bites. The larval feeding choice was dependent on the background context. Fragment spectra and a matching precursor ion mass of 165.882 m/z enabled the putative identification of 4-coumaric acid in sorghum leaves exposed to fungal VOCs, which may be associated with larval deterrent responses. These results provide valuable insights into the bipartite interaction of B. bassiana with lepidopterans through VOC emission, with the plant as a mediator of the interaction.PMID:38921424 | DOI:10.3390/jof10060438

Arbuscular Mycorrhizal Fungi Regulate Lipid and Amino Acid Metabolic Pathways to Promote the Growth of <em>Poncirus trifoliata</em> (L.) Raf

Wed, 26/06/2024 - 12:00
J Fungi (Basel). 2024 Jun 18;10(6):427. doi: 10.3390/jof10060427.ABSTRACTArbuscular mycorrhizal (AM) fungi can enhance the uptake of soil nutrients and water by citrus, promoting its growth. However, the specific mechanisms underlying the action of AM fungi in promoting the growth of citrus were not fully elucidated. This study aimed to explore the role of AM fungi Funneliformis mosseae in the regulatory mechanisms of P. trifoliata growth. Pot experiments combined with non-targeted metabolomics methods were used to observe the growth process and changes in metabolic products of P. trifoliata under the conditions of F. mosseae inoculation. The results showed that F. mosseae could form an excellent symbiotic relationship with P. trifoliata, thereby enhancing the utilization of soil nutrients and significantly promoting its growth. Compared with the control, the plant height, stem diameter, number of leaves, and aboveground and underground dry weight in the F. mosseae inoculation significantly increased by 2.57, 1.29, 1.57, 4.25, and 2.78 times, respectively. Moreover, the root system results confirmed that F. mosseae could substantially promote the growth of P. trifoliata. Meanwhile, the metabolomics data indicated that 361 differential metabolites and 56 metabolic pathways were identified in the roots of P. trifoliata and were inoculated with F. mosseae. This study revealed that the inoculated F. mosseae could participate in ABC transporters by upregulating their participation, glycerophospholipid metabolism, aminoacyl tRNA biosynthesis, tryptophan metabolism and metabolites from five metabolic pathways of benzoxazinoid biosynthesis [mainly enriched in lipid (39.50%) and amino acid-related metabolic pathways] to promote the growth of P. trifoliata.PMID:38921413 | DOI:10.3390/jof10060427

Identification and Characterization of <em>Hibiscus mutabilis</em> Varieties Resistant to <em>Bemisia tabaci</em> and Their Resistance Mechanisms

Wed, 26/06/2024 - 12:00
Insects. 2024 Jun 14;15(6):454. doi: 10.3390/insects15060454.ABSTRACTHibiscus mutabilis, the city flower of Chengdu, is culturally significant and has nutritional and medicinal benefits. However, frequent infestations of Bemisia tabaci have caused economic losses. This study aimed to identify insect-resistant H. mutabilis varieties. Over two years, varieties like Jinqiusong, Zuiyun, and Zuifurong showed moderate to high resistance based on reproductive indices. Assessments of antixenosis and developmental impacts revealed that adult B. tabaci exhibited low selectivity toward these resistant varieties, indicating a strong repellent effect. Gas chromatography-mass spectrometry analysis identified volatile organic compounds, such as alcohols, alkanes, and terpenes. Notably, 2-ethylhexanol and 6-methylheptanol exhibited repellent properties. Using nontargeted metabolomics, this study compared the metabolite profiles of the insect-resistant variety Jinqiusong (JQS), moderately resistant Bairihuacai (BRHC), and highly susceptible Chongbanbai (CBB) post B. tabaci infestation. Fifteen key metabolites were linked to resistance, emphasizing the phenylpropanoid biosynthesis pathway as crucial in defense. These findings offer a theoretical foundation for breeding insect-resistant H. mutabilis varieties and developing eco-friendly strategies against B. tabaci infestations.PMID:38921168 | DOI:10.3390/insects15060454

The Omics Revolution in Understanding Chicken Reproduction: A Comprehensive Review

Wed, 26/06/2024 - 12:00
Curr Issues Mol Biol. 2024 Jun 20;46(6):6248-6266. doi: 10.3390/cimb46060373.ABSTRACTOmics approaches have significantly contributed to our understanding of several aspects of chicken reproduction. This review paper gives an overview of the use of omics technologies such as genomics, transcriptomics, proteomics, and metabolomics to elucidate the mechanisms of chicken reproduction. Genomics has transformed the study of chicken reproduction by allowing the examination of the full genetic makeup of chickens, resulting in the discovery of genes associated with reproductive features and disorders. Transcriptomics has provided insights into the gene expression patterns and regulatory mechanisms involved in reproductive processes, allowing for a better knowledge of developmental stages and hormone regulation. Furthermore, proteomics has made it easier to identify and quantify the proteins involved in reproductive physiology to better understand the molecular mechanisms driving fertility, embryonic development, and egg quality. Metabolomics has emerged as a useful technique for understanding the metabolic pathways and biomarkers linked to reproductive performance, providing vital insights for enhancing breeding tactics and reproductive health. The integration of omics data has resulted in the identification of critical molecular pathways and biomarkers linked with chicken reproductive features, providing the opportunity for targeted genetic selection and improved reproductive management approaches. Furthermore, omics technologies have helped to create biomarkers for fertility and embryonic viability, providing the poultry sector with tools for effective breeding and reproductive health management. Finally, omics technologies have greatly improved our understanding of chicken reproduction by revealing the molecular complexities that underpin reproductive processes.PMID:38921044 | DOI:10.3390/cimb46060373

Multi Omics Applications in Biological Systems

Wed, 26/06/2024 - 12:00
Curr Issues Mol Biol. 2024 Jun 11;46(6):5777-5793. doi: 10.3390/cimb46060345.ABSTRACTTraditional methodologies often fall short in addressing the complexity of biological systems. In this regard, system biology omics have brought invaluable tools for conducting comprehensive analysis. Current sequencing capabilities have revolutionized genetics and genomics studies, as well as the characterization of transcriptional profiling and dynamics of several species and sample types. Biological systems experience complex biochemical processes involving thousands of molecules. These processes occur at different levels that can be studied using mass spectrometry-based (MS-based) analysis, enabling high-throughput proteomics, glycoproteomics, glycomics, metabolomics, and lipidomics analysis. Here, we present the most up-to-date techniques utilized in the completion of omics analysis. Additionally, we include some interesting examples of the applicability of multi omics to a variety of biological systems.PMID:38921016 | DOI:10.3390/cimb46060345

Free Salivary Amino Acid Profile in Breast Cancer: Clinicopathological and Molecular Biological Features

Wed, 26/06/2024 - 12:00
Curr Issues Mol Biol. 2024 Jun 5;46(6):5614-5631. doi: 10.3390/cimb46060336.ABSTRACTThe study of salivary amino acid profiles has attracted the attention of researchers, since amino acids are actively involved in most metabolic processes, including breast cancer. In this study, we analyzed the amino acid profile of saliva in a sample including all molecular biological subtypes of breast cancer to obtain a more complete picture and evaluate the potential utility of individual amino acids or their combinations for diagnostic purposes. This study included 116 patients with breast cancer, 24 patients with benign breast disease, and 25 healthy controls. From all patients, strictly before the start of treatment, saliva samples were collected, and the quantitative content of 26 amino acids was determined. Statistically significant differences between the three groups are shown in the content of Asp, Gly, Leu + Ile, Orn, Phe, Pro, Thr, and Tyr. To differentiate the three groups from each other, a decision tree was built. To construct it, we selected those amino acids for which the change in concentrations in the subgroups was multidirectional (GABA, Hyl, Arg, His, Pro, and Car). For the first time, it is shown that the amino acid profile of saliva depends on the molecular biological subtype of breast cancer. The most significant differences are shown for the luminal B HER2-positive and TNBC subgroups. In our opinion, it is critically important to consider the molecular biological subtype of breast cancer when searching for potential diagnostic markers.PMID:38921007 | DOI:10.3390/cimb46060336

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020-2023)

Wed, 26/06/2024 - 12:00
Int J Neonatal Screen. 2024 May 23;10(2):38. doi: 10.3390/ijns10020038.ABSTRACTNewborn bloodspot screening (NBS) began in the early 1960s based on the work of Dr. Robert "Bob" Guthrie in Buffalo, NY, USA. His development of a screening test for phenylketonuria on blood absorbed onto a special filter paper and transported to a remote testing laboratory began it all. Expansion of NBS to large numbers of asymptomatic congenital conditions flourishes in many settings while it has not yet been realized in others. The need for NBS as an efficient and effective public health prevention strategy that contributes to lowered morbidity and mortality wherever it is sustained is well known in the medical field but not necessarily by political policy makers. Acknowledging the value of national NBS reports published in 2007, the authors collaborated to create a worldwide NBS update in 2015. In a continuing attempt to review the progress of NBS globally, and to move towards a more harmonized and equitable screening system, we have updated our 2015 report with information available at the beginning of 2024. Reports on sub-Saharan Africa and the Caribbean, missing in 2015, have been included. Tables popular in the previous report have been updated with an eye towards harmonized comparisons. To emphasize areas needing attention globally, we have used regional tables containing similar listings of conditions screened, numbers of screening laboratories, and time at which specimen collection is recommended. Discussions are limited to bloodspot screening.PMID:38920845 | DOI:10.3390/ijns10020038

Fetus Exposure to Drugs and Chemicals: A Holistic Overview on the Assessment of Their Transport and Metabolism across the Human Placental Barrier

Wed, 26/06/2024 - 12:00
Diseases. 2024 Jun 1;12(6):114. doi: 10.3390/diseases12060114.ABSTRACTBACKGROUND: The placenta exerts a crucial role in fetus growth and development during gestation, protecting the fetus from maternal drugs and chemical exposure. However, diverse drugs and chemicals (xenobiotics) can penetrate the maternal placental barrier, leading to deleterious, adverse effects concerning fetus health. Moreover, placental enzymes can metabolize drugs and chemicals into more toxic compounds for the fetus. Thus, evaluating the molecular mechanisms through which drugs and chemicals transfer and undergo metabolism across the placental barrier is of vital importance. In this aspect, this comprehensive literature review aims to provide a holistic approach by critically summarizing and scrutinizing the potential molecular processes and mechanisms governing drugs and chemical transfer and metabolism across the placental barrier, which may lead to fetotoxicity effects, as well as analyzing the currently available experimental methodologies used to assess xenobiotics placental transfer and metabolism.METHODS: A comprehensive and in-depth literature review was conducted in the most accurate scientific databases such as PubMed, Scopus, and Web of Science by using relevant and effective keywords related to xenobiotic placental transfer and metabolism, retrieving 8830 published articles until 5 February 2024. After applying several strict exclusion and inclusion criteria, a final number of 148 relevant published articles were included.RESULTS: During pregnancy, several drugs and chemicals can be transferred from the mother to the fetus across the placental barrier by either passive diffusion or through placental transporters, resulting in fetus exposure and potential fetotoxicity effects. Some drugs and chemicals also appear to be metabolized across the placental barrier, leading to more toxic products for both the mother and the fetus. At present, there is increasing research development of diverse experimental methodologies to determine the potential molecular processes and mechanisms of drug and chemical placental transfer and metabolism. All the currently available methodologies have specific strengths and limitations, highlighting the strong demand to utilize an efficient combination of them to obtain reliable evidence concerning drug and chemical transfer and metabolism across the placental barrier. To derive the most consistent and safe evidence, in vitro studies, ex vivo perfusion methods, and in vivo animal and human studies can be applied together with the final aim to minimize potential fetotoxicity effects.CONCLUSIONS: Research is being increasingly carried out to obtain an accurate and safe evaluation of drug and chemical transport and metabolism across the placental barrier, applying a combination of advanced techniques to avoid potential fetotoxic effects. The improvement of the currently available techniques and the development of novel experimental protocols and methodologies are of major importance to protect both the mother and the fetus from xenobiotic exposure, as well as to minimize potential fetotoxicity effects.PMID:38920546 | DOI:10.3390/diseases12060114

Effects of Oxidative Stress on Serum Metabolism in Acute Pancreatitis Rats Based on Untargeted Metabolomics

Wed, 26/06/2024 - 12:00
Comb Chem High Throughput Screen. 2024 Jun 12. doi: 10.2174/0113862073291605240525144749. Online ahead of print.ABSTRACTOBJECTIVES: Acute pancreatitis(AP) is a common digestive tract disease, often accompanied by severe metabolic disorders, but there are no specific markers and treatment methods, and the potential metabolic pathways behind it remain to be explored.METHODS: Establish mild acute pancreatitis and severe acute pancreatitis models in rats and intervene with antioxidant NAC. Analyze serum oxidative stress indicators and pathological changes in pancreatic tissue. In addition, non-targeted metabolomics analysis of serum differential metabolites between groups was conducted based on the LC/MS system.RESULTS: The pathological score of the model group rats increased, and the levels of oxidative stress factors ROS and MDA significantly increased, while the activity of the antioxidant enzyme SOD decreased. After NAC intervention, oxidative stress damage in rats was alleviated. Non-targeted metabolomics experiments suggest significant differences in serum metabolic profiles among different groups of rats.CONCLUSION: Metabolomics results show that the obtained differential metabolites are expected to become serum biomarkers for AP.PMID:38920067 | DOI:10.2174/0113862073291605240525144749

Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease

Wed, 26/06/2024 - 12:00
Hemasphere. 2024 Jun 25;8(6):e109. doi: 10.1002/hem3.109. eCollection 2024 Jun.ABSTRACTMitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3-DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin. The PK activator mitapivat has been shown to decrease levels of 2,3-DPG and increase levels of ATP in RBCs in patients with SCD. In this phase 2, investigator-initiated, open-label study (https://www.clinicaltrialsregister.eu/ NL8517; EudraCT 2019-003438-18), untargeted metabolomics was used to explore the overall metabolic effects of 8-week treatment with mitapivat in the dose-finding period. In total, 1773 unique metabolites were identified in dried blood spots of whole blood from ten patients with SCD and 42 healthy controls (HCs). The metabolic phenotype of patients with SCD revealed alterations in 139/1773 (7.8%) metabolites at baseline when compared to HCs (false discovery rate-adjusted p < 0.05), including increases of (derivatives of) polyamines, purines, and acyl carnitines. Eight-week treatment with mitapivat in nine patients with SCD altered 85/1773 (4.8%) of the total metabolites and 18/139 (12.9%) of the previously identified altered metabolites in SCD (unadjusted p < 0.05). Effects were observed on a broad spectrum of metabolites and were not limited to glycolytic intermediates. Our results show the relevance of metabolic profiling in SCD, not only to unravel potential pathophysiological pathways and biomarkers in multisystem diseases but also to determine the effect of treatment.PMID:38919958 | PMC:PMC11196954 | DOI:10.1002/hem3.109

Unraveling the genetic and molecular basis of heat stress in cotton

Wed, 26/06/2024 - 12:00
Front Genet. 2024 Jun 11;15:1296622. doi: 10.3389/fgene.2024.1296622. eCollection 2024.ABSTRACTHuman activities and climate change have resulted in frequent and intense weather fluctuations, leading to diverse abiotic stresses on crops which hampers greatly their metabolic activities. Heat stress, a prevalent abiotic factor, significantly influences cotton plant biological activities resulting in reducing yield and production. We must deepen our understanding of how plants respond to heat stress across various dimensions, encompassing genes, RNAs, proteins, metabolites for effective cotton breeding. Multi-omics methods, primarily genomics, transcriptomics, proteomics, metabolomics, and phenomics, proves instrumental in studying cotton's responses to abiotic stresses. Integrating genomics, transcriptomics, proteomics, and metabolomic is imperative for our better understanding regarding genetics and molecular basis of heat tolerance in cotton. The current review explores fundamental omics techniques, covering genomics, transcriptomics, proteomics, and metabolomics, to highlight the progress made in cotton omics research.PMID:38919956 | PMC:PMC11196824 | DOI:10.3389/fgene.2024.1296622

Metabolomic and transcriptomic analysis of the flavonoid biosynthesis pathway in Epimedium sagittatum (Sieb. et Zucc.) Maxim. from distinct locations

Wed, 26/06/2024 - 12:00
Front Plant Sci. 2024 Jun 11;15:1424956. doi: 10.3389/fpls.2024.1424956. eCollection 2024.ABSTRACTEpimedium sagittatum (Sieb. et Zucc.) Maxim. (ESM) which accumulates several principal flavonoid compounds including epimedin A, B, C and icariin, is extensively utilized in traditional herbs for sexual dysfunction, osteoporosis etc. In China, ESM has a wealth of wild plant resources and characterized by significant variability in medicinal compounds accumulation. Understanding the diversity of ESMs can lead to better utilization of these plant resources. In this study, we integrated the metabolomic and transcriptomic analysis of three ESMs that originated in Anhui, Hubei and Jiangxi in China. Results showed that the flavonoid biosynthesis as well as the related gene expression in these ESMs revealed substantial differences. For example, the epimedin A, B, C and icariin as well as some related gene expression in ESMs from Anhui are significantly lower than those of in others. These results suggested that the ESMs from wild population without quality checkout may not be suitable for directly use as the materials for preparation of Chinese medicine and ESMs with different accumulation of metabolites could be used for distinct applications.PMID:38919822 | PMC:PMC11196779 | DOI:10.3389/fpls.2024.1424956

The use of omics technologies in creating LBP and postbiotics based on the <em>Limosilactobacillus fermentum</em> U-21

Wed, 26/06/2024 - 12:00
Front Microbiol. 2024 Jun 11;15:1416688. doi: 10.3389/fmicb.2024.1416688. eCollection 2024.ABSTRACTIn recent years, there has been an increasing tendency to create drugs based on certain commensal bacteria of the human microbiota and their ingredients, primarily focusing on live biotherapeutics (LBPs) and postbiotics. The creation of such drugs, termed pharmacobiotics, necessitates an understanding of their mechanisms of action and the identification of pharmacologically active ingredients that determine their target properties. Typically, these are complexes of biologically active substances synthesized by specific strains, promoted as LBPs or postbiotics (including vesicles): proteins, enzymes, low molecular weight metabolites, small RNAs, etc. This study employs omics technologies, including genomics, proteomics, and metabolomics, to explore the potential of Limosilactobacillus fermentum U-21 for innovative LBP and postbiotic formulations targeting neuroinflammatory processes. Proteomic techniques identified and quantified proteins expressed by L. fermentum U-21, highlighting their functional attributes and potential applications. Key identified proteins include ATP-dependent Clp protease (ClpL), chaperone protein DnaK, protein GrpE, thioredoxin reductase, LysM peptidoglycan-binding domain-containing protein, and NlpC/P60 domain-containing protein, which have roles in disaggregase, antioxidant, and immunomodulatory activities. Metabolomic analysis provided insights into small-molecule metabolites produced during fermentation, revealing compounds with anti-neuroinflammatory activity. Significant metabolites produced by L. fermentum U-21 include GABA (γ-aminobutyric acid), niacin, aucubin, and scyllo-inositol. GABA was found to stabilize neuronal activity, potentially counteracting neurodegenerative processes. Niacin, essential for optimal nervous system function, was detected in vesicles and culture fluid, and it modulates cytokine production, maintaining immune homeostasis. Aucubin, an iridoid glycoside usually secreted by plants, was identified as having antioxidant properties, addressing issues of bioavailability for therapeutic use. Scyllo-inositol, identified in vesicles, acts as a chemical chaperone, reducing abnormal protein clumps linked to neurodegenerative diseases. These findings demonstrate the capability of L. fermentum U-21 to produce bioactive substances that could be harnessed in the development of pharmacobiotics for neurodegenerative diseases, contributing to their immunomodulatory, anti-neuroinflammatory, and neuromodulatory activities. Data of the HPLC-MS/MS analysis are available via ProteomeXchange with identifier PXD050857.PMID:38919499 | PMC:PMC11197932 | DOI:10.3389/fmicb.2024.1416688

Editorial: Omics approaches to delineate the role of gut microbiota-derived metabolites in obesity and metabolic disorders

Wed, 26/06/2024 - 12:00
Front Endocrinol (Lausanne). 2024 Jun 11;15:1436678. doi: 10.3389/fendo.2024.1436678. eCollection 2024.NO ABSTRACTPMID:38919475 | PMC:PMC11196811 | DOI:10.3389/fendo.2024.1436678

Identification of putative alpha-glucosidase inhibitors and antioxidants in Zingiber officinale rhizome using LCMS-based metabolomics and in silico molecular docking

Wed, 26/06/2024 - 12:00
Nat Prod Res. 2024 Jun 25:1-6. doi: 10.1080/14786419.2024.2369224. Online ahead of print.ABSTRACTMetabolite profiling is required to reveal bioactive chemicals in ginger rhizome for supporting its traditional claim as anti-diabetic agent. This study aimed to evaluate α-glucosidase inhibitory (AGI) and antioxidant activities of the rhizome, to identify its putative α-glucosidase inhibitors, and to analyse the protein-ligand interaction of the inhibitors. The ginger extracts were tested to in vitro AGI assay and analysed using LCMS-based metabolomics to pinpoint the putative α-glucosidase inhibitors. The methanol extract exhibited the highest AGI activity (IC50 = 185.2 µg/mL) compared to the other extracts. This extract showed antioxidant activities with DPPH-IC50 and FRAP value of 125.0 µg/mL and 16.95 mmol TE/mgDW, respectively. The LCMS-based metabolomics revealed α-glucosidase inhibitors in the extract, namely 7-methoxycoumarin, supinine and 12-hydroxycorynoline. The presence of these compounds in ginger is being reported for the first time in this study. The activity of these compounds was supported by computational study using in silico molecular docking.PMID:38919043 | DOI:10.1080/14786419.2024.2369224

Identification of the serum metabolites associated with cow milk consumption in Chinese Peri-/Postmenopausal women

Wed, 26/06/2024 - 12:00
Int J Food Sci Nutr. 2024 Jun 25:1-13. doi: 10.1080/09637486.2024.2366223. Online ahead of print.ABSTRACTCow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health.PMID:38918932 | DOI:10.1080/09637486.2024.2366223

Combined Transcriptomics and Metabolomics Analysis Reveals Profenofos-Induced Invisible Injury in Pakchoi (Brassica rapa L.) through Inhibition of Carotenoid Accumulation

Tue, 25/06/2024 - 12:00
J Agric Food Chem. 2024 Jun 25. doi: 10.1021/acs.jafc.4c03262. Online ahead of print.ABSTRACTProfenofos insecticide poses risks to nontarget organisms including mammals and hydrobionts, and its effects on crops are not known. This study examined the invisible toxicity of profenofos on pakchoi (Brassica rapa L.), using transcriptome and metabolome analyses. Profenofos inhibited the photosynthetic efficiency and light energy absorption by leaves and severely damaged the chloroplasts, causing the accumulation of reactive oxygen species (ROS). Metabolomic analysis confirmed that profenofos promoted the conversion of β-carotene into abscisic acid (ABA), as evidenced by the upregulation of the carotenoid biosynthesis pathway genes: zeaxanthin epoxidase (ZEP), 9-cis-epoxycarotenoid dioxygenase (NCED3), and xanthoxin dehydrogenase (XanDH). The inhibitory effects on carotenoid accumulation, photosynthesis, and increased ABA and ROS contents of the leaves led to invisible injury and stunted growth of the pakchoi plants. The findings of this study revealed the toxicological risk of profenofos to nontarget crops and provide guidance for the safe use of insecticides.PMID:38917998 | DOI:10.1021/acs.jafc.4c03262

Responses of the blood acid-base balance and blood plasma metabolomics of broiler chickens after change to diets with high free amino acid levels

Tue, 25/06/2024 - 12:00
Poult Sci. 2024 Jun 6;103(8):103956. doi: 10.1016/j.psj.2024.103956. Online ahead of print.ABSTRACTFree amino acids (AA) are needed to fulfill the AA requirements of broiler chickens in diets low in CP. This study investigated whether the acid-base balance and the blood plasma metabolome are affected immediately after a change to diets with high free AA levels. Male broiler chickens received a starter diet with 164 g CP/kg and 80 g soy protein isolate/kg until d 7 post-hatch. From this day on, birds were offered a diet almost identical to the starter diet (0FAA) or 2 diets with 50% (50FAA) or 100% (100FAA) of the digestible AA from soy protein isolate substituted with free AA. Blood was sampled to determine the acid-base status and for untargeted metabolomics analysis on d 0, 1, 2, 4, 7, and 14 and d 1, 7, and 14 after diet change, respectively (n = 14 birds/treatment). Compared to 0FAA, blood pH was decreased on d 4 and 7 for 100FAA and on d 4 for 50FAA (P ≤ 0.019). On d 4, 7, and 14, bicarbonate, base excess, and total carbon dioxide were lower for 100FAA than for 0FAA (P ≤ 0.006). The partial pressure of carbon dioxide was higher for 50FAA than for 0FAA on d 4 (P = 0.047). Compared to 0FAA, chloride was higher for 100FAA on d 1, 2, 4, 7, and 14, and for 50FAA on d 1, 2, and 4 (P ≤ 0.030). In the metabolomics assay, 602, 463, and 302 metabolites were affected by treatment on d 1, 7, and 14, respectively (P < 0.050), but they did not indicate that metabolic pathways were affected. Flavonoids were the most consistently affected category of metabolites. The results indicated a metabolic acidosis for 100FAA from d 4 to 7 and a respiratory acidosis for 50FAA on d 4 after diet change. These types of acidosis were compensated later on in the experiment. The metabolomics analysis did not indicate that high free AA inclusion affected metabolic pathways.PMID:38917606 | DOI:10.1016/j.psj.2024.103956

The DNA methylation status of the vitamin A signaling associated with testicular degeneration induced by long-day photoperiods in Magang geese

Tue, 25/06/2024 - 12:00
Poult Sci. 2024 Apr 14;103(8):103769. doi: 10.1016/j.psj.2024.103769. Online ahead of print.ABSTRACTMagang geese are typical short-day breeders whose reproductive behaviors are significantly influenced by photoperiod. Exposure to a long-day photoperiod results in testicular regression and spermatogenesis arrest in Magang geese. To investigate the epigenetic influence of DNA methylation on the seasonal testicular regression in Magang geese, we conducted whole-genome bisulfite sequencing and transcriptome sequencing of testes across 3 reproductive phases during a long-day photoperiod. A total of 250,326 differentially methylated regions (DMR) were identified among the 3 comparison groups, with a significant number showing hypermethylation, especially in intronic regions of the genome. Integrating bisulfite sequencing with transcriptome sequencing data revealed that DMR-associated genes tend to be differentially expressed in the testes, highlighting a potential regulatory role for DNA methylation in gene expression. Furthermore, there was a significant negative correlation between changes in the methylation of CG DMRs and changes in the expression of their associated genes in the testes. A total of 3,359 DMR-associated differentially expressed genes (DEG) were identified; functional enrichment analyses revealed that motor proteins, MAPK signaling pathway, ECM-receptor interaction, phagosome, TGF-beta signaling pathway, and calcium signaling might contribute to the testicular regression process. GSEA revealed that the significantly enriched activated hallmark gene set was associated with apoptosis and estrogen response during testicular regression, while the repressed hallmark gene set was involved in spermatogenesis. Our study also revealed that methylation changes significantly impacted the expression level of vitamin A metabolism-related genes during testicular degeneration, with hypermethylation of STRA6 and increased calmodulin levels indicating vitamin A efflux during the testicular regression. These findings were corroborated by pyrosequencing and real-time qPCR, which revealed that the vitamin A metabolic pathway plays a pivotal role in testicular degeneration under long-day conditions. Additionally, metabolomics analysis revealed an insufficiency of vitamin A and an abnormally high level of oxysterols accumulated in the testes during testicular regression. In conclusion, our study demonstrated that testicular degeneration in Magang geese induced by a long-day photoperiod is linked to vitamin A homeostasis disruption, which manifests as the hypermethylation status of STRA6, vitamin A efflux, and a high level of oxysterol accumulation. These findings offer new insights into the effects of DNA methylation on the seasonal testicular regression that occurs during long-day photoperiods in Magang geese.PMID:38917605 | DOI:10.1016/j.psj.2024.103769

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