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

Integrating Metabolomics and Transcriptomics to Analyse and Reveal the Regulatory Mechanisms of Mung Bean Polyphenols on Intestinal Cell Damage Under Different Heat Stress Temperatures

Sat, 11/01/2025 - 12:00
Nutrients. 2024 Dec 29;17(1):88. doi: 10.3390/nu17010088.ABSTRACTBACKGROUND/OBJECTIVES: Polyphenols represent a new strategy of dietary intervention for heat stress regulation.METHODS: The metabolic and genetic effects of three heat stress-regulated mung bean polyphenols on mouse small intestinal epithelial Mode-k cells were investigated by metabolomics-transcriptomics correlation analysis at different heat stress levels.RESULTS: Lipid metabolism, energy metabolism, and nervous system pathways were the key metabolic regulatory pathways. Under the heat stresses of 39 °C, 41 °C, and 43 °C, the key pathways regulated by mung bean polyphenols on intestinal epithelial Mode-k cells were choline metabolism, pyrimidine metabolism, and the retrograde endorphin signalling pathway in cancer, respectively. FoxO, Rap1, and PI3K-Akt signalling pathways were the key environmental regulatory signalling pathways. Mung bean polyphenols can alleviate heat stress-induced cells at 39 °C by inhibiting cell apoptosis and promoting lipid and amino acid accumulation. Mung bean polyphenols can alleviate the threat of cell death caused by heat stress at 41 °C by regulating heat shock proteins, inhibiting mitochondrial function and some nerve disease-related genes. The threat of cell death by heat stress at 43 °C can be alleviated by regulating nerve-related genes.CONCLUSIONS: This study confirmed that mung bean polyphenols can regulate heat stress. The results provide a reference for analysing the mechanism of dietary polyphenol regulating heat stress.PMID:39796522 | DOI:10.3390/nu17010088

Folic Acid and Methyltetrahydrofolate Supplementation in the <em>Mthfr<sup>677C&gt;T</sup></em> Mouse Model with Hepatic Steatosis

Sat, 11/01/2025 - 12:00
Nutrients. 2024 Dec 28;17(1):82. doi: 10.3390/nu17010082.ABSTRACTBACKGROUND/OBJECTIVES: The MTHFR677C>T gene variant results in a thermolabile MTHFR enzyme associated with elevated plasma homocysteine in TT individuals. Health risks associated with the TT genotype may be modified by dietary and supplemental folate intake. Supplementation with methyltetrahydrofolate (methylTHF) may be preferable to folic acid because it is the MTHFR product, and does not require reduction by DHFR to enter one-carbon folate metabolism. In the Mthfr677C>T mouse model for this variant, female 677TT (TT) mice have an increased incidence of hepatic steatosis. The objective of this study was to compare the effects of methylTHF and folic acid supplementation on hepatic steatosis and one-carbon metabolism in this model.METHODS: Male and female C57BL/6J 677CC (CC) and TT mice were fed control (CD), 5xmethylTHF-supplemented (MFSD), or 5xfolic-acid-supplemented (FASD) diets for 4 months. Liver sections were assessed for steatosis by Oil Red O staining. One-carbon metabolites were measured in the liver and plasma. MTHFR protein expression was evaluated in the liver.RESULTS: MFSD had no significant effect on plasma homocysteine, liver SAM/SAH ratios, or hepatic steatosis in males or females as compared to CD. MTHFR protein increased in MFSD TT female liver, but remained <50% of the CC. FASD had no effect on plasma homocysteine but it decreased the liver MTHFR protein and SAM/SAH ratios, and increased hepatic steatosis in CC females.CONCLUSIONS: MethylTHF and folic acid supplementation had limited benefits for TT mice, while folic acid supplementation had negative effects on CC females. Further investigation is required to determine if these effects are relevant in humans.PMID:39796516 | DOI:10.3390/nu17010082

Plasma Bacterial Metabolites in Crohn's Disease Pathogenesis and Complications

Sat, 11/01/2025 - 12:00
Nutrients. 2024 Dec 28;17(1):74. doi: 10.3390/nu17010074.ABSTRACTBACKGROUND/OBJECTIVES: Crohn's disease is known for being associated with an abnormal composition of the bacterial flora, dysbiosis and intestinal function disorders. Metabolites produced by gut microbiota play a pivotal role in the pathogenesis of CD, and the presence of unspecific extraintestinal manifestations.METHODS: The aim of this study was a determination of the level of bacterial metabolites in blood plasma in patients with Crohn's disease. CD patients (29) and healthy individuals (30) were recruited for this study. Bacterial metabolites (SCFAs and TMAO panel) were measured by a liquid chromatography-mass spectrometry system.RESULTS: A significant correlation (p-value < 0.05) between CD and bacterial metabolites was obtained for three of eight tested SCFAs; acetic acid (reduced in CD; FC 1.7; AUC = 0.714), butyric acid (increased; FC 0.68; AUC = 0.717), 2MeBA (FC 1.168; AUC = 0.702), and indoxyl (FC 0.624). The concentration of CA (FC 0.82) and choline (FC 0.78) in plasma was significantly disturbed according to the biological treatment. Choline level (FC 1.28) was also significantly disturbed in the patients treated with glucocorticoids. In total, 68.97% of Crohn's patients presented extraintestinal manifestations (EIMs) of Crohn's disease, mainly osteoarticular complications. The level of BA was statistically significantly elevated in patients with extraintestinal (FC 0.602) manifestations, while in the group of patients with osteoarticular complications, a significant difference in the level of betaine (FC 1.647) was observed.CONCLUSIONS: The analyzed bacterial metabolites of plasma may significantly help in the diagnostic process, and in the monitoring of the disease course and treatment, in a lowly invasive way, as biomarkers after additional research on a larger group of patients.PMID:39796508 | DOI:10.3390/nu17010074

Role of Increasing Body Mass Index in Gut Barrier Dysfunction, Systemic Inflammation, and Metabolic Dysregulation in Obesity

Sat, 11/01/2025 - 12:00
Nutrients. 2024 Dec 28;17(1):72. doi: 10.3390/nu17010072.ABSTRACTAIMS: This study explores the link between body mass index (BMI), intestinal permeability, and associated changes in anthropometric and impedance parameters, lipid profiles, inflammatory markers, fecal metabolites, and gut microbiota taxa composition in participants having excessive body mass.METHODS: A cohort of 58 obese individuals with comparable diet, age, and height was divided into three groups based on a priori clustering analyses that fit with BMI class ranges: Group I (25-29.9), Group II (30-39.9), and Group III (>40). Anthropometric and clinical parameters were assessed, including plasma C-reactive protein and cytokine profiles as inflammation markers. Intestinal permeability was measured using a multisaccharide assay, with fecal/serum zonulin and serum claudin-5 and claudin-15 levels. Fecal microbiota composition and metabolomic profiles were analyzed using a phylogenetic microarray and GC-MS techniques.RESULTS: The statistical analyses of the clinical parameters were based on the full sample set, whereas a subset composed of 37 randomized patients was inspected for the GC/MS metabolite profiling of fecal specimens. An increase in potentially pro-inflammatory bacterial genera (e.g., Slackia, Dorea, Granulicatella) and a reduction in beneficial genera (e.g., Adlercreutzia, Clostridia UCG-014, Roseburia) were measured. The gas chromatography/mass spectrometry analysis of urine samples evidenced a statistically significant increase in m-cymen-8-ol, 1,3,5-Undecatriene, (E, Z) and a decreased concentration of p-cresol, carvone, p-cresol, and nonane.CONCLUSIONS: Together, these data demonstrated how an increased BMI led to significant changes in inflammatory markers, intestinal barrier metabolites, glucose metabolism, endocrine indicators, and fecal metabolomic profiles that can indicate a different metabolite production from gut microbiota. Our findings suggest that targeting intestinal permeability may offer a therapeutic approach to prevent and manage obesity and related metabolic complications, reinforcing the link between gut barrier function and obesity.PMID:39796506 | DOI:10.3390/nu17010072

Effects of Long-Term Fasting on Gut Microbiota, Serum Metabolome, and Their Association in Male Adults

Sat, 11/01/2025 - 12:00
Nutrients. 2024 Dec 26;17(1):35. doi: 10.3390/nu17010035.ABSTRACTBACKGROUND: Long-term fasting demonstrates greater therapeutic potential and broader application prospects in extreme environments than intermittent fasting.METHOD: This pilot study of 10-day complete fasting (CF), with a small sample size of 13 volunteers, aimed to investigate the time-series impacts on gut microbiome, serum metabolome, and their interrelationships with biochemical indices.RESULTS: The results show CF significantly affected gut microbiota diversity, composition, and interspecies interactions, characterized by an expansion of the Proteobacteria phylum (about six-fold) and a decrease in Bacteroidetes (about 50%) and Firmicutes (about 34%) populations. Notably, certain bacteria taxa exhibited complex interactions and strong correlations with serum metabolites implicated in energy and amino acid metabolism, with a particular focus on fatty acylcarnitines and tryptophan derivatives. A key focus of our study was the effect of Ruthenibacterium lactatiformans, which was highly increased during CF and exhibited a strong correlation with fat metabolic indicators. This bacterium was found to mitigate high-fat diet-induced obesity, glucose intolerance, dyslipidemia, and intestinal barrier dysfunction in animal experiments. These effects suggest its potential as a probiotic candidate for the amelioration of dyslipidemia and for mediating the benefits of fasting on fat metabolism.CONCLUSIONS: Our pilot study suggests that alterations in gut microbiota during CF contribute to the shift of energy metabolic substrate and the establishment of a novel homeostatic state during prolonged fasting.PMID:39796469 | DOI:10.3390/nu17010035

Metabolomics Unveiled the Accumulation Characteristics of Taste Compounds During the Development and Maturation of Litchi Fruit

Sat, 11/01/2025 - 12:00
Foods. 2025 Jan 6;14(1):144. doi: 10.3390/foods14010144.ABSTRACTLitchi is one of the ancient fruits that originated in China, renowned for its high nutrition and rich flavor, and Xianjinfeng (XJF) stands as one of the most notable varieties in terms of its flavor. Investigating the metabolic changes in taste compounds during fruit development offers deeper insights into the formation patterns of fruit quality. In this study, we conducted extensive metabonomic research on the accumulation patterns of taste compounds (carbohydrates, organic acids, and amino acids) across three developmental stages of XJF litchi. A total of 238 taste metabolites were detected. Cluster analysis and PCA revealed significant changes in metabolite composition and content across different stages, closely correlating with the developmental phase. The abundance of total taste metabolites in stage S1 was notably lower than stages S2 and S3. The total abundance of sugar continued to rise, yet monosaccharides and disaccharides exhibited distinct behaviors, highlighting the characteristic accumulation of reducing sugars. Most organic acids demonstrated a notable downward trend, whereas the abundance of most essential and flavor-contributing amino acids showed an upward trend. The number of DAMs across the three stages followed the trend of S1 vs. S3 > S1 vs. S2 > S2 vs. S3. KEGG functional annotation and enrichment revealed that amino acid biosynthesis, D-amino acid metabolism, 2-oxocarboxylic acid metabolism, glyoxylate and dicarboxylate metabolism, the pentose phosphate pathway, the tricarboxylic acid cycle, and carbon metabolism were the most significantly enriched primary metabolic pathways. More differential metabolites and metabolic pathways indicated that the critical stage from the green fruit stage to the color transition stage laid a solid foundation for litchi flavor. This experiment will offer valuable references for cultivation, breeding, processing, and consumption.PMID:39796434 | DOI:10.3390/foods14010144

Synergistic Synbiotic-Containing <em>Lactiplantibacillus plantarum</em> and Fructo-Oligosaccharide Alleviate the Allergenicity of Mice Induced by Soy Protein

Sat, 11/01/2025 - 12:00
Foods. 2025 Jan 2;14(1):109. doi: 10.3390/foods14010109.ABSTRACTPrebiotics and probiotics have key roles in the intervention and treatment of food allergies. This study assesses the effect of Lactiplantibacillus plantarum synergistic fructo-oligosaccharide (Lp-FOS) intervention using an allergic mouse model induced by soy protein. The results showed that Lp synergistic FOS significantly decreased clinical allergy scores, inhibited specific antibodies (IgE, IgG, and IgG1), IL-4, IL-6, and IL-17A levels, and increased IFN-γ and IL-10 levels. Meanwhile, flow cytometry showed that Lp-FOS intervention inhibited the percentage of dendritic cell (DC) subsets in splenocytes and increased the Th1/Th2 and Treg/Th17 ratios. Furthermore, Lp-FOS intervention upregulated the mRNA levels of T-bet and Foxp3 and downregulated the mRNA levels of GATA3. Finally, non-targeted metabolomic analysis showed that Lp-FOS improved serum metabolic disorders caused by food allergies through regulating glycine, serine, and threonine metabolism, butanoate metabolism, glyoxylate and dicarboxylate metabolism, the biosynthesis of cofactors, and glycerophospholipid metabolism. These data showed that the combination formulation Lp-FOS could be a promising adjuvant treatment for food allergies.PMID:39796399 | DOI:10.3390/foods14010109

Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Improves Alzheimer's Learning and Memory Abilities Through Short-Chain Fatty Acids

Sat, 11/01/2025 - 12:00
Foods. 2025 Jan 2;14(1):101. doi: 10.3390/foods14010101.ABSTRACTAlzheimer's disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer's learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.PMID:39796390 | DOI:10.3390/foods14010101

Xenia Effect on Nutritional and Flavor Components of 'Jingbaili' Pear

Sat, 11/01/2025 - 12:00
Foods. 2025 Jan 2;14(1):94. doi: 10.3390/foods14010094.ABSTRACTThe 'Jingbaili' pear is a national geographical indication product of China, featuring an oblate shape and being rich in nutrients. But the quality of the 'Jingbaili' pear is unstable. Xenia can cause changes in the quality of pears, but the effect of xenia on the 'Jingbaili' pear is unknown, and its mechanism is still unclear. In order to clarify the effect of pollination on the fruit quality of the 'Jingbaili' pear, this research pollinated 'Jingbaili' pear flowers with the pollen of 'Yali' (JY), 'Suli' (JS) and 'Huangli' (JH). The results indicated that the mass, transverse diameter and longitudinal diameter of the JY group were significantly higher than the JS group and JH group. On the other hand, the pears of the JY group and JS group obtained higher soluble sugar content. The aroma content of characteristic compounds was higher in the JY group than in the JS group and JH group. Multivariate analysis revealed significant differences in the nonvolatile metabolites among the JY group, JS group and JH group, potentially explaining the variations in the nutritional and flavor compounds of the pears. Furthermore, this research investigated metabolic changes in the pears during development and ripening under the three types of pollination. The results showed that amino acid metabolism differed among these pollination types during development. These differences may be the cause of the observed variations in the pears. This research clarified the effect of xenia on the nutritional components and flavor substances in the 'Jingbaili' pear and could provide data support for improving the quality of the 'Jingbaili' pear.PMID:39796384 | DOI:10.3390/foods14010094

Correlating Microbial Dynamics with Key Metabolomic Profiles in Three Submerged Culture-Produced Vinegars

Sat, 11/01/2025 - 12:00
Foods. 2024 Dec 28;14(1):56. doi: 10.3390/foods14010056.ABSTRACTAlthough vinegar is a product obtained by a well-known bioprocess from a technical point of view, the complex microbiota responsible for its production and their involvement in the organoleptic profiles are not clear yet. In this work, three acetification profiles in submerged culture using both synthetic and raw materials from Andalusia (Spain) were characterized by metagenomic (16S rRNA amplicon sequencing) and metabolomic tools (stir-bar sorptive extraction with thermo-desorption coupled to gas chromatography-mass spectrometry (SBSE-TD-GC-MS) and high-performance liquid chromatography (HPLC)). A total of 29 phyla, 208 families, and many more genera were identified, comprising bacteria and archaea as well as 75 metabolites, including minor volatile compounds, amino acids, biogenic amines, and other nitrogenous compounds. It can be concluded that Komagataeibacter and Acetobacter were not only the predominant genera but also the ones that most influenced vinegar metabolite profiles by using different metabolic strategies for mutual collaboration, and together with other microbial groups, some of them were previously practically unknown in vinegar. These results can be of interest not only to deepen the basic knowledge about vinegar but also to the vinegar industry by elucidating microbial succession and the key associated metabolites.PMID:39796346 | DOI:10.3390/foods14010056

Foodomics as a Tool for Evaluating Food Authenticity and Safety from Field to Table: A Review

Sat, 11/01/2025 - 12:00
Foods. 2024 Dec 25;14(1):15. doi: 10.3390/foods14010015.ABSTRACTThe globalization of the food industry chain and the increasing complexity of the food supply chain present significant challenges for food authenticity and raw material processing. Food authenticity identification now extends beyond mere adulteration recognition to include quality evaluation, label compliance, traceability determination, and other quality-related aspects. Consequently, the development of high-throughput, accurate, and rapid analytical techniques is essential to meet these diversified needs. Foodomics, an innovative technology emerging from advancements in food science, enables both a qualitative judgment and a quantitative analysis of food authenticity and safety. This review also addresses crucial aspects of fully processing food, such as verifying the origin, processing techniques, label authenticity, and detecting adulterants, by summarizing the omics technologies of proteomics, lipidomics, flavoromics, metabolomics, genomics, and their analytical methodologies, recent developments, and limitations. Additionally, we analyze the advantages and application prospects of multi-omics strategies. This review offers a comprehensive perspective on the food chain, food safety, and food processing from field to table through omics approaches, thereby promoting the stable and sustained development of the food industry.PMID:39796305 | DOI:10.3390/foods14010015

Comparative Investigation of Untargeted and Targeted Metabolomics in Turmeric Dietary Supplements and Rhizomes

Sat, 11/01/2025 - 12:00
Foods. 2024 Dec 24;14(1):7. doi: 10.3390/foods14010007.ABSTRACTIn the present study, we analyzed the bioactive curcuminoids content in eight capsules (DS-1-DS-7 and DS-9), one tablet (DS-8), three ground turmeric samples (DS-10-DS-12), and three ground turmeric rhizomes (TR-1, TR-2, and TR-3). Initial screening with infrared and ultraviolet-visible spectroscopy coupled with a principal component analysis (PCA) revealed distinct differences between the samples analyzed. Hence, targeted and untargeted analyses were performed using ultra-high-performance liquid chromatography and gas chromatography coupled with mass spectrometry detections. The results show that the total curcuminoids content ranged from 1.3 to 69.8 mg/100 mg and the volatile component ranged from 0.7 to 9.1 mg/100 mg. The percentage ratio of the three prominent curcuminoids, bisdesmethoxycurcumin (BMC), desmethoxycurcumin (DMC), and curcumin (CUR), also varied remarkably compared to the expected ratio (BMC:DMC:CUR ratio of 1:2:6) described in the literature. The three prominent volatile compounds identified in most samples were ar-turmerone, turmerone, and curlone. The results demonstrated significant differences in the volatile compound levels among the DS and dried rhizome samples. The non-targeted analysis resulted in the identification of over 40 compounds, including bioactives such as piperine, phenolic acids, and amino acids. A disintegration study was performed on limited DS according to the United States Pharmacopeia protocol. The results reveal that all the selected DS samples passed the disintegration test. An analysis of curcuminoids from DS samples in neutral and acidic solutions demonstrated that all curcuminoids (BMC, DMC, and CUR) existed in the keto and enol forms and their concentrations changed with pH. This study will be of significant interest to manufacturers, consumers, and pharmacologists to accurately understand the bioactivities of three curcuminoids in different isomeric forms.PMID:39796297 | DOI:10.3390/foods14010007

Glutaminase-2 Expression Induces Metabolic Changes and Regulates Pyruvate Dehydrogenase Activity in Glioblastoma Cells

Sat, 11/01/2025 - 12:00
Int J Mol Sci. 2025 Jan 6;26(1):427. doi: 10.3390/ijms26010427.ABSTRACTGlutaminase controls the first step in glutaminolysis, impacting bioenergetics, biosynthesis and oxidative stress. Two isoenzymes exist in humans, GLS and GLS2. GLS is considered prooncogenic and overexpressed in many tumours, while GLS2 may act as prooncogenic or as a tumour suppressor. Glioblastoma cells usually lack GLS2 while they express high GLS. We investigated how GLS2 expression modifies the metabolism of glioblastoma cells, looking for changes that may explain GLS2's potential tumour suppressive role. We developed LN-229 glioblastoma cells stably expressing GLS2 and performed isotope tracing using U-13C-glutamine and metabolomic quantification to analyze metabolic changes. Treatment with GLS inhibitor CB-839 was also included to concomitantly inhibit endogenous GLS. GLS2 overexpression resulted in extensive metabolic changes, altering the TCA cycle by upregulating part of the cycle but blocking the synthesis of the 6-carbon intermediates from acetyl-CoA. Expression of GLS2 caused downregulation of PDH activity through phosphorylation of S293 of PDHA1. GLS2 also altered nucleotide levels and induced the accumulation of methylated metabolites and S-adenosyl methionine. These changes suggest that GLS2 may be a key regulator linking glutamine and glucose metabolism, also impacting nucleotides and epigenetics. Future research should ascertain the mechanisms involved and the generalizability of these findings in cancer or physiological conditions.PMID:39796278 | DOI:10.3390/ijms26010427

Integrated Transcriptome and Metabolome Analysis Reveals the Resistance Mechanisms of Brassica napus Against Xanthomonas campestris

Sat, 11/01/2025 - 12:00
Int J Mol Sci. 2025 Jan 3;26(1):367. doi: 10.3390/ijms26010367.ABSTRACTRapeseed (Brassica napus L.) is an important crop for healthy edible oil and stockfeed worldwide. However, its growth and yield are severely hampered by black rot, a destructive disease caused by Xanthomonas campestris pv. campestris (Xcc). Despite the identification of several quantitative trait loci (QTLs) associated with resistance to black rot in Brassica crops, the underlying molecular mechanisms remain largely unexplored. In this study, we investigated Xcc-induced transcriptomic and metabolic changes in the leaves of two rapeseed varieties: Westar (susceptible) and ZS5 (resistant). Our findings indicated that Xcc infection elicited more pronounced overall transcriptomic and metabolic changes in Westar compared to ZS5. Transcriptomic analyses revealed that the phenylpropanoid biosynthesis, cutin, suberine and wax biosynthesis, tryptophan metabolism, and phenylalanine metabolism were enriched in both varieties. Notably, photosynthesis was down-regulated in Westar after infection, whereas this down-regulation occurred at a later stage in ZS5. Integrated analyses of transcriptome and metabolome revealed that the tryptophan metabolism pathway was enriched in both varieties. Indolic glucosinolates and indole-3-acetic acid (IAA) are two metabolites derived from tryptophan. The expression of genes involved in the indolic glucosinolate pathway and the levels of indolic glucosinolates were significantly elevated in both varieties post-infection. Additionally, exogenous application of IAA promoted the development of black rot, whereas the use of an IAA synthesis inhibitor attenuated black rot development in both resistant and susceptible rapeseed varieties. These findings provide valuable molecular insights into the interactions between rapeseed and Xcc, facilitating the advancement of black rot resistance breeding in Brassica crops.PMID:39796224 | DOI:10.3390/ijms26010367

Physiological and Multi-Omics Integrative Analysis Provides New Insights into Tolerance to Waterlogging Stress in Sesame (<em>Sesamum indicum</em> L.)

Sat, 11/01/2025 - 12:00
Int J Mol Sci. 2025 Jan 3;26(1):351. doi: 10.3390/ijms26010351.ABSTRACTPlant growth and development require water, but excessive water hinders growth. Sesame (Sesamum indicum L.) is an important oil crop; it is drought-tolerant but sensitive to waterlogging, and its drought tolerance has been extensively studied. However, the waterlogging tolerance of sesame still has relatively few studies. In this study, two kinds of sesame, R (waterlogging-tolerant) and S (waterlogging-intolerant), were used as materials, and they were treated with waterlogging stress for 0, 24, 72, and 120 h. Physiological analysis showed that after waterlogging, sesame plants responded to stress by increasing the contents of ascorbate peroxidase (APX), glutathione (GSH), and some other antioxidants. The results of the multi-omics analysis of sesame under waterlogging stress revealed 15,652 (R) and 12,156 (S) differentially expressed genes (DEGs), 41 (R) and 47 (S) differentially expressed miRNAs (DEMis), and 896 (R) and 1036 (S) differentially accumulated metabolites (DAMs). The combined DEMi-DEG analysis that 24 DEMis regulated 114 DEGs in response to waterlogging stress. In addition, 13 hub genes and three key pathways of plant hormone signal transduction, glutathione metabolism, and glyoxylate and dicarboxylate metabolism were identified by multi-omics analysis under waterlogging stress. The results showed that sesame regulated the content of hormones and antioxidants and promoted energy conversion in the plant through the above pathways to adapt to waterlogging stress. In summary, this study further analyzed the response mechanism of sesame to waterlogging stress and provides helpful information for the breeding of plants for waterlogging tolerance and genetic improvement.PMID:39796205 | DOI:10.3390/ijms26010351

Mechanism of P-Hydroxy Benzyl Alcohol Against Cerebral Ischemia Based on Metabonomics Analysis

Sat, 11/01/2025 - 12:00
Int J Mol Sci. 2025 Jan 1;26(1):317. doi: 10.3390/ijms26010317.ABSTRACTStroke is the leading cause of death and disability worldwide, with ischemic stroke accounting for the majority of these. HBA is the active ingredient in Gastrodia elata and has potential therapeutic effects on central nervous system diseases. In this study, the cell model of cerebral ischemia was replicated by the culture method of oxygen-glucose deprivation/reoxygenation, and the rat model of vascular dementia was established by the two-vessel occlusion method. Metabolomics technology was employed to analyze the metabolic changes in ischemic neurons induced by HBA, and potential therapeutic targets were verified. The protective effects of HBA on ischemic neurons and their mitochondria were examined through multiple indicators, and the related mechanisms were verified. HBA can improve post-ischemic cognitive impairment in rats, and its mechanism is related to the regulation of the choline-activated phospholipase D2/Sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway to improve mitochondrial function and reduce autophagic activity to maintain mitochondrial homeostasis. It is concluded that HBA has a protective effect on neuronal damage and cognitive impairment caused by cerebral ischemia by regulating key metabolites and signaling pathways, and that it provides a new molecular target for the treatment of cerebral ischemia.PMID:39796170 | DOI:10.3390/ijms26010317

Standardization to Characterize the Complexity of Vessel Network Using the Aortic Ring Model

Sat, 11/01/2025 - 12:00
Int J Mol Sci. 2024 Dec 31;26(1):291. doi: 10.3390/ijms26010291.ABSTRACTRegeneration after ischemia requires to be promoted by (re)perfusion of the affected tissue, and, to date, there is no therapy that covers all needs. In treatment with mesenchymal stem cells (MSC), the secretome acts via paracrine mechanisms and has a positive influence on vascular regeneration via proangiogenic factors. A lack of standardization and the high complexity of vascular structures make it difficult to compare angiogenic readouts from different studies. This emphasizes the need for improved approaches and the introduction of an index in the preclinical setting. A characterization of human MSC secretomes obtained from one of the three formats-single cells, small, and large spheroids-was performed using the chicken aortic ring assay in combination with a modified angiogenic activity index (AAI) and an angiogenic profile. While the secretome of the small spheroid group showed an inhibitory effect on angiogenesis, the large spheroid group impressed with a fully pro-angiogenic response, and a higher AAI compared to the single cell group, underlying the suitability of these three-stem cell-derived secretomes with their distinct angiogenic properties to validate the AAI and the novel angiogenic profile established here.PMID:39796147 | DOI:10.3390/ijms26010291

Metabolomic and Transcriptomic Analyses of Flavonoid Biosynthesis in Different Colors of Soybean Seed Coats

Sat, 11/01/2025 - 12:00
Int J Mol Sci. 2024 Dec 31;26(1):294. doi: 10.3390/ijms26010294.ABSTRACTSoybean has outstanding nutritional and medicinal value because of its abundant protein, oil, and flavonoid contents. This crop has rich seed coat colors, such as yellow, green, black, brown, and red, as well as bicolor variants. However, there are limited reports on the synthesis of flavonoids in the soybean seed coats of different colors. Thus, the seed coat metabolomes and transcriptomes of five soybean germplasms with yellow (S141), red (S26), brown (S62), green (S100), and black (S124) seed coats were measured. In this study, 1645 metabolites were detected in the soybean seed coat, including 426 flavonoid compounds. The flavonoids differed among the different-colored seed coats of soybean germplasms, and flavonoids were distributed in all varieties. Procyanidins A1, B1, B6, C1, and B2, cyanidin 3-O-(6″-malonyl-arabinoside), petunidin 3-(6″-p-coumaryl-glucoside) 5-glucoside, and malvidin 3-laminaribioside were significantly upregulated in S26_vs._S141, S62_vs._S141, S100_vs._S141, and S124_vs._S141 groups, with a variation of 1.43-2.97 × 1013 in terms of fold. The differences in the contents of cyanidin 3-O-(6″-malonyl-arabinoside) and proanthocyanidin A1 relate to the seed coat color differences of red soybean. Malvidin 3-laminaribioside, petunidin 3-(6″-p-coumaryl-glucoside) 5-glucoside, cyanidin 3-O-(6″-malonyl-arabinoside), and proanthocyanidin A1 affect the color of black soybean. The difference in the contents of procyanidin B1 and malvidin 3-glucoside-4-vinylphenol might be related to the seed coat color differences of brown soybeans. Cyanidin 3-gentiobioside affects the color of green soybean. The metabolomic-transcriptomic combined analysis showed that flavonoid biosynthesis is the key synthesis pathway for soybean seed color formation. Transcriptome analysis revealed that the upregulation of most flavonoid biosynthesis genes was observed in all groups, except for S62_vs._S141, and promoted flavonoid accumulation. Furthermore, CHS, CHI, DFR, FG3, ANR, FLS, LAR, and UGT88F4 exhibited differential expression in all groups. This study broadens our understanding of the metabolic and transcriptomic changes in soybean seed coats of different colors and provides new insights into developing bioactive substances from soybean seed coats.PMID:39796145 | DOI:10.3390/ijms26010294

Secretome of the Olfactory Ensheathing Cells Influences the Behavior of Neural Stem Cells

Sat, 11/01/2025 - 12:00
Int J Mol Sci. 2024 Dec 31;26(1):281. doi: 10.3390/ijms26010281.ABSTRACTOlfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear. We harvested the secretome from human mucosal OECs and characterized its protein content, identifying 709 proteins in the human OEC secretome from three donors in two passages. Thirty-nine proteins, including neurological-related proteins, such as profilin-1, and antioxidants, such as peroxiredoxin-1 and glutathione S-transferase, were shared between the six samples. The secretome consistently demonstrated potential effects such as antioxidant activity, neuronal differentiation, and quiescence exit of neural stem cells (NSCs). The total secretome produced by OECs protects NSCs from H2O2-induced reactive oxygen species accumulation. During induction of neuronal differentiation, secretomes promoted neurite outgrowth, axon elongation, and expression of neuronal markers. The secretome ameliorated bone morphogenetic protein 4- and fibroblast growth factor 2-induced quiescence of NSCs. The human OEC secretome triggers NSCs to exit prime quiescence, which is related to increased phosphoribosomal protein S6 expression and RNA synthesis. The human OEC secretome has beneficial effects on NSCs and may be applied in neurological disease studies.PMID:39796134 | DOI:10.3390/ijms26010281

Transgenic Cotton Expressing ds<em>AgCYP6CY3</em> Significantly Delays the Growth and Development of <em>Aphis gossypii</em> by Inhibiting Its Glycolysis and TCA Cycle

Sat, 11/01/2025 - 12:00
Int J Mol Sci. 2024 Dec 31;26(1):264. doi: 10.3390/ijms26010264.ABSTRACTIn our previous research, we found that CYP6CY3 not only participates in the detoxification metabolism of neonicotinoid insecticides in cotton aphid but also affects their growth and development. However, how does transgenic cotton expressing dsAgCYP6CY3 affect the growth and development of cotton aphid? In this study, we combined transcriptome and metabolome to analyze how to inhibit the growth and development of cotton aphid treated with transgenic cotton expressing dsAgCYP6CY3-P1 (TG cotton). The results suggested that a total of 509 differentially expressed genes (DEGs) were identified based on the DESeq method, and a total of 431 differential metabolites (DAMs) were discovered using UPLC-MS in the metabolic analysis. Additionally, multiple DEGs and DAMs of glycolytic and The tricarboxylic acid (TCA) cycle pathways were significantly down-regulated. Pyruvate carboxylase (PC), citrate synthase (CS), malate dehydrogenase (MDH) enzyme activities and pyruvate content were reduced in cotton aphid treated with TG cotton. In addition, TG cotton could significantly decrease the total sugar content from the body and honeydew in cotton aphid. The above results indicated that TG cotton inhibited glycolysis and the TCA cycle, and this inhibition is consistent with previous studies showing that cotton aphid fed on TG cotton showed significantly reduced body length and weight as well as delayed molting. These findings provide a new strategy for reducing the transmission of viruses by cotton aphid honeydew, preventing fungal growth, mitigating impacts on normal photosynthesis and improving cotton quality.PMID:39796120 | DOI:10.3390/ijms26010264

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