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

Untargeted Metabolomic Analysis of Sjögren-Larsson Syndrome Reveals a Distinctive Pattern of Multiple Disrupted Biochemical Pathways

Tue, 27/06/2023 - 12:00
Metabolites. 2023 May 23;13(6):682. doi: 10.3390/metabo13060682.ABSTRACTSjögren-Larsson syndrome (SLS) is a rare inherited neurocutaneous disease characterized by ichthyosis, spastic diplegia or tetraplegia, intellectual disability and a distinctive retinopathy. SLS is caused by bi-allelic mutations in ALDH3A2, which codes for fatty aldehyde dehydrogenase (FALDH) and results in abnormal lipid metabolism. The biochemical abnormalities in SLS are not completely known, and the pathogenic mechanisms leading to symptoms are still unclear. To search for pathways that are perturbed in SLS, we performed untargeted metabolomic screening in 20 SLS subjects along with age- and sex-matched controls. Of 823 identified metabolites in plasma, 121 (14.7%) quantitatively differed in the overall SLS cohort from controls; 77 metabolites were decreased and 44 increased. Pathway analysis pointed to disrupted metabolism of sphingolipids, sterols, bile acids, glycogen, purines and certain amino acids such as tryptophan, aspartate and phenylalanine. Random forest analysis identified a unique metabolomic profile that had a predictive accuracy of 100% for discriminating SLS from controls. These results provide new insight into the abnormal biochemical pathways that likely contribute to disease in SLS and may constitute a biomarker panel for diagnosis and future therapeutic studies.PMID:37367841 | DOI:10.3390/metabo13060682

Integrated Metabolome and Transcriptome during Fruit Development Reveal Metabolic Differences and Molecular Basis between <em>Lycium barbarum</em> and <em>Lycium ruthenicum</em>

Tue, 27/06/2023 - 12:00
Metabolites. 2023 May 23;13(6):680. doi: 10.3390/metabo13060680.ABSTRACTWolfberry (Lycium barbarum) is a traditional cash crop in China and is well-known worldwide for its outstanding nutritional and medicinal value. Lycium ruthenicum is a close relative of Lycium barbarum but differs significantly in size, color, flavor and nutritional composition. To date, the metabolic differences between the fruits of the two wolfberry varieties and the genetic basis behind them are unclear. Here, we compared metabolome and transcriptome data of two kinds of wolfberry fruits at five stages of development. Metabolome results show that amino acids, vitamins and flavonoids had the same accumulation pattern in various developmental stages of fruit but that Lycium ruthenicum accumulated more metabolites than Lycium barbarum during the same developmental stage, including L-glutamate, L-proline, L-serine, abscisic acid (ABA), sucrose, thiamine, naringenin and quercetin. Based on the metabolite and gene networks, many key genes that may be involved in the flavonoid synthesis pathway in wolfberry were identified, including PAL, C4H, 4CL, CHS, CHI, F3H, F3'H and FLS. The expression of these genes was significantly higher in Lycium ruthenicum than in Lycium barbarum, indicating that the difference in the expression of these genes was the main reason for the variation in flavonoid accumulation between Lycium barbarum and Lycium ruthenicum. Taken together, our results reveal the genetic basis of the difference in metabolomics between Lycium barbarum and Lycium ruthenicum and provide new insights into the flavonoid synthesis of wolfberry.PMID:37367839 | DOI:10.3390/metabo13060680

Antibacterial Activities and Life Cycle Stages of <em>Asparagopsis armata</em>: Implications of the Metabolome and Microbiome

Tue, 27/06/2023 - 12:00
Mar Drugs. 2023 Jun 17;21(6):363. doi: 10.3390/md21060363.ABSTRACTThe red alga Asparagopsis armata is a species with a haplodiplophasic life cycle alternating between morphologically distinct stages. The species is known for its various biological activities linked to the production of halogenated compounds, which are described as having several roles for the algae such as the control of epiphytic bacterial communities. Several studies have reported differences in targeted halogenated compounds (using gas chromatography-mass spectrometry analysis (GC-MS)) and antibacterial activities between the tetrasporophyte and the gametophyte stages. To enlarge this picture, we analysed the metabolome (using liquid chromatography-mass spectrometry (LC-MS)), the antibacterial activity and the bacterial communities associated with several stages of the life cycle of A. armata: gametophytes, tetrasporophytes and female gametophytes with developed cystocarps. Our results revealed that the relative abundance of several halogenated molecules including dibromoacetic acid and some more halogenated molecules fluctuated depending on the different stages of the algae. The antibacterial activity of the tetrasporophyte extract was significantly higher than that of the extracts of the other two stages. Several highly halogenated compounds, which discriminate algal stages, were identified as candidate molecules responsible for the observed variation in antibacterial activity. The tetrasporophyte also harboured a significantly higher specific bacterial diversity, which is associated with a different bacterial community composition than the other two stages. This study provides elements that could help in understanding the processes that take place throughout the life cycle of A. armata with different potential energy investments between the development of reproductive elements, the production of halogenated molecules and the dynamics of bacterial communities.PMID:37367688 | DOI:10.3390/md21060363

Fish Skin Mucus Extracts: An Underexplored Source of Antimicrobial Agents

Tue, 27/06/2023 - 12:00
Mar Drugs. 2023 Jun 7;21(6):350. doi: 10.3390/md21060350.ABSTRACTThe slow discovery of new antibiotics combined with the alarming emergence of antibiotic-resistant bacteria underscores the need for alternative treatments. In this regard, fish skin mucus has been demonstrated to contain a diverse array of bioactive molecules with antimicrobial properties, including peptides, proteins, and other metabolites. This review aims to provide an overview of the antimicrobial molecules found in fish skin mucus and its reported in vitro antimicrobial capacity against bacteria, fungi, and viruses. Additionally, the different methods of mucus extraction, which can be grouped as aqueous, organic, and acidic extractions, are presented. Finally, omic techniques (genomics, transcriptomics, proteomics, metabolomics, and multiomics) are described as key tools for the identification and isolation of new antimicrobial compounds. Overall, this study provides valuable insight into the potential of fish skin mucus as a promising source for the discovery of new antimicrobial agents.PMID:37367675 | DOI:10.3390/md21060350

OMICS and Other Advanced Technologies in Mycological Applications

Tue, 27/06/2023 - 12:00
J Fungi (Basel). 2023 Jun 19;9(6):688. doi: 10.3390/jof9060688.ABSTRACTFungi play many roles in different ecosystems. The precise identification of fungi is important in different aspects. Historically, they were identified based on morphological characteristics, but technological advancements such as polymerase chain reaction (PCR) and DNA sequencing now enable more accurate identification and taxonomy, and higher-level classifications. However, some species, referred to as "dark taxa", lack distinct physical features that makes their identification challenging. High-throughput sequencing and metagenomics of environmental samples provide a solution to identifying new lineages of fungi. This paper discusses different approaches to taxonomy, including PCR amplification and sequencing of rDNA, multi-loci phylogenetic analyses, and the importance of various omics (large-scale molecular) techniques for understanding fungal applications. The use of proteomics, transcriptomics, metatranscriptomics, metabolomics, and interactomics provides a comprehensive understanding of fungi. These advanced technologies are critical for expanding the knowledge of the Kingdom of Fungi, including its impact on food safety and security, edible mushrooms foodomics, fungal secondary metabolites, mycotoxin-producing fungi, and biomedical and therapeutic applications, including antifungal drugs and drug resistance, and fungal omics data for novel drug development. The paper also highlights the importance of exploring fungi from extreme environments and understudied areas to identify novel lineages in the fungal dark taxa.PMID:37367624 | DOI:10.3390/jof9060688

Uncovering Phytotoxic Compounds Produced by <em>Colletotrichum</em> spp. Involved in Legume Diseases Using an OSMAC-Metabolomics Approach

Tue, 27/06/2023 - 12:00
J Fungi (Basel). 2023 May 25;9(6):610. doi: 10.3390/jof9060610.ABSTRACTDifferent fungal species belonging to the Colletotrichum genus cause anthracnose disease in a range of major crops, resulting in huge economic losses worldwide. Typical symptoms include dark, sunken lesions on leaves, stems, or fruits. Colletotrichum spp. have synthesized, in vitro, a number of biologically active and structurally unusual metabolites that are involved in their host's infection process. In this study, we applied a one strain many compounds (OSMAC) approach, integrated with targeted and non-targeted metabolomics profiling, to shed light on the secondary phytotoxic metabolite panels produced by pathogenic isolates of Colletotrichum truncatum and Colletotrichum trifolii. The phytotoxicity of the fungal crude extracts was also assessed on their primary hosts and related legumes, and the results correlated with the metabolite profile that arose from the different cultural conditions. To the best of our knowledge, this is the first time that the OSMAC strategy integrated with metabolomics approaches has been applied to Colletotrichum species involved in legume diseases.PMID:37367546 | DOI:10.3390/jof9060610

Transcriptome and Metabolome Integration Reveals the Impact of Fungal Elicitors on Triterpene Accumulation in <em>Sanghuangporus sanghuang</em>

Tue, 27/06/2023 - 12:00
J Fungi (Basel). 2023 May 24;9(6):604. doi: 10.3390/jof9060604.ABSTRACTSanghuangporus sanghuang is a large wood-decaying mushroom highly valued in traditional Chinese medicine due to its medicinal properties, including hypoglycemic, antioxidant, antitumor, and antibacterial properties effects. Its key bioactive compounds include flavonoids and triterpenoids. Specific fungal genes can be selectively induced by fungal elicitors. To investigate the effect of fungal polysaccharides derived from Perenniporia tenuis mycelia on the metabolites of S. sanghuang, we conducted metabolic and transcriptional profiling with and without elicitor treatment (ET and WET, respectively). Correlation analysis showed significant differences in triterpenoid biosynthesis between the ET and WET groups. In addition, the structural genes associated with triterpenoids and their metabolites in both groups were verified using quantitative real-time polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Through metabolite screening, three triterpenoids were identified: betulinol, betulinic acid, and 2-hydroxyoleanolic acid. Excitation treatment increased the level of betulinic acid by 2.62-fold and 2-hydroxyoleanolic acid by 114.67-fold compared to WET. The qRT-PCR results of the four genes expressed in secondary metabolic pathways, defense gene activation, and signal transduction showed significant variation between the ET and WET groups. Overall, our study suggests that the fungal elicitor induced the aggregation of pentacyclic triterpenoid secondary metabolites in S. sanghuang.PMID:37367540 | DOI:10.3390/jof9060604

Microbe-Plant Interactions Targeting Metal Stress: New Dimensions for Bioremediation Applications

Tue, 27/06/2023 - 12:00
J Xenobiot. 2023 Jun 1;13(2):252-269. doi: 10.3390/jox13020019.ABSTRACTIn the age of industrialization, numerous non-biodegradable pollutants like plastics, HMs, polychlorinated biphenyls, and various agrochemicals are a serious concern. These harmful toxic compounds pose a serious threat to food security because they enter the food chain through agricultural land and water. Physical and chemical techniques are used to remove HMs from contaminated soil. Microbial-metal interaction, a novel but underutilized strategy, might be used to lessen the stress caused by metals on plants. For reclaiming areas with high levels of heavy metal contamination, bioremediation is effective and environmentally friendly. In this study, the mechanism of action of endophytic bacteria that promote plant growth and survival in polluted soils-known as heavy metal-tolerant plant growth-promoting (HMT-PGP) microorganisms-and their function in the control of plant metal stress are examined. Numerous bacterial species, such as Arthrobacter, Bacillus, Burkholderia, Pseudomonas, and Stenotrophomonas, as well as a few fungi, such as Mucor, Talaromyces, Trichoderma, and Archaea, such as Natrialba and Haloferax, have also been identified as potent bioresources for biological clean-up. In this study, we additionally emphasize the role of plant growth-promoting bacteria (PGPB) in supporting the economical and environmentally friendly bioremediation of heavy hazardous metals. This study also emphasizes future potential and constraints, integrated metabolomics approaches, and the use of nanoparticles in microbial bioremediation for HMs.PMID:37367495 | DOI:10.3390/jox13020019

Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis

Tue, 27/06/2023 - 12:00
Curr Issues Mol Biol. 2023 Jun 20;45(6):5215-5231. doi: 10.3390/cimb45060331.ABSTRACTAtopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence in the developed countries. It is associated with atopic and non-atopic diseases, and its close correlation with atopic comorbidities has been genetically demonstrated. One of the main roles of genetic studies is to comprehend the defects of the cutaneous barrier due to filaggrin deficit and epidermal spongiosis. Recently, epigenetic studies started to analyze the influence of the environmental factors on gene expression. The epigenome is considered to be a superior second code that controls the genome, which includes alterations of the chromatin. The epigenetic changes do not alter the genetic code, however, changes in the chromatin structure could activate or inhibit the transcription process of certain genes and consequently, the translation process of the new mRNA into a polypeptide chain. In-depth analysis of the transcriptomic, metabolomic and proteomic studies allow to unravel detailed mechanisms that cause AD. The extracellular space and lipid metabolism are associated with AD that is independent of the filaggrin expression. On the other hand, around 45 proteins are considered as the principal components in the atopic skin. Moreover, genetic studies based on the disrupted cutaneous barrier can lead to the development of new treatments targeting the cutaneous barrier or cutaneous inflammation. Unfortunately, at present, there are no target therapies that focus on the epigenetic process of AD. However, in the future, miR-143 could be an important objective for new therapies, as it targets the miR-335:SOX axis, thereby restoring the miR-335 expression, and repairing the cutaneous barrier defects.PMID:37367080 | DOI:10.3390/cimb45060331

Potential Diagnostic Biomarker Detection for Prostate Cancer Using Untargeted and Targeted Metabolomic Profiling

Tue, 27/06/2023 - 12:00
Curr Issues Mol Biol. 2023 Jun 8;45(6):5036-5051. doi: 10.3390/cimb45060320.ABSTRACTProstate cancer (PCa) remains one of the leading causes of cancer mortality in men worldwide, currently lacking specific, early detection and staging biomarkers. In this regard, modern research focuses efforts on the discovery of novel molecules that could represent potential future non-invasive biomarkers for the diagnosis of PCa, as well as therapeutic targets. Mounting evidence shows that cancer cells express an altered metabolism in their early stages, making metabolomics a promising tool for the discovery of altered pathways and potential biomarker molecules. In this study, we first performed untargeted metabolomic profiling on 48 PCa plasma samples and 23 healthy controls using ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-[ESI+]-MS) for the discovery of metabolites with altered profiles. Secondly, we selected five molecules (L-proline, L-tryptophan, acetylcarnitine, lysophosphatidylcholine C18:2 and spermine) for the downstream targeted metabolomics and found out that all the molecules, regardless of the PCa stage, were decreased in the PCa plasma samples when compared to the controls, making them potential biomarkers for PCa detection. Moreover, spermine, acetylcarnitine and L-tryptophan had very high diagnostic accuracy, with AUC values of 0.992, 0.923 and 0.981, respectively. Consistent with other literature findings, these altered metabolites could represent future specific and non-invasive candidate biomarkers for PCa detection, which opens novel horizons in the field of metabolomics.PMID:37367069 | DOI:10.3390/cimb45060320

Comparative analysis of flavonoids, polyphenols and volatiles in roots, stems and leaves of five mangroves

Tue, 27/06/2023 - 12:00
PeerJ. 2023 Jun 22;11:e15529. doi: 10.7717/peerj.15529. eCollection 2023.ABSTRACTMangrove plants contain a variety of secondary metabolites, including flavonoids, polyphenols, and volatiles, which are important for their survival and adaptation to the coastal environment, as well as for producing bioactive compounds. To reveal differences in these compounds among five mangrove species' leaf, root, and stem, the total contents of flavonoids and polyphenols, types and contents of volatiles were determined, analyzed and compared. The results showed that Avicennia marina leaves contained the highest levels of flavonoids and phenolics. In mangrove parts, flavonoids are usually higher than phenolic compounds. A total of 532 compounds were detected by a gas chromatography-mass spectrometry (GC-MS) method in the leaf, root, and stem parts of five mangrove species. These were grouped into 18 classes, including alcohols, aldehydes, alkaloids, alkanes, etc. The number of volatile compounds in A. ilicifolius (176) and B. gymnorrhiza (172) was lower than in the other three species. The number of volatile compounds and their relative contents differed among all three parts of five mangrove species, where the mangrove species factor had a greater impact than the part factor. A total of 71 common compounds occurring in more than two species or parts were analyzed by a PLS-DA model. One-way ANOVA revealed 18 differential compounds among mangrove species and nine differential compounds among parts. Principal component analysis and hierarchical clustering analysis showed that both unique and common compounds significantly differed in composition and concentration between species and parts. In general, A. ilicifolius and B. gymnorrhiza differed significantly from the other species in terms of compound content, while the leaves differed significantly from the other parts. VIP screening and pathway enrichment analysis were performed on 17 common compounds closely related to mangrove species or parts. These compounds were mainly involved in terpenoid pathways such as C10 isoprenoids and C15 isoprenoids and fatty alcohols. The correlation analysis showed that the content of flavonoids/phenolics, the number of compounds, and the content of some common compounds in mangroves were correlated with their salt and waterlogging tolerance levels. These findings will help in the development of genetic varieties and medicinal utilization of mangrove plants.PMID:37366424 | PMC:PMC10290835 | DOI:10.7717/peerj.15529

The adipose-derived stem cell peptide ADSCP2 alleviates hypertrophic scar fibrosis via binding with pyruvate carboxylase and remodeling the metabolic landscape

Tue, 27/06/2023 - 12:00
Acta Physiol (Oxf). 2023 Jun 27:e14010. doi: 10.1111/apha.14010. Online ahead of print.ABSTRACTAIM: The purpose of this study was to investigate the function and mechanism of a novel peptide derived from adipose-derived stem cell-conditioned medium (ADSC-CM).METHODS: Mass spectrometry was applied to identify expressed peptides in ADSC-CM obtained at different time points. The cell counting kit-8 assay and quantitative reverse transcription polymerase chain reactions were performed to screen the functional peptides contained within ADSC-CM. RNA-seq, western blot, a back skin excisional model of BALB/c mice, the peptide pull-down assay, rescue experiments, untargeted metabolomics, and mixOmics analysis were performed to thoroughly understand the functional mechanism of selected peptide.RESULTS: A total of 93, 827, 1108, and 631 peptides were identified in ADSC-CM at 0, 24, 48, and 72 h of conditioning, respectively. A peptide named ADSCP2 (DENREKVNDQAKL) derived from ADSC-CM inhibited collagen and ACTA2 mRNAs in hypertrophic scar fibroblasts. Moreover, ADSCP2 facilitated wound healing and attenuated collagen deposition in a mouse model. ADSCP2 bound with the pyruvate carboxylase (PC) protein and inhibited PC protein expression. Overexpressing PC rescued the reduction in collagen and ACTA2 mRNAs caused by ADSCP2. Untargeted metabolomics identified 258 and 447 differential metabolites in the negative and positive mode, respectively, in the ADSCP2-treated group. The mixOmics analysis, which integrated RNA-seq and untargeted metabolomics data, provided a more holistic view of the functions of ADSCP2.CONCLUSION: Overall, a novel peptide derived from ADSC-CM, named ADSCP2, attenuated hypertrophic scar fibrosis in vitro and in vivo, and the novel peptide ADSCP2 might be a promising drug candidate for clinical scar therapy.PMID:37366253 | DOI:10.1111/apha.14010

Integrating sperm cell transcriptome and seminal plasma metabolome to analyze the molecular regulatory mechanism of sperm motility in Holstein stud bulls

Tue, 27/06/2023 - 12:00
J Anim Sci. 2023 Jun 27:skad214. doi: 10.1093/jas/skad214. Online ahead of print.ABSTRACTConsidering that artificial insemination is the most widely used assisted reproductive technique in the dairy industry, the semen quality of bulls is very important for selecting excellent stud bulls. Sperm motility is one of the important traits of semen quality, and related genes may be regulated by environmental factors. Seminal plasma can affect sperm cell transcriptome and further affect sperm motility through exosome or other processes. However, the molecular regulation mechanism of bull sperm motility has not been studied by combining the sperm cell transcriptome with seminal plasma metabolome. The number of motile sperm per ejaculate (NMSPE) is an integrated indicator for assessing sperm motility in stud bulls. In the present study, we selected 7 bulls with higher NMSPE (5,698.55 million +/- 945.40 million) as group H and 7 bulls with lower NMSPE (2,279.76 million +/- 1,305.69 million) as group L from 53 Holstein stud bulls. The differentially expressed genes (DEG) in sperm cells were evaluated between the two groups (H vs. L). We conducted gene co-expression network analysis (WGCNA) on H and L groups of bulls, as well as two monozygotic (MZ) twin Holstein bulls with different NMSPE values, to screen candidate genes for NMSPE. The regulatory effect of seminal plasma metabolome on the candidate genes of NMSPE was also investigated. A total of 1,099 differentially expressed genes (DEG) were identified in the sperm cells of H and L groups. These DEGs were primarily concentrated in energy metabolism and sperm cell transcription. The significantly enriched KEGG pathways of the 57 differential metabolites were the aminoacyl-tRNA biosynthesis pathway and vitamin B6 metabolism pathway. Our study discovered 14 genes as the potential candidate markers for sperm motility, including FBXO39. We observed a broad correlation between transcriptome of sperm cells and seminal plasma metabolome, such as three metabolites, namely, mesaconic acid, 2-coumaric acid, and 4-formylaminoantipyrine, might regulate FBXO39 expression through potential pathways. The genes related to seminal plasma metabolites expressed in sperm cells are not only located near the quantitative trait loci of reproductive traits, but also enriched in the GWAS signal of sire conception rate. Collectively, this study was the first to investigate the interplays among transcriptome of sperm cells and seminal plasma metabolome from Holstein stud bulls with different sperm motility.PMID:37366074 | DOI:10.1093/jas/skad214

Ready Biodegradability study and insights with ultra-high-performance liquid chromatograph coupled to a quadrupole time of flight of a Metformin-based drug and of Metarecod, a natural substance-based medical device

Tue, 27/06/2023 - 12:00
J Mass Spectrom. 2023 May 1:e4924. doi: 10.1002/jms.4924. Online ahead of print.ABSTRACTDrugs are indispensable products with incontrovertible benefits to human health and lifestyle. However, due to their overuse and improper disposal, unwanted residues of active pharmaceutical ingredients (APIs) have been found in different compartments of the environment and now are considered as contaminants of emerging concern (CECs). Therefore, they are very likely to have a boomerang effect on human health, because they can enter into the food cycle. In the current legislation framework, one of the tests first used to evaluate biodegradation of APIs as well as chemical compounds is the ready biodegradability test (RBT). This test can be performed according to a series of protocols prepared by Organization for Economic Co-operation and Development (OECD) and usually is carried out on pure compounds. RBTs, largely used due to their relatively low cost, perceived standardization, and straightforward implementation and interpretation, are known to have a number of well-documented limitations. In this work, following a recently reported approach, we propose to improve the evaluation of the RBT results applying advanced analytical techniques based on mass spectrometry, not only to the APIs but also to complex formulated products, as the biodegradability can potentially be affected by the formulation. We evaluated the ready biodegradability of two therapeutic products, Product A-a drug based on Metformin-and Product B-Metarecod a natural substance-based medical device-through the acquisition of the fingerprint by ultra-high-performance chromatograph coupled to a quadrupole time of flight (UHPLC-qToF) of samples coming from the RBT OECD 301F. Untargeted and targeted evaluation confirmed the different behavior of the two products during the respirometry-manometric test, which showed a difficulty of the Metformin-based drug to come back in the life cycle, whereas Metarecod resulted ready biodegradable. The positive results of this research will hopefully be useful in the future for a better evaluation of the risk/benefit ratio of APIs extended to the environment.PMID:37365837 | DOI:10.1002/jms.4924

PM<sub>2.5</sub> and its respiratory tract depositions on blood pressure, anxiety, depression and health risk assessment: A mechanistic study based on urinary metabolome

Mon, 26/06/2023 - 12:00
Environ Res. 2023 Jun 24:116481. doi: 10.1016/j.envres.2023.116481. Online ahead of print.ABSTRACTEffects of fine particulate matter (PM2.5) and regional respiratory tract depositions on blood pressure (BP), anxiety, depression, health risk and the underlying mechanisms need further investigations. A repeated-measures panel investigation among 40 healthy young adults in Hefei, China was performed to explore the acute impacts of PM2.5 exposure and its deposition doses in 3 regions of respiratory tract over diverse lag times on BP, anxiety, depression, health risk, and the potential mechanisms. We collected PM2.5 concentrations, its deposition doses, BP, the Self-Rating Anxiety Scale (SAS) score and the Self-Rating Depression Scale (SDS) score. An untargeted metabolomics approach was used to detect significant urine metabolites, and the health risk assessment model was used to evaluate the non-carcinogenic risks associated with PM2.5. We applied linear mixed-effects models to assess the relationships of PM2.5 with the aforementioned health indicators We further evaluate the non-carcinogenic risks associated with PM2.5. We found deposited PM2.5 dose in the head accounted for a large proportion. PM2.5 and its three depositions exposures at a specific lag day was significantly related to increased BP levels and higher SAS and SDS scores. Metabolomics analysis showed significant alterations in urinary metabolites (i.e., glucoses, lipids and amino acids) after PM2.5 exposure, simultaneously accompanied by activation of the cAMP signaling pathway. Health risk assessment presented that the risk values for the residents in Hefei were greater than the lower limits of non-cancer risk guidelines. This real-world investigation suggested that acute PM2.5 and its depositions exposures may increase health risks by elevating BP, inducing anxiety and depression, and altering urinary metabolomic profile via activating the cAMP signaling pathway. And the further health risk assessment indicated that there are potential non-carcinogenic risks of PM2.5 via the inhalation route in this area.PMID:37364626 | DOI:10.1016/j.envres.2023.116481

Early hyperlipidemia triggers metabolomic reprogramming with increased SAH, increased acetyl-CoA-cholesterol synthesis, and decreased glycolysis

Mon, 26/06/2023 - 12:00
Redox Biol. 2023 Jun 16;64:102771. doi: 10.1016/j.redox.2023.102771. Online ahead of print.ABSTRACTTo identify metabolomic reprogramming in early hyperlipidemia, unbiased metabolome was screened in four tissues from ApoE-/- mice fed with high fat diet (HFD) for 3 weeks. 30, 122, 67, and 97 metabolites in the aorta, heart, liver, and plasma, respectively, were upregulated. 9 upregulated metabolites were uremic toxins, and 13 metabolites, including palmitate, promoted a trained immunity with increased syntheses of acetyl-CoA and cholesterol, increased S-adenosylhomocysteine (SAH) and hypomethylation and decreased glycolysis. The cross-omics analysis found upregulation of 11 metabolite synthetases in ApoE‾/‾ aorta, which promote ROS, cholesterol biosynthesis, and inflammation. Statistical correlation of 12 upregulated metabolites with 37 gene upregulations in ApoE‾/‾ aorta indicated 9 upregulated new metabolites to be proatherogenic. Antioxidant transcription factor NRF2-/- transcriptome analysis indicated that NRF2 suppresses trained immunity-metabolomic reprogramming. Our results have provided novel insights on metabolomic reprogramming in multiple tissues in early hyperlipidemia oriented toward three co-existed new types of trained immunity.PMID:37364513 | DOI:10.1016/j.redox.2023.102771

Metabolomics-based study on the changes of endogenous metabolites during adventitious bud formation from leaf margin of Bryophyllum pinnatum (Lam.) Oken

Mon, 26/06/2023 - 12:00
Plant Physiol Biochem. 2023 Jun 22;201:107845. doi: 10.1016/j.plaphy.2023.107845. Online ahead of print.ABSTRACTBryophyllum pinnatum (Lam.) Oken is an ornamental and ethno-medicine plant, which can grow a circle of adventitious bud around the leaf margin. The dynamic change of metabolites during the development of B. pinnatum remains poorly understood. Here, leaves from B. pinnatum at four developmental stages were sampled based on morphological characteristics. A non-targeted metabolomics approach was used to evaluate the changes of endogenous metabolites during adventitious bud formation in B. pinnatum. The results showed that differential metabolites were mainly enriched in sphingolipid metabolism, flavone and flavonol biosynthesis, phenylalanine metabolism, and tricarboxylic acid cycle pathway. The metabolites assigned to amino acids, flavonoids, sphingolipids, and the plant hormone jasmonic acid decreased from period Ⅰ to Ⅱ, and then increased from period Ⅲ to Ⅳ with the emergence of adventitious bud (period Ⅲ). While the metabolites related to the tricarboxylic acid cycle showed a trend of first increasing and then decreasing during the four observation periods. Depending on the metabolite changes, leaves may provide conditions similar to in vitro culture for adventitious bud to occur, thus enabling adventitious bud to grow at the leaf edge. Our results provide a basis for illustrating the regulatory mechanisms of adventitious bud in B. pinnatum.PMID:37364508 | DOI:10.1016/j.plaphy.2023.107845

FTZ polysaccharides ameliorate kidney injury in diabetic mice by regulating gut-kidney axis

Mon, 26/06/2023 - 12:00
Phytomedicine. 2023 Jun 20;118:154935. doi: 10.1016/j.phymed.2023.154935. Online ahead of print.ABSTRACTBACKGROUND: The Fufang-zhenzhu-tiaozhi formula (FTZ), a traditional Chinese medicine (TCM) commonly used to treat metabolic diseases, potentially impacts the microbial ecosystem. Increasing evidence suggests that polysaccharides, bioactive components of TCMs, have great potential on kinds of diseases such as DKD by regulating intestinal flora.PURPOSE: This study aimed to investigate whether the polysaccharide components in FTZ (FTZPs) have beneficial effects in DKD mice via the gut-kidney axis.STUDY DESIGN AND METHODS: The DKD model in mice was established by streptozotocin combined with a high-fat diet (STZ/HFD). Losartan was used as a positive control, and FTZPs were administered at doses of 100 and 300 mg/kg daily. Renal histological changes were measured by H&E and Masson staining. Western blotting, quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to analyze the effects of FTZPs on renal inflammation and fibrosis, which were further confirmed using RNA sequencing. Immunofluorescence was used to analyze the effects of FTZPs on colonic barrier function in DKD mice. Faecal microbiota transplantation (FMT) was used to evaluate the contribution of intestinal flora. 16S rRNA sequencing was utilized to analyze the composition of intestinal bacteria, and UPLC-QTOF-MS-based untargeted metabolomics was used to identify the metabolite profiles.RESULTS: Treatment with FTZPs attenuated kidney injury, as indicated by the decreased urinary albumin/creatinine ratio and improved renal architecture. FTZPs downregulated the expression of renal genes associated with inflammation, fibrosis, and systematically blunted related pathways. FTZPs also restored the colonic mucosal barrier and increased the expression of tight junction proteins (E-cadherin). The FMT experiment confirmed the substantial contribution of the FTZPs-reshaped microbiota to relieving DKD symptoms. Moreover, FTZPs elevated the content of short-chain fatty acids (propionic acid and butanoic acid) and increased the level of the SCFAs transporter Slc22a19. Intestinal flora disorders caused by diabetes, including the growth of the genera Weissella, Enterococcus and Akkermansia, were inhibited by FTZPs treatment. Spearman's analysis revealed that these bacteria were positively correlated with indicators of renal damage.CONCLUSION: These results show that oral administration of FTZPs, by altering SCFAs levels and the gut microbiome, is a therapeutic strategy for the treatment of DKD.PMID:37364420 | DOI:10.1016/j.phymed.2023.154935

Spatial lipidomics and metabolomics of multicellular tumor spheroids using MALDI-2 and trapped ion mobility imaging

Mon, 26/06/2023 - 12:00
Talanta. 2023 Jun 20;265:124795. doi: 10.1016/j.talanta.2023.124795. Online ahead of print.ABSTRACTLipids and metabolites are small biological molecules that act major roles in cellular functions. Multicellular tumor spheroids (MCTS) are a highly beneficial three-dimensional cellular model for cancer research due to their ability to imitate numerous characteristics of tumor tissues. Increasing studies have performed spatial lipidomics and metabolomics in MCTS using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). However, these approaches often lack the sensitivity and specificity to offer a comprehensive characterization of lipids and metabolites within MCTS. In this study, we addressed this challenge by utilizing MALDI combined with laser-induced postionization (MALDI-2) and trapped ion mobility spectrometry (TIMS) imaging in H295R adrenocortical MCTS. Our results showed that MALDI-2 could detect more lipids and metabolites in MCTS than the traditional MALDI. TIMS data revealed a successful separation of many isomeric and isobaric ions of lipids and metabolites with different locations (e.g., proliferative region and necrotic region) within MCTS, suggesting an enhanced peak capacity for spatial lipidomics and metabolomics. To further identify these isomeric and isobaric ions, we performed MS/MS imaging experiments to compare the differences in signal intensities and spatial distributions of product ions. Our data highlight the strong potential of MALDI-2 and TIMS imaging for analyzing lipids and metabolites in MCTS, which may serve as valuable tools for numerous fields of biological and medical research.PMID:37364385 | DOI:10.1016/j.talanta.2023.124795

LC-MS metabolomics profiling of Salvia aegyptiaca L. and S. lanigera Poir. with the antimicrobial properties of their extracts

Mon, 26/06/2023 - 12:00
BMC Plant Biol. 2023 Jun 26;23(1):340. doi: 10.1186/s12870-023-04341-5.ABSTRACTBACKGROUND: Salvia L. (Lamiaceae) found in almost all countries in temperate and tropical regions. Both S. aegyptiaca L. and S. lanigera Poir. have a rather wide distribution in Egypt (Mediterranean region, Gebel Elba and nearly the whole Sinai). Salvia species showed antibacterial and antifungal activities against several groups of food microorganisms and pathogens, so they are considered as a natural foods preservatives.AIM: Investigate the phytochemical profiles of S. aegyptiaca & S. lanigera collected from their natural habitats in Egypt and test the antimicrobial activities of both species against some bacteria and fungi pathogenic strains.METHODOLOGY: In the present study, S. aegyptiaca and S. lanigera were collected from their natural habitat. Total phenolics and flavonoids contents were measured for aerial parts of both Salvia spp.. The separation and identification of the pure active materials of both Salvia sp. by using LC-MS system (UHPLC-TSQ Quantum Mass Spectrometer). The antimicrobial activities of the ethanol, water and benzene extracts of the two species were tested against different pathogenic strains and compared with the standard antimicrobial drug (Gentamycin). Antimicrobial activity was determined by using agar disk diffusion method.RESULTS: The phenolics content in S. lanigera 132.61±6.23 mg/g and S. aegyptiaca 125.19±4.97 mg/g, while the flavonoids content was 35.68±1.84 and 40.63±2.11 mg/g, respectively. Through LC-MS analysis, two compounds were detected in both species; heptadecanoyl coenzyme A, that the highest percentage (13.5%) in S. aegyptiaca and (11.5 %) in S. lanigera. Oenin, in a peak area of 3.1% in S. aegyptiaca and 1.2 % in S. lanigera. Ethanol extract of the two species had the most inhibitory effect against all tested microorganisms that exceeded the effect of the standard, except for Mucor reinelloids which was more sensitive to the water extract. Moreover, S. lanigera ethanol extract showed larger inhibition zone than S. aegyptiaca in all tested microorganisms except for Pseudomonas aeruginosa.CONCLUSION: This study shows the important phytochemicals that improve the antibacterial and antifungal activities of Salvia aegyptiaca and S. lanigera.PMID:37365525 | DOI:10.1186/s12870-023-04341-5

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