Organic Acid Metabolism Research Articles

P1224 Bidirectional association between sleep pattern and inflammatory bowel disease: a large population-based prospective cohort study

Abstract Background Disturbances in sleep have been associated with systemic inflammation and increased susceptibility to various chronic diseases. However, the specific mechanisms by which sleep influences plasma protein expression and contributes to the increased risk of inflammatory bowel disease (IBD) have not been fully elucidated. Methods We analysed data from 381,228 participants in the UK Biobank. Sleep was scored with chronotype, sleep duration, insomnia, and daytime sleepiness. Adjusted odds ratios (ORs) for prevalent IBD in unhealthy sleep patterns were estimated, as well as adjusted hazard ratios (HRs) for incident IBD by sleep patterns. A subset cohort of 40,392 participants was used for proteomic profiling, with differential expression analysis and weighted gene co-expression network analysis (WGCNA) conducted. A proteomic prognostic risk model was also established using the least absolute shrinkage and selection operator (LASSO)-Cox regression. Results Among the 381,228 participants in the clinical cohort, 100,622 (26.4%) had unhealthy sleep (sleep score 0-2) at baseline. Prevalent IBD was associated with increased odds of unhealthy sleep (OR = 1.250, 95% CI: 1.165-1.340, p < 0.001, Figure 1). Participants with unhealthy sleep had a higher risk of incident IBD (HR = 1.237, 95% CI: 1.136-1.348, p < 0.001). In the proteomic cohort, unhealthy sleep and IBD displayed 182 common differentially expressed proteins. Enrichment analysis revealed significant inflammatory pathways, including positive regulation of cytokine production and immune cell activation. WGCNA identified seven module eigengenes, with unhealthy sleep impacting IBD through cell activation and chemotaxis pathway and amino acid and organic acid metabolism. Incorporating protein biomarkers enhanced the performance of predicted models that achieved an AUC of 0.81 for predicting 2-year IBD onset. Unhealthy sleep participants with high protein scores were at high risk of incident IBD (HR=3.370, 95% CI: 2.300-4.938, p < 0.001), highlighting the importance of monitoring systemic inflammation. Conclusion Unhealthy sleep and IBD are bidirectionally linked, with inflammatory and metabolic proteins mediating the effect of poor sleep on IBD risk. Patients with sleep disturbances should be screened for inflammatory biomarkers to evaluate their IBD risk. Enhancing sleep quality may serve as an effective strategy for preventing and managing IBD. References Sleep disorders and inflammatory disease activity: chicken or the egg? Am J Gastroenterol. 2015 Apr;110(4):484-8.

Combining untargeted and targeted metabolomic profiling reveals principal differences between osteopenia, Osteoporosis and healthy controls

BackgroundOsteopenia (ON) and osteoporosis (OP) are highly prevalent among postmenopausal women and poses a challenge for early diagnosis. Therefore, identifying reliable biomarkers for early prediction using metabolomics is critically important.MethodsInitially, non-targeted metabolomics was employed to identify differential metabolites in plasma samples from cohort 1, which included healthy controls (HC, n = 23), osteonecrosis (ON, n = 36), and osteoporosis (OP, n = 37). Subsequently, we performed targeted metabolomic validation of 37 amino acids and their derivatives in plasma samples from cohort 2, consisting of healthy controls (HC, n = 10), osteonecrosis (ON, n = 10), and osteoporosis (OP, n = 10).ResultsThe non-targeted metabolomic analysis revealed an increase in differential metabolites with the progression of the disease, showing abnormalities in lipid and organic acid metabolism in ON and OP patients. Several substances were found to correlate positively or negatively with bone mineral density (BMD), for example, N-undecanoylglycine, sphingomyelins, and phosphatidylinositols exhibited positive correlations with BMD, while acetic acid, phenylalanine, taurine, inosine, and pyruvic acid showed negative correlations with BMD. Subsequently, targeted validation of 37 amino acids and their metabolites revealed six amino acids related to ON and OP.ConclusionSignificant metabolomic features were identified between HC and patients with ON/OP, with multiple metabolites correlating positively or negatively with BMD. Integrating both targeted and non-targeted metabolomic results suggests that lipid, organic acid, and amino acid metabolism may represent important metabolomic characteristics of patients with OP, offering new insights into the development of metabolomic applications in OP.

Correlation analysis of transcriptome and metabolomics and functional study of Galactinol synthase gene (VcGolS3) of blueberry under salt stress.

Soil salinity poses a significant environmental challenge for the growth and development of blueberries. However, the specific mechanisms by which blueberries respond to salt stress are still not fully understood. Here, we employed a comprehensive approach integrating physiological, metabolomic, and transcriptomic analyses to identify key metabolic pathways in blueberries under salt stress. Our findings indicate that blueberries primarily adapt to salt stress by modulating pathways associated with carbohydrate metabolism, organic acid metabolism, amino acid metabolism, and various organic compounds. Key metabolites involved in this response include sucrose, propionic acid, and palmitic acid. A total of 241 transcription factors were differentially expressed, with significant involvement from families such as AP2, Dof, GATA, WRKY, and TCP. Notably, the galactose metabolism pathway was associated with 5 DAMs and 24 DEGs, while the starch and sucrose metabolism pathway contained 5 DAMs and 23 DEGs, highlighting their crucial roles in mitigating salt stress. Overexpression of VcGolS3 in transgenic Arabidopsis conferred tolerance to salt and drought stresses, primarily evidenced by a significant increase in GolS enzyme activity and reduced ROS accumulation. This study provides valuable insights into the molecular mechanisms underlying the blueberry response to salt stress and lays the groundwork for breeding salt- and drought-tolerant blueberry varieties.

Comparative Transcriptome Analysis Reveals Potential Molecular Regulation of Organic Acid Metabolism During Fruit Development in Late-Maturing Hybrid Citrus Varieties.

Late-maturing hybrid citrus is a significant fruit that combines the best traits of both parents and is highly prized for its unique flavor. Not only can organic acids alter the flavor of citrus pulp, but they are also essential for cellular metabolism, energy conversion, and maintaining the acidbase balance in plant tissues. Although organic acids play a key role in the quality formation of citrus fruits, there is still insufficient research on the metabolic processes of organic acids in late-maturing hybrid citrus varieties. In this study, three late-maturing citrus varieties with different acidity levels, namely 'Huangjinjia' (HJ), 'Kiyomi' (QJ), and 'Harumi' (CJ), were selected to systematically investigate the metabolic regulation mechanism of organic acids in late-maturing citrus through transcriptome sequencing technology, combined with physiological and biochemical analyses. This study revealed gene expression differences related to organic acid synthesis and degradation. Through gene expression profiling, several genes closely associated with organic acid metabolism were identified, and a preliminary gene network related to the regulation of organic acid metabolism was constructed. The results showed that there were significant differences in the organic acid metabolic pathways between different varieties and growth stages of the fruit. Specifically, HJ had a higher TA content than QJ and CJ, primarily due to the significantly higher citric acid and malic acid contents in HJ compared to the other two varieties. Further analysis revealed that four gene modules showed a high correlation with the levels of major organic acids in the fruits. The genes involved in these modules are closely related to organic acid synthesis, degradation, and transport. Additionally, we also identified several key genes (AS1, BZP44, COL4, TCP4, IDD10, YAB2, and GAIPB) that might be involved in the regulation of organic acid metabolism. The functions of these genes could have a significant impact on the expression levels changes of enzymes related to organic acid metabolism. This study provides a foundation for exploring the intrinsic mechanisms regulating the organic acid content in late-maturing hybrid citrus fruits and contributes to the functional research of organic acids in late-maturing hybrid citrus and the molecular design of high-quality varieties.

Horizontal and longitudinal targeted metabolomics in healthy pregnancy and gestational diabetes mellitus.

The objective is to investigate the differences in urinary organic acid (OA) profiles and metabolism between healthy control (HC) pregnant women and those with gestational diabetes mellitus (GDM) during the second trimester and third trimester of pregnancy. A total of 66 HC pregnant women and 32 pregnant women with GDM were assessed for 107 hydrophilic metabolites in urine samples collected during the second and third trimester of pregnancy using tandem mass spectrometry. The urine OA profiles for each group were obtained, and metabolomic analysis and discussion were conducted. This study identified a total of 50 metabolic biomarkers. In the third trimester of pregnancy, short-chain dicarboxylic acids (DCAs) and tryptophan (Trp)-related metabolites were significantly upregulated in the urine of both the HC group and the GDM group. Comparatively, the glycine (Gly) levels and related synthetic precursor metabolites were lower in the GDM2 group. The overall dietary polyphenol metabolic intermediates level in the GDM group was lower than in the HC group. Among the pathways enriched for differentially expressed metabolites, the predominant metabolic pathway in the GDM group was the citric acid cycle. In contrast, in the HC group, it was the metabolism of alanine, aspartate, and glutamate. The study reveals the differences in metabolomics between pregnant women with HC and those with GDM, identifying several metabolites associated with the occurrence and development of GDM. Demonstrating the presence of abnormal mitochondrial and peroxisomal functions at the metabolite level in GDM will contribute to future exploration of the condition.

The intervention of B. longum metabolites in Fnevs' carcinogenic capacity: A potential double-edged sword.

Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Fusobacterium nucleatum and its metabolites are effective biological targets for colon cancer promotion. Probiotics such as Bifidobacterium can block the occurrence and development of CRC by regulating the host intestinal mucosal immunity, eliminating carcinogens, and interfering with tumor cell proliferation and apoptosis. We selected six Bifidobacterium species to explore the inhibitory effect of their cell-free supernatant (CFS) on Fusobacterium nucleatum, and screened the best functional strain Bifidobacterium longum (B. longum) to explore its intervention effect on Fnevs infection of CRC cells. In the genus Bifidobacterium, B. longum-CFS can effectively inhibit the growth and membrane formation of Fusobacterium nucleatum. The metabolites of B. longum can inhibit the proliferation, migration and invasion of Fnevs-infected CRC cells. However, the transcriptomic analysis of Fnevs-infected CRC cells treated with Bl-CFS revealed that Bl-CFS exerted inhibitory effects on the expression of specific oncogenes (e.g., Myc, IL16, KCNN2, ACSBG1, Pum1, MET, NR5A2), while simultaneously promoting the expression of other oncogenes. This modulation potentially enhances the proliferation, epithelial-mesenchymal transition (EMT), stemness properties and other characteristics associated with CRC cells. Metabolomics also showed that Bl-CFS altered organic acid and lipid metabolism in Fnevs-infected CRC cells, and switched energy supply from aerobic glucose metabolism (TCA cycle) to anaerobic glycolysis, which increased the malignancy potential of CRC cells. The observed outcome may be attributed to the presence of both probiotics and toxic substances in the metabolites derived from Bifidobacterium longum. Therefore, this study concludes that the anti-colorectal cancer (CRC) effect of natural metabolites derived from Bifidobacterium longum is limited. Future investigations should focus on refining these natural substances and optimizing their composition ratios to extract their essence while eliminating impurities, thereby obtaining anticancer biologics with exceptional and consistent efficacy.

Integrated proteomic and metabolomic analysis reveals the potential therapeutic mechanism of Quanduzhong capsule in rats with spontaneous hypertension and knee osteoarthritis

Quanduzhong capsule (QDZ), derived from Eucommia ulmoides Oliv., has been traditionally used in Chinese medicine for its beneficial effects on musculoskeletal health. Its clinical application has extended to conditions such as spontaneous hypertension combined with knee osteoarthritis (SKOA). However, the specific mechanisms by which QDZ alleviates symptoms and improves outcomes in this complex condition remain to be fully elucidated. This study aims to evaluate the therapeutic potential of QDZ in treating SKOA. By performing serum proteomics and metabolomics, we seek to explore the related biological pathways and elucidate the mechanisms underlying QDZ's effects on SKOA. Serum samples from control, spontaneous hypertension (SHR), SKOA, and SKOA treated with QDZ groups were analyzed using data-independent acquisition-based proteomics to identify differentially expressed proteins. Serum levels of angiotensin II, norepinephrine, endothelin-1, classical pro-inflammatory factors such as macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-1 beta were measured. Additionally, serum metabolomics was performed to examine the changes in metabolite profiles. Correlation analysis was conducted to link changed proteins and metabolites with key pathways affected by QDZ. Proteomics analysis revealed significant alterations in serum protein expression between control, SHR, and SKOA groups, with changes in pathways related to immune regulation and vascular function. KEGG enrichment analysis highlighted pathways such as endocytosis, synaptic vesicle cycling, and immune responses were enriched in SKOA group compared with control group. QDZ treatment significantly modulated above pathways and reduced inflammatory and cardiovascular markers which were upregulated in SKOA group. Metabolomics analysis showed that QDZ reversed SKOA-induced changes in amino acid and organic acid metabolism, affecting pathways including valine, leucine, and isoleucine metabolism, as well as the TCA cycle. Correlation analysis revealed significant relationships between key proteins and metabolites, underscoring the integrated role of immune and metabolic pathways in QDZ's effects. Our results indicate QDZ has a significant therapeutic potential for SKOA by modulating both protein and metabolite profiles associated with inflammation, vascular dysfunction, and metabolic imbalance. Our findings provide insights into the mechanisms through which QDZ exerts its effects and support its use as a promising treatment for SKOA. This study highlights the impact of QDZ on proteomic and metabolomic alterations, offering a basis for its broader application in treating SKOA.

Combination transcriptomic and metabolomic reveal deterioration of the blue honeysuckle (Lonicera caerulea L.) fruit and candidate genes regulating metabolism in the post-harvest stage

Blue honeysuckle, a new berry with high nutritional value, possesses typical berry postharvest properties, including extreme perishability, rapid quality loss, and high sensitivity to microbial infections. At present, the underlying mechanisms of postharvest quality deterioration, senescence, and low-temperature regulation remain largely unknown. This study aimed to elucidate the metabolic shifts and genetic regulation underlying the preservation or deterioration of blue honeysuckle during storage at room temperature (25 °C) and low temperature (4 °C). Storage at 4 °C inhibited fruit decay and preserved better visual quality, weight, firmness, and total soluble solid and acid contents. We identified 24 key differentially accumulated metabolites that specifically changed during the qualitative shift at room temperature and were effectively regulated by 4 °C. Commonly associated metabolites, sorbitol, succinic acid, malic acid, naringenin, pinobanksin, and taxifolin, characterize the deterioration of blue honeysuckle. These metabolites were integrated with transcriptomic data for weighted correlation network analysis (WGCNA). Regulatory networks were used for the identification of key genes and transcription factors (TFs) influencing sugar, organic acid, flavonoid, and phenolic acid metabolism during storage. The findings provide insight into metabolic regulation and the improvement of flavor in postharvest blue honeysuckle fruit.

Genetic and biochemical determinants in potentially toxic metals resistance and plant growth promotion in Rhizobium sp LBMP-C04.

The association of bacteria resistant to potentially toxic metals (PTMs) with plants to remove, transfer, or stabilize these elements from the soil is an appropriate tool for phytoremediation processes in metal-contaminated environments. The objective of this study was to evaluate the potential ofRhizobiumsp. LBMP-C04 forphytoremediation processes and plant growth promotion in metal-contaminated soils. Functional annotation allowed us to predict a variety of genes related to PTMs resistance and plant growth promotion in the bacterial genome. Resistance genes are mainly associated with DNA repair, and the import or export of metals in bacterial cells to maintain cell homeostasis. Genes that promote plant growth are related to mechanisms of osmotic stress tolerance, phosphate solubilization, nitrogen metabolism, biological nitrogen fixation, biofilm formation, heat shock responses, indole-3-acetic acid (IAA) biosynthesis, tryptophan, and organic acids metabolism. Biochemical tests indicated thatRhizobiumsp. LBMP-C04 can solubilize calcium phosphate and produce siderophores and IAAin vitroin the presence of the PTMs Cd2+,Cu2+,Cr3+,Cr6+, Zn2+, and Ni2+. Results indicate the possibility of usingRhizobiumsp. LBMP-C04 as a potentially efficient bacterium in phytoremediation processesin environments contaminated by PTMs and simultaneously promote plant growth.

Basic Molecular Biology, Metabolic and Immunological Mechanisms of Fecal Microbiota Transplantation

Aim: demonstration of basic molecular biological, metabolic and immunological effects of fecal microbiota transplantation (FMT), on the example of a rare case of acute graft-versus-host disease (GVHD) with intestinal damage in a patient after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Materials and methods. To monitor the basic effects of FMT, we performed targeted DNA sequencing of 16S rRNA gene (V3–V4) using MiSeq platform as well as multiplex real-time PCR, MS/gas chromatography technique, immunophenotyping of blood lymphocytes, histological and immunohistochemical techniques.Clinical case. A 40-year-old female patient diagnosed with myelodysplastic syndrome, with a history of two unsuccessful allo-HSCTs due to graft failure, underwent the third haploidentical HSCT (haplo-HSCT) from her father as ‘salvage’ therapy. Due to early viral/bacterial colitis post-transplant associated with a multidrug-resistant strain of K. pneumoniae and herpes virus type 6, FMT was performed on days 46 and 47 after allo-HSCT. Complete resolution of the enteropathy symptoms was noted following FMT. However, immunosuppressive therapy was canceled on D+106 after haplo-HSCT due to the detection of minimal residual disease causing development of the ‘overlap’-type GVHD with damage skin lesions grade 4, and intestinal mucous membranes grade 3. This complication required resumption and subsequent intensification of immunosuppressive therapy with complete resolution of GVHD symptoms. Following FMT treatment, the patient showed complete resolution of clinical colitis symptoms. According to results of 16S rRNA sequencing, the species-specific diversity of fecal microbiota increased significantly, along with decreased relative contents of opportunistic bacteria (Klebsiella, Enterococcus, Streptococcus genera). A significant growth was revealed for commensal Bacteroidota, and re-emergence of Faecalibacterium, Blautia, Roseburia. Acute gastrointestinal GVHD promoted by tacrolimus withdrawal was associated with repeated depletion of intestinal microbiota. Upon resolution of GVHD and resumed immunosuppression, increased microbiota diversity (Shannon index) was again recorded, and the parameters of patient’s fecal microbiota reached the donor values. The microbiota shifts at all clinical stages (before and after FMT, at the peak of acute intestinal GVHD and intensive immunosuppressive therapy) showed some relations with metabolism of bile and fatty acids in blood plasma and immune parameters.Conclusions. FMT may be a component of complex therapy aimed at early reconstitution of immune system and organic acid metabolism in patients after allo-HSCT. The composition of fecal microbiota, metabolic profile and spectrum of lymphocyte subpopulations may be markers for monitoring complex rehabilitation after allo-HSCT.

Proteomic analysis of natural photoheterotrophic mixed consortium for biohydrogen production under nongrowing conditions.

A biohydrogen and polyhydroxyalkanoates(PHA)-producing natural photoheterotrophic mixed culture composed mainly by Rhodopseudomonas palustris and Clostridium sp was studied by a proteomic analysis under non-growth conditions (nitrogen-absence and organic acids). Proteins in C. pasteurianum were upregulated, particularly those related to stress response. In contrast, C. pasteurianum in the consortium did not present such proteins, showing the advantage of being part of it. Both cultures showed proteins involved in organic acid metabolism and biohydrogen production, such as lactate dehydrogenase, ferredoxins, and hydrogenases. Proteomes of R. palustris as single culture and in consortium showed that organic acids were redirect into central carbon pathways to generate reduced equivalents for biohydrogen production. Light-harvesting proteins and fatty acid metabolism linked to PHA accumulation were also upregulated. This study provides insights into how the proteomes of individual organisms and their consortium counterparts adapt to non-growth conditions, shedding light on how microbial interactions influence protein expression.

Culture medium based on whey permeate for biomass production of lactobacilli with technological aptitudes

The objective of this study was to formulate a culture medium to produce lactobacilli biomass using cheese whey permeate, as well as to study its effect on the metabolic activity of both Lacticaseibacillus rhamnosus 73 (L73) and Lacticaseibacillus paracasei 90 (L90) when grown under controlled or free pH conditions. The optimized media demonstrated to be efficient in obtaining high levels of L73 and L90, being also suitable to grow other lactobacilli strains with great potential as adjunct cultures for cheeses. The pH control enhanced biomass production for L73 but not for L90. In general, the peptidase activities and the metabolism of lactose and organic acids were influenced by the control of pH. Similarly, both L73 and L90 showed different volatile compound profiles depending on the pH condition. The diverse flavour-forming abilities of these strains might be of great value to cheese industries, by providing cheese with novel flavour profiles.

Exogenous GABA improves tomato fruit quality by contributing to regulation of the metabolism of amino acids, organic acids and sugars

To better explore the impact of exogenous GABA on tomato fruit quality, we explored the effects of GABA (20 mM) on tomato fruits at different developmental stages. The results showed that spraying GABA 3 days before harvest improved the quality of fruits, primarily in terms of amino acid, organic acid, and soluble sugar content. Transcriptome and metabolome data indicated that exogenous GABA enters cells and mitochondria through GABA transporters, thereby simulating endogenous GABA metabolism and enhancing the activity of genes related to amino acids and organic acids metabolism, and elevating the levels of amino acids and organic acids. Moreover, the application of exogenous GABA promoted the contents of glucose, fructose, and sucrose by affecting the expression of genes related to sugar metabolism. It was found that the mechanism of exogenous GABA in increasing fruit sugar content involved promoting sucrose synthesis, partially inhibiting glycolysis, and increasing the content of trehalose 6-phosphate. This study also provides a new model for the mechanism through which exogenous GABA affects tomato quality.

Drought is a lesser evil than cold for photosynthesis and assimilation metabolism of maize

Cold is one of the abiotic environmental factors that severely affect plant metabolism. It causes changes in the fluidity of biological membranes, induces oxidative and osmotic stress, photoinhibition, reduces photosynthetic rates and slows down numerous metabolic enzyme activities. Some effects of cold overlap with drought response processes. Drought itself has a dualistic effect on plants. Severe drought stress is detrimental, while a mild preceding drought may prepare the otherwise sensitive maize to cope with cold. This study focused on the effects of mild drought on photosynthesis, sugar and amino acid metabolism at low temperature. Maize (Zea mays L.) plants were drought-hardened (15±5% relative soil moisture) between stages V4 and V6 at 25°C for 10 days and then subjected to cold treatmet at 10°C for 2 weeks at two light levels (PPFD=450 and 150 µmol m-2 s-1). The control population was watered daily (35±5% soil moisture), and in completely dried pots, 5±3% soil moisture was measured. The present results confirmed that photosynthetic performance and glutamine biosynthesis were positively affected by drought under both light intensities. Plants exposed to combined cold and moderate drought stress had a higher dry weight than those exposed to cold stress alone. The metabolism of several sugars, organic acids and amino acids was maintained by mild drought acclimation. The cold protective DHN2-like dehydrin gene was induced by moderate drought treatment, which may have contributed to the drought-induced higher tolerance to low temperature. However, cold stress markers were lower in low light than in normal growth light under drought acclimation, suggesting that drought-induced stress defense may require a certain level of light.

Multi-Omics Analysis Uncovers the Mechanism for Enhanced Organic Acid Accumulation in Peach (Prunus persica L.) Fruit from High-Altitude Areas.

The early-ripening peach industry has undergone rapid development in the Panxi region of the Sichuan Basin in recent years. However, after the introduction of some new peach varieties to the high-altitude peach-producing areas in Panxi, the titratable acid content in peach fruit has significantly increased. This study compared the fruit quality indicators of early-ripening peach varieties cultivated in Xide County (a high-altitude peach-producing area) and Longquanyi District (a low-altitude peach-producing area) in Sichuan Province and analyzed the differences in organic acid metabolism by combining primary metabolomic and transcriptomic approaches. The results showed that the 'Zhongtaohongyu' fruit from the high-altitude peach-producing area had a much higher accumulation of malic acid and, accordingly, a significantly higher organic acid content than the other samples. The lower annual average temperature and stronger ultraviolet radiation in high-altitude peach-producing areas may lead to the increased expression of genes (PpNAD-ME1, PpNADP-ME3, and PpPEPC1) in the organic acid synthesis pathway and the decreased expression of genes (PpACO2, PpNAD-MDH2/3/4/5, and PpPEPCK2) in the organic acid degradation pathway in peach fruit, ultimately resulting in the accumulation of more organic acids. Among them, the downregulation of the key genes PpNAD-MDH3/4/5 involved in malic acid metabolism may be the main reason for the higher malic acid accumulation in peach fruit from high-altitude peach-producing areas. Overall, this study elucidates the mechanism by which environmental factors enhance the accumulation of organic acids in peach fruit from high-altitude peach-producing areas from a multi-omics perspective, as well as providing a theoretical basis for screening key genes involved in organic acid metabolism in peach fruit.

VOLATILE ANTIDIABETIC PROPERTIES OF PIPER NIGRUM L. ETHANOL EXTRACT (ORIGINAL AND PLANT STEM CELL): NETWORK PHARMACOLOGY STUDY AND ANTIOXIDANT ACTIVITY

Objective: This study aims to identify and compare the active chemical components in the ethanol extracts of Piper nigrum L. (black pepper) plant and its callus and to investigate their potential roles in treating diabetes mellitus through Protein-Protein Interaction (PPI) analysis. Methods: Ethanol extracts were prepared from both the original black pepper plant and its callus. Chemical analysis identified key active substances, including piperine and β-D-Glucopyranoside, using Retention Times (RT). PPI investigations were conducted to determine the interactions involved in diabetes management. The antioxidant capacities of the extracts were assessed using IC50 values, and the biological processes and molecular functions related to diabetes treatment were evaluated. Results: Both the original plant and callus extracts contained active substances such as piperine (37.715%, RT: 28.1967) and β-D-Glucopyranoside (54.272%, RT: 16.5768). The primary biological processes identified were the P450 epoxygenase pathway and glycogen production. Additionally, the organic acid metabolic process and nucleosome core were implicated in the management of diabetes mellitus by the extracts. The main molecular functions predicted were p53 binding and cyclin. The antioxidant capacities of the extracts were moderate for the callus extract (IC50: 129.92±0.83) and poor for the original plant extract (IC50: 156.69±1.36). Conclusion: The study reveals that the ethanol extracts from the black pepper callus and the original plant possess distinct chemical profiles and mechanisms in treating diabetes mellitus. The callus extract demonstrates a more favorable antioxidant capacity compared to the original plant extract. Both extracts engage in similar biological processes but exhibit differences in their chemical composition and potential therapeutic pathways for diabetes management.

Integrative analyses of genetic mechanisms responsible for bone-fat imbalance in osteoporosis.

Osteoporosis manifests through adipocyte accrual and osteoblast diminution within bone marrow. However, the precise mechanisms driving the shift from osteogenesis to adipogenesis in bone marrow mesenchymal stem cells (BMSCs) remain largely undefined. In this study, we harnessed the power of bioinformatic tools to analyze gene expression patterns of BMSCs during adipogenic differentiation and osteoporosis using the data from Gene Expression Omnibus (GEO) repositories (GSE113253 and GSE35956), complemented by in vitro and in vivo experiments to validate the findings. Five distinct expression profiles of differentially expressed genes across the adipogenic timeline were identified. The initial phase is marked by ribosome biogenesis and rRNA processing, which is followed by the metabolism of organic acids and processing of inorganic ions. In contrast, the terminal phase is characterized by lipid transport, accumulation, and metabolism, alongside inorganic cation metabolism, thereby underscoring unique transcriptional signatures during the early and late stages of adipogenic differentiation. In BMSCs derived from osteoporotic samples, there is a notable decline in cellular proliferation and a diminished osteogenic capacity. Critically, the genes common to both adipogenesis and osteoporosis in BMSCs are predominantly involved in the negative regulation of Wnt signaling and cellular proliferation. Key genes including SOCS1, MYC, CEBPB, FYN, AXIN2, and RXRA are identified and show downregulation in BMSCs from aged mice. Subsequent in vitro experiments have validated the regulatory influence of RXRA on both adipogenic and osteogenic differentiations of BMSCs, highlighting its crucial role as a central modulator in bone formation and the pathophysiology of osteoporosis.

Relationships Between Organic Acid Metabolism and the Accumulation of Sugars and Calcium in Fruits of Cerasus humilis During Different Development Stages.

Cerasus humilis fruit is known for its high acidity, surpassing that of most other fruits. The metabolism of organic acids in these fruits significantly influences sugar and calcium accumulation. However, research on this metabolic process is limited. This study investigates the organic acid metabolism and the accumulation patterns of sugars and calcium during the development of Cerasus humilis fruits. Using low-acid and high-acid varieties from Inner Mongolia, we compared organic acid components and the activity of relevant metabolic enzymes during fruit maturation. We also measured the content and proportions of various sugars and calcium forms, performing correlation analyses. Throughout the development and ripening of Cerasus humilis fruits, organic acids, sugars, and calcium exhibited consistent patterns of change across the two acidity types. Malic acid emerged as the most significant organic acid, while fructose was the primary sugar, and active calcium was the dominant calcium component. Correlation analyses indicated that malic acid and total acid positively correlated with sugar and water-soluble calcium content, negatively regulating other calcium forms. Conversely, NADP-ME, citric acid, and oxalic acid negatively correlated with sugars and water-soluble calcium, while positively affecting other calcium forms. In conclusion, the metabolism of organic acids during the development and maturation of Cerasus humilis fruits is closely linked to the accumulation of sugars and calcium. Malic acid, primarily regulated by NAD-MDH and NADP-ME, promotes the accumulation of sugars and water-soluble calcium but inhibits other calcium forms, while citric and oxalic acids inhibit sugar accumulation and promote non-water-soluble calcium forms.

Identification and Functional Analysis of Key Genes Regulating Organic Acid Metabolism in Jujube Fruit

Organic acids are crucial indicators of fruit flavor quality, but the metabolic characteristics and regulatory genes of organic acids during jujube fruit development remain largely unexplored. In this study, the cultivar ‘Heigeda’ with a high organic acid content was used as the experimental material. The organic acid content was quantified, and key candidate genes were identified through transcriptome analysis. The results indicated that malic acid and citric acid were the main organic acid content in jujube fruit and increased gradually with fruit development. Transcriptome analysis identified nine genes associated with malic acid and seven with citric acid, with four genes co-regulating malic acid and citric acid. Functional assays by transient overexpression and silencing of these four genes in the jujube fruits revealed that overexpression significantly upregulated the malic and citric acid content. However, only the silencing of aconitase1 (ZjACO1) and aconitase3 (ZjACO3) significantly downregulated the content of malic and citric acids. Therefore, aconitase1 (ZjACO1) and aconitase3 (ZjACO3) are considered the key genes that regulate the metabolism of citric acid and malic acid in jujube fruits. Our study can enrich the regulation mechanism of the organic acid metabolism of jujube fruit and provide theoretical support for the efficient cultivation of jujube fruit.

Multifaceted analyses reveal sugar and organic acid metabolism affecting the palatability in mulched Phyllostachys violascens shoots with varied sheath colors

The color of bamboo shoot sheaths influences both appearance and palatability in mulched Phyllostachys violascens shoots, but the mechanisms linking sheath color to flavor and texture are unclear. This study combined metabolomics and transcriptomics to investigate the relationship between sheath color and palatability, focusing on sugar and organic acid metabolism. We identified 5698 metabolites and 33 differentially expressed genes across bamboo shoots with different sheath colors. Darker shoots (black-brown, BSD) exhibited enhanced organic acids and flavor amino acid synthesis, contributing to moderate sweetness. In contrast, as the sheath color lightens (bright-red, BSM; yellow-green, BSL), sugar degradation and cell wall metabolism (e.g., lignin, pectin, cellulose) became more pronounced. BSL shoots, with the lightest sheath color, demonstrated reduced sugar degradation and increased synthesis of pectin and cellulose, resulting in greater sweetness and improved texture. These findings demonstrate that variations in sheath color are closely linked to metabolic shifts that influence both flavor and texture, offering valuable insights for targeted breeding programs aimed at enhancing bamboo shoot quality.