PubMed

Cell Metab. 2023 Jun 28:S1550-4131(23)00215-2. doi: 10.1016/j.cmet.2023.06.005. Online ahead of print.ABSTRACTTumor cell phenotypes and anti-tumor immune responses are shaped by local metabolite availability, but intratumoral metabolite heterogeneity (IMH) and its phenotypic consequences remain poorly understood. To study IMH, we profiled tumor/normal regions from clear cell renal cell carcinoma (ccRCC) patients. A common pattern of IMH transcended all patients, characterized by correlated fluctuations in the abundance of metabolites and processes associated with ferroptosis. Analysis of intratumoral metabolite-RNA covariation revealed that the immune composition of the microenvironment, especially the abundance of myeloid cells, drove intratumoral metabolite variation. Motivated by the strength of RNA-metabolite covariation and the clinical significance of RNA biomarkers in ccRCC, we inferred metabolomic profiles from the RNA sequencing data of ccRCC patients enrolled in 7 clinical trials, and we ultimately identifyied metabolite biomarkers associated with response to anti-angiogenic agents. Local metabolic phenotypes, therefore, emerge in tandem with the immune microenvironment, influence ongoing tumor evolution, and are associated with therapeutic sensitivity.PMID:37413991 | DOI:10.1016/j.cmet.2023.06.005

Curr Opin Plant Biol. 2023 Jul 4;75:102410. doi: 10.1016/j.pbi.2023.102410. Online ahead of print.ABSTRACTThe survival of extreme water deficit stress by tolerant organisms requires a coordinated series of responses, including those at cellular, transcriptional, translational and metabolic levels. Small molecules play a pivotal role in creating the proper chemical environment for the preservation of cellular integrity and homeostasis during dehydration. This review surveys recent insights in the importance of primary and specialised metabolites in the response to drying of angiosperms with vegetative desiccation tolerance, i.e. the ability to survive near total loss of water. Important metabolites include sugars such as sucrose, trehalose and raffinose family of oligosaccharides, amino acids and organic acids, as well as antioxidants, representing a common core mechanism of desiccation tolerance. Additional metabolites are discussed in the context of species specificity and adaptation.PMID:37413962 | DOI:10.1016/j.pbi.2023.102410

Poult Sci. 2023 Jun 19;102(9):102878. doi: 10.1016/j.psj.2023.102878. Online ahead of print.ABSTRACTThe gut is the first line of defense for body health and is essential to the overall health of geese. Grape seed procyanidins (GSPs) are proverbial for their antioxidant, anti-inflammatory, and microflora-regulating capabilities. This study aimed to inquire into the influences of dietary GSPs on the intestinal antioxidant function, barrier function, microflora, and metabolites of geese based on 16S rRNA sequencing and metabolomics. In total, 240 twenty-one-day-old Sichuan white geese were randomly divided into 4 groups, each of which was supplied with 1 of 4 diets: basal diet or a basal diet supplemented with 50, 100, or 150 mg/kg GSPs. Diets supplemented with GSPs at different concentrations significantly increased the total antioxidant capacity and superoxide dismutase activity in cecal mucosa (P < 0.001). Dietary supplementation with 50 or 100 mg/kg GSPs significantly increased catalase activity (P < 0.001). The serum diamine oxidase, D-lactic acid, and endotoxin concentrations were decreased by GSP supplementation in the goose diet. Dietary GSP supplementation increased microbial richness and diversity, enhanced the relative abundance of Firmicutes, and decreased that of Bacteroidetes in the cecum. Diets supplemented with 50 or 100 mg/kg GSPs enriched Eubacterium coprostanoligenes and Faecalibacterium. Dietary GSPs substantially raised the acetic and propionic acid concentrations in the cecum. The butyric acid concentration increased when the GSP dosage was 50 or 100 mg/kg. Additionally, dietary GSPs increased the levels of metabolites that belong to lipids and lipid-like molecules or organic acids and derivatives. Dietary GSP supplementation at 100 or 150 mg/kg reduced the levels of spermine (a source of cytotoxic metabolites) and N-acetylputrescine, which promotes in-vivo inflammation. In conclusion, dietary supplementation with GSPs was beneficial to gut health in geese. Dietary GSPs improved antioxidant activity; protected intestinal barrier integrity; increased the abundance and diversity of cecal microflora; promoted the proliferation of some beneficial bacteria; increased the production of acetic, propionic, and butyric acids in the cecum; and downregulated metabolites associated with cytotoxicity and inflammation. These results offer a strategy for promoting intestinal health in farmed geese.PMID:37413950 | DOI:10.1016/j.psj.2023.102878

J Pharm Biomed Anal. 2023 May 24;234:115481. doi: 10.1016/j.jpba.2023.115481. Online ahead of print.ABSTRACTScutellaria baicalensis Georgi (SG) and Scutellaria rehderiana Diels (SD) belong to the same genus of Scutellaria in the Labiatae (Lamiaceae) family. SG is confirmed as the medicinal source according to the Chinese Pharmacopeia, but SD is often used as a substitute for SG due to its abundant plant resources. However, the current quality standards are far from sufficient to judge the quality differences between SG and SD. In this study, an integrated strategy of "biosynthetic pathway (specificity) - plant metabolomics (difference) - bioactivity evaluation (effectiveness)" was established to evaluate this quality differences. First, an ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS/MS) method was developed for the identification of chemical components. The abundant components information was obtained and the characteristic constituents were screened according to the location in the biosynthetic pathway as well as species specificity. Then, plant metabolomics combined with multivariate statistical analysis to find differential components between SG and SD. The chemical markers for quality analysis were determined based on the differential and characteristic components, and the content of each marker was tentatively evaluated through the semi-quantitative analysis of UHPLC-Q/TOF-MS/MS. Finally, the anti-inflammatory activity of SG and SD was compared by measuring the inhibitory effect on the release of NO from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Under this analytical strategy, a total of 113 compounds were tentatively identified in both SG and SD, among which baicalein, wogonin, chrysin, oroxylin A 7-O-β-D-glucuronoside, pinocembrin and baicalin were selected as chemical markers due to their species characteristics and differentiation. The contents of oroxylin A 7-O-β-D-glucuronoside and baicalin was higher in SG, and the others were higher in SD. In addition, both SG and SD exhibited prominent anti-inflammatory activity, but SD was less effective. The analysis strategy combining phytochemistry and bioactivity evaluation realized the scientific evaluation of the intrinsic quality differences between SG and SD, which provides a reference for fully utilizing and expanding the medicinal resources, and also provides a reference for the comprehensive quality control of herbal medicines.PMID:37413917 | DOI:10.1016/j.jpba.2023.115481

J Chromatogr A. 2023 Jun 24;1705:464176. doi: 10.1016/j.chroma.2023.464176. Online ahead of print.ABSTRACTWe describe a freely available web server called Retention Index Predictor (RIpred) (https://ripred.ca) that rapidly and accurately predicts Gas Chromatographic Kováts Retention Indices (RI) using SMILES strings as chemical structure input. RIpred performs RI prediction for three different stationary phases (semi-standard non-polar (SSNP), standard non-polar (SNP), and standard polar (SP)) for both derivatized (trimethylsilyl (TMS) and tert‑butyldimethylsilyl (TBDMS) derivatized) and underivatized (base compound) forms of GC-amenable structures. RIpred was developed to address the need for freely available, fast, highly accurate RI predictions for a wide range of derivatized and underivatized chemicals for all common GC stationary phases. RIpred was trained using a Graph Neural Network (GNN) that used compound structures, their extracted features (mostly atom-level features) and the GC-RI data from the National Institute of Standards and Technology databases (NIST 17 and NIST 20). We curated this NIST 17 and NIST 20 GC-RI data, which is available for all three stationary phases, to create appropriate inputs (molecular graphs in this case) needed to enhance our model performance. The performance of different RIpred predictive models was evaluated using 10-fold cross validation (CV). The best performing RIpred models were identified and when tested on hold-out test sets from all stationary phases, achieved a Mean Absolute Error (MAE) of <73 RI units (SSNP: 16.5-29.5, SNP: 38.5-45.9, SP: 46.52-72.53). The Mean Absolute Percentage Error (MAPE) of these models were typically within 3% (SSNP: 0.78-1.62%, SNP: 1.87-2.88%, SP: 2.34-4.05%). When compared to the best performing model by Qu et al., 2021, RIpred performed similarly (MAE of 16.57 RI units [RIpred] vs. 16.84 RI units [Qu et al., 2021 predictor] for derivatized compounds). RIpred also includes ∼5 million predicted RI values for all GC-amenable compounds (∼57,000) in the Human Metabolome Database HMDB 5.0 (Wishart et al., 2022).PMID:37413909 | DOI:10.1016/j.chroma.2023.464176

Curr Opin Chem Biol. 2023 Jul 4;76:102362. doi: 10.1016/j.cbpa.2023.102362. Online ahead of print.ABSTRACTMass spectrometry imaging (MSI) is an emerging technology in cancer metabolomics. Desorption electrospray ionization (DESI) and matrix-assisted laser desorption ionization (MALDI) MSI are complementary techniques to identify hundreds of metabolites in space with close to single-cell resolution. This technology leap enables research focusing on tumor heterogeneity, cancer cell plasticity, and the communication signals between cancer and stromal cells in the tumor microenvironment (TME). Currently, unprecedented knowledge is generated using spatial metabolomics in fundamental cancer research. Yet, also translational applications are emerging, including the assessment of spatial drug distribution in organs and tumors. Moreover, clinical research investigates the use of spatial metabolomics as a rapid pathology tool during cancer surgeries. Here, we summarize MSI applications, the knowledge gained by this technology in space, future directions, and developments needed.PMID:37413787 | DOI:10.1016/j.cbpa.2023.102362

Parasit Vectors. 2023 Jul 6;16(1):226. doi: 10.1186/s13071-023-05842-w.ABSTRACTBACKGROUND: Iron is an essential element for cellular functions, such as energy metabolism. Trichomonas vaginalis, a human urogenital tract pathogen, is capable of surviving in the environment without sufficient iron supplementation. Pseudocysts (cyst-like structures) are an environmentally tolerated stage of this parasite while encountering undesired conditions, including iron deficiency. We previously demonstrated that iron deficiency induces more active glycolysis but a drastic downregulation of hydrogenosomal energy metabolic enzymes. Therefore, the metabolic direction of the end product of glycolysis is still controversial.METHODS: In the present work, we conducted an LC‒MS-based metabolomics analysis to obtain accurate insights into the enzymatic events of T. vaginalis under iron-depleted (ID) conditions.RESULTS: First, we showed the possible digestion of glycogen, cellulose polymerization, and accumulation of raffinose family oligosaccharides (RFOs). Second, a medium-chain fatty acid (MCFA), capric acid, was elevated, whereas most detected C18 fatty acids were reduced significantly. Third, amino acids were mostly reduced, especially alanine, glutamate, and serine. Thirty-three dipeptides showed significant accumulation in ID cells, which was probably associated with the decrease in amino acids. Our results indicated that glycogen was metabolized as the carbon source, and the structural component cellulose was synthesized at same time. The decrease in C18 fatty acids implied possible incorporation in the membranous compartment for pseudocyst formation. The decrease in amino acids accompanied by an increase in dipeptides implied incomplete proteolysis. These enzymatic reactions (alanine dehydrogenase, glutamate dehydrogenase, and threonine dehydratase) were likely involved in ammonia release.CONCLUSION: These findings highlighted the possible glycogen utilization, cellulose biosynthesis, and fatty acid incorporation in pseudocyst formation as well as NO precursor ammonia production induced by iron-depleted stress.PMID:37415204 | DOI:10.1186/s13071-023-05842-w

Gut Pathog. 2023 Jul 6;15(1):33. doi: 10.1186/s13099-023-00553-0.ABSTRACTBACKGROUND: Women suffer from various distress and disturbances after menopause, including osteoporosis, a risk factor associated with multiple diseases. Altered gut microbiota has been implicated in postmenopausal osteoporosis. In this study, to understand gut microbiota signatures and fecal metabolite changes in postmenopausal women with osteoporosis, 108 postmenopausal women were recruited for intestinal microbiota and fecal metabolite detection. Among these participants, 98 patients, who met the inclusion criteria, were divided into postmenopausal osteoporosis (PMO) and non-postmenopausal osteoporosis (non-PMO) groups based on bone mineral density (BMD). The compositions of gut bacteria and fungi were examined by 16 S rRNA gene sequencing and ITS sequencing, respectively. Meanwhile, fecal metabolites were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS).RESULTS: We found that bacterial α-diversity and β-diversity were significantly altered in PMO compared to non-PMO patients. Interestingly, fungi composition showed larger changes, and the differences in β-diversity were more significant between PMO and non-PMO patients. Metabolomics analysis revealed that fecal metabolites, such as levulinic acid, N-Acetylneuraminic acid, and the corresponding signaling pathways were also changed significantly, especially in the alpha-Linolenic acid metabolism and selenocompound metabolism. The screened differential bacteria, fungi, and metabolites closely correlated with clinical findings between these two groups, for example, the bacterial genus, Fusobacterium, the fungal genus, Devriesia, and the metabolite, L-pipecolic acid, were significantly associated with BMD.CONCLUSIONS: Our findings indicated that there were remarkable changes in gut bacteria, fungi, and fecal metabolites in postmenopausal women, and such changes were notably correlated with patients' BMD ​​and clinical findings. These correlations provide novel insights into the mechanism of PMO development, potential early diagnostic indicators, and new therapeutic approaches to improve bone health in postmenopausal women.PMID:37415173 | DOI:10.1186/s13099-023-00553-0

J Microbiol Biotechnol. 2023 Jun 12;33(10):1-10. doi: 10.4014/jmb.2301.01036. Online ahead of print.ABSTRACTEndocrine-disrupting chemicals (EDCs) are compounds that disturb hormonal homeostasis by binding to receptors. EDCs are metabolized through hepatic enzymes, causing altered transcriptional activities of hormone receptors, and thus necessitating the exploration of the potential endocrinedisrupting activities of EDC-derived metabolites. Accordingly, we have developed an integrative workflow for evaluating the post-metabolic activity of potential hazardous compounds. The system facilitates the identification of metabolites that exert hormonal disruption through the integrative application of an MS/MS similarity network and predictive biotransformation based on known hepatic enzymatic reactions. As proof-of-concept, the transcriptional activities of 13 chemicals were evaluated by applying the in vitro metabolic module (S9 fraction). Identified among the tested chemicals were three thyroid hormone receptor (THR) agonistic compounds that showed increased transcriptional activities after phase I+II reactions (T3, 309.1 ± 17.3%; DITPA, 30.7 ± 1.8%; GC-1, 160.6 ± 8.6% to the corresponding parents). The metabolic profiles of these three compounds showed common biotransformation patterns, particularly in the phase II reactions (glucuronide conjugation, sulfation, GSH conjugation, and amino acid conjugation). Data-dependent exploration based on molecular network analysis of T3 profiles revealed that lipids and lipid-like molecules were the most enriched biotransformants. The subsequent subnetwork analysis proposed 14 additional features, including T4 in addition to 9 metabolized compounds that were annotated by prediction system based on possible hepatic enzymatic reaction. The other 10 THR agonistic negative compounds showed unique biotransformation patterns according to structural commonality, which corresponded to previous in vivo studies. Our evaluation system demonstrated highly predictive and accurate performance in determining the potential thyroiddisrupting activity of EDC-derived metabolites and for proposing novel biotransformants.PMID:37415082 | DOI:10.4014/jmb.2301.01036

Nat Med. 2023 Jul 6. doi: 10.1038/s41591-023-02453-x. Online ahead of print.ABSTRACTFecal microbiota transplantation (FMT) represents a potential strategy to overcome resistance to immune checkpoint inhibitors in patients with refractory melanoma; however, the role of FMT in first-line treatment settings has not been evaluated. We conducted a multicenter phase I trial combining healthy donor FMT with the PD-1 inhibitors nivolumab or pembrolizumab in 20 previously untreated patients with advanced melanoma. The primary end point was safety. No grade 3 adverse events were reported from FMT alone. Five patients (25%) experienced grade 3 immune-related adverse events from combination therapy. Key secondary end points were objective response rate, changes in gut microbiome composition and systemic immune and metabolomics analyses. The objective response rate was 65% (13 of 20), including four (20%) complete responses. Longitudinal microbiome profiling revealed that all patients engrafted strains from their respective donors; however, the acquired similarity between donor and patient microbiomes only increased over time in responders. Responders experienced an enrichment of immunogenic and a loss of deleterious bacteria following FMT. Avatar mouse models confirmed the role of healthy donor feces in increasing anti-PD-1 efficacy. Our results show that FMT from healthy donors is safe in the first-line setting and warrants further investigation in combination with immune checkpoint inhibitors. ClinicalTrials.gov identifier NCT03772899 .PMID:37414899 | DOI:10.1038/s41591-023-02453-x

Sci Rep. 2023 Jul 6;13(1):9594. doi: 10.1038/s41598-023-36368-x.ABSTRACTGiven the absence of written records, the main source of information available to analyze gender inequalities in early complex societies is the human body itself. And yet, for decades, archaeologists have struggled with the sex estimation of poorly preserved human remains. Here we present an exceptional case study that shows how ground-breaking new scientific methods may address this problem. Through the analysis of sexually dimorphic amelogenin peptides in tooth enamel, we establish that the most socially prominent person of the Iberian Copper Age (c. 3200-2200 BC) was not male, as previously thought, but female. The analysis of this woman, discovered in 2008 at Valencina, Spain, reveals that she was a leading social figure at a time where no male attained a remotely comparable social position. Only other women buried a short time after in the Montelirio tholos, part of the same burial area, appear to have enjoyed a similarly high social position. Our results invite to reconsider established interpretations about the political role of women at the onset of early social complexity, and question traditionally held views of the past. Furthermore, this study anticipates the changes that newly developed scientific methods may bring to prehistoric archaeology and the study of human social evolution.PMID:37414858 | DOI:10.1038/s41598-023-36368-x

Cell Death Dis. 2023 Jul 6;14(7):401. doi: 10.1038/s41419-023-05932-8.ABSTRACTSepsis involves endothelial cell (EC) dysfunction, which contributes to multiple organ failure. To improve therapeutic prospects, elucidating molecular mechanisms of vascular dysfunction is of the essence. ATP-citrate lyase (ACLY) directs glucose metabolic fluxes to de novo lipogenesis by generating acetyl-Co-enzyme A (acetyl-CoA), which facilitates transcriptional priming via protein acetylation. It is well illustrated that ACLY participates in promoting cancer metastasis and fatty liver diseases. Its biological functions in ECs during sepsis remain unclear. We found that plasma levels of ACLY were increased in septic patients and were positively correlated with interleukin (IL)-6, soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule 1 (sVCAM-1), and lactate levels. ACLY inhibition significantly ameliorated lipopolysaccharide challenge-induced EC proinflammatory response in vitro and organ injury in vivo. The metabolomic analysis revealed that ACLY blockade fostered ECs a quiescent status by reducing the levels of glycolytic and lipogenic metabolites. Mechanistically, ACLY promoted forkhead box O1 (FoxO1) and histone H3 acetylation, thereby increasing the transcription of c-Myc (MYC) to facilitate the expression of proinflammatory and gluco-lipogenic genes. Our findings revealed that ACLY promoted EC gluco-lipogenic metabolism and proinflammatory response through acetylation-mediated MYC transcription, suggesting ACLY as the potential therapeutic target for treating sepsis-associated EC dysfunction and organ injury.PMID:37414769 | DOI:10.1038/s41419-023-05932-8

J Nat Prod. 2023 Jul 6. doi: 10.1021/acs.jnatprod.3c00148. Online ahead of print.ABSTRACTThe saprotrophic filamentous fungus Myrothecium inundatum represents a chemically underexplored ascomycete with a high number of putative biosynthetic gene clusters in its genome. Here, we present new linear lipopeptides from nongenetic gene activation experiments using nutrient and salt variations. Metabolomics studies revealed four myropeptins, and structural analyses by NMR, HRMS, Marfey's analysis, and ECD assessment for their helical properties established their absolute configuration. A myropeptin biosynthetic gene cluster in the genome was identified. The myropeptins exhibit general nonspecific toxicity against all cancer cell lines in the NCI-60 panel, larval zebrafish with EC50 concentrations of 5-30 μM, and pathogenic bacteria and fungi (MICs of 4-32 μg/mL against multidrug-resistant S. aureus and C. auris). In vitro hemolysis, cell viability, and ionophore assays indicate that the myropeptins target mitochondrial and cellular membranes, inducing cell depolarization and cell death. The toxic activity is modulated by the length of the lipid side chain, which provides valuable insight into their structure-activity relationships.PMID:37411007 | DOI:10.1021/acs.jnatprod.3c00148

J Agric Food Chem. 2023 Jul 6. doi: 10.1021/acs.jafc.3c02125. Online ahead of print.ABSTRACTThe potential of probiotics to benefit digestion has been widely reported, while its utilization in high-risk patients and potential adverse reactions have focused interest on postbiotics. A variable data-independent acquisition (vDIA)-based spatial-omics strategy integrated with unsupervised variational autoencoders was applied to profile the functional mechanism underlying the action of Lactobacillus casei-derived postbiotic supplementation in goat milk digestion in an infant digestive system, from a metabolomics-peptidomics-proteomics perspective. Amide and olefin derivatives were proved to elevate the activities of pepsin and trypsin through hydrogen bonding and hydrophobic forces based on allosteric effects, and recognition of nine endopeptidases and their cleavage to serine, proline, and aspartate were introduced by postbiotics, thereby promoting the generation of hydrophilic peptides and elevating the bioaccessibility of goat milk protein. The peptides originating from αs1-casein, β-casein, β-lactoglobulin, Ig-like domain-containing protein, κ-casein, and serum amyloid A protein, with multiple bioactivities including angiotensin I-converting enzyme (ACE)-inhibitory, osteoanabolic, dipeptidyl peptidase IV (DPP-IV) inhibitory, antimicrobial, bradykinin-potentiating, antioxidant, and anti-inflammatory activities, were significantly increased in the postbiotic supplementation group, which was also considered to potentially prevent necrotizing enterocolitis through inhibiting the multiplication of pathogenic bacteria and blocking signal transducer and activator of transcription 1 and nuclear factor kappa-light-chain-enhancer of activated B cells inflammatory pathways. This research deepened the understanding of the mechanism underlying the postbiotics affecting goat milk digestion, which established a critical groundwork for the clinical application of postbiotics in infant complementary foods.PMID:37410960 | DOI:10.1021/acs.jafc.3c02125

PLoS One. 2023 Jul 6;18(7):e0286525. doi: 10.1371/journal.pone.0286525. eCollection 2023.ABSTRACTReprogramming metabolism is of great therapeutic interest for reducing morbidity and mortality during sepsis-induced critical illness. Disappointing results from randomized controlled trials targeting glutamine and antioxidant metabolism in patients with sepsis have begged a deeper understanding of the tissue-specific metabolic response to sepsis. The current study sought to fill this gap. We analyzed skeletal muscle transcriptomics of critically ill patients, versus elective surgical controls, which revealed reduced expression of genes involved in mitochondrial metabolism and electron transport, with increases in glutathione cycling, glutamine, branched chain, and aromatic amino acid transport. We then performed untargeted metabolomics and 13C isotope tracing to analyze systemic and tissue specific metabolic phenotyping in a murine polymicrobial sepsis model. We found an increased number of correlations between the metabolomes of liver, kidney, and spleen, with loss of correlations between the heart and quadriceps and all other organs, pointing to a shared metabolic signature within vital abdominal organs, and unique metabolic signatures for muscles during sepsis. A lowered GSH:GSSG and elevated AMP:ATP ratio in the liver underlie the significant upregulation of isotopically labeled glutamine's contribution to TCA cycle anaplerosis and glutamine-derived glutathione biosynthesis; meanwhile, the skeletal muscle and spleen were the only organs where glutamine's contribution to the TCA cycle was significantly suppressed. These results highlight tissue-specific mitochondrial reprogramming to support liver energetic demands and antioxidant synthesis, rather than global mitochondrial dysfunction, as a metabolic consequence of sepsis.PMID:37410734 | DOI:10.1371/journal.pone.0286525

PLoS Comput Biol. 2023 Jul 6;19(7):e1011224. doi: 10.1371/journal.pcbi.1011224. eCollection 2023 Jul.ABSTRACTData are the most important elements of bioinformatics: Computational analysis of bioinformatics data, in fact, can help researchers infer new knowledge about biology, chemistry, biophysics, and sometimes even medicine, influencing treatments and therapies for patients. Bioinformatics and high-throughput biological data coming from different sources can even be more helpful, because each of these different data chunks can provide alternative, complementary information about a specific biological phenomenon, similar to multiple photos of the same subject taken from different angles. In this context, the integration of bioinformatics and high-throughput biological data gets a pivotal role in running a successful bioinformatics study. In the last decades, data originating from proteomics, metabolomics, metagenomics, phenomics, transcriptomics, and epigenomics have been labelled -omics data, as a unique name to refer to them, and the integration of these omics data has gained importance in all biological areas. Even if this omics data integration is useful and relevant, due to its heterogeneity, it is not uncommon to make mistakes during the integration phases. We therefore decided to present these ten quick tips to perform an omics data integration correctly, avoiding common mistakes we experienced or noticed in published studies in the past. Even if we designed our ten guidelines for beginners, by using a simple language that (we hope) can be understood by anyone, we believe our ten recommendations should be taken into account by all the bioinformaticians performing omics data integration, including experts.PMID:37410704 | DOI:10.1371/journal.pcbi.1011224

Microb Biotechnol. 2023 Jul 6. doi: 10.1111/1751-7915.14308. Online ahead of print.ABSTRACTWhitmania pigra is widely used in traditional Chinese medicine. However, W. pigra is being threatened by an edema disease with unknown causes (WPE). In this study, a comprehensive exploration of virome, microbiome, and metabolome aberrations in the intestine of W. pigra was performed to address the aetiology of WPE. Virome analysis indicated that eukaryotic viruses did not contribute to WPE, whereas an expansion of Caudovirales was observed in WPE. Compared to the control, the microbial richness and diversity in diseased W. pigra decreased remarkably. Nine genera, including Aeromonas, Anaerotruncus, Vibrio, Proteocatella, Acinetobacter, and Brachyspira were overrepresented in WPE, whereas eleven genera, including Bifidobacterium, Phascolarctobacterium, Lactobacillus, Bacillus and AF12, were enriched in healthy individuals. Furthermore, certain metabolites, especially amino acids, short-chain fatty acids, and bile acids, were found to be linked to intestinal microbiota alterations in WPE. An integration of the microbiome and metabolome in WPE found that dysbiosis of the gut microbiota or metabolites caused WPE. Notably, W. pigra accepted intestinal microbiota transplantation from WPE donors developed WPE clinical signs eventually, and the dysbiotic intestinal microbiota can be recharacterized in this recipient W. pigra. Strikingly, pathological features of metanephridium and uraemic toxin enrichment in the gut indicated a putative interconnection between the gut and metanephridium in WPE, which represents the prototype of the gut-kidney axis in mammals. These finding exemplify the conservation of "microecological Koch's postulates" from annelids to insects and other vertebrates, which provides a direction of prevention and treatment for WPE and opens a new insight into the pathogenesis of aquatic animal diseases from an ecological perspective.PMID:37410351 | DOI:10.1111/1751-7915.14308

Curr Osteoporos Rep. 2023 Jul 6. doi: 10.1007/s11914-023-00812-8. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Recent advancements in "omics" technologies and bioinformatics have afforded researchers new tools to study bone biology in an unbiased and holistic way. The purpose of this review is to highlight recent studies integrating multi-omics data gathered from multiple molecular layers (i.e.; trans-omics) to reveal new molecular mechanisms that regulate bone biology and underpin skeletal diseases.RECENT FINDINGS: Bone biologists have traditionally relied on single-omics technologies (genomics, transcriptomics, proteomics, and metabolomics) to profile measureable differences (both qualitative and quantitative) of individual molecular layers for biological discovery and to investigate mechanisms of disease. Recently, literature has grown on the implementation of integrative multi-omics to study bone biology, which combines computational and informatics support to connect multiple layers of data derived from individual "omic" platforms. This emerging discipline termed "trans-omics" has enabled bone biologists to identify and construct detailed molecular networks, unveiling new pathways and unexpected interactions that have advanced our mechanistic understanding of bone biology and disease. While the era of trans-omics is poised to revolutionize our capacity to answer more complex and diverse questions pertinent to bone pathobiology, it also brings new challenges that are inherent when trying to connect "Big Data" sets. A concerted effort between bone biologists and interdisciplinary scientists will undoubtedly be needed to extract physiologically and clinically meaningful data from bone trans-omics in order to advance its implementation in the field.PMID:37410317 | DOI:10.1007/s11914-023-00812-8

Methods Mol Biol. 2023;2688:173-186. doi: 10.1007/978-1-0716-3319-9_15.ABSTRACTMatrix-assisted laser desorption/ionization mass spectrometry imaging with laser-induced postionization (MALDI-2-MSI) has proven a powerful tool for the in situ analysis of N-linked glycosylation, or N-glycans, directly from clinical tissue samples. Here we describe a sample preparation protocol for the analysis of N-glycans from formalin-fixed, paraffin-embedded tissue sections.PMID:37410293 | DOI:10.1007/978-1-0716-3319-9_15

Methods Mol Biol. 2023;2688:161-172. doi: 10.1007/978-1-0716-3319-9_14.ABSTRACTMolecular visualization of metabolites, lipids, and proteins by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is becoming an in-demand analytical approach to aid the histopathological analysis of breast cancer. Particularly, proteins seem to play a role in cancer progression, and specific proteins are currently used in the clinic for staging. Formalin-fixed paraffin-embedded (FFPE) tissues are ideal for correlating the molecular markers with clinical outcomes due to their long-term storage. So far, to obtain proteomic information by MSI from this kind of tissue, antigen retrieval and tryptic digestion steps are required. In this chapter, we present a protocol to spatially detect small proteins in tumor and necrotic regions of patient-derived breast cancer xenograft FFPE tissues without employing any on-tissue digestion. This protocol can be used for other kinds of FFPE tissue following specific optimization of the sample preparation phases.PMID:37410292 | DOI:10.1007/978-1-0716-3319-9_14