PubMed

Biomed Pharmacother. 2023 Oct 16;168:115626. doi: 10.1016/j.biopha.2023.115626. Online ahead of print.ABSTRACTHealing of wounds is the most deteriorating diabetic experience. Felty germander (Teucrium polium) possesses antioxidant, anti-inflammatory and antimicrobial activities that could accelerate wound healing. Further, nanohydrogels help quicken healing and are ideal biomaterials for drug delivery. In the current study, the chemical profiling, and standardization of T. polium methanolic extract by LC-ESI/TOF/MS/MS and quantitative HPLC-DAD analyses were achieved. The wound healing enhancement in diabetic rats by T. polium nanopreparation (TP-NP) as chitosan nanogel (CS-NG) and investigating the potential mechanisms were investigated. The prepared hydrogel-based TP-NP were characterized with respect to particle size, zeta potential, pH, viscosity, and release of major components. LC-ESI/TOF/MS/MS metabolomic profiling of T. polium revealed the richness of the plant with phenolic compounds, particularly flavonoids. In addition, several terpenoids were detected. Kaempferol content of T. polium was estimated to be 7.85 ± 0.022 mg/ g of dry extract. The wound healing activity of TP-NP was explored in streptozotocin-induced diabetic rats. Diabetic animals were subjected to surgical wounding (1 cm diameter). Then they were divided in 5 groups (10 each). These included Group 1 (untreated control rats), Group 2 received the vehicle of CS-NG; Group 3 (0.5 g of TP prepared in hydrogel), Group 4 (0.5 g of TP-NP), Group 5 represented a positive control treated with 0.5 g of a commercial product. All treatments were applied topically for 21 days. Application of TP-NP on skin wounds of diabetic animals accelerated the healing process as evidenced by epithelium regeneration, formation of granulation tissue followed by epidermal proliferation, along with keratinization as verified by H&E. This was confirmed through enhanced collagen synthesis, as shown by raised hydroxyproline content and Col1A1 gene expression. Moreover, TP-NP significantly alleviated wound oxidative burst and diminished the expressions of inflammatory biomarkers. Meanwhile, TP-NP could enhance the expressions of transforming growth factor beta1 (TGF-β1), in addition to the angiogenic markers; vascular endothelia growth factor A (VEGFA) and platelet-derived growth factor receptor alpha (PDGFRα). Collectively, chitosan nanogel of T. polium accelerates wound healing in diabetic rats, which could be explained - at least partly - through alleviating oxidative stress and inflammation coupled with pro-angiogenic capabilities.PMID:37852098 | DOI:10.1016/j.biopha.2023.115626

Plant Physiol Biochem. 2023 Oct 16;204:108069. doi: 10.1016/j.plaphy.2023.108069. Online ahead of print.ABSTRACTA possible mechanism for the improved availability of zinc (Zn) in soil by combining nitrogen (N) with Zn supply was investigated based on the root exudates of winter wheat. N, Zn supply as well as their combination significantly regulated nine root exudates in winter wheat; in which, the secretion of cis-aconitic acid involving in the TCA cycle, C5-branched dibasic acid metabolism, glyoxylate and dicarboxylate metabolism and 2-oxocarboxylic acid metabolism was upregulated by N, Zn supply as well as their combination. N-Zn combination induced the activities of citrate synthase and cis-aconitase in roots and shoots of winter wheat thus to increase the concentrations of citric and aconitic acid; the decrease of isocitric acid concentrations in shoots indicated the inhibited conversion of aconitic acid to isocitric acid by N-Zn combination. It revealed a possible reason for the enhanced secretion of cis-aconitic acid by N-Zn combination. Exogenous addition of 10 μ plant-1 cis-aconitate significantly increased available Zn concentrations in soil and Zn concentrations in winter wheat under N-Zn combination. Thus, the N-Zn combination regulated the metabolism of cis-aconitic acid in winter wheat, thus enhancing the secretion of cis-aconitic acid to increase the bioavailability of Zn in soil.PMID:37852066 | DOI:10.1016/j.plaphy.2023.108069

BMC Complement Med Ther. 2023 Oct 18;23(1):367. doi: 10.1186/s12906-023-04208-0.ABSTRACTINTRODUCTION: Infants who are born from mothers with HIV (infants who are HIV exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent clinical health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses. Therefore, we will assess microbiological and immunological phenotypes and clinical outcomes in a randomized, double-blinded trial of B. infantis Rosell®-33 versus placebo given during the first month of life in South African iHEU.METHODS: This is a parallel, randomised, controlled trial. Two-hundred breastfed iHEU will be enrolled from the Khayelitsha Site B Midwife Obstetric Unit in Cape Town, South Africa and 1:1 randomised to receive 8 × 109 CFU B. infantis Rosell®-33 daily or placebo for the first 4 weeks of life, starting on day 1-3 of life. Infants will be followed over 36 weeks with extensive collection of meta-data and samples. Primary outcomes include gut microbiome composition and diversity, intestinal inflammation and microbial translocation and cellular vaccine responses. Additional outcomes include biological (e.g. gut metabolome and T cell phenotypes) and clinical (e.g. growth and morbidity) outcome measures.DISCUSSION: The results of this trial will provide evidence whether B. infantis supplementation during early life could improve health outcomes for iHEU.ETHICS AND DISSEMINATION: Approval for this study has been obtained from the ethics committees at the University of Cape Town (HREC Ref 697/2022) and Seattle Children's Research Institute (STUDY00003679).TRIAL REGISTRATION: Pan African Clinical Trials Registry Identifier: PACTR202301748714019.TRIALS: gov: NCT05923333.PROTOCOL VERSION: Version 1.8, dated 18 July 2023.PMID:37853370 | DOI:10.1186/s12906-023-04208-0

Metabolomics. 2023 Oct 18;19(11):87. doi: 10.1007/s11306-023-02048-0.ABSTRACTINTRODUCTION: Since the beginning of the SARS-CoV-2 pandemic in December 2019 multiple metabolomics studies have proposed predictive biomarkers of infection severity and outcome. Whilst some trends have emerged, the findings remain intangible and uninformative when it comes to new patients.OBJECTIVES: In this study, we accurately quantitate a subset of compounds in patient serum that were found predictive of severity and outcome.METHODS: A targeted LC-MS method was used in 46 control and 95 acute COVID-19 patient samples to quantitate the selected metabolites. These compounds included tryptophan and its degradation products kynurenine and kynurenic acid (reflective of immune response), butyrylcarnitine and its isomer (reflective of energy metabolism) and finally 3',4'-didehydro-3'-deoxycytidine, a deoxycytidine analogue, (reflective of host viral defence response). We subsequently examine changes in those markers by disease severity and outcome relative to those of control patients' levels.RESULTS & CONCLUSION: Finally, we demonstrate the added value of the kynurenic acid/tryptophan ratio for severity and outcome prediction and highlight the viral detection potential of ddhC.PMID:37853293 | DOI:10.1007/s11306-023-02048-0

Nat Biotechnol. 2023 Oct 18. doi: 10.1038/s41587-023-02025-x. Online ahead of print.NO ABSTRACTPMID:37853256 | DOI:10.1038/s41587-023-02025-x

Mar Biotechnol (NY). 2023 Oct 19. doi: 10.1007/s10126-023-10263-y. Online ahead of print.ABSTRACTThe sea cucumber Holothuria leucospilota is an economically and ecologically important tropical species. Following development into juveniles, H. leucospilota undergoes a color change from white to black, involving a pigmentation process for over a period of several months. In this study, a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Next-Generation sequencing (NGS) were employed to investigate the changes in metabolomic and transcriptomic profiles during pigmentation in H. leucospilota juveniles. The metabolomic analysis identified a total of 341 metabolites, of which 52 were found to be differentially regulated (P < 0.05 and VIP > 1), with 27 being upregulated in white individuals and 25 in black individuals. Additionally, 632 differentially expressed genes (DEGs) were identified, with 380 genes upregulated in white samples and 252 genes upregulated in black samples. Interestingly, the melanin content and tyrosinase transcript levels did not display significant differences between the two groups. Metabolomic data suggested the involvement of the linoleic acid metabolic pathway in pigmentation. Transcriptomic analysis, coupled with realtime PCR validation, revealed a decrease in the transcript levels of digestive enzymes like α-amylase, maltase-glucoamylase, and trehalase after the juveniles changed to black. Furthermore, the mRNA expressions of major yolk proteins showed a decline, indicating a shift in the accumulation of protein nutrient sources. Overall, our findings suggest that during the pigmentation process in H. leucospilota, no significant changes were observed in the classical melanin pathway, while notable alterations were observed in their nutritional status. This study provides valuable insights into the regulatory mechanisms of pigmentation in marine organisms.PMID:37853250 | DOI:10.1007/s10126-023-10263-y

Environ Sci Technol. 2023 Oct 18. doi: 10.1021/acs.est.3c06480. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) receive significant research attention due to their potential adverse effects on human health. Evidence shows that the kidney is one of the target organs of PFAS. In occupational exposure scenarios, high PFAS concentrations may adversely affect kidney metabolism, but whether this effect is reflected in the small metabolic molecules contained in urine remains unknown. In this study, 72 matched serum and urine samples from occupational workers of a fluorochemical manufactory as well as 153 urine samples from local residents were collected, and 23 PFAS levels were quantified. The concentrations of Σ23PFAS in the serum and urine samples of workers were 5.43 ± 1.02 μg/mL and 201 ± 46.9 ng/mL, respectively, while the Σ23PFAS concentration in the urine of the residents was 6.18 ± 0.76 ng/mL. For workers, high levels of urinary PFAS were strongly correlated with levels in serum (r = 0.57-0.93), indicating that urinary PFAS can be a good indicator for serum PFAS levels. Further, a urine nontargeted metabolomics study was conducted. The results of association models, including Bayesian kernel machine regression, demonstrated positive correlations between urinary PFAS levels and key small kidney molecules. A total of eight potential biomarkers associated with PFAS exposure were identified, and all of them showed significant positive correlations with markers of kidney function. These findings provide the first evidence that urine can serve as a matrix to indicate the adverse health effects of high levels of exposure to PFAS on the kidneys.PMID:37851943 | DOI:10.1021/acs.est.3c06480

Hypertension. 2023 Nov;80(11):2372-2385. doi: 10.1161/HYPERTENSIONAHA.123.20914. Epub 2023 Sep 7.ABSTRACTBACKGROUND: Hypoxic pulmonary hypertension is a difficult disease to manage that is characterized by sustained elevation of pulmonary vascular resistance and pulmonary artery pressure due to vasoconstriction, perivascular inflammation, and vascular remodeling. Consumption of soluble-fiber is associated with lower systemic blood pressure, but little is known about its ability to affect the pulmonary circulation.METHODS: Mice were fed either a low- or high-soluble-fiber diet (0% or 16.9% inulin) and then exposed to hypoxia (FiO2, 0.10) for 21 days to induce pulmonary hypertension. The impact of diet on right ventricular systolic pressure and pulmonary vascular resistance was determined in vivo or in ex vivo isolated lungs, respectively, and correlated with alterations in the composition of the gut microbiome, plasma metabolome, pulmonary inflammatory cell phenotype, and lung proteome.RESULTS: High-soluble-fiber diet increased the abundance of short-chain fatty acid-producing bacteria, with parallel increases in plasma propionate levels, and reduced the abundance of disease-related bacterial genera such as Staphylococcus, Clostridioides, and Streptococcus in hypoxic mice with parallel decreases in plasma levels of p-cresol sulfate. High-soluble-fiber diet decreased hypoxia-induced elevations of right ventricular systolic pressure and pulmonary vascular resistance. These changes were associated with reduced proportions of interstitial macrophages, dendritic cells, and nonclassical monocytes. Whole-lung proteomics revealed proteins and molecular pathways that may explain the effect of soluble-fiber supplementation.CONCLUSIONS: This study demonstrates for the first time that a high-soluble-fiber diet attenuates hypoxia-induced pulmonary vascular remodeling and the development of pulmonary hypertension in a mouse model of hypoxic pulmonary hypertension and highlights diet-derived metabolites that may have an immuno-modulatory role in the lung.PMID:37851762 | DOI:10.1161/HYPERTENSIONAHA.123.20914

J Chem Inf Model. 2023 Oct 18. doi: 10.1021/acs.jcim.3c01221. Online ahead of print.ABSTRACTMolecular modeling and simulations are essential tools in polymer science and engineering, enabling researchers to predict and understand the properties of macromolecules, including their structure, dynamics, thermodynamics, and overall material characteristics. However, one of the key challenges in polymer simulation and modeling lies in the initial topology design, as existing programs often lack the capability to generate all types of polymer forms. In this study, we present PolyFlin, a powerful Python module that addresses this limitation by allowing the generation of a wide range of polymer structures, from simple homopolymers to complex copolymers, including grafts, cyclic, star, dendrimers, and nets. PolyFlin offers a versatile and efficient tool for exploring and creating diverse polymer architectures, facilitating advancements in various fields that require precise polymer modeling and simulation.PMID:37851376 | DOI:10.1021/acs.jcim.3c01221

Eur J Pediatr. 2023 Oct 18. doi: 10.1007/s00431-023-05267-8. Online ahead of print.ABSTRACTThis study aims to assess the role of methotrexate-related gene polymorphisms in children with acute lymphoblastic leukemia (ALL) during high-dose methotrexate (HD-MTX) therapy and to explore their effects on serum metabolites before and after HD-MTX treatment. The MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435C>T, and GSTP1 313A>G genotypes of 189 children with ALL who received chemotherapy with the CCCG-ALL-2020 regimen from January 2020 to April 2023 were analyzed, and toxic effects were reported according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Fasting peripheral blood serum samples were collected from 27 children before and after HD-MTX treatment, and plasma metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The results of univariate and multivariate analyses showed that MTHFR 677C>T and ABCB1 3435 C>T gene polymorphisms were associated with the delayed MTX clearance (P < 0.05) and lower platelet count after treatment in children with MTHFR 677 mutation compared with wild-type ones (P < 0.05), and pure mutations in ABCB1 3435 were associated with higher serum creatinine levels (P < 0.05). No significant association was identified between MTHFR 677C>T, MTHFR 1298A>C, ABCB1 3435 C>T, and GSTP1 313A>G genes and hepatotoxicity or nephrotoxicity (P > 0.05). However, the serum metabolomic analysis indicated that the presence of the MTHFR 677C > T gene polymorphism could potentially contribute to delayed MTX clearance by influencing L-phenylalanine metabolism, leading to the occurrence of related toxic side effects.CONCLUSION: MTHFR 677C>T and ABCB1 3435 C>T predicted the risk of delayed MTX clearance during HD-MTX treatment in children with ALL. Serum L-phenylalanine levels were significantly elevated after HD-MTX treatment in children with the MTHFR 677C>T mutation gene.TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (registration number: ChiCTR2000035264; registration: 2020/08/05; https://www.chictr.org.cn/ ).WHAT IS KNOWN: • MTX-related genes play an important role in MTX pharmacokinetics and toxicity, but results from different studies are inconsistent and the mechanisms involved are not clear.WHAT IS NEW: • Characteristics, prognosis, polymorphisms of MTX-related genes, and metabolite changes were comprehensively evaluated in children treated with HD-MTX chemotherapy. • Analysis revealed that both heterozygous and pure mutations in MTHFR 677C>T resulted in a significantly increased risk of delayed MTX clearance, and that L-phenylalanine has the potential to serve as a predictive marker for the metabolic effects of the MTHFR 677C>T polymorphism.PMID:37851084 | DOI:10.1007/s00431-023-05267-8

ACS Infect Dis. 2023 Oct 18. doi: 10.1021/acsinfecdis.3c00312. Online ahead of print.ABSTRACTThe latest RNA genomic mutation of SARS-CoV-2 virus, termed the Omicron variant, has generated a stream of highly contagious and antibody-resistant strains, which in turn led to classifying Omicron as a variant of concern. We systematically collected Raman spectra from six Omicron subvariants available in Japan (i.e., BA.1.18, BA.2, BA.4, BA.5, XE, and BA.2.75) and applied machine-learning algorithms to decrypt their structural characteristics at the molecular scale. Unique Raman fingerprints of sulfur-containing amino acid rotamers, RNA purines and pyrimidines, tyrosine phenol ring configurations, and secondary protein structures clearly differentiated the six Omicron subvariants. These spectral characteristics, which were linked to infectiousness, transmissibility, and propensity for immune evasion, revealed evolutionary motifs to be compared with the outputs of genomic studies. The availability of a Raman "metabolomic snapshot", which was then translated into a barcode to enable a prompt subvariant identification, opened the way to rationalize in real-time SARS-CoV-2 activity and variability. As a proof of concept, we applied the Raman barcode procedure to a nasal swab sample retrieved from a SARS-CoV-2 patient and identified its Omicron subvariant by coupling a commercially available magnetic bead technology with our newly developed Raman analyses.PMID:37850869 | DOI:10.1021/acsinfecdis.3c00312

J Agric Food Chem. 2023 Oct 18. doi: 10.1021/acs.jafc.3c01380. Online ahead of print.ABSTRACTThe fresh leaves were processed into beauty tea from the Camellia sinensis "Jinxuan" cultivar, which were punctured by tea green leafhoppers to different extents. Low-puncturing dry tea (LPDT) exhibited a superior quality. Altogether, 101 and 129 differential metabolites, including tea polyphenols, lipids, and saccharides, were identified from the fresh leaves and dry beauty tea, respectively. Most metabolite levels increased in the fresh leaves punctured by leafhoppers, but the opposite was observed for the dry beauty tea. According to relative odor activity values (rOAVs) and partial least-squares discriminant analysis (PLS-DA), four characteristic volatiles, including linalool, geraniol, benzeneacetaldehyde, and dihydrolinalool, were selected. Mechanical injury to leaves caused by leafhoppers, watery saliva secreted by the leafhopper, and different water contents of the fresh leaves in different puncturing degrees are the possible reasons for the difference in the quality of the beauty tea with different levels of puncturing. Overall, this study identified a wide range of chemicals that are affected by the degrees of leafhopper puncturing.PMID:37850863 | DOI:10.1021/acs.jafc.3c01380

Eur J Rheumatol. 2023 Oct 18. doi: 10.5152/eurjrheum.2023.23062. Online ahead of print.ABSTRACTBACKGROUND: Behçet's disease is a systemic, inflammatory disease affecting multiple organs. Vascular involvement is the main cause of morbidity and mortality in Behçet's disease patients. Though clinically well-defined, there is limited information related to disease pathogenesis and vascular incidence in this patient group. The aim of this study is to investigate the unique metabolic signatures of Behçet's disease patients with vascular involvement.METHODS: Metabolomic profiling was performed on serum samples of 48 Behçet's disease patients (18 with vascular involvement) and 40 healthy controls using gas chromatography-mass spectrometrybased untargeted metabolomics analysis. Multivariate and univariate statistical analyses were performed to find altered metabolites and pathways.RESULTS: Untargeted metabolomics results showed that a total of 168 metabolites were identified. The comparison between the groups of Behçet's disease, vascular involvement in Behçet's disease, and the healthy control group showed that altered amino acid and oxidative stress pathways, especially with glutathione synthesis, could be an important stage for developing Behçet's disease.CONCLUSION: In the present work, the untargeted metabolomics approach provided new molecular insights for a better understanding of Behçet's disease pathogenesis and also developing vascular involvement in Behçet's disease at the metabolite level. The results showed that vascular involvement in Behçet's disease could be highly linked with amino acid metabolism and also the antioxidant system, and these disease-related pathways could be evaluated with further experiments for diagnosis and prognosis of Behçet's disease and also for vascular involvement in Behçet's disease.PMID:37850605 | DOI:10.5152/eurjrheum.2023.23062

ERJ Open Res. 2023 Oct 16;9(5):00214-2023. doi: 10.1183/23120541.00214-2023. eCollection 2023 Sep.ABSTRACTBACKGROUND: The concentration of exhaled octane has been postulated as a reliable biomarker for acute respiratory distress syndrome (ARDS) using metabolomics analysis with gas chromatography and mass spectrometry (GC-MS). A point-of-care (POC) breath test was developed in recent years to accurately measure octane at the bedside. The aim of the present study was to validate the diagnostic accuracy of exhaled octane for ARDS using a POC breath test in invasively ventilated intensive care unit (ICU) patients.METHODS: This was an observational cohort study of consecutive patients receiving invasive ventilation for at least 24 h, recruited in two university ICUs. GC-MS and POC breath tests were used to quantify the exhaled octane concentration. ARDS was assessed by three experts following the Berlin definition and used as the reference standard. The area under the receiver operating characteristic curve (AUC) was used to assess diagnostic accuracy.RESULTS: 519 patients were included and 190 (37%) fulfilled the criteria for ARDS. The median (interquartile range) concentration of octane using the POC breath test was not significantly different between patients with ARDS (0.14 (0.05-0.37) ppb) and without ARDS (0.11 (0.06-0.26) ppb; p=0.64). The AUC for ARDS based on the octane concentration in exhaled breath using the POC breath test was 0.52 (95% CI 0.46-0.57). Analysis of exhaled octane with GC-MS showed similar results.CONCLUSIONS: Octane in exhaled breath has insufficient diagnostic accuracy for ARDS. This disqualifies the use of octane as a biomarker in the diagnosis of ARDS and challenges most of the research performed up to now in the field of exhaled breath metabolomics.PMID:37850212 | PMC:PMC10577595 | DOI:10.1183/23120541.00214-2023

Can J Infect Dis Med Microbiol. 2023 Oct 9;2023:7253779. doi: 10.1155/2023/7253779. eCollection 2023.ABSTRACTBACKGROUND: SARS-CoV-2 induces apoptosis and amplifies the immune response by continuously stressing the endoplasmic reticulum (ER) after invading cells. This study aimed to establish a protein-metabolic pathway associated with ER dysfunction based on the invasion mechanism of SARS-CoV-2.METHODS: This study included 17 healthy people and 46 COVID-19 patients, including 38 mild patients and 8 severe patients. Proteomics and metabolomics were measured in the patient plasma collected at admission and one week after admission. The patients were further divided into the aggravation and remission groups based on disease progression within one week of admission.RESULTS: Cross-sectional comparison showed that endoplasmic reticulum molecular chaperone-binding immunoglobulin protein (ERC-BiP), angiotensinogen (AGT), ceramide acid (Cer), and C-reactive protein (CRP) levels were significantly increased in COVID-19 patients, while the sphingomyelin (SM) level was significantly decreased (P < 0.05). In addition, longitudinal comparative analysis found that the temporal fold changes of ERC-BiP, AGT, Cer, CRP, and SM were significantly different between the patients in the aggravation and remission groups (P < 0.05). ERC-BiP, AGT, and Cer levels were significantly increased in aggravation patients, while SM was significantly decreased (P < 0.05). Meanwhile, ERC-BiP was significantly correlated with AGT (r = 0.439; P < 0.001).CONCLUSIONS: ERC-BiP can be used as a core index to reflect the degree of ER stress in COVID-19 patients, which is of great value for evaluating the functional state of cells. A functional pathway for AGT/ERC-BiP/glycolysis can directly assess the activation of unfolded protein reactions. The ERC-BiP pathway is closer to the intracellular replication pathway of SARS-CoV-2 and may help in the development of predictive protocols for COVID-19 exacerbation.PMID:37849973 | PMC:PMC10578982 | DOI:10.1155/2023/7253779

Front Mol Biosci. 2023 Oct 2;10:1223863. doi: 10.3389/fmolb.2023.1223863. eCollection 2023.ABSTRACTIn recent years, the popularity of fermented foods has strongly increased based on their proven health benefits and the adoption of new trends among consumers. One of these health-promoting products is water kefir, which is a fermented sugary beverage based on kefir grains (symbiotic colonies of yeast, lactic acid and acetic acid bacteria). According to previous knowledge and the uniqueness of each water kefir fermentation, the following project aimed to explore the microbial and chemical composition of a water kefir fermentation and its microbial consortium, through the integration of culture-dependent methods, compositional metagenomics, and untargeted metabolomics. These methods were applied in two types of samples: fermentation grains (inoculum) and fermentation samples collected at different time points. A strains culture collection of ∼90 strains was established by means of culture-dependent methods, mainly consisting of individuals of Pichia membranifaciens, Acetobacter orientalis, Lentilactobacillus hilgardii, Lacticaseibacillus paracasei, Acetobacter pomorum, Lentilactobacillus buchneri, Pichia kudriavzevii, Acetobacter pasteurianus, Schleiferilactobacillus harbinensis, and Kazachstania exigua, which can be further studied for their use in synthetic consortia formulation. In addition, metabarcoding of each fermentation time was done by 16S and ITS sequencing for bacteria and yeast, respectively. The results show strong population shifts of the microbial community during the fermentation time course, with an enrichment of microbial groups after 72 h of fermentation. Metataxonomics results revealed Lactobacillus and Acetobacter as the dominant genera for lactic acid and acetic acid bacteria, whereas, for yeast, P. membranifaciens was the dominant species. In addition, correlation and systematic analyses of microbial growth patterns and metabolite richness allowed the recognition of metabolic enrichment points between 72 and 96 h and correlation between microbial groups and metabolite abundance (e.g., Bile acid conjugates and Acetobacter tropicalis). Metabolomic analysis also evidenced the production of bioactive compounds in this fermented matrix, which have been associated with biological activities, including antimicrobial and antioxidant. Interestingly, the chemical family of Isoschaftosides (C-glycosyl flavonoids) was also found, representing an important finding since this compound, with hepatoprotective and anti-inflammatory activity, had not been previously reported in this matrix. We conclude that the integration of microbial biodiversity, cultured species, and chemical data enables the identification of relevant microbial population patterns and the detection of specific points of enrichment during the fermentation process of a food matrix, which enables the future design of synthetic microbial consortia, which can be used as targeted probiotics for digestive and metabolic health.PMID:37849822 | PMC:PMC10577418 | DOI:10.3389/fmolb.2023.1223863

Phytochem Anal. 2023 Oct 18. doi: 10.1002/pca.3294. Online ahead of print.ABSTRACTINTRODUCTION: Solanum nigrum L. is a traditional medicinal herb and edible plant. Many studies provide evidence that S. nigrum L. is a nutritious vegetable. Polyphenols and steroidal glycoalkaloids are the main components.OBJECTIVES: This study aimed to systemically evaluate the phytochemical profile, quantification, and bioactivities of polyphenolics and glycoalkaloids in different parts of S. nigrum L.RESULTS: Total polyphenols (TPC) and total glycoalkaloids (TGK) were determined using the Folin-Ciocalteu and acid dye colorimetric methods, respectively. A total of 55 polyphenolic constituents (including 22 phenolic acids and 33 flavonoids) and 24 steroidal glycoalkaloids were identified from different parts using ultrahigh-performance liquid chromatography Q-exactive high-resolution mass spectrometry (UHPLC-QE-HRMS), of which 40 polyphenols (including 15 phenolic acids and 25 flavonoids) and one steroidal glycoalkaloid were characterised for the first time in S. nigrum L. Moreover, typical polyphenols and glycoalkaloids were determined using HPLC-UV and HPLC-evaporative light-scattering detector (ELSD), respectively. In addition, the TPC and TGK and their typical constituents were compared in different anatomical parts. Finally, the antioxidant capacities of polyphenolic extracts from different parts of S. nigrum L. were evaluated by ·OH, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric-reducing antioxidant power (FRAP) assay in vitro. In addition, the antitumour effects of TGK from different parts of S. nigrum L. on the proliferation of PC-3 cells were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polyphenolic and glycoalkaloid extracts from different parts of S. nigrum L. showed different antioxidant and cytotoxic capacities in vitro.CONCLUSION: This is the first study to systematically differentiate between polyphenolic and glycoalkaloid profiles from different parts of S. nigrum L.PMID:37849391 | DOI:10.1002/pca.3294

Gynecol Endocrinol. 2023 Dec;39(1):2260500. doi: 10.1080/09513590.2023.2260500. Epub 2023 Oct 17.ABSTRACTOBJECTIVE: To investigate the effect of Bushen Huoxue Recipe (BSHXR) on serum metabolomics in polycystic ovary syndrome rat (PCOSR).METHODS: In our study, twenty-four 6-week-old Sprague-Dawley (SD) female rats were randomly divided into three groups: treatment group, model group and blank group. The blank group and other groups were gavaged in different ways each morning, and the rats were treated with normal saline or BSHXR containing liquid each afternoon. Liquid chromatography-mass spectrometry (LC-MS) was employed to study serum metabolites in the treatment group after the study as well as in the model and blank groups.RESULTS: There was a tendency to normalize the histomorphology of ovarian pathology and the abnormal sex hormone level of PCOSR was significantly improved after BSHXR treatment. The level of serum metabolites was greatly changed in PCOSR treated with the BSHXR. We identified 32 metabolic targets of BSHXR in PCOSR using LC-MS, and further revealed BSHXR targeted five major metabolic pathway: retrograde endocannabinoid signaling, taurine and hypotaurine metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis, arginine and proline metabolism. Conclusion: Our study found that BSHXR plays a role in the treatment of PCOS by regulating key metabolic pathways in the PCOSR.PMID:37849277 | DOI:10.1080/09513590.2023.2260500

Mol Nutr Food Res. 2023 Oct 17:e2300372. doi: 10.1002/mnfr.202300372. Online ahead of print.ABSTRACTSCOPE: Liver is an important metabolic organ regulating whole-body homeostasis. This study aims to investigate how prebiotic-induced changes in the metabolic activity of the gut microbiome (GM) and dietary calcium depletion modulates the hepatic metabolome and transcriptome.METHODS AND RESULTS: The serum metabolome, liver metabolome, and transcriptome are determined on samples from ovariectomized (OVX) rats fed a control diet (Control, n = 7), a control diet supplemented with 5% w/w inulin (Inulin, n = 7), or a calcium-deficient diet (CaDef, n = 7). Inulin fortification is associated with higher serum concentrations of acetate, 3-hydroxybutyrate, and reduced concentration of dimethyl sulfone, revealing that changes in the metabolic activity of the GM are reflected in circulating metabolites. Metabolomics also reveal that the inulin-fortified diet results in lower concentrations of hepatic glutamate, serine, and hypoxanthine while transcriptomics reveal accompanying effects on the hepatic expression of ferric iron binding-related genes. Inulin fortification also induces effects on the hepatic expression of genes involved in olfactory transduction, suggesting that prebiotics regulate liver function through yet unidentified mechanisms involving olfactory receptors.CONCLUSION: Inulin ingestion impacts hepatic gene expression and is associated with an upregulation of ferritin synthesis-related genes and liver ferritin content.PMID:37849247 | DOI:10.1002/mnfr.202300372

Brain. 2023 Oct 18:awad303. doi: 10.1093/brain/awad303. Online ahead of print.ABSTRACTAlzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.PMID:37849234 | DOI:10.1093/brain/awad303