PubMed

Metabolites. 2022 Nov 16;12(11):1124. doi: 10.3390/metabo12111124.ABSTRACTSoftening dry food with water is believed to be more beneficial to the intestinal health and nutrients absorption of dogs by some owners, but there appears to be little scientific basis for this belief. Thus, this study aimed to compare feeding dry food (DF) and water-softened dry food (SDF) on stress response, intestinal microbiome, and metabolic profile in dogs. Twenty healthy 5-month-old beagle dogs were selected and divided into two groups according to their gender and body weight using a completely randomized block design. Both groups were fed the same basal diet, with one group fed DF and the other fed SDF. The trial lasted for 21 days. The apparent total tract digestibility (ATTD) of nutrients, inflammatory cytokines, stress hormones, heat shock protein-70 (HSP-70), fecal microbiota, short-chain fatty acids (SCFAs), branch-chain fatty acids (BCFAs), and metabolomics were measured. Results showed that there was no significant difference in body weight, ATTD, and SCFAs between the DF and SDF groups (p > 0.05), whereas feeding with SDF caused a significant increase in serum cortisol level (p < 0.05) and tended to have higher interleukin-2 (p = 0.062) and HSP-70 (p = 0.097) levels. Fecal 16S rRNA gene sequencing found that the SDF group had higher alpha diversity indices (p < 0.05). Furthermore, the SDF group had higher levels of Streptococcus, Enterococcus, and Escherichia_Shigella, and lower levels of Faecalibacterium (p < 0.05). Serum and fecal metabolomics further showed that feeding with SDF significantly influenced the purine metabolism, riboflavin metabolism, and arginine and proline metabolism (p < 0.05). Overall, feeding with SDF caused higher cortisol level and generated effects of higher intestinal microbial diversity in dogs, but it caused an increase in some pathogenic bacteria, which may result in intestinal microbiome disturbance and metabolic disorder in dogs. In conclusion, feeding with SDF did not provide digestive benefits but caused some stress and posed a potential threat to the intestinal health of dogs. Thus, SDF is not recommended in the feeding of dogs.PMID:36422265 | DOI:10.3390/metabo12111124

Metabolites. 2022 Nov 16;12(11):1125. doi: 10.3390/metabo12111125.ABSTRACTEarly detection and proper management of chronic kidney disease (CKD) can delay progression to end-stage kidney disease. We applied metabolomics to discover novel biomarkers to predict the risk of deterioration in patients with different causes of CKD. We enrolled non-dialytic diabetic nephropathy (DMN, n = 124), hypertensive nephropathy (HTN, n = 118), and polycystic kidney disease (PKD, n = 124) patients from the KNOW-CKD cohort. Within each disease subgroup, subjects were categorized as progressors (P) or non-progressors (NP) based on the median eGFR slope. P and NP pairs were randomly selected after matching for age, sex, and baseline eGFR. Targeted metabolomics was performed to quantify 188 metabolites in the baseline serum samples. We selected ten progression-related biomarkers for DMN and nine biomarkers each for HTN and PKD. Clinical parameters showed good ability to predict DMN (AUC 0.734); however, this tendency was not evident for HTN (AUC 0.659) or PKD (AUC 0.560). Models constructed with selected metabolites and clinical parameters had better ability to predict CKD progression than clinical parameters only. When selected metabolites were used in combination with clinical indicators, random forest prediction models for CKD progression were constructed with AUCs of 0.826, 0.872, and 0.834 for DMN, HTN, and PKD, respectively. Select novel metabolites identified in this study can help identify high-risk CKD patients who may benefit from more aggressive medical treatment.PMID:36422264 | DOI:10.3390/metabo12111125

Metabolites. 2022 Nov 15;12(11):1113. doi: 10.3390/metabo12111113.ABSTRACTThe goal of this study was to determine the metabolism of multiparous female yaks during the late perinatal period and identify its effects on reproductive recovery in order to explain the low reproduction rate of yaks. Eight multiparous female yaks were randomly selected as the sample, and serum was collected from the yaks every 7 days from the day of delivery until 28 days after the delivery (five time points). The presence of serum metabolic profiles and reproductive hormones was identified using ELISA. The key metabolites were identified using liquid chromatography-mass spectrometry, and a dynamic metabolic network representation was created using bioinformatics analysis. A total of 117 different metabolites were identified by calculating the fold change of the metabolite expression at each time point. The dynamic metabolic network was created to represent the activities of the key metabolites, metabolic indexes and reproductive hormones. The initial efficiency of the glucose metabolism in the late perinatal period was found to be low, but it increased during the final period. The initial efficiencies of the lipid and amino acid metabolisms were high but decreased during the final period. We inferred that there was a postpartum negative energy balance in female yaks and that the synthesis and secretion of estrogen were blocked due to an excessive fatty acid mobilization. As a result, the reproductive hormone synthesis and secretion were maintained at a low level in the late perinatal period, and this was the main reason for the delayed recovery of the reproductive function postpartum. However, the specific mechanism needs to be further verified.PMID:36422253 | DOI:10.3390/metabo12111113

Metabolites. 2022 Nov 14;12(11):1110. doi: 10.3390/metabo12111110.ABSTRACTLiquid chromatography coupled with mass spectrometry (LC-MS) metabolomic approaches are widely used to investigate underlying pathogenesis of gastrointestinal disease and mechanism of action of treatments. However, there is an unmet requirement to assess faecal metabolite extraction methods for large-scale metabolomics studies. Current methods often rely on biphasic extractions using harmful halogenated solvents, making automation and large-scale studies challenging. The present study reports an optimised monophasic faecal extraction protocol that is suitable for untargeted and targeted LC-MS analyses. The impact of several experimental parameters, including sample weight, extraction solvent, cellular disruption method, and sample-to-solvent ratio, were investigated. It is suggested that a 50 mg freeze-dried faecal sample should be used in a methanol extraction (1:20) using bead beating as the means of cell disruption. This is revealed by a significant increase in number of metabolites detected, improved signal intensity, and wide metabolic coverage given by each of the above extraction parameters. Finally, we addressed the applicability of the method on faecal samples from patients with Crohn's disease (CD) and coeliac disease (CoD), two distinct chronic gastrointestinal diseases involving metabolic perturbations. Untargeted and targeted metabolomic analysis demonstrated the ability of the developed method to detect and stratify metabolites extracted from patient groups and healthy controls (HC), highlighting characteristic changes in the faecal metabolome according to disease. The method developed is, therefore, suitable for the analysis of patients with gastrointestinal disease and can be used to detect and distinguish differences in the metabolomes of CD, CoD, and HC.PMID:36422250 | DOI:10.3390/metabo12111110

Metabolites. 2022 Nov 13;12(11):1108. doi: 10.3390/metabo12111108.ABSTRACTRecurrent respiratory infections are a leading cause of morbidity and mortality in early life, but there is no broadly accepted means to identify infection-prone children during this highly vulnerable period. In this study, we investigated associations between steroid metabolites and incident respiratory infections in two pre-birth cohorts to identify novel metabolomic signatures of early infection proneness. Children from the Vitamin D Antenatal Asthma Reduction Trial and the Copenhagen Prospective Studies on Asthma in Childhood were included, and profiling was performed on plasma samples collected at ages 1 and 6 years. Both cohorts recorded incidence of lower respiratory infections, upper respiratory infections, ear infections, and colds. Poisson regression analysis assessed the associations between 18 steroid metabolites and the total number of respiratory infections that occurred in offspring during follow-up. We found that steroid metabolites across androgenic, corticosteroid, pregnenolone, and progestin classes were reduced in children that suffered more infections, and these patterns persisted at age 6 years, generally reflecting consistency in direction of effect and significance. Our analysis suggested steroid metabolite measurement may be useful in screening for infection proneness during this critical developmental period. Future studies should clinically evaluate their potential utility as a clinical screening tool.PMID:36422248 | DOI:10.3390/metabo12111108

Metabolites. 2022 Nov 12;12(11):1105. doi: 10.3390/metabo12111105.ABSTRACTCyclophosphamide (CP) has been proven to be an embryo-fetal toxic. However, the mechanism responsible for the toxicity of the teratogenic agent has not been fully explored. This study aimed to examine the teratogenicity of CP when administered in the sensitive period of pregnant rats. The effect of CP on the lipid and metabolic profiles of amniotic fluid was evaluated using a UHPLC-Q-Exactive Orbitrap MS-based method. Metabolome analysis was performed using the MS-DIAL software with LipidBlast and NIST. Initially, we identified 636 and 154 lipid compounds in the positive and negative ion modes and 118 metabolites for differential analysis. Mainly 4 types of oxidized lipids in the amniotic fluid were found to accumulate most significantly after CP treatment, including very-long-chain unsaturated fatty acids (VLCUFAs), polyunsaturated fatty acid (PUFA)-containing triglycerides (TGs), oxidized phosphatidylcholine (PC), and sphingomyelin (SM). Tryptophan and some long-chain saturated fatty acids were lowered pronouncedly after CP treatment. These findings suggest that CP may exert teratogenic toxicity on pregnant rats through maternal and fetal oxidative stress. The UHPLC-Q-Exactive Orbitrap MS-based lipidomics approach is worthy of wider application for evaluating the potential toxicity of other agents (toxicants) during embryonic development.PMID:36422245 | DOI:10.3390/metabo12111105

Metabolites. 2022 Nov 11;12(11):1098. doi: 10.3390/metabo12111098.ABSTRACTFreezing and thawing plasma samples is known to perturb metabolite stability. However, no study has systematically tested how different freezing and thawing methods affect plasma metabolite levels. The objective of this study was to isolate the effects of freezing from thawing on mouse plasma metabolite levels, by comparing a matrix of freezing and thawing conditions through 10 freeze-thaw cycles. We tested freezing with liquid nitrogen (LN2), at -80 °C, or at -20 °C, and thawing quickly in room temperature water or slowly on ice. Plasma samples were extracted and the relative abundance of 87 metabolites was obtained via liquid chromatography-mass spectrometry (LC-MS). Observed changes in metabolite abundance by treatment group correlated with the amount of time it took for samples to freeze or thaw. Thus, snap-freezing with LN2 and quick-thawing with water led to minimal changes in metabolite levels. Conversely, samples frozen at -20 °C exhibited the most changes in metabolite levels, likely because freezing required about 4 h, versus freezing instantaneously in LN2. Overall, our results show that plasma samples subjected to up to 10 cycles of LN2 snap-freezing with room temperature water quick-thawing exhibit remarkable metabolomic stability.PMID:36422241 | DOI:10.3390/metabo12111098

J Pers Med. 2022 Nov 11;12(11):1889. doi: 10.3390/jpm12111889.ABSTRACTDiabetic nephropathy (DN) is one of the specific complications of diabetes mellitus and one of the leading kidney-related disorders, often requiring renal replacement therapy. Currently, the tests commonly used for the diagnosis of DN, albuminuria (AU) and glomerular filtration rate (GFR), have limited sensitivity and specificity and can usually be noted when typical morphological changes in the kidney have already been manifested. That is why the extreme urgency of the problem of early diagnosis of this disease exists. The untargeted metabolomics analysis of blood plasma samples from 80 patients with type 1 diabetes and early and late stages of DN according to GFR was performed using direct injection mass spectrometry and bioinformatics analysis for diagnosing signatures construction. Among the dysregulated metabolites, combinations of 15 compounds, including amino acids and derivatives, monosaccharides, organic acids, and uremic toxins were selected for signatures for DN diagnosis. The selected metabolite combinations have shown high performance for diagnosing of DN, especially for the late stage (up to 99%). Despite the metabolite signature determined for the early stage of DN being characterized by a diagnostic performance of 81%, these metabolites as potential biomarkers might be useful in the evaluation of treatment of the disease, especially at early stages that may reduce the risk of kidney failure development.PMID:36422065 | DOI:10.3390/jpm12111889

J Fungi (Basel). 2022 Nov 15;8(11):1208. doi: 10.3390/jof8111208.ABSTRACTPepper leaf spot is a common disease of Zanthoxylum schinifolium. When it is serious, it directly affects the growth of Z. schinifolium, making the plant unable to blossom and bear fruit, which seriously restricts the development of the Z. schinifolium industry. Therefore, the pathogenic mechanism of leaf spots should be explored to provide a basis for a comprehensive understanding of the disease. Using liquid chromatography-mass spectrometry (LC-MS) technology combined with the data-dependent acquisition, the full spectrum analysis of pathogen mycelium samples was carried out. Partial least squares discriminant analysis (PLS-DA) was used to reveal the differences in metabolic patterns among different groups. Hierarchical clustering analysis (HCA) and PLS-DA were used to reveal the relationship between samples and metabolites, which reflected the metabolomics changes of Pestalotiopsis kenyana in the logarithmic growth phase of mycelia, the stable growth phase of mycelia, the massive spore stage, the induction culture conditions of PDA and Z. schinifolium leaves, and the possible pathogenic substances were selected for pathogenicity detection. PLS-DA had a strong predictive ability, indicating a clear analysis trend between different groups. The results of the metabolomics analysis showed that the differential metabolites of pathogenic bacteria were abundant at different stages and under different medium conditions, and the content of metabolites changed significantly. There were 3922 differential metabolites in nine groups under positive and negative ion modes, including lipids and lipid molecules, organic acids and their derivatives, organic heterocyclic compounds, organic oxygen compounds, carbohydrate polyketides, nucleosides, nucleotides, and analogs. The results of the pathogenicity test showed that the leaves treated with 3,5-dimethoxy benzoic acid, S-(5-adenosy)-l-homocysteine, 2-(1H-indol-3-yl) acetic acid, l-glutamic acid, and 2-(2-acetyl-3,5-dihydroxy phenyl) acetic acid showed different degrees of yellowish-brown lesions. This indicated that these substances may be related to the pathogenicity of P. kenyana, and the incidence was more serious when treated with 3,5-dimethoxybenzoic acid and S-(5-adenosy)- l -homocysteine. This study provides a basis for further analysis of differential metabolites and provides a theoretical reference for the prevention and treatment of Z. schinifolium leaf spot.PMID:36422029 | DOI:10.3390/jof8111208

Mar Drugs. 2022 Nov 14;20(11):713. doi: 10.3390/md20110713.ABSTRACTNovel high-throughput cultivation techniques create a demand to pre-select strains for in-depth follow-up studies. We report a workflow to identify promising producers of novel natural products by systematically characterizing their metabolomes. For this purpose, 60 strains from four phyla (Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes) comprising 16 novel species and six novel genera were cultivated from marine and terrestrial sources. Their cellular metabolomes were recorded by LC-MS/MS; data analysis comprised databases MS/MS matching, in silico compound assignment, and GNPS-based molecular networking. Overall, 1052 different molecules were identified from 6418 features, among them were unusual metabolites such as 4-methoxychalcone. Only a minor portion of the 755 features were found in all phyla, while the majority occurred in a single phylogroup or even in a single strain. Metabolomic methods enabled the recognition of highly talented strains such as AEG42_45, which had 107 unique features, among which a family of 28 potentially novel and related compounds according to MS/MS similarities. In summary, we propose that high-throughput cultivation and isolation of bacteria in combination with the presented systematic and unbiased metabolome analysis workflow is a promising approach to capture and assess the enormous metabolic potential of previously uncultured bacteria.PMID:36421991 | DOI:10.3390/md20110713

Genes (Basel). 2022 Nov 17;13(11):2142. doi: 10.3390/genes13112142.ABSTRACTCurrently, metabolic-associated fatty liver disease (MAFLD) is a leading global cause of chronic liver disease, and is expected to become one of the most common indications of liver transplantation. MAFLD is associated with obesity, involving multiple mechanisms such as alterations in lipid metabolism, insulin resistance, hyperinflammation, mitochondrial dysfunction, cell apoptosis, oxidative stress, and extracellular matrix formation. However, the onset and progression of MAFLD is variable among individuals, being influenced by intrinsic (personal) and external environmental factors. In this context, sequence structural variants across the human genome, epigenetic phenomena (i.e., DNA methylation, histone modifications, and long non-coding RNAs) affecting gene expression, gut microbiota dysbiosis, and metabolomics/lipidomic fingerprints may account for differences in MAFLD outcomes through interactions with nutritional features. This knowledge may contribute to gaining a deeper understanding of the molecular and physiological processes underlying MAFLD pathogenesis and phenotype heterogeneity, as well as facilitating the identification of biomarkers of disease progression and therapeutic targets for the implementation of tailored nutritional strategies. This comprehensive literature review highlights the potential of nutrigenetic, nutriepigenetic, nutrimetagenomic, nutritranscriptomics, and nutrimetabolomic approaches for the prevention and management of MAFLD in humans through the lens of precision nutrition.PMID:36421817 | DOI:10.3390/genes13112142

Antioxidants (Basel). 2022 Nov 16;11(11):2261. doi: 10.3390/antiox11112261.ABSTRACTCurcuma is one of the most famous medicinal and tropical aromatic plants. Its health benefits have been appreciated and exploited in traditional Asian medicine since ancient times. Various studies have investigated its complex chemical composition and demonstrated the remarkable therapeutic properties of curcuma's phytoconstituents. Oxidative stress is a decisive driving factor triggering numerous pathologies (neurodegenerative, psychiatric and cardiovascular diseases; diabetes; tumors, etc.). Numerous recent studies have focused on the use of natural compounds and nanomaterials as innovative molecular targeting agents as effective therapeutic strategies. In this study, we report, for the first time, the development of a simple target phytocarrier system that capitalizes on the bioactive properties of curcuma and AgNPs. The complete metabolic profile of curcuma was determined based on gas chromatography-mass spectrometry (GC-MS) and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). A total of 80 metabolites were identified under mass spectra (MS)-positive mode from 10 secondary metabolite categories: terpenoids, amino acids, diarylheptanoids, flavonoids, phenolic acids, steroids, fatty acids, coumarins, alkaloids and miscellaneous. In addition, the biological activity of each class of metabolites was discussed. A comprehensive characterization (FT-IR, UV-Vis, DLS, SEM, TEM, EDS, zeta potential and XRD) was performed to study the morphostructural properties of this new phytocarrier system. Antioxidant activity of the new phytocarrier system was evaluated using a combination of in vitro methods (total phenolic assay, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and cyclic voltammetric method (Trolox equivalent antioxidant capacity (TEAC) electrochemical assay)). Antioxidants assays showed that the phytocarrier system exhibits superior antioxidant properties to those of its components, i.e., curcuma or citrate-coated-AgNPs. These data confirm the potential to enhance relevant theoretical knowledge in the area of innovative antioxidant agents, with potential application in neurodegenerative therapeutic strategies.PMID:36421447 | DOI:10.3390/antiox11112261

Antioxidants (Basel). 2022 Nov 16;11(11):2258. doi: 10.3390/antiox11112258.ABSTRACTWounds adversely affect people's quality of life and have psychological, social, and economic impacts. Herbal remedies of Launaea procumbens (LP) are used to treat wounds. In an excision wound model, topical application of LP significantly promoted wound closure (on day 14, LP-treated animals had the highest percentages of wound closure in comparison with the other groups, as the wound was entirely closed with a closure percentage of 100%, p < 0.05). Histological analysis revealed a considerable rise in the number of fibroblasts, the amount of collagen, and its cross-linking in LP-treated wounds. Gene expression patterns showed significant elevation of TGF-β levels (2.1-fold change after 7 days treatment and 2.7-fold change in 14 days treatment) and downregulation of the inflammatory TNF-α and IL-1β levels in LP-treated wounds. Regarding in vitro antioxidant activity, LP extract significantly diminished the formation of H2O2 radical (IC50 = 171.6 μg/mL) and scavenged the superoxide radical (IC50 of 286.7 µg/mL), indicating antioxidant potential in a dose-dependent manner. Dereplication of the secondary metabolites using LC-HRMS resulted in the annotation of 16 metabolites. The identified compounds were docked against important wound-healing targets, including vascular endothelial growth factor (VEGF), collagen α-1, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and transforming growth factor-β (TGF-β). Among dereplicated compounds, luteolin 8-C-glucoside (orientin) demonstrated binding potential to four investigated targets (VEGF, interleukin 1β, TNF-α, and collagen α-1). To conclude, Launaea procumbens extract could be regarded as a promising topical therapy to promote wound healing in excisional wounds, and luteolin 8-C-glucoside (orientin), one of its constituents, is a potential wound-healing drug lead.PMID:36421445 | DOI:10.3390/antiox11112258

Biology (Basel). 2022 Nov 18;11(11):1679. doi: 10.3390/biology11111679.ABSTRACTMobilization and repartition of nutrients and energy are prerequisites for the normal sexual maturity of broodstock. However, there are few studies on the mechanisms of hepatic nutrients and energy metabolism during sexual maturation in female rainbow trout (Oncorhynchus mykiss). This study investigated hepatic metabolite changes and explored the potential nutritional regulation mechanism between mature and immature female rainbow trout by combining UPLC-QTOF/MS metabolomics and biochemical assays. It was observed that hepatic biochemical assays differed considerably between the two groups, such as glucose, triglycerides, hexokinase, lipase, and aspartate aminotransferase. Liver metabolomics showed that various differential metabolites involved in amino acid and lipid metabolism markedly increased, suggesting the enhancement of lipid metabolism and amino acid anabolism in the liver provides the necessary material basis for ovarian development. Meanwhile, glycogen catabolism and glycolysis hold the key to maintaining organismal energy homeostasis with normal sexual maturation of female rainbow trout. Overall, the results from this study suggested that the liver undergoes drastic reprogramming of the metabolic profile in response to mobilization and repartition of nutrients and energy during the sexual maturation of female rainbow trout. This study further deepened the understanding of the reproductive biology of rainbow trout, and provided the theoretical basis and practical ramifications for nutritional requirements of breeding high-quality broodstock in the artificial propagation of rainbow trout.PMID:36421392 | DOI:10.3390/biology11111679

Antibiotics (Basel). 2022 Nov 19;11(11):1658. doi: 10.3390/antibiotics11111658.ABSTRACTApicomplexan parasites are the causal agents of different medically important diseases, such as toxoplasmosis, cryptosporidiosis, and malaria. Toxoplasmosis is considered a neglected parasitosis, even though it can cause severe cerebral complications and death in immunocompromised patients, including children and pregnant women. Drugs against Toxoplasma gondii, the etiological agent of toxoplasmosis, are highly toxic and lack efficacy in eradicating tissue cysts, promoting the establishment of latent infection and acute relapsing disease. Cryptosporidiosis has been recognized as the most frequent waterborne parasitosis in US outbreaks; anti-cryptosporidium drug discovery still faces a major obstacle: drugs that can act on the epicellular parasite. Severe malaria is most commonly caused by the progression of infection with Plasmodium falciparum. In recent years, great progress has been made in the field of antimalarial drugs and vaccines, although the resistance of P. falciparum to artemisinin has recently gained a foothold in Africa. As seen, the search for new drugs against these parasites remains a challenge. Peptide-based drugs seem to be attractive alternative therapeutic agents recently recognized by the pharmaceutical industry, as they can kill different infectious agents and modulate the immune response. A review of the experimental effects of bioactive peptides on these parasites follows, along with comments. In addition, some biological and metabolomic generalities of the parasites are reviewed to elucidate peptide mechanisms of action on Apicomplexan targets.PMID:36421302 | DOI:10.3390/antibiotics11111658

Antibiotics (Basel). 2022 Nov 15;11(11):1631. doi: 10.3390/antibiotics11111631.ABSTRACTMalaria is a persistent illness with a great public health concern. To combat this fatal disease, developing effective antimalarial medications has become a necessity. In the present study, we described the actinomycetes associated with the Red Sea soft coral Nephthea sp. and isolated a strain that was sub-cultured in three different media (M1, ISP2, and OLIGO). Actinomycete isolate's phylogenetic analysis of the 16S rRNA gene revealed that it belongs to the genus Rhodococcus. In vitro screening of the antimalarial activity for three extracts against Plasmodium falciparum was carried out. Non-targeted metabolomics for the chemical characterization of the isolated actinomycete species UA111 derived extracts were employed using high-resolution liquid chromatography-mass spectrometry (LC-HR-MS) for dereplication purposes. Additionally, statistical analysis of the vast LC-MS data was performed using MetaboAnalyst 5.0. Finally, an in silico analysis was conducted to investigate the potential chemical compounds that could be the source of the antimalarial potential. The results revealed that ISP2 media extract is the most effective against Plasmodium falciparum, according to antimalarial screening (IC50 8.5 µg/mL), in contrast, OLIGO media extract was inactive. LC-HRMS-based metabolomics identified a range of metabolites, mainly alkaloids, from the genus Rhodococcus. On the other hand, multivariate analysis showed chemical diversity between the analyzed samples, with ISP2 extract being optimal. The docking analysis was able to anticipate the various patterns of interaction of the annotated compounds with three malarial protein targets (P. falciparum kinase, P. falciparum cytochrome bc1 complex, and P. falciparum lysyl-tRNA synthetase). Among all of the test compounds, perlolyrine (11) and 3097-B2 (12) displayed the best docking profiles. In conclusion, this work demonstrated the value of the established method for the metabolic profiling of marine actinomycetes using the data from liquid chromatography-mass spectrometry (LC-MS), which helps to streamline the difficult isolation stages required for their chemical characterization. In addition, the antimalarial efficacy of this strain has intriguing implications for future pharmaceutical development.PMID:36421275 | DOI:10.3390/antibiotics11111631

Antibiotics (Basel). 2022 Nov 11;11(11):1595. doi: 10.3390/antibiotics11111595.ABSTRACTInvasive plants efficiently colonize non-native territories, suggesting a great production of bioactive metabolites which could be effective antibiofilm weapons. Our study aimed to look for original molecules able to inhibit bispecies biofilm formed by S. aureus and C. albicans. Extracts from five invasive macrophytes (Ludwigia peploides, Ludwigia grandiflora, Myriophyllum aquaticum, Lagarosiphon major and Egeria densa) were prepared and tested in vitro against 24 h old bispecies biofilms using a crystal violet staining (CVS) assay. The activities of the extracts reducing the biofilm total biomass by 50% or more were comparatively analyzed against each microbial species forming the biofilm by flow cytometry (FCM) and scanning electron microscopy. Extracts active against both species were fractionated. Obtained fractions were analyzed by UHPLC-MS/MS and evaluated by the CVS assay. Chemical and biological data were combined into a bioactivity-based molecular networking (BBMN) to identify active compounds. The aerial stem extract of L. grandiflora showed the highest antibiofilm activity (>50% inhibition at 50 µg∙mL-1). The biological, chemical and BBMN investigations of its fractions highlighted nine ions correlated with the antibiofilm activity. The most correlated compound, identified as betulinic acid (BA), inhibited bispecies biofilms regardless of the three tested couples of strains (ATCC strains: >40% inhibition, clinical isolates: ≈27% inhibition), confirming its antibiofilm interest.PMID:36421241 | DOI:10.3390/antibiotics11111595

Artif Organs. 2022 Nov 24. doi: 10.1111/aor.14466. Online ahead of print.ABSTRACTBACKGROUND: Haemodialysis (HD) techniques that best remove molecules in the middle to high molecular weight range are on-line hemodiafiltration (OL-HDF) and HD with medium cut-off (MCO) membranes. The aim of this study was to compare efficacy and safety of OL-HDF with FxCordiax HDF 800TM , with HD with 2 MCO dialysers: Theranova 500® and the new Elisio21 HXTM dialyser.METHODS: Fourteen patients following treatment with OL-HDF using FxCordiax HDF 800TM were randomised to receive a consecutive 1-week HD treatment with Theranova 500® and Elisio 21HXTM .The reduction rate (RR) of differently sized molecules was compared, as well as the variation rate in molecules smaller than 1000 , detected by nuclear magnetic resonance based chemometrics (metabolomics). Albumin loss in dialysate was quantified.RESULTS: Lower RRs were found for molecules around 20,000 with Elisio 21HXTM compared to OL- HDF (RR prolactin 58.5% versus 66.7%, P=0.034; RR Kappa light chain 63.1% versus 71.8%, P=0.010). Albumin loss per session was higher with Theranova 500® than with OL-HDF and with Elisio 21HXTM (2249.9±714.1 mg, 815.2 ±474.0 mg, 442.9±135.9 mg, P<0.001, respectively). Metabolomic studies suggested, by semi-quantitative analysis, a greater depurative capacity of OL-HDF, followed by Elisio 21HXTM , and then Theranova 500®.CONCLUSIONS: In this study, HD with Theranova 500® has proven to be very similar in efficacy to OL-HDF, although with a significantly higher albumin loss. HD with Elisio21HXTM resulted in lower removal of molecules around 20,000 compared to OL-HDF, with no significant difference compared to Theranova 500®, and with less albumin loss than Theranova 500®.PMID:36420938 | DOI:10.1111/aor.14466

Nucleic Acids Res. 2022 Nov 24:gkac1083. doi: 10.1093/nar/gkac1083. Online ahead of print.ABSTRACTThe Bioinformation and DNA Data Bank of Japan (DDBJ) Center (https://www.ddbj.nig.ac.jp) maintains database archives that cover a wide range of fields in life sciences. As a founding member of the International Nucleotide Sequence Database Collaboration (INSDC), our primary mission is to collect and distribute nucleotide sequence data, as well as their study and sample information, in collaboration with the National Center for Biotechnology Information in the United States and the European Bioinformatics Institute. In addition to INSDC resources, the Center operates databases for functional genomics (GEA: Genomic Expression Archive), metabolomics (MetaboBank), and human genetic and phenotypic data (JGA: Japanese Genotype-Phenotype Archive). These databases are built on the supercomputer of the National Institute of Genetics, whose remaining computational capacity is actively utilized by domestic researchers for large-scale biological data analyses. Here, we report our recent updates and the activities of our services.PMID:36420889 | DOI:10.1093/nar/gkac1083

Crit Rev Clin Lab Sci. 2022 Nov 24:1-18. doi: 10.1080/10408363.2022.2140329. Online ahead of print.ABSTRACTThe two common progressive lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are the leading causes of morbidity and mortality worldwide. Asthma-COPD overlap, referred to as ACO, is another complex pulmonary disease that manifests itself with features of both asthma and COPD. The disease has no clear diagnostic or therapeutic guidelines, thereby making both diagnosis and treatment challenging. Though a number of studies on ACO have been documented, gaps in knowledge regarding the pathophysiologic mechanism of this disorder exist. Addressing this issue is an urgent need for improved diagnostic and therapeutic management of the disease. Metabolomics, an increasingly popular technique, reveals the pathogenesis of complex diseases and holds promise in biomarker discovery. This comprehensive narrative review, comprising 99 original research articles in the last five years (2017-2022), summarizes the scientific advances in terms of metabolic alterations in patients with asthma, COPD, and ACO. The analytical tools, nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), commonly used to study the expression of the metabolome, are discussed. Challenges frequently encountered during metabolite identification and quality assessment are highlighted. Bridging the gap between phenotype and metabotype is envisioned in the future.PMID:36420874 | DOI:10.1080/10408363.2022.2140329