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

Anabolic steroids in livestock production: Background and implications for chemical food safety

Fri, 05/04/2024 - 12:00
Steroids. 2024 Apr 3:109420. doi: 10.1016/j.steroids.2024.109420. Online ahead of print.ABSTRACTThe use of steroids in livestock animals is a source of concern for consumers because of the risks associated with the presence of their residues in foodstuffs of animal origin. Technological advances such as mass spectrometry have made it possible to play a fundamental role in controlling such practices, firstly for the discovery of marker metabolites but also for the monitoring of these compounds under the regulatory framework. Current control strategies rely on the monitoring of either the parent drug or its metabolites in various matrices of interest. As some of these steroids also have an endogenous status specific strategies have to be applied for control purposes. This review aims to provide a comprehensive and up-to-date knowledge of analytical strategies, whether targeted or non-targeted, and whether they focus on markers of exposure or effect in the specific context of chemical food safety regarding the use of anabolic steroids in livestock. The role of new approaches in data acquisition (e.g. ion mobility), processing and analysis, (e.g. molecular networking), is also discussed.PMID:38580048 | DOI:10.1016/j.steroids.2024.109420

Effects of dietary selenized glucose on intestinal microbiota and tryptophan metabolism in rats: Assessing skatole reduction potential

Fri, 05/04/2024 - 12:00
Environ Res. 2024 Apr 3:118874. doi: 10.1016/j.envres.2024.118874. Online ahead of print.ABSTRACT3-Methylindole (Skatole), a degradation product of tryptophan produced by intestinal microbial activity, significantly contributes to odor nuisance. Its adverse effects on animal welfare, human health, and environmental pollution have been noted. However, it is still unclear whether the intestinal microbiota mediates the impact of selenium (Se) on skatole production and what the underlying mechanisms remain elusive. A selenized glucose (SeGlu) derivative is a novel organic selenium compound. In this study, a diverse range of dietary SeGlu-treated levels, including SeGlu-deficient (CK), SeGlu-adequate (0.15 mg Se per L), and SeGlu-supranutritional (0.4 mg Se per L) conditions, were used to investigate the complex interaction of SeGlu on intestinal microbiome and serum metabolome changes in male Sprague-Dawley (SD) rats. The study showed that SeGlu supplementation enhanced the antioxidant ability in rats, significantly manifested in the increases of the activity of catalase (CAT) and glutathione peroxidase (GSH-Px), while no change in the level of malonaldehyde (MDA). Metagenomic sequencing analysis verified that the SeGlu treatment group significantly increased the abundance of beneficial microorganisms such as Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus, and Alloprevotella while reducing the abundance of opportunistic pathogens such as Bacteroides and Alistipes significantly. Further metabolomic analysis revealed phenylalanine, tyrosine, and tryptophan biosynthesis changes in the SeGlu treatment group. Notably, the biosynthesis of indole, a critical pathway, was affected by SeGlu treatment, with several crucial enzymes implicated. Correlation analysis demonstrated strong associations between specific bacterial species - Treponema, Bacteroides, and Ruminococcus, and changes in indole and derivative concentrations. Moreover, the efficacy of SeGlu-treated fecal microbiota was confirmed through fecal microbiota transplantation, leading to a decrease in the concentration of skatole in rats. Collectively, the analysis of microbiota and metabolome response to diverse SeGlu levels suggests that SeGlu is a promising dietary additive in modulating intestinal microbiota and reducing odor nuisance in the livestock and poultry industry.PMID:38579995 | DOI:10.1016/j.envres.2024.118874

The interaction between seminal plasma, sperm, and endometrium in inter- and intra-species breeding in equids

Fri, 05/04/2024 - 12:00
Reproduction. 2024 Apr 1:REP-23-0472. doi: 10.1530/REP-23-0472. Online ahead of print.ABSTRACTAnecdotal experience suggests horse mares have less post-breeding inflammation and better fertility when bred with donkeys. This study aimed to compare the post-breeding inflammatory response of mares exposed to donkey and horse semen and seminal plasma and evaluate the proteome and metabolome of donkey and horse sperm and seminal plasma. Uterine edema, intrauterine fluid accumulation, PMNs on cytology, and concentrations of progesterone, and pro- and anti-inflammatory cytokines (IL1, IL1, IL4, IL6, CXCL8, IL10) concentrations were assessed pre-and post-infusion of semen and seminal plasma (donkey and horse). The metabolome and proteome were analyzed by LC-MS/MS. Mare cycles bred with horse semen had a greater progesterone concentration than those cycles bred with donkey semen at 8 days post-ovulation (P=0.046). At 6 h post-infusion, the inflammatory response due to the donkey semen tended to be lower (P=0.074). Donkey seminal plasma had anti-inflammatory properties compared to horse semen and seminal plasma, as determined by fewer neutrophils on uterine cytology (P<0.05). Horse semen induced resulted in a greater concentrations of IL6 and lesser concentrations of IL1 (P<0.05). Concentrations of PGE1, PGE3, and lactoferrin PGE1, PGE3, and lactoferrin concentrations were significantly more abundant in donkey sperm and seminal plasma. Prostaglandins play an important role in immunomodulation and might contribute to the response triggered in inter-species breeding. In conclusion, breeding horse mares with donkey semen induces a similar post-breeding endometritis to horse semen. Donkey seminal plasma results in a lower post-infusion inflammatory response than other combinations in the immediate post-breeding.PMID:38579760 | DOI:10.1530/REP-23-0472

Revealing quality chemicals of Tetrastigma hemsleyanum roots in different geographical origins using untargeted metabolomics and random-forest based spectrum-effect analysis

Fri, 05/04/2024 - 12:00
Food Chem. 2024 Mar 31;449:139207. doi: 10.1016/j.foodchem.2024.139207. Online ahead of print.ABSTRACTTetrastigma hemsleyanum root is a popular functional food in China, and the price varies based on the origin of the product. The link between the origin, metabolic profile, and bioactivity of T. hemsleyanum must be investigated. This study compares the metabolic profiles of 254 samples collected from eight different areas with 49 potential key chemical markers using plant metabolomics. The metabolic pathways of the five critical flavonoid metabolites were annotated and enriched using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Moreover, a random forest model aiding the spectrum-effect relationship analysis was developed for the first time indicating catechin and darendoside B as potential quality markers of antioxidant activity. The findings of this study provide a comprehensive understanding of the chemical composition and bioactive compounds of T. hemsleyanum as well as valuable information on the evaluation of the quality of various samples and products in the market.PMID:38579655 | DOI:10.1016/j.foodchem.2024.139207

Dauricine attenuates ovariectomized-induced bone loss and RANKL-induced osteoclastogenesis via inhibiting ROS-mediated NF-κB and NFATc1 activity

Fri, 05/04/2024 - 12:00
Phytomedicine. 2024 Mar 20;129:155559. doi: 10.1016/j.phymed.2024.155559. Online ahead of print.ABSTRACTBACKGROUND: Osteoclast plays an important role in maintaining the balance between bone anabolism and bone catabolism. The abnormality of osteoclast is closely related to osteolytic bone diseases such as osteoporosis, rheumatoid arthritis and tumor bone metastasis.PURPOSE: We aim to search for natural compound that may suppress osteoclast formation and function.STUDY DESIGN: In this study, we assessed the impact of Dauricine (Dau) on the formation and function of osteoclasts in vitro, as well as its potential in preventing bone loss in an ovariectomy mouse model in vivo.METHODS: Multiple in vitro experiments were carried out, including osteoclastogenesis, podosomal belt formation, bone resorption assay, RNA-sequencing, real-time quantitative PCR, ROS level detection, surface plasmon resonance assay, luciferase assay and western blot. To verify the effect in vivo, an ovariectomized mouse model (OVX model) was constructed, and bone parameters were measured using micro-CT and histology. Furthermore, metabolomics analysis was performed on blood serum samples from the OVX model.RESULTS: In vitro experiments demonstrated that Dau inhibits RANKL-induced osteoclastogenesis, podosomal belt formation, and bone resorption function. RNA-sequencing results revealed that Dau significantly suppresses genes related to osteoclast. Functional enrichment analysis indicated that Dau's inhibition of osteoclasts may be associated with NF-κB signaling pathway and reactive oxygen metabolism pathway. Molecular docking, surface plasmon resonance assay and western blot analysis further confirmed that Dau inhibits RANKL-induced osteoclastogenesis by modulating the ROS/NF-κB/NFATc1 pathway. Moreover, administration of Dau to OVX-induced mice validated its efficacy in treating bone loss disease.CONCLUSION: Dau prevents OVX-induced bone loss by inhibiting osteoclast activity and bone resorption, potentially offering a new approach for preventing and treating metabolic bone diseases such as osteoporosis. This study provides innovative insights into the inhibitory effects of Dau in an in vivo OVX model and elucidates the underlying mechanism.PMID:38579642 | DOI:10.1016/j.phymed.2024.155559

Multi-pathways-mediated mechanisms of selenite reduction and elemental selenium nanoparticles biogenesis in the yeast-like fungus Aureobasidium melanogenum I15

Fri, 05/04/2024 - 12:00
J Hazard Mater. 2024 Apr 3;470:134204. doi: 10.1016/j.jhazmat.2024.134204. Online ahead of print.ABSTRACTSelenium (Se) plays a critical role in diverse biological processes and is widely used across manufacturing industries. However, the contamination of Se oxyanions also poses a major public health concern. Microbial transformation is a promising approach to detoxify Se oxyanions and produce elemental selenium nanoparticles (SeNPs) with versatile industrial potential. Yeast-like fungi are an important group of environmental microorganisms, but their mechanisms for Se oxyanions reduction remain unknown. In this study, we found that Aureobasidium melanogenum I15 can reduce 1.0 mM selenite by over 90% within 48 h and efficiently form intracellular or extracellular spherical SeNPs. Metabolomic and proteomic analyses disclosed that A. melanogenum I15 evolves a complicated selenite reduction mechanism involving multiple metabolic pathways, including the glutathione/glutathione reductase pathway, the thioredoxin/thioredoxin reductase pathway, the siderophore-mediated pathway, and multiple oxidoreductase-mediated pathways. This study provides the first report on the mechanism of selenite reduction and SeNPs biogenesis in yeast-like fungi and paves an alternative avenue for the bioremediation of selenite contamination and the production of functional organic selenium compounds.PMID:38579586 | DOI:10.1016/j.jhazmat.2024.134204

Revealing the mechanism of post-harvest processing on rose quality based on dynamic changes in water content, enzyme activity, volatile and non-volatile metabolites

Fri, 05/04/2024 - 12:00
Food Chem. 2024 Mar 31;448:139202. doi: 10.1016/j.foodchem.2024.139202. Online ahead of print.ABSTRACTExisting studies on post-harvest processing of edible roses have mainly focused on processing techniques and physicochemical properties of the final dried products, with limited studies on how changes in metabolites during processing affect the quality of these products. This study investigated changes in water content and status, enzyme activity, phenolic compounds, and volatile and non-volatile compounds during processing and revealed the mechanisms by which post-harvest processing (drying without blanching (WBD) and drying with blanching (BD)) affects the quality of dried roses by establishing their correlations. Results showed that the blanching reduced the relative content of free water and water activity, thus reducing the subsequent drying time and enzyme activity. The BD method caused higher levels of phenolic compounds than the WBD method in terms of gallic acid, ellagic acid, epicatechin, and quercetin. The OPLS-DA analysis identified 6 differential volatiles out of 72 detected volatiles, contributing to the unique aroma of dried roses by activating olfactory receptors through hydrogen bonding and hydrophobic interactions. 58 differential metabolites were screened from 964 non-volatile metabolites. KEGG pathway analysis revealed that the changes in volatile and non-volatile metabolites induced by different processing methods were due to the effect of blanching on glutathione and fatty acid metabolism. These findings provide a comprehensive understanding of how post-harvest processing affects the quality of dried roses.PMID:38579556 | DOI:10.1016/j.foodchem.2024.139202

Understanding PFAS toxicity through cell culture metabolomics: Current applications and future perspectives

Fri, 05/04/2024 - 12:00
Environ Int. 2024 Apr 2;186:108620. doi: 10.1016/j.envint.2024.108620. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, pose significant challenges to ecosystems and human health. While cell cultures have emerged as new approach methodologies (NAMs) in ecotoxicity research, metabolomics is an emerging technique used to characterize the small-molecule metabolites present in cells and to understand their role in various biological processes. Integration of metabolomics with cell cultures, known as cell culture metabolomics, provides a novel and robust tool to unravel the complex molecular responses induced by PFAS exposure. In vitro testing also reduces reliance on animal testing, aligning with ethical and regulatory imperatives. The current review summarizes key findings from recent studies utilizing cell culture metabolomics to investigate PFAS toxicity, highlighting alterations in metabolic pathways, biomarker identification, and the potential linkages between metabolic perturbations. Additionally, the paper discusses different types of cell cultures and metabolomics methods used for studies of environmental contaminants and particularly PFAS. Future perspectives on the combination of metabolomics with other advanced technologies, such as single-cell metabolomics (SCM), imaging mass spectrometry (IMS), extracellular flux analysis (EFA), and multi-omics are also explored, which offers a holistic understanding of environmental contaminants. The synthesis of current knowledge and identification of research gaps provide a foundation for future investigations that aim to elucidate the complexities of PFAS-induced cellular responses and contribute to the development of effective strategies for mitigating their adverse effects on human health.PMID:38579451 | DOI:10.1016/j.envint.2024.108620

Optical imaging reveals chemotherapy-induced metabolic reprogramming of residual disease and recurrence

Fri, 05/04/2024 - 12:00
Sci Adv. 2024 Apr 5;10(14):eadj7540. doi: 10.1126/sciadv.adj7540. Epub 2024 Apr 5.ABSTRACTFewer than 20% of triple-negative breast cancer patients experience long-term responses to mainstay chemotherapy. Resistant tumor subpopulations use alternative metabolic pathways to escape therapy, survive, and eventually recur. Here, we show in vivo, longitudinal metabolic reprogramming in residual disease and recurrence of triple-negative breast cancer xenografts with varying sensitivities to the chemotherapeutic drug paclitaxel. Optical imaging coupled with metabolomics reported an increase in non-glucose-driven mitochondrial metabolism and an increase in intratumoral metabolic heterogeneity during regression and residual disease in resistant MDA-MB-231 tumors. Conversely, sensitive HCC-1806 tumors were primarily reliant on glucose uptake and minimal changes in metabolism or heterogeneity were observed over the tumors' therapeutic life cycles. Further, day-matched resistant HCC-1806 tumors revealed a higher reliance on mitochondrial metabolism and elevated metabolic heterogeneity compared to sensitive HCC-1806 tumors. Together, metabolic flexibility, increased reliance on mitochondrial metabolism, and increased metabolic heterogeneity are defining characteristics of persistent residual disease, features that will inform the appropriate type and timing of therapies.PMID:38579004 | DOI:10.1126/sciadv.adj7540

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains

Fri, 05/04/2024 - 12:00
Sci Adv. 2024 Apr 5;10(14):eadk8093. doi: 10.1126/sciadv.adk8093. Epub 2024 Apr 5.ABSTRACTTrained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.PMID:38578989 | DOI:10.1126/sciadv.adk8093

Metabolites and Cognitive Decline in a Puerto Rican Cohort

Fri, 05/04/2024 - 12:00
J Alzheimers Dis. 2024 Mar 30. doi: 10.3233/JAD-230053. Online ahead of print.ABSTRACTBACKGROUND: Recent studies have identified plasma metabolites associated with cognitive decline and Alzheimer's disease; however, little research on this topic has been conducted in Latinos, especially Puerto Ricans.OBJECTIVE: This study aims to add to the growing body of metabolomics research in Latinos to better understand and improve the health of this population.METHODS: We assessed the association between plasma metabolites and global cognition over 12 years of follow-up in 736 participants of the Boston Puerto Rican Health Study (BPRHS). Metabolites were measured with untargeted metabolomic profiling (Metabolon, Inc) at baseline. We used covariable adjusted linear mixed models (LMM) with a metabolite * time interaction term to identify metabolites (of 621 measured) associated with ∼12 years cognitive trajectory.RESULTS: We observed strong inverse associations between medium-chain fatty acids, caproic acid, and the dicarboxylic acids, azelaic and sebacic acid, and global cognition. N-formylphenylalanine, a tyrosine pathway metabolite, was associated with improvement in cognitive trajectory.CONCLUSIONS: The metabolites identified in this study are generally consistent with prior literature and highlight a role medium chain fatty acid and tyrosine metabolism in cognitive decline.PMID:38578885 | DOI:10.3233/JAD-230053

Domestication has altered gene expression and secondary metabolites in pea seed coat

Fri, 05/04/2024 - 12:00
Plant J. 2024 Apr 5. doi: 10.1111/tpj.16734. Online ahead of print.ABSTRACTThe mature seed in legumes consists of an embryo and seed coat. In contrast to knowledge about the embryo, we know relatively little about the seed coat. We analyzed the gene expression during seed development using a panel of cultivated and wild pea genotypes. Gene co-expression analysis identified gene modules related to seed development, dormancy, and domestication. Oxidoreductase genes were found to be important components of developmental and domestication processes. Proteomic and metabolomic analysis revealed that domestication favored proteins involved in photosynthesis and protein metabolism at the expense of seed defense. Seed coats of wild peas were rich in cell wall-bound metabolites and the protective compounds predominated in their seed coats. Altogether, we have shown that domestication altered pea seed development and modified (mostly reduced) the transcripts along with the protein and metabolite composition of the seed coat, especially the content of the compounds involved in defense. We investigated dynamic profiles of selected identified phenolic and flavonoid metabolites across seed development. These compounds usually deteriorated the palatability and processing of the seeds. Our findings further provide resources to study secondary metabolism and strategies for improving the quality of legume seeds which comprise an important part of the human protein diet.PMID:38578789 | DOI:10.1111/tpj.16734

Phenylalanine treatment induces tomato resistance to Tuta absoluta via increased accumulation of benzenoid/phenylpropanoid volatiles serving as defense signals

Fri, 05/04/2024 - 12:00
Plant J. 2024 Apr 5. doi: 10.1111/tpj.16745. Online ahead of print.ABSTRACTTuta absoluta ("leafminer"), is a major pest of tomato crops worldwide. Controlling this insect is difficult due to its efficient infestation, rapid proliferation, and resilience to changing weather conditions. Furthermore, chemical pesticides have only a short-term effect due to rapid development of T. absoluta strains. Here, we show that a variety of tomato cultivars, treated with external phenylalanine solutions exhibit high resistance to T. absoluta, under both greenhouse and open field conditions, at different locations. A large-scale metabolomic study revealed that tomato leaves absorb and metabolize externally given Phe efficiently, resulting in a change in their volatile profile, and repellence of T. absoluta moths. The change in the volatile profile is due to an increase in three phenylalanine-derived benzenoid phenylpropanoid volatiles (BPVs), benzaldehyde, phenylacetaldehyde, and 2-phenylethanol. This treatment had no effect on terpenes and green leaf volatiles, known to contribute to the fight against insects. Phe-treated plants also increased the resistance of neighboring non-treated plants. RNAseq analysis of the neighboring non-treated plants revealed an exclusive upregulation of genes, with enrichment of genes related to the plant immune response system. Exposure of tomato plants to either benzaldehyde, phenylacetaldehyde, or 2-phenylethanol, resulted in induction of genes related to the plant immune system that were also induced due to neighboring Phe-treated plants. We suggest a novel role of phenylalanine-derived BPVs as mediators of plant-insect interactions, acting as inducers of the plant defense mechanisms.PMID:38578218 | DOI:10.1111/tpj.16745

The alteration of fecal microbial and metabolic profile of gallstone patients in Taiwan: Single center study

Fri, 05/04/2024 - 12:00
J Chin Med Assoc. 2024 Apr 5. doi: 10.1097/JCMA.0000000000001094. Online ahead of print.ABSTRACTBACKGROUND: Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone (CS) patients, pigmented gallstone (PS) patients, and controls.METHODS: We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics.RESULT: Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium, Prevotella 9 and Bacteroides plebeius DSM 17135. The CS group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the PS group had more abundant Escherichia-Shigella. In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group (p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences, but was correlated to the serum cholesterol level and bacterial richness and evenness.CONCLUSION: Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort.PMID:38578093 | DOI:10.1097/JCMA.0000000000001094

Sepsis, Management & Advances in Metabolomics

Fri, 05/04/2024 - 12:00
Nanotheranostics. 2024 Feb 25;8(3):270-284. doi: 10.7150/ntno.94071. eCollection 2024.ABSTRACTThough there have been developments in clinical care and management, early and accurate diagnosis and risk stratification are still bottlenecks in septic shock patients. Since septic shock is multifactorial with patient-specific underlying co-morbid conditions, early assessment of sepsis becomes challenging due to variable symptoms and clinical manifestations. Moreover, the treatment strategies are traditionally based on their progression and corresponding clinical symptoms, not personalized. The complex pathophysiology assures that a single biomarker cannot identify, stratify, and describe patients affected by septic shock. Traditional biomarkers like CRP, PCT, and cytokines are not sensitive and specific enough to be used entirely for a patient's diagnosis and prognosis. Thus, the need of the hour is a sensitive and specific biomarker after comprehensive analysis that may facilitate an early diagnosis, prognosis, and drug development. Integration of clinical data with metabolomics would provide means to understand the patient's condition, stratify patients better, and predict the clinical outcome.PMID:38577320 | PMC:PMC10988213 | DOI:10.7150/ntno.94071

Integrated transcriptomic and metabolomic analysis reveals the regulation mechanism of early bolting and flowering in two cultivars of Angelica sinensis

Fri, 05/04/2024 - 12:00
Heliyon. 2024 Mar 27;10(7):e28636. doi: 10.1016/j.heliyon.2024.e28636. eCollection 2024 Apr 15.ABSTRACTThe root of Angelica sinensis is utilized in Traditional Chinese medicine to enhance blood replenishment and facilitate blood circulation. The early bolting and flowering (EBF) of A. sinensis, however, compromises the quality of the roots and restricts the yield of medicinal substances. The study was conducted to compare the transcriptomic and metabolomic profiles between EBF plants and normal plants of two cultivars of A. sinensis, followed by validation of the transcriptome results using qRT-PCR. There were 3677 DEGs in EBF plants compared to normal plants of cultivar 2 (Mingui No.2), and cultivar 4 (Mingui No.4) was 3354. The main differential metabolites in the EBF and normal plants were phenolic acids, flavonoids, lignans, and coumarins. The analysis of 5 EBF-related pathways revealed 28 genes exhibiting differential expression and 5 metabolites showing differential accumulation. The expression of the Lhcb5, Lhcb2, Lhcb6, Lhcb1, Lhca4, ATPG1, EGLC, CELB, AMY, glgA, CYCD3, SnRK2, PYL, AHK2, AUX1, BSK, FabI/K, ACACA and FabV decreased and the expression of the PsbR, PsbA, LHY, FT, CO, malQ, HK, GPI and DELLA increased in EBF plants. In addition, the Abscisic acid, d-Glucose-6P, α-d-Glucose-1P, NADP+, and ADP were more significantly enriched in EBF plants. The findings offer novel perspectives on the EBF mechanisms in A. sinensis and other medicinal plants of the Apiaceae family.PMID:38576577 | PMC:PMC10990851 | DOI:10.1016/j.heliyon.2024.e28636

Transcriptomics and metabonomics study on the effect of exercise combined with curcumin supplementation on breast cancer in mice

Fri, 05/04/2024 - 12:00
Heliyon. 2024 Mar 29;10(7):e28807. doi: 10.1016/j.heliyon.2024.e28807. eCollection 2024 Apr 15.ABSTRACTCurcumin and exercise have been reported to show good anti-tumour effects. However, relevant research on the combined effects of physical exercise and curcumin supplementation on cancer and the underlying mechanisms is still lacking. The current study aimed to construct an anti-breast tumour mouse model using the combined effects of curcumin treatment and swimming exercise. Transcriptomic and metabolomic techniques were used to screen for differentially expressed genes and metabolites, evaluate the anticancer effects, and analyse the molecular regulatory mechanisms related to metabolism. Observation of the mouse phenotypes, including tumour appearance, in-vivo tumour imaging, and HE staining results of pathological sections, suggested a more obvious inhibitory effect of the combination of curcumin administration and exercise intervention on breast cancer than that of a single treatment. The combination treatment group had a total of 445 differentially expressed (154 upregulated and 291 downregulated) genes. Functional enrichment analysis showed the calcium signalling pathway, Wnt signalling pathway, PI3K Akt signalling pathway, and IL-17 signalling pathway to significantly participate in the anti-breast cancer process of curcumin-exercise combination treatment. Results of the intergroup differential metabolite analysis showed that the combined effect of curcumin and exercise involves two unique pathways, namely the amino sugar and nucleotide sugar metabolism, which includes chitosan, d-glucosamine 6-phosphate, l-fucose, and N-acetyl beta-mannosamine, and the amino acid biosynthesis, which includes dl-isoleucine, dl-tyrosine, and homocysteine. Collectively, the top-ranked genes and metabolites with the highest degree of associations were further revealed by O2PLS analysis. Overall, the study helped reveal the mechanism of action of curcumin-exercise combination treatment on breast cancer at multi-omics level.PMID:38576560 | PMC:PMC10990956 | DOI:10.1016/j.heliyon.2024.e28807

Revealing the specific regulations of nitric oxide on the postharvest ripening and senescence of bitter melon fruit

Fri, 05/04/2024 - 12:00
aBIOTECH. 2024 Mar 21;5(1):29-45. doi: 10.1007/s42994-023-00110-y. eCollection 2024 Mar.ABSTRACTBitter melon fruit is susceptible to yellowing, softening, and rotting under room-temperature storage conditions, resulting in reduced commercial value. Nitric oxide (NO) is an important signaling molecule and plays a crucial role in regulating the fruit postharvest quality. In this study, we investigated the effects of NO treatment on changes in sensory and firmness of bitter melon fruit during postharvest storage. Moreover, transcriptomic, metabolomic, and proteomic analyses were performed to elucidate the regulatory mechanisms through which NO treatment delays the ripening and senescence of bitter melon fruit. Our results show that differentially expressed genes (DEGs) were involved in fruit texture (CSLE, β-Gal, and PME), plant hormone signal transduction (ACS, JAR4, and AUX28), and fruit flavor and aroma (SUS2, LOX, and GDH2). In addition, proteins differentially abundant were associated with fruit texture (PLY, PME, and PGA) and plant hormone signal transduction (PBL15, JAR1, and PYL9). Moreover, NO significantly increased the abundance of key enzymes involved in the phenylpropanoid biosynthetic pathway, thus enhancing the disease resistance and alleviating softening of bitter melon fruit. Finally, differential metabolites mainly included phenolic acids, terpenoids, and flavonoids. These results provide a theoretical basis for further studies on the physiological changes associated with postharvest ripening and senescence of bitter melon fruit.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42994-023-00110-y.PMID:38576434 | PMC:PMC10987440 | DOI:10.1007/s42994-023-00110-y

Unveiling behaviors of 8:2 fluorotelomer sulfonic acid (8:2 FTSA) in Arabidopsis thaliana: Bioaccumulation, biotransformation and molecular mechanisms of phytotoxicity

Thu, 04/04/2024 - 12:00
Sci Total Environ. 2024 Apr 2:172165. doi: 10.1016/j.scitotenv.2024.172165. Online ahead of print.ABSTRACT8:2 fluorotelomer sulfonic acid (8:2 FTSA) has been commonly detected in the environment, but its behaviors in plants are not sufficiently known. Here, the regular and multi-omics analyses were used to comprehensively investigate the bioaccumulation, biotransformation, and toxicity of 8:2 FTSA in Arabidopsis thaliana. Our results demonstrated that 8:2 FTSA was taken up by A. thaliana roots and translocated to leaves, stems, flowers, and seeds. 8:2 FTSA could be successfully biotransformed to several intermediates and stable perfluorocarboxylic acids (PFCAs) catalyzed by plant enzymes. The plant revealed significant growth inhibition and oxidative damage under 8:2 FTSA exposure. Metabolomics analysis showed that 8:2 FTSA affected the porphyrin and secondary metabolisms, resulting in the promotion of plant photosynthesis and antioxidant capacity. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were related to transformation and transport processes. Integrative transcriptomic and metabolomic analysis revealed that DEGs and differentially expressed metabolites (DEMs) in plants were predominantly enriched in the carbohydrate metabolism, amino acid metabolism, and lipid metabolism pathways, resulting in greater energy consumption, generation of more nonenzymatic antioxidants, alteration of the cellular membrane composition, and inhibition of plant development. This study provides the first insights into the molecular mechanisms of 8:2 FTSA stress response in plants.PMID:38575024 | DOI:10.1016/j.scitotenv.2024.172165

In situ profiling reveals spatially metabolic injury in the initiation of polystyrene nanoplastic-derived intestinal epithelial injury in mice

Thu, 04/04/2024 - 12:00
Sci Total Environ. 2024 Apr 2:172037. doi: 10.1016/j.scitotenv.2024.172037. Online ahead of print.ABSTRACTDespite increasing concerns regarding the harmful effects of plastic-induced gut injury, mechanisms underlying the initiation of plastic-derived intestinal toxicity remain unelucidated. Here, mice were subjected to long-term exposure to polystyrene nanoplastics (PS-NPs) of varying sizes (80, 200, and 1000 nm) at doses relevant to human dietary exposure. PS-NPs exposure did not induce a significant inflammatory response, histopathological damage, or intestinal epithelial dysfunction in mice at a dosage of 0.5 mg/kg/day for 28 days. However, PS-NPs were detected in the mouse intestine, coupled with observed microstructural changes in enterocytes, including mild villous lodging, mitochondrial membrane rupture, and endoplasmic reticulum (ER) dysfunction, suggesting that intestinal-accumulating PS-NPs resulted in the onset of intestinal epithelial injury in mice. Mechanistically, intragastric PS-NPs induced gut microbiota dysbiosis and specific bacteria alterations, accompanied by abnormal metabolic fingerprinting in the plasma. Furthermore, integrated data from mass spectrometry imaging-based spatial metabolomics and metallomics revealed that PS-NPs exposure led to gut dysbiosis-associated host metabolic reprogramming and initiated intestinal injury. These findings provide novel insights into the critical gut microbial-host metabolic remodeling events vital to nanoplastic-derived-initiated intestinal injury.PMID:38575003 | DOI:10.1016/j.scitotenv.2024.172037

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