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

Octreotide may improve pharyngocutaneous fistula healing through downregulation of cystatins: A pilot study

Mon, 27/02/2023 - 12:00
Laryngoscope Investig Otolaryngol. 2022 Nov 28;8(1):113-119. doi: 10.1002/lio2.962. eCollection 2023 Feb.ABSTRACTBACKGROUND: Pharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide.METHODS: Four healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration.RESULTS: There were 3076 human, 332 Streptococcus mitis, 102 G. haemolyans, and 42 Granulicatella adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and ~300 proteins that had a p < .05 between the pre- and post-octreotide groups ~50 proteins with an FDR-corrected p < .05 between pre- and post-groups. These results were visualized using a volcano plot after filtering on proteins quantified by 2 more or unique precursors. Both human and bacterial proteins were among the proteins altered by octreotide treatment. Notably, four isoforms of the human cystatins, belonging to a family of cysteine proteases, that had significantly lower abundance after treatment.CONCLUSION: This pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotide's effects on saliva and reports of improved PCF healing.PMID:36846407 | PMC:PMC9948565 | DOI:10.1002/lio2.962

Metabolomic Phenotypes Reflect Patient Sex and Injury Status: A Cross-Sectional Analysis of Human Synovial Fluid

Mon, 27/02/2023 - 12:00
bioRxiv. 2023 Feb 4:2023.02.03.527040. doi: 10.1101/2023.02.03.527040. Preprint.ABSTRACTBACKGROUND: Post-traumatic osteoarthritis (PTOA) is caused by knee injuries like anterior cruciate ligament (ACL) injuries. Often, ACL injuries are accompanied by damage to other tissues and structures within the knee including the meniscus. Both are known to cause PTOA but underlying cellular mechanisms driving disease remain unknown. Aside from injury, patient sex is a prevalent risk factor associated with PTOA.HYPOTHESIS: Metabolic phenotypes of synovial fluid that differ by knee injury pathology and participant sex will be distinct from each other.STUDY DESIGN: A cross-sectional study.METHODS: Synovial fluid from n=33 knee arthroscopy patients between 18 and 70 years with no prior knee injuries was obtained pre-procedure and injury pathology assigned post-procedure. Synovial fluid was extracted and analyzed via liquid chromatography mass spectrometry metabolomic profiling to examine differences in metabolism between injury pathologies and participant sex. Additionally, samples were pooled and underwent fragmentation to identify metabolites.RESULTS: Metabolite profiles revealed that injury pathology phenotypes were distinct from each other where differences in endogenous repair pathways that are triggered post-injury were detected. Specifically, acute differences in metabolism mapped to amino acid metabolism, lipid-related oxidative metabolism, and inflammatory-associated pathways. Lastly, sexual dimorphic metabolic phenotypes were examined between male and female participants, and within injury pathology. Specifically, Cervonyl Carnitine and other identified metabolites differed in concentration between sexes.CONCLUSIONS: The results of this study suggest that different injuries (e.g., ligament vs. meniscus), as well as sex are associated with distinct metabolic phenotypes. Considering these phenotypic associations, a greater understanding of metabolic mechanisms associated with specific injuries and PTOA development may yield data regarding how endogenous repair pathways differ between injury types. Furthermore, ongoing metabolomic analysis of synovial fluid in injured male and female patients can be performed to monitor PTOA development and progression.CLINICAL RELEVANCE: Extension of this work may potentially lead to the identification of biomarkers as well as drug targets that slow, stop, or reverse PTOA progression based on injury type and patient sex.PMID:36846378 | PMC:PMC9959930 | DOI:10.1101/2023.02.03.527040

Editorial: Methods and applications in metabolic physiology

Mon, 27/02/2023 - 12:00
Front Physiol. 2023 Feb 9;14:1156826. doi: 10.3389/fphys.2023.1156826. eCollection 2023.NO ABSTRACTPMID:36846341 | PMC:PMC9948399 | DOI:10.3389/fphys.2023.1156826

<em>TM7</em> (<em>Saccharibacteria</em>) regulates the synthesis of linolelaidic acid and tricosanoic acid, and alters the key metabolites in diapause <em>Clanis bilineata tsingtauica</em>

Mon, 27/02/2023 - 12:00
Front Physiol. 2023 Feb 10;14:1093713. doi: 10.3389/fphys.2023.1093713. eCollection 2023.ABSTRACTGood exploitation and utilization of edible insects can effectively alleviate global food security crisis in years. The study on diapause larvae of Clanis bilineata tsingtauica (DLC) was conducted to explore how gut microbiota regulate the nutrients synthesis and metabolism of edible insects. The results showed that C. bilineata tsingtauica maintained a total and stable nutrition levels at early phase of diapause. The activity of instetinal enzymes in DLC fluctuated markedly with diapause time. Additionally, Proteobacteria and Firmicutes were the predominant taxa, and TM7 (Saccharibacteria) was the marker species of gut microbiota in DLC. Combined the gene function prediction analysis with Pearson correlation analysis, TM7 in DLC was mainly involved in the biosynthesis of diapause-induced differential fatty acids, i.e., linolelaidic acid (LA) and tricosanoic acid (TA), which was probably regulated by changing the activity of protease and trehalase, respectively. Moreover, according to the non-target metabolomics, TM7 might regulate the significant differential metabolites, i.e., D-glutamine, N-acetyl-d-glucosamine and trehalose, via the metabolism of amino acid and carbohydrate pathways. These results suggest that TM7 increased LA and decreased TA via the intestinal enzymes, and altered intestinal metabolites via the metabolism pathways, maybe a key mechanism for regulating the nutrients synthesis and metabolisms in DLC.PMID:36846329 | PMC:PMC9950637 | DOI:10.3389/fphys.2023.1093713

Brachial plexus avulsion induced changes in gut microbiota promotes pain related anxiety-like behavior in mice

Mon, 27/02/2023 - 12:00
Front Neurol. 2023 Feb 8;14:1084494. doi: 10.3389/fneur.2023.1084494. eCollection 2023.ABSTRACTINTRODUCTION: Brachial plexus avulsion (BPA) injury develops frequent and intense neuropathic pain, involving in both peripheral and central nervous systems. The incidence of anxiety or depression caused by BPA-induced neuropathic pain is high, but the underlying mechanism remains unclear.METHODS: We established a BPA mice model and assessed its negative emotions through behavioral tests. To further explore the role of the microbiota-gut-brain axis in the unique emotional behavior after BPA, we performed intestinal fecal 16s and metabolomics assays. Psychobiotics (PB) supplementation was administered to BPA mice to check the probiotics effects on BPA-induced anxiety behaviors.RESULTS: Pain related anxiety-like behavior was observed at the early stage after BPA (7 days), while no depression-like behavior was detected. Intriguingly, gut microbiota diversity was increased in BPA mice, and the most abundant probiotics, Lactobacillus, showed obvious changes. Lactobacillus_reuteri was significantly decreased in BPA mice. Metabolomics analysis showed that Lactobacillus_reuteri-related bile acid pathway and some neurotransmitter amino acids were significantly altered. Further PB (dominated by Lactobacillus_reuteri) supplementation could significantly relieve BPA-induced anxiety-like behaviors in mice.CONCLUSION: Our study suggests that pathological neuralgia after BPA could alter intestinal microbiota diversity, especially Lactobacillus, and the changes in neurotransmitter amino acid metabolites may be the key reason for the onset of anxiety-like behaviors in BPA mice.PMID:36846129 | PMC:PMC9944865 | DOI:10.3389/fneur.2023.1084494

Study on the Mechanism of Qing-Fei-Shen-Shi Decoction on Asthma Based on Integrated 16S rRNA Sequencing and Untargeted Metabolomics

Mon, 27/02/2023 - 12:00
Evid Based Complement Alternat Med. 2023 Feb 15;2023:1456844. doi: 10.1155/2023/1456844. eCollection 2023.ABSTRACTQing-Fei-Shen-Shi decoction (QFSS) consists of Prunus armeniaca L., Gypsum Fibrosum, Smilax glabra Roxb., Coix lacryma-jobi L., Benincasa hispida (Thunb.) Cogn., Plantago asiatica L., Pyrrosia lingua (Thunb.) Farw., Houttuynia cordata Thunb., Fritillaria thunbergii Miq., Cicadae Periostracum, and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle. QFSS shows significant clinical efficacy in the treatment of asthma. However, the specific mechanism of QFSS on asthma remains unclear. Recently, multiomics techniques are widely used in elucidating the mechanisms of Chinese herbal formulas. The use of multiomics techniques can better illuminate the multicomponents and multitargets of Chinese herbal formulas. In this study, ovalbumin (OVA) was first employed to induce an asthmatic mouse model, followed by a gavage of QFSS. First, we evaluated the therapeutic effects of QFSS on the asthmatic model mice. Second, we investigated the mechanism of QFSS in treating asthma by using an integrated 16S rRNA sequencing technology and untargeted metabolomics. Our results showed that QFSS treatment ameliorated asthma in mice. In addition, QFSS treatment affected the relative abundances of gut microbiota including Lactobacillus, Dubosiella, Lachnospiraceae_NK4A136_group, and Helicobacter. Untargeted metabolomics results showed that QFSS treatment regulated the metabolites such as 2-(acetylamino)-3-[4-(acetylamino) phenyl] acrylic acid, D-raffinose, LysoPC (15 : 1), methyl 10-undecenoate, PE (18 : 1/20 : 4), and D-glucose6-phosphate. These metabolites are associated with arginine and proline metabolism, arginine biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism. Correlation analysis indicated that arginine and proline metabolism and pyrimidine metabolism metabolic pathways were identified as the common metabolic pathways of 16s rRNA sequencing and untargeted metabolomics. In conclusion, our results showed that QFSS could ameliorate asthma in mice. The possible mechanism of QFSS on asthma may be associated with regulating the gut microbiota and arginine and proline metabolism and pyrimidine metabolism. Our study may be useful for researchers to study the integrative mechanisms of Chinese herbal formulas based on modulating gut microbiota and metabolism.PMID:36846048 | PMC:PMC9946754 | DOI:10.1155/2023/1456844

Propanol and 1, 3-propanediol enhance fatty acid accumulation synergistically in <em>Schizochytrium</em> ATCC 20888

Mon, 27/02/2023 - 12:00
Front Microbiol. 2023 Feb 9;13:1106265. doi: 10.3389/fmicb.2022.1106265. eCollection 2022.ABSTRACTThe effects of propanol and 1, 3-propanediol on fatty acid and biomass accumulation in Schizochytrium ATCC 20888 were explored. Propanol increased the contents of saturated fatty acids and total fatty acids by 55.4 and15.3%, while 1, 3-propanediol elevated the polyunsaturated fatty acids, total fatty acids and biomass contents by 30.7, 17.0, and 6.89%. Although both of them quench ROS to increase fatty acids biosynthesis, the mechanisms are different. The effect of propanol did not reflect on metabolic level while 1, 3-propanediol elevated osmoregulators contents and activated triacylglycerol biosynthetic pathway. The triacylglycerol content and the ratio of polyunsaturated fatty acids to saturated fatty acids were significantly increased by 2.53-fold, which explained the higher PUFA accumulation in Schizochytrium after adding 1, 3- propanediol. At last, the combination of propanol and 1, 3-propanediol further elevated total fatty acids by approximately 1.2-fold without compromising cell growth. These findings are valuable for scale-up production of designed Schizochytrium oil for various application purposes.PMID:36845976 | PMC:PMC9947470 | DOI:10.3389/fmicb.2022.1106265

Expanding the diversity of Chardonnay aroma through the metabolic interactions of <em>Saccharomyces cerevisiae</em> cocultures

Mon, 27/02/2023 - 12:00
Front Microbiol. 2023 Feb 9;13:1032842. doi: 10.3389/fmicb.2022.1032842. eCollection 2022.ABSTRACTYeast co-inoculations in winemaking are often studied in the framework of modulating the aromatic profiles of wines. Our study aimed to investigate the impact of three cocultures and corresponding pure cultures of Saccharomyces cerevisiae on the chemical composition and the sensory profile of Chardonnay wine. Coculture makes it possible to obtain completely new aromatic expressions that do not exist in the original pure cultures attributed to yeast interactions. Esters, fatty acids and phenol families were identified as affected. The sensory profiles and metabolome of the cocultures, corresponding pure cultures and associated wine blends from both pure cultures were found to be different. The coculture did not turn out to be the addition of the two pure culture wines, indicating the impact of interaction. High resolution mass spectrometry revealed thousands of cocultures biomarkers. The metabolic pathways involved in these wine composition changes were highlighted, most of them belonging to nitrogen metabolism.PMID:36845971 | PMC:PMC9947296 | DOI:10.3389/fmicb.2022.1032842

Metabolomic biomarkers for the diagnosis and post-transplant outcomes of AFP negative hepatocellular carcinoma

Mon, 27/02/2023 - 12:00
Front Oncol. 2023 Feb 9;13:1072775. doi: 10.3389/fonc.2023.1072775. eCollection 2023.ABSTRACTBACKGROUND: Early diagnosis for α-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) remains a critical problem. Metabolomics is prevalently involved in the identification of novel biomarkers. This study aims to identify new and effective markers for AFP negative HCC.METHODS: In total, 147 patients undergoing liver transplantation were enrolled from our hospital, including liver cirrhosis patients (LC, n=25), AFP negative HCC patients (NEG, n=44) and HCC patients with AFP over 20 ng/mL (POS, n=78). 52 Healthy volunteers (HC) were also recruited in this study. Metabolomic profiling was performed on the plasma of those patients and healthy volunteers to select candidate metabolomic biomarkers. A novel diagnostic model for AFP negative HCC was established based on Random forest analysis, and prognostic biomarkers were also identified.RESULTS: 15 differential metabolites were identified being able to distinguish NEG group from both LC and HC group. Random forest analysis and subsequent Logistic regression analysis showed that PC(16:0/16:0), PC(18:2/18:2) and SM(d18:1/18:1) are independent risk factor for AFP negative HCC. A three-marker model of Metabolites-Score was established for the diagnosis of AFP negative HCC patients with an area under the time-dependent receiver operating characteristic curve (AUROC) of 0.913, and a nomogram was then established as well. When the cut-off value of the score was set at 1.2895, the sensitivity and specificity for the model were 0.727 and 0.92, respectively. This model was also applicable to distinguish HCC from cirrhosis. Notably, the Metabolites-Score was not correlated to tumor or body nutrition parameters, but difference of the score was statistically significant between different neutrophil-lymphocyte ratio (NLR) groups (≤5 vs. >5, P=0.012). Moreover, MG(18:2/0:0/0:0) was the only prognostic biomarker among 15 metabolites, which is significantly associated with tumor-free survival of AFP negative HCC patients (HR=1.160, 95%CI 1.012-1.330, P=0.033).CONCLUSION: The established three-marker model and nomogram based on metabolomic profiling can be potential non-invasive tool for the diagnosis of AFP negative HCC. The level of MG(18:2/0:0/0:0) exhibits good prognosis prediction performance for AFP negative HCC.PMID:36845695 | PMC:PMC9947281 | DOI:10.3389/fonc.2023.1072775

Editorial: Advances and challenges in untargeted metabolomics

Mon, 27/02/2023 - 12:00
Front Mol Biosci. 2023 Feb 10;10:1097443. doi: 10.3389/fmolb.2023.1097443. eCollection 2023.NO ABSTRACTPMID:36845548 | PMC:PMC9951091 | DOI:10.3389/fmolb.2023.1097443

Metabolomics investigation on the volatile and non-volatile composition in enzymatic hydrolysates of Pacific oyster (<em>Crassostrea gigas</em>)

Mon, 27/02/2023 - 12:00
Food Chem X. 2023 Jan 9;17:100569. doi: 10.1016/j.fochx.2023.100569. eCollection 2023 Mar 30.ABSTRACTTo investigate the differences of volatile and non-volatile metabolites between oyster enzymatic hydrolysates and boiling concentrates, molecular sensory analysis and untargeted metabolomics were employed. "Grassy," "fruity," "oily/fatty," "fishy," and "metallic" were identified as sensory attributes used to evaluate different processed oyster homogenates. Sixty-nine and 42 volatiles were identified by gas chromatography-ion mobility spectrometry and gas chromatography-mass spectrometry, respectively. Pentanal, 1-penten-3-ol, hexanal, (E)-2-pentenal, heptanal, (E)-2-hexenal, 4-octanone, (E)-4-heptenal, 3-octanone, octanal, nonanal, 1-octen-3-ol, benzaldehyde, (E)-2-nonenal, and (E, Z)-2,6-nonadienal were detected as the key odorants (OAV > 1) after enzymatic hydrolysis. Hexanal, (E)-4-heptenal, and (E)-2-pentenal were significantly associated with off-odor, and 177 differential metabolites were classified. Aspartate, glutamine, alanine, and arginine were the key precursors affecting the flavor profile. Linking sensory descriptors to volatile and nonvolatile components of different processed oyster homogenates will provide information for the process and quality improvement of oyster products.PMID:36845524 | PMC:PMC9945435 | DOI:10.1016/j.fochx.2023.100569

Comparative nutritional and metabolic analysis reveals the taste variations during yellow rambutan fruit maturation

Mon, 27/02/2023 - 12:00
Food Chem X. 2023 Jan 19;17:100580. doi: 10.1016/j.fochx.2023.100580. eCollection 2023 Mar 30.ABSTRACTThe metabolic reasons for rambutan taste variations during maturity are unknown. Here, we obtained a unique rambutan cultivar Baoyan No.2 (BY2) with a strong yellow pericarp and excellent taste, the sugar-acid ratios of which ranged from 21.7 to 94.5 during maturation. Widely targeted metabolomics analysis was performed to reveal the metabolic reasons behind these taste variations. The results showed that 51 metabolites were identified as common different metabolites (DMs), including 16 lipids, 12 amino acids and others. Among them, the abundance level of 3,4-digalloylshikimic acid exhibited a positive correlation with the titratable acids (R2 = 0.9996) and a negative correlation with the sugar-acid ratio (R2 = 0.9999). Therefore, it could be a taste biomarker of BY2 rambutan. Moreover, all DMs were enriched in "galactose metabolism", "fructose and mannose metabolism" and "biosynthesis of amino acids" pathways, which predominantly accounted for the taste variation. Our findings provided new metabolic evidence for the taste variation of rambutan.PMID:36845499 | PMC:PMC9944575 | DOI:10.1016/j.fochx.2023.100580

Metabolomics analysis reveals the accumulation patterns of flavonoids and phenolic acids in quinoa (<em>Chenopodium quinoa</em> Willd.) grains of different colors

Mon, 27/02/2023 - 12:00
Food Chem X. 2023 Feb 6;17:100594. doi: 10.1016/j.fochx.2023.100594. eCollection 2023 Mar 30.ABSTRACTQuinoa grains are gaining increasing popularity owing to their high nutritional merits. However, only limited information is available on the metabolic profiles of quinoa grains. In this study, we determined the metabolic profiles of black, red, and white quinoa grains via an ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS)-based metabolomics. A total of 689 metabolites were identified, among which 251, 182, and 317 metabolites displayed different accumulation patterns in the three comparison groups (Black vs Red, Black vs White, and Red vs White), respectively. In particular, flavonoid and phenolic acid contents displayed considerable differences, with 22 flavonoids, 5 phenolic acids, and 1 betacyanin being differentially accumulated among the three quinoa cultivars. Additionally, correlation analysis showed that flavonoids and phenolic acids could act as betanin co-pigments in quinoa grains. In conclusion, this study provides comprehensive insights into the adequate utilization and development of novel quinoa-based functional foods.PMID:36845489 | PMC:PMC9945449 | DOI:10.1016/j.fochx.2023.100594

HS-SPME-GC × GC/MS combined with multivariate statistics analysis to investigate the flavor formation mechanism of tank-fermented broad bean paste

Mon, 27/02/2023 - 12:00
Food Chem X. 2022 Dec 27;17:100556. doi: 10.1016/j.fochx.2022.100556. eCollection 2023 Mar 30.ABSTRACTWith the advancement of industrialization, tank fermentation technology is promising for Pixian broad bean paste. This study identified and analyzed the general physicochemical factors and volatile metabolites of fermented broad beans in a thermostatic fermenter. Headspace solid-phase microextraction (HS-SPME)-two-dimensional gas chromatography-mass spectrometry (GC × GC-MS) was applied to detect the volatile compounds in fermented broad beans, while metabolomics was used to explore their physicochemical characteristics and analyze the possible metabolic mechanism. A total of 184 different metabolites were detected, including 36 alcohols, 29 aldehydes, 26 esters, 21 ketones, 14 acids, 14 aromatic compounds, ten heterocycles, nine phenols, nine organonitrogen compounds, seven hydrocarbons, two ethers, and seven other types, which were annotated to various branch metabolic pathways of carbohydrate and amino acid metabolism. This study provides references for subsequent functional microorganism mining to improve the quality of the tank-fermented broad beans and upgrade the Pixian broad bean paste industry.PMID:36845488 | PMC:PMC9943836 | DOI:10.1016/j.fochx.2022.100556

HPLC-QTRAP-MS-based metabolomics approach investigates the formation mechanisms of meat quality and flavor of Beijing You chicken

Mon, 27/02/2023 - 12:00
Food Chem X. 2022 Dec 21;17:100550. doi: 10.1016/j.fochx.2022.100550. eCollection 2023 Mar 30.ABSTRACTChicken meat quality and flavor are determined by abundant metabolites. In this study, HPLC-QTRAP-MS-based metabolomic analysis was used to evaluate the characteristic metabolites in the breast muscle of Beijing You chickens aged 56, 98, and 120 days. A total of 544 metabolites in 32 categories were identified, among which amino acids and organic acids were the most abundant. 60 and 55 differential metabolites were identified between 56 and 98 days of age, 98 and 120 days of age, respectively. The content of l-carnitine, l-methionine and 3-hydroxybutyrate increased significantly at 98 or 120 days of age. Arginine biosynthesis, purine metabolism, alanine, aspartic acid, and glutamic acid metabolism were important metabolic pathways that affect chicken meat flavor. This study can help to elucidate the metabolic mechanism of breast muscle during Beijing You chicken development and provide a theoretical reference for the improvement of chicken meat quality and flavor.PMID:36845483 | PMC:PMC9943843 | DOI:10.1016/j.fochx.2022.100550

Metabonomic analysis of human and 12 kinds of livestock mature milk

Mon, 27/02/2023 - 12:00
Food Chem X. 2023 Jan 20;17:100581. doi: 10.1016/j.fochx.2023.100581. eCollection 2023 Mar 30.ABSTRACTMature milk, as a nutrient-rich endogenous metabolite, has various beneficial effects on the human body. In order to investigate the specific nutrients provided by different dairy products to humans, we used UHPLC-Q-TOF MS to analyze the highly significantly differentially expressed metabolites in 13 species of mammalian mature milk, which were grouped into 17 major metabolite classes with 1992 metabolites based on chemical classification. KEGG shows that 5 pathways in which differentially significant metabolites are actively involved are ABC transporters, Purine metabolism, Pyrimidine metabolism, Phosphotransferase system, Galactose metabolism. The study found that pig milk and goat milk are closer to human milk and contain more nutrients that are beneficial to human health, followed by camel milk and cow milk. In the context of dairy production, the development of goat milk is more likely to meet human needs and health.PMID:36845482 | PMC:PMC9944509 | DOI:10.1016/j.fochx.2023.100581

Short communication: unique metabolic signature of proliferative retinopathy in the tear fluid of diabetic patients with comorbidities - preliminary data for PPPM validation

Mon, 27/02/2023 - 12:00
EPMA J. 2023 Feb 22:1-9. doi: 10.1007/s13167-023-00318-4. Online ahead of print.ABSTRACTType 2 diabetes (T2DM) defined as the adult-onset type that is primarily not insulin-dependent, comprises over 95% of all diabetes mellitus (DM) cases. According to global records, 537 million adults aged 20-79 years are affected by DM that means at least 1 out of 15 persons. This number is projected to grow by 51% by the year 2045. One of the most common complications of T2DM is diabetic retinopathy (DR) with an overall prevalence over 30%. The total number of the DR-related visual impairments is on the rise, due to the growing T2DM population. Proliferative diabetic retinopathy (PDR) is the progressing DR and leading cause of preventable blindness in working-age adults. Moreover, PDR with characteristic systemic attributes including mitochondrial impairment, increased cell death and chronic inflammation, is an independent predictor of the cascading DM-complications such as ischemic stroke. Therefore, early DR is a reliable predictor appearing upstream of this "domino effect". Global screening, leading to timely identification of DM-related complications, is insufficiently implemented by currently applied reactive medicine. A personalised predictive approach and cost-effective targeted prevention shortly - predictive, preventive and personalised medicine (PPPM / 3PM) could make a good use of the accumulated knowledge, preventing blindness and other severe DM complications. In order to reach this goal, reliable stage- and disease-specific biomarker panels are needed characterised by an easy way of the sample collection, high sensitivity and specificity of analyses. In the current study, we tested the hypothesis that non-invasively collected tear fluid is a robust source for the analysis of ocular and systemic (DM-related complications) biomarker patterns suitable for differential diagnosis of stable DR versus PDR. Here, we report the first results of the comprehensive ongoing study, in which we correlate individualised patient profiles (healthy controls versus patients with stable D as well as patients with PDR with and without co-morbidities) with their metabolic profiles in the tear fluid. Comparative mass spectrometric analysis performed has identified following metabolic clusters which are differentially expressed in the groups of comparison: acylcarnitines, amino acid & related compounds, bile acids, ceramides, lysophosphatidyl-choline, nucleobases & related compounds, phosphatidyl-cholines, triglycerides, cholesterol esters, and fatty acids. Our preliminary data strongly support potential clinical utility of metabolic patterns in the tear fluid indicating a unique metabolic signature characteristic for the DR stages and PDR progression. This pilot study creates a platform for validating the tear fluid biomarker patterns to stratify T2DM-patients predisposed to the PDR. Moreover, since PDR is an independent predictor of severe T2DM-related complications such as ischemic stroke, our international project aims to create an analytical prototype for the "diagnostic tree" (yes/no) applicable to healthrisk assessment in diabetes care.PMID:36845280 | PMC:PMC9944425 | DOI:10.1007/s13167-023-00318-4

Quiescence preconditioned nucleus pulposus stem cells alleviate intervertebral disc degeneration by enhancing cell survival <em>via</em> adaptive metabolism pattern in rats

Mon, 27/02/2023 - 12:00
Front Bioeng Biotechnol. 2023 Feb 10;11:1073238. doi: 10.3389/fbioe.2023.1073238. eCollection 2023.ABSTRACTQuiescence is a cellular state of reversible growth arrest required to maintain homeostasis and self-renewal. Entering quiescence allows the cells to remain in the non-dividing stage for an extended period of time and enact mechanisms to protect themselves from damage. Due to the extreme nutrient-deficient microenvironment in the intervertebral disc (IVD), the therapeutic effect of cell transplantation is limited. In this study, nucleus pulposus stem cells (NPSCs) were preconditioned into quiescence through serum starvation in vitro and transplanted to repair intervertebral disc degeneration (IDD). In vitro, we investigated apoptosis and survival of quiescent NPSCs in a glucose-free medium without fetal bovine serum. Non-preconditioned proliferating NPSCs served as controls. In vivo, the cells were transplanted into a rat model of IDD induced by acupuncture, and the intervertebral disc height, histological changes, and extracellular matrix synthesis were observed. Finally, to elucidate the mechanisms underlying the quiescent state of NPSCs, the metabolic patterns of the cells were investigated through metabolomics. The results revealed that quiescent NPSCs decreased apoptosis and increased cell survival when compared to proliferating NPSCs both in vitro and in vivo, as well as maintained the disc height and histological structure significantly better than that by proliferating NPSCs. Furthermore, quiescent NPSCs have generally downregulated metabolism and reduced energy requirements in response to a switch to a nutrient-deficient environment. These findings support that quiescence preconditioning maintains the proliferation and biological function potential of NPSCs, increases cell survival under the extreme environment of IVD, and further alleviates IDD via adaptive metabolic patterns.PMID:36845177 | PMC:PMC9950514 | DOI:10.3389/fbioe.2023.1073238

Bacterial volatile organic compounds (VOCs) promote growth and induce metabolic changes in rice

Mon, 27/02/2023 - 12:00
Front Plant Sci. 2023 Feb 9;13:1056082. doi: 10.3389/fpls.2022.1056082. eCollection 2022.ABSTRACTPlant growth-promoting bacteria (PGPB) represent an eco-friendly alternative to reduce the use of chemical products while increasing the productivity of economically important crops. The emission of small gaseous signaling molecules from PGPB named volatile organic compounds (VOCs) has emerged as a promising biotechnological tool to promote biomass accumulation in model plants (especially Arabidopsis thaliana) and a few crops, such as tomato, lettuce, and cucumber. Rice (Oryza sativa) is the most essential food crop for more than half of the world's population. However, the use of VOCs to improve this crop performance has not yet been investigated. Here, we evaluated the composition and effects of bacterial VOCs on the growth and metabolism of rice. First, we selected bacterial isolates (IAT P4F9 and E.1b) that increased rice dry shoot biomass by up to 83% in co-cultivation assays performed with different durations of time (7 and 12 days). Metabolic profiles of the plants co-cultivated with these isolates and controls (without bacteria and non-promoter bacteria-1003-S-C1) were investigated via 1H nuclear magnetic resonance. The analysis identified metabolites (e.g., amino acids, sugars, and others) with differential abundance between treatments that might play a role in metabolic pathways, such as protein synthesis, signaling, photosynthesis, energy metabolism, and nitrogen assimilation, involved in rice growth promotion. Interestingly, VOCs from IAT P4F9 displayed a more consistent promotion activity and were also able to increase rice dry shoot biomass in vivo. Molecular identification by sequencing the 16S rRNA gene of the isolates IAT P4F9 and E.1b showed a higher identity with Serratia and Achromobacter species, respectively. Lastly, volatilomes of these and two other non-promoter bacteria (1003-S-C1 and Escherichia coli DH5α) were evaluated through headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. Compounds belonging to different chemical classes, such as benzenoids, ketones, alcohols, sulfide, alkanes, and pyrazines, were identified. One of these VOCs, nonan-2-one, was validated in vitro as a bioactive compound capable of promoting rice growth. Although further analyses are necessary to properly elucidate the molecular mechanisms, our results suggest that these two bacterial isolates are potential candidates as sources for bioproducts, contributing to a more sustainable agriculture.PMID:36844905 | PMC:PMC9948655 | DOI:10.3389/fpls.2022.1056082

A Brief History of Microbial Study and Techniques for Exploring the Gastrointestinal Microbiome

Mon, 27/02/2023 - 12:00
Clin Colon Rectal Surg. 2023 Jan 25;36(2):98-104. doi: 10.1055/s-0042-1760678. eCollection 2023 Mar.ABSTRACTOver the past 20 years, the study of microbial communities has benefited from simultaneous advancements across several fields resulting in a high-resolution view of human consortia. Although the first bacterium was described in the mid-1600s, the interest in community membership and function has not been a focus or feasible until recent decades. With strategies such as shotgun sequencing, microbes can be taxonomically profiled without culturing and their unique variants defined and compared across phenotypes. Approaches such as metatranscriptomics, metaproteomics, and metabolomics can define the current functional state of a population through the identification of bioactive compounds and significant pathways. Prior to sample collection in microbiome-based studies it is critical to evaluate the requirements of downstream analyses to ensure accurate processing and storage for generation of high data quality. A common pipeline for the analysis of human samples includes approval of collection protocols and method finalization, patient sample collection, sample processing, data analysis, and visualization. Human-based microbiome studies are inherently challenging but with the application of complementary multi-omic strategies there is an unbounded potential for discovery.PMID:36844714 | PMC:PMC9946713 | DOI:10.1055/s-0042-1760678

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