PubMed

Metabolites. 2023 Mar 31;13(4):506. doi: 10.3390/metabo13040506.ABSTRACTThis prospective observational study aimed to evaluate the association of metabolomic alterations with weight loss outcomes following sleeve gastrectomy (SG). We evaluated the metabolomic profile of serum and feces prior to SG and three months post-SG, along with weight loss outcomes in 45 adults with obesity. The percent total weight loss for the highest versus the lowest weight loss tertiles (T3 vs. T1) was 17.0 ± 1.3% and 11.1 ± 0.8%, p < 0.001. Serum metabolite alterations specific to T3 at three months included a decrease in methionine sulfoxide concentration as well as alterations to tryptophan and methionine metabolism (p < 0.03). Fecal metabolite changes specific to T3 included a decrease in taurine concentration and perturbations to arachidonic acid metabolism, and taurine and hypotaurine metabolism (p < 0.002). Preoperative metabolites were found to be highly predictive of weight loss outcomes in machine learning algorithms, with an average area under the curve of 94.6% for serum and 93.4% for feces. This comprehensive metabolomics analysis of weight loss outcome differences post-SG highlights specific metabolic alterations as well as machine learning algorithms predictive of weight loss. These findings could contribute to the development of novel therapeutic targets to enhance weight loss outcomes after SG.PMID:37110164 | DOI:10.3390/metabo13040506

Metabolites. 2023 Mar 31;13(4):505. doi: 10.3390/metabo13040505.ABSTRACTThe in utero environment is important for newborn size at birth, which is associated with childhood adiposity. We examined associations between maternal metabolite levels and newborn birthweight, sum of skinfolds (SSF), and cord C-peptide in a multinational and multi-ancestry cohort of 2337 mother-newborn dyads. Targeted and untargeted metabolomic assays were performed on fasting and 1 h maternal serum samples collected during an oral glucose tolerance test performed at 24-32 week gestation in women participating in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Anthropometric measurements were obtained on newborns at birth. Following adjustment for maternal BMI and glucose, per-metabolite analyses demonstrated significant associations between maternal metabolite levels and birthweight, SSF, and cord C-peptide. In the fasting state, triglycerides were positively associated and several long-chain acylcarnitines were inversely associated with birthweight and SSF. At 1 h, additional metabolites including branched-chain amino acids, proline, and alanine were positively associated with newborn outcomes. Network analyses demonstrated distinct clusters of inter-connected metabolites significantly associated with newborn phenotypes. In conclusion, numerous maternal metabolites during pregnancy are significantly associated with newborn birthweight, SSF, and cord C-peptide independent of maternal BMI and glucose, suggesting that metabolites in addition to glucose contribute to newborn size at birth and adiposity.PMID:37110162 | DOI:10.3390/metabo13040505

Metabolites. 2023 Mar 29;13(4):495. doi: 10.3390/metabo13040495.ABSTRACTOur current understanding of organophosphorus agent (pesticides and chemical warfare nerve agents) metabolism in humans is limited to the general transformation by cytochrome P450 enzymes and, to some extent, by esterases and paraoxonases. The role of compound concentrations on the rate of clearance is not well established and is further explored in the current study. We discuss the metabolism of 56 diverse organophosphorus compounds (both pesticides and chemical warfare nerve agent simulants), many of which were explored at two variable dose regimens (high and low), determining their clearance rates (Clint) in human liver microsomes. For compounds that were soluble at high concentrations, 1D-NMR, 31P, and MRM LC-MS/MS were used to calculate the Clint and the identity of certain metabolites. The determined Clint rates ranged from 0.001 to 2245.52 µL/min/mg of protein in the lower dose regimen and from 0.002 to 98.57 µL/min/mg of protein in the high dose regimen. Though direct equivalency between the two regimens was absent, we observed (1) both mono- and bi-phasic metabolism of the OPs and simulants in the microsomes. Compounds such as aspon and formothion exhibited biphasic decay at both high and low doses, suggesting either the involvement of multiple enzymes with different KM or substrate/metabolite effects on the metabolism. (2) A second observation was that while some compounds, such as dibrom and merphos, demonstrated a biphasic decay curve at the lower concentrations, they exhibited only monophasic metabolism at the higher concentration, likely indicative of saturation of some metabolic enzymes. (3) Isomeric differences in metabolism (between Z- and E- isomers) were also observed. (4) Lastly, structural comparisons using examples of the oxon group over the original phosphorothioate OP are also discussed, along with the identification of some metabolites. This study provides initial data for the development of in silico metabolism models for OPs with broad applications.PMID:37110155 | DOI:10.3390/metabo13040495

Metabolites. 2023 Mar 29;13(4):494. doi: 10.3390/metabo13040494.ABSTRACTHeat stress (HS) during late gestation implies unfavorable effects on dairy cows and their in-utero heat stressed offspring. The objective of the present study was to elucidate the effect of intrauterine (maternal) HS during the last week of gestation on blood metabolite concentrations of female dairy calves during their first week of life. We defined the mean temperature humidity index (mTHI) during the last gestation week of ≥60 as threshold for maternal HS. In this regard, we compared differences in metabolite concentrations of maternally heat stressed (MHSCALVES) (n = 14) and not heat stressed (NMHSCALVES) (n = 33) calves. We identified 15 metabolites from five different biochemical classes (phosphatidylcholines, cholesteryl esters, sphingomyelins, cresols and hexoses) as potential biomarkers for maternal HS in calves. The plasma concentrations of all significantly affected metabolites were lower in MHSCALVES when compared to NMHSCALVES. The effect of maternal HS during the last week of gestation on blood metabolite concentrations of the female offspring during the first week after birth might be due to HS induced intergenerational physiological alterations, impaired colostrum quality or epigenetic modifications of the calf genome. The results of this pilot study should be validated in ongoing fully standardized studies.PMID:37110153 | DOI:10.3390/metabo13040494

Sci Total Environ. 2023 Apr 25:163615. doi: 10.1016/j.scitotenv.2023.163615. Online ahead of print.ABSTRACTBisphenol A (BPA) has attracted growing attention as a well-known environmental pollutant due to its high risk of male reproductive toxicity. In this study, transcriptomics profiling combined with metabolomic techniques was applied to explore the intervention effects of BPA-induced male reproductive toxicity. We demonstrated that cyanidin-3-O-glucoside (C3G) and its main metabolite protocatechuic acid (PCA) significantly increased testosterone and luteinizing hormone (LH) levels in the serum of rats, and improved sperm quality. Furthermore, we identified and screened differentially expressed genes (DEGs) and metabolites (DMs) that functionally enriched in the steroidogenesis-related pathways. Next, the validated results found that C3G and PCA significantly up-regulated the gene expressions of Star, Cyp11a1, Cyp17a1, Cyp19a1, Cyp7a1, Hsd3b1, Hsd3b2, Hsd17b3, Scrab1, and Ass1 in testicular. In Leydig cells, C3G and PCA dramatically alleviated apoptosis, ROS accumulation, and cell cycle arrest caused by BPA. In addition, molecular docking and simulation results implied that C3G and PCA competitively with BPA bind to the estrogen receptors α and β (ERα and ERβ) and shared common key amino acids. The main interaction modes between small molecules and estrogen receptors included π-π stacking, salt bridges, hydrogen bonds, and hydrophobic interactions. Therefore, our study sheds light on C3G and PCA supplementation can protect male reproduction from BPA-induced injury.PMID:37105472 | DOI:10.1016/j.scitotenv.2023.163615

J Equine Vet Sci. 2023 Apr 25:104499. doi: 10.1016/j.jevs.2023.104499. Online ahead of print.ABSTRACTCryopreservation of stallion semen does not achieve the post-thaw quality or fertility results observed in other species like cattle. There are many reasons for this, but the membrane composition and intracellular changes in stallion sperm predispose them to low resistance to the cooling, freezing, and subsequent thawing process. Damage to the sperm results from different processes activated during cryopreservation, including oxidative stress, apoptosis, and structural modifications in the sperm membrane that increase the deleterious effect on sperm. In addition, significant individual variability is observed among stallions in the ability of sperm to survive the freeze-thaw process. Recent advances in genomics, transcriptomics, proteomics, metabolomics and epigenetics are making it possible to advance our understanding of the cellular and molecular processes involved in the cryopreservation process, opening new possibilities for improvement. This review addresses the ongoing research on stallion semen cryopreservation, focusing on the cellular and molecular consequences of this procedure in stallions and discusses the new tools currently available to increase the tolerance of equine spermatozoa to freeze-thaw.PMID:37105416 | DOI:10.1016/j.jevs.2023.104499

Osteoarthritis Cartilage. 2023 Apr 25:S1063-4584(23)00761-6. doi: 10.1016/j.joca.2023.04.007. Online ahead of print.ABSTRACTOBJECTIVE: To investigate host and gut-microbiota related Tryptophan metabolism in hand osteoarthritis (HOA).METHODS: The baseline serum concentration of 20 Tryptophan metabolites was measured in 416 HOA patients in a cross-sectional analysis of the DIGICOD cohort. Tryptophan metabolites levels, metabolite-ratios and metabolism pathway activation were compared between erosive (N=141) and non-erosive HOA (N=275) by multiple logistic regressions adjusted on age, BMI and sex. The association between Tryptophan metabolite levels and HOA symptoms was investigated by a Spearman's rank correlation analysis.RESULTS: Four serum Tryptophan metabolites, eight metabolite ratios and one metabolism pathway were associated with erosive HOA. Erosive HOA was negatively associated with Tryptophan (odds ratio (OR)=0.41, 95% confidence interval [0.24-0.70]), indole-3-aldehyde (OR=0.67 [0.51-0.90]) and 3-OH-anthranilic acid (OR=1.32 [1.13-1.54]) and positively with 5-OH-Tryptophan levels (OR=1.41 [1.13-1.77]). The pro-inflammatory kynurenine-indoleamine 2,3-dioxygenase pathway was upregulated in erosive HOA (OR=1.60 [1.11-2.29]). Eleven metabolites were correlated with HOA symptoms and were mostly pain-related. Serotonin and N-acetyl serotonin levels were negatively correlated with number of tender joints. Indole-3-aldehyde level was negatively correlated and 3-OH-anthranilic acid, 3-OH-kynurenine and 5-OH-Tryptophan levels were positively correlated with number of patients-reported painful joints. Quinolinic acid and 3-OH-kynurenine levels correlated positively with AUSCAN pain.CONCLUSIONS: Tryptophan metabolites disturbance is associated with erosive HOA and pain and emphasize the role of low-grade inflammation and gut dysbiosis in HOA.PMID:37105396 | DOI:10.1016/j.joca.2023.04.007

Poult Sci. 2023 Mar 29;102(6):102672. doi: 10.1016/j.psj.2023.102672. Online ahead of print.ABSTRACTThe passion fruit peel (PFP) is the by-product of juice processing and is rich in phenolic compounds and dietary fibers. As the high ADF content in PFP (34.20%), we proceeded to treat PFP with cellulase. The ADF decreased to 16.70% after enzymatic processing, and we supposed that enzymolytic passion fruit peel (EPF) should have a greater growth performance than PFP to broilers. Two trials were conducted to evaluate the effects of dietary PFP or EPF supplementation on growth performance, serum biochemical indices, meat quality, and cecal short-chain fatty acids, microbiota, and metabolites in broilers. In Exp. 1, 180 1-day-old Sanhuang broilers (male, 36.17 ± 2.47 g) were randomly allocated into 3 treatments, with 6 replicates in each treatment. The 3 experimental diets included 1 basal diet (control) and 2 PFP-added diets supplemented with 1 and 2% PFP, respectively. The trial lasted for 42 d. In Exp. 2, 144 Sanhuang broilers (male, 112-day-old, 1.62 ± 0.21 kg) were randomly allocated to 3 treatments. Each treatment was distributed among 6 pens, and each pen contained 8 broilers. The 3 treatment diets included: a control diet, a positive control diet supplementing 75 mg/kg chlortetracycline, and the experimental diet supplementing 3% EPF. The trial lasted for 56 d. Results showed that dietary 1 and 2% PFP addition did not affect growth performance in Exp. 1, and the 3% EPF supplementation had a negative effect on ADFI (P < 0.05) in Exp. 2. A decreased serum triglyceride (P < 0.05) in broilers was observed in Exp. 1. Broilers fed EPF had a higher glutathione peroxidase (GSH-Px) (P < 0.05), and lower levels of tumor necrosis factor-α (TNF-α) (P < 0.05) and glucose (P < 0.05) in Exp. 2. We also found that broilers from PFP or EPF-treated treatments had an increased butyrate content and higher microbial diversity in the cecum. The effects of antioxidation, anti-inflammatory function, and elevated SCFAs were confirmed after the microbe and untargeted metabolomic analysis. Dietary EPF supplementation significantly increased the SCFA-generating bacteria, anti-inflammatory-related bacteria, the antioxidant-related and anti-inflammatory-related metabolites. Moreover, dietary 3% EPF addition positively affects the biosynthesis of phenylpropanoids, which strongly correlate with the antioxidant and anti-inflammatory properties. In conclusion, the proper addition level did not affect the growth performance, and the PFP and EPF could improve the antioxidation state, anti-inflammatory activity, and intestinal functions of Sanhuang broilers to some extent.PMID:37104904 | DOI:10.1016/j.psj.2023.102672

Microbiome. 2023 Apr 28;11(1):94. doi: 10.1186/s40168-023-01526-w.ABSTRACTBACKGROUND: Excessive hedonic consumption is one of the main drivers for weight gain. Identifying contributors of this dysregulation would help to tackle obesity. The gut microbiome is altered during obesity and regulates host metabolism including food intake.RESULTS: By using fecal material transplantation (FMT) from lean or obese mice into recipient mice, we demonstrated that gut microbes play a role in the regulation of food reward (i.e., wanting and learning processes associated with hedonic food intake) and could be responsible for excessive motivation to obtain sucrose pellets and alterations in dopaminergic and opioid markers in reward-related brain areas. Through untargeted metabolomic approach, we identified the 3-(3'-hydroxyphenyl)propanoic acid (33HPP) as highly positively correlated with the motivation. By administrating 33HPP in mice, we revealed its effects on food reward.CONCLUSIONS: Our data suggest that targeting the gut microbiota and its metabolites would be an interesting therapeutic strategy for compulsive eating, preventing inappropriate hedonic food intake. Video Abstract.PMID:37106463 | DOI:10.1186/s40168-023-01526-w

BMC Plant Biol. 2023 Apr 28;23(1):226. doi: 10.1186/s12870-023-04225-8.ABSTRACTBACKGROUND: Continuous cropping is a significant obstacle to sustainable development in the pea (Pisum sativum L.) industry, but the underlying mechanisms of this remain unclear. In this study, we used 16 S rDNA sequencing, transcriptomics, and metabolomics to analyze the response mechanism of roots and soil bacteria to continuous cropping and the relationship between soil bacteria and root phenotypes of different pea genotypes (Ding wan 10 and Yun wan 8).RESULTS: Continuous cropping inhibited pea growth, with a greater effect on Ding wan 10 than Yun wan 8. Metabolomics showed that the number of differentially accumulated metabolites (DAMs) in pea roots increased with the number of continuous cropping, and more metabolic pathways were involved. Transcriptomics revealed that the number of differentially expressed genes (DEGs) increased with the number of continuous cropping. Continuous cropping altered the expression of genes involved in plant-pathogen interaction, MAPK signal transduction, and lignin synthesis pathways in pea roots, with more DEGs in Ding wan 10 than in Yun wan 8. The up-regulated expression of genes in the ethylene signal transduction pathway was evident in Ding wan 10. Soil bacterial diversity did not change, but the relative abundance of bacteria significantly responded to continuous cropping. Integrative analysis showed that the bacteria with significant relative abundance in the soil were strongly associated with the antioxidant synthesis and linoleic acid metabolism pathway of pea roots under continuous cropping once. Under continuous cropping twice, the bacteria with significant relative abundance changes were strongly associated with cysteine and methionine metabolism, fatty acid metabolism, phenylpropanoid biosynthesis, terpenoid backbone biosynthesis, linoleic acid, and amino sugar and nucleotide sugar metabolism.CONCLUSION: Ding wan 10 was more sensitive to continuous cropping than Yun wan 8. Continuous cropping times and pea genotypes determined the differences in root metabolic pathways. There were common metabolic pathways in the two pea genotypes in response to continuous cropping, and the DEGs and DAMs in these metabolic pathways were strongly associated with the bacteria with significant changes in relative abundance in the soil. This study provides new insights into obstacles to continuous cropping in peas.PMID:37106450 | DOI:10.1186/s12870-023-04225-8

Microb Cell Fact. 2023 Apr 27;22(1):83. doi: 10.1186/s12934-023-02091-5.ABSTRACTVarious factors contribute to the development of the acute inflammation process, like the pro-inflammatory cytokines, certain enzymes as well as oxidative stress mediators. The anti-inflammatory potential of the endophytic fungus Penicillium brefeldianum was explored in carrageenan-induced inflammation in rats. After isolation of the fungus from Acalypha hispida leaves, it was identified by 18S rRNA gene sequencing. Then, its phytochemical profile was elucidated using LC-ESI-MS/MS technique. There was a remarkable decrease in the edema weight in the endophytic fungi-treated group (200 mg/kg). Also, this group had few inflammatory cells and thickened epidermis with underlying moderate collagenosis when stained with haematoxylin and eosin. Besides, immunostaining with monoclonal antibodies of cyclooxygenase-2 and tumor necrosis factor alpha showed a decrease in the positive immune cells in the endophytic fungi treated group (200 mg/kg) in relation to the positive control. Interestingly, the levels of the inflammatory as well as oxidative stress markers, including prostaglandin E2, nitric oxide, and malondialdehyde, which are hallmarks of the inflammatory process, considerably diminished (p < 0.05) in this group. qRT-PCR was utilised to elucidate the impact of the endophytic fungi treatment on the expression of interleukins (IL-1β and IL-6) genes, which decreased in comparison with the positive control group. Consequently, we can deduce that P. brefeldianum endophytic fungus has a promising anti-inflammatory potential and should be extensively studied on a broader range in the near future.PMID:37106372 | DOI:10.1186/s12934-023-02091-5

J Dairy Sci. 2023 Apr 25:S0022-0302(23)00197-2. doi: 10.3168/jds.2022-22609. Online ahead of print.ABSTRACTEnhancing the ability of animals to convert feed into meat or milk by optimizing feed efficiency (FE) has become a priority in livestock research. Although untargeted metabolomics is increasingly used in this field and may improve our understanding of FE, no information in this regard is available in dairy ewes. This study was conducted to (1) discriminate sheep divergent for FE and (2) provide insights into the physiological mechanisms contributing to FE through high-throughput metabolomics. The ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS) technique was applied to easily accessible animal fluids (plasma and milk) to assess whether their metabolome differs between high- and low-feed efficient lactating ewes (H-FE and L-FE groups, respectively; 8 animals/group). Blood and milk samples were collected on the last day of the 3-wk period used for FE estimation. A total of 793 features were detected in plasma and 334 in milk, with 100 and 38 of them, respectively, showing differences between H-FE and L-FE. The partial least-squares discriminant analysis separated both groups of animals regardless of the type of sample. Plasma allowed the detection of a greater number of differential features; however, results also supported the usefulness of milk, more easily accessible, to discriminate dairy sheep divergent for FE. Regarding pathway analysis, nitrogen metabolism (either anabolism or catabolism) seemed to play a central role in FE, with plasma and milk consistently indicating a great impact of AA metabolism. A potential influence of pathways related to energy/lipid metabolism on FE was also observed. The variable importance in the projection plot revealed 15 differential features in each matrix that contributed the most for the separation in H-FE and L-FE, such as l-proline and phosphatidylcholine 20:4e in plasma or l-pipecolic acid and phosphatidylethanolamine (18:2) in milk. Overall, untargeted metabolomics provided valuable information into metabolic pathways that may underlie FE in dairy ewes, with a special relevance of AA metabolism in determining this complex phenotype in the ovine. Further research is warranted to validate these findings.PMID:37105878 | DOI:10.3168/jds.2022-22609

Diabetes Care. 2023 Apr 27:dc222440. doi: 10.2337/dc22-2440. Online ahead of print.ABSTRACTOBJECTIVE: The Rare and Atypical Diabetes Network (RADIANT) will perform a study of individuals and, if deemed informative, a study of their family members with uncharacterized forms of diabetes.RESEARCH DESIGN AND METHODS: The protocol includes genomic (whole-genome [WGS], RNA, and mitochondrial sequencing), phenotypic (vital signs, biometric measurements, questionnaires, and photography), metabolomics, and metabolic assessments.RESULTS: Among 122 with WGS results of 878 enrolled individuals, a likely pathogenic variant in a known diabetes monogenic gene was found in 3 (2.5%), and six new monogenic variants have been identified in the SMAD5, PTPMT1, INS, NFKB1, IGF1R, and PAX6 genes. Frequent phenotypic clusters are lean type 2 diabetes, autoantibody-negative and insulin-deficient diabetes, lipodystrophic diabetes, and new forms of possible monogenic or oligogenic diabetes.CONCLUSIONS: The analyses will lead to improved means of atypical diabetes identification. Genetic sequencing can identify new variants, and metabolomics and transcriptomics analysis can identify novel mechanisms and biomarkers for atypical disease.PMID:37104866 | DOI:10.2337/dc22-2440

Toxins (Basel). 2023 Mar 31;15(4):255. doi: 10.3390/toxins15040255.ABSTRACTAflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) are universally found as environmental pollutants. AFB1 and AFM1 are group 1 human carcinogens. Previous sufficient toxicological data show that they pose a health risk. The intestine is vital for resistance to foreign pollutants. The enterotoxic mechanisms of AFB1 and AFM1 have not been clarified at the metabolism levels. In the present study, cytotoxicity evaluations of AFB1 and AFM1 were conducted in NCM 460 cells by obtaining their half-maximal inhibitory concentration (IC50). The toxic effects of 2.5 μM AFB1 and AFM1 were determined by comprehensive metabolomics and lipidomics analyses on NCM460 cells. A combination of AFB1 and AFM1 induced more extensive metabolic disturbances in NCM460 cells than either aflatoxin alone. AFB1 exerted a greater effect in the combination group. Metabolomics pathway analysis showed that glycerophospholipid metabolism, fatty acid degradation, and propanoate metabolism were dominant pathways that were interfered with by AFB1, AFM1, and AFB1+AFM1. Those results suggest that attention should be paid to lipid metabolism after AFB1 and AFM1 exposure. Further, lipidomics was used to explore the fluctuation of AFB1 and AFM1 in lipid metabolism. The 34 specific lipids that were differentially induced by AFB1 were mainly attributed to 14 species, of which cardiolipin (CL) and triacylglycerol (TAG) accounted for 41%. AFM1 mainly affected CL and phosphatidylglycerol, approximately 70% based on 11 specific lipids, while 30 specific lipids were found in AFB1+AFM1, mainly reflected in TAG up to 77%. This research found for the first time that the lipid metabolism disorder caused by AFB1 and AFM1 was one of the main causes contributing to enterotoxicity, which could provide new insights into the toxic mechanisms of AFB1 and AFM1 in animals and humans.PMID:37104193 | DOI:10.3390/toxins15040255

Toxins (Basel). 2023 Mar 31;15(4):254. doi: 10.3390/toxins15040254.ABSTRACTCyanobacterial blooms that release biologically active metabolites into the environment are increasing in frequency as a result of the degradation of freshwater ecosystems globally. The microcystins are one group of cyanopeptides that are extensively studied and included in water quality risk management frameworks. Common bloom-forming cyanobacteria produce incredibly diverse mixtures of other cyanopeptides; however, data on the abundance, distribution, and biological activities of non-microcystin cyanopeptides are limited. We used non-targeted LC-MS/MS metabolomics to study the cyanopeptide profiles of five Microcystis strains: four M. aeruginosa and one M. flos-aquae. Multivariate analysis and GNPS molecular networking demonstrated that each Microcystis strain produced a unique mixture of cyanopeptides. In total, 82 cyanopeptides from the cyanopeptolin (n = 23), microviridin (n = 18), microginin (n = 12), cyanobactin (n = 14), anabaenopeptin (n = 6), aeruginosin (n = 5), and microcystin (n = 4) classes were detected. Microcystin diversity was low compared with the other detected cyanopeptide classes. Based on surveys of the literature and spectral databases, most cyanopeptides represented new structures. To identify growth conditions yielding high amounts of multiple cyanopeptide groups, we next examined strain-specific cyanopeptide co-production dynamics for four of the studied Microcystis strains. When strains were cultivated in two common Microcystis growth media (BG-11 and MA), the qualitative cyanopeptides profiles remained unchanged throughout the growth cycle. For each of the cyanopeptide groups considered, the highest relative cyanopeptide amounts were observed in the mid-exponential growth phase. The outcomes of this study will guide the cultivation of strains producing common and abundant cyanopeptides contaminating freshwater ecosystems. The synchronous production of each cyanopeptide group by Microcystis highlights the need to make more cyanopeptide reference materials available to investigate their distributions and biological functions.PMID:37104192 | DOI:10.3390/toxins15040254

Neurol Ther. 2023 Apr 27. doi: 10.1007/s40120-023-00477-6. Online ahead of print.ABSTRACTINTRODUCTION: Spinal muscular atrophy (SMA) can cause multiple system dysfunction, especially lipid metabolic disorders, for which management strategies are currently lacking. Microbes are related to metabolism and the pathogenesis of neurological diseases. This study aimed to preliminarily explore the alterations in the gut microbiota in SMA and the potential relationship between altered microbiota and lipid metabolic disorders.METHODS: Fifteen patients with SMA and 17 gender- and age-matched healthy controls were enrolled in the study. Feces and fasting plasma samples were collected. 16S ribosomal RNA sequencing and nontargeted metabolomics analysis were performed to explore the correlation between microbiota and differential lipid metabolites.RESULTS: No significant difference was found in microbial diversity (α- and β-diversity) between the SMA and control groups, with both groups having a relatively similar community structure. However, compared to the control group, the SMA group showed an increased relative abundance of the genera Ruminiclostridium, Gordonibacter, Enorma, Lawsonella, Frisingicoccus, and Anaerofilum and a decreased abundance of the genera Catabacter, Howardella, Marine_Methylotrophic_Group_3, and Lachnospiraceae_AC2044_group. The concurrent metabolomic analysis showed that the SMA group had 56 different kinds of lipid metabolite levels than did the control group. Additionally, the Spearman correlation suggested a correlation between the altered differential lipid metabolites and the above-mentioned altered microbiota.CONCLUSIONS: The gut microbiome and lipid metabolites differed between the patients with SMA and the control subjects. The altered microbiota may be related with the lipid metabolic disorders in SMA. However, further study is necessary to clarify the mechanism of lipid metabolic disorders and develop management strategies to improve the related complications in SMA.PMID:37103747 | DOI:10.1007/s40120-023-00477-6

Appl Biochem Biotechnol. 2023 Apr 27. doi: 10.1007/s12010-023-04554-2. Online ahead of print.ABSTRACTHigh-temperature ethanol fermentation (> 40 °C) can be applied as effective bioprocess technology to increase ethanol production. Thermotolerant yeast Pichia kudriavzevii 1P4 showed the ability to produce ethanol at optimum 37 °C. Thus, this study evaluated the ethanol productivity of isolate 1P4 at high-temperature ethanol fermentation (42 and 45 °C) and the identification of metabolite biomarkers using untargeted metabolomics with liquid chromatography-tandem mass spectrometry (LC-MS/MS). 1P4 showed tolerance to temperature stress up to 45 °C and thus relevant for high-temperature fermentation. As measured by gas chromatography (GC), bioethanol production of 1P4 at 30, 37, 42, and 45 °C was 5.8 g/l, 7.1 g/l, 5.1 g/l, and 2.8 g/l, respectively. The classification of biomarker compounds was based on orthogonal projection analysis to latent structure discriminant analysis (OPLS-DA), resulting in L-proline being a suspected biomarker compound for isolate 1P4 tolerance against high-temperature stress. Indeed, supplementation of L-proline on fermentation medium supported the growth of 1P4 at high temperatures (> 40 °C) than without L-proline. The bioethanol production with the addition of the L-proline resulted in the highest ethanol concentration (7.15 g/l) at 42 °C. Supplementation of L-proline as a stress-protective compound increased ethanol productivity at high-temperature fermentation of 42 and 45 °C by 36.35% and 83.33%, respectively, compared without the addition of L-proline. Preliminary interpretation of these results indicates that bioprocess engineering through supplementation of stress-protective compounds L-proline increases the fermentation efficiency of isolate 1P4 at higher temperatures (42 °C and 45 °C).PMID:37103737 | DOI:10.1007/s12010-023-04554-2

Clin Exp Med. 2023 Apr 27. doi: 10.1007/s10238-023-01073-6. Online ahead of print.ABSTRACTIdiopathic inflammatory myopathy (IIM) are heterogeneous autoimmune diseases that primarily affect the proximal muscles. IIM subtypes include dermatomyositis (DM), polymyositis (PM), and anti-synthetase syndrome (ASS). Metabolic disturbances may cause irreversible structural damage to muscle fibers in patients with IIM. However, the metabolite profile of patients with different IIM subtypes remains elusive. To investigate metabolic alterations and identify patients with different IIM subtypes, we comprehensively profiled plasma metabolomics of 46 DM, 13 PM, 12 ASS patients, and 30 healthy controls (HCs) using UHPLC-Q Exactive HF mass spectrometer. Multiple statistical analyses and random forest were used to discover differential metabolites and potential biomarkers. We found that tryptophan metabolism, phenylalanine and tyrosine metabolism, fatty acid biosynthesis, beta-oxidation of very long chain fatty acids, alpha-linolenic acid and linoleic acid metabolism, steroidogenesis, bile acid biosynthesis, purine metabolism, and caffeine metabolism are all enriched in the DM, PM, and ASS groups. We also found that different subtypes of IIM have their unique metabolic pathways. We constructed three models (five metabolites) to identify DM, PM, ASS from HC in the discovery and validation sets. Five to seven metabolites can distinguish DM from PM, DM from ASS, and PM from ASS. A panel of seven metabolites can identify anti-melanoma differentiation-associated gene 5 positive (MDA5 +) DM with high accuracy in the discovery and validation sets. Our results provide potential biomarkers for diagnosing different subtypes of IIM and a better understanding of the underlying mechanisms of IIM.PMID:37103652 | DOI:10.1007/s10238-023-01073-6

Panminerva Med. 2023 Apr 27. doi: 10.23736/S0031-0808.23.04838-3. Online ahead of print.ABSTRACTThe identification of markers capable of evaluating oocyte quality, its maturation, function, and embryo progression and implantation potential has frequently initiated research interest. However, to date, univocal criteria of oocyte competence do not exist. A major cause of low oocyte quality is evidently advanced maternal age. However, other factors may influence oocyte competence. Among these are obesity, lifestyle factors, genetic and systematic pathologies, ovarian stimulation protocols, laboratory procedures, culture, and environmental conditions. The morphological and maturational evaluation of oocytes is probably the most widely used. Several morphological features, both cytoplasmic (cytoplasmic pattern and hue, presence of vacuoles, refractile bodies, granulation, and smooth endoplasmic reticulum clusters) and extra-cytoplasmic (perivitelline space, zona pellucida thickness, oocyte shape, and polar bodies), have been proposed to distinguish oocytes with the best reproductive potential among a cohort. No single abnormality seems to be sufficiently predictive of the developmental capacity of the oocyte. Some abnormalities such as cumulus cells dysmorphisms, central granulation, vacuoles, and smooth endoplasmic reticulum clusters, however, seem to be associated with poor developmental potential of the embryo, although oocyte dysmorphisms are very common and the data in the literature is limited and provide conflicting views. Other criteria involving gene expression of cumulus cells as well as the metabolomic analysis of spent culture media have been explored. Also, sophisticated technologies such as polar bodies biopsy, meiotic spindle visualization, mitochondrial activity, oxygen consumption, and measurement of glucose-6-phosphate dehydrogenase activity have been proposed. Many of these approaches, however, remain largely research-based and have not found widespread application in clinical service. Due to the lack of consistent data for the assessment of oocyte quality and competence, probably oocyte morphology and oocyte maturity remain important indicators to determine oocyte quality. The aim of this review was to provide spherical attributes and evidence on recent and present research on the topic by analyzing the current methods for evaluation of the oocyte quality, and the impact of oocyte quality on reproductive outcomes. Additionally, current limitations of oocyte quality evaluation are highlighted and insights on future research are provided to optimize the selection techniques of oocytes to improve ART outcomes.PMID:37103487 | DOI:10.23736/S0031-0808.23.04838-3

Insects. 2023 Mar 31;14(4):347. doi: 10.3390/insects14040347.ABSTRACTBombyx mori is a model lepidopteran insect of great economic value. Mulberry leaves are its only natural food source. The development of artificial diets can not only resolve the seasonal shortage of mulberry leaves but also enable changes to be made to the feed composition according to need. Metabolomic differences between the midguts of male and female silkworms fed either on fresh mulberry leaves or an artificial diet were studied using liquid chromatography-mass spectrography (LC-MS/MS) analysis. A total of 758 differential metabolites were identified. Our analysis showed that they were mainly involved in disease resistance and immunity, silk quality, and silkworm growth and development. These experimental results provide insights into the formulation of optimized artificial feed for silkworms.PMID:37103160 | DOI:10.3390/insects14040347