PubMed

Phytomedicine. 2023 Aug 25;120:155048. doi: 10.1016/j.phymed.2023.155048. Online ahead of print.ABSTRACTBACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in older men worldwide. However, there is currently no effective treatment for BPH. Bushen Tongluo Formula (Kidney-supplementing and collaterals-unblocking formula [KCF]) is a traditional Chinese medicine formula commonly used to ameliorate the symptoms of BPH, although the specific molecular mechanisms remain unclear.PURPOSE: We aimed to discover the effects and potential mechanisms of KCF against BPH.METHODS: Sixty male SD rats were randomly assigned to one of six group (n = 10): control, low-dosage KCF, medium-dosage KCF, high-dosage KCF, BPH model, and finasteride. A rat model of BPH was established by surgical castration followed by subcutaneous injection of testosterone propionate (TP) for 4 weeks. After treatment, the prostate index, histopathological staining, serum levels of estradiol (E2) and dihydrotestosterone (DHT), protein/mRNA levels of E-cadherin, TGF-β1, caspase-3, Ki67, and vimentin, abundances of serum metabolites, and the proliferation, cell cycle, and apoptosis of BPH-1 cells were documented.RESULTS: KCF treatment for 4 weeks reduced the prostate volume and prostate index, alleviated histopathological changes to the prostate of rats with TP-induced BPH, decreased serum levels of E2 and DHT, reduced protein/mRNA levels of TGF-β1 and vimentin, and increased E-cadherin levels. Moreover, KCF-spiked serum inhibited proliferation of BPH-1 cells, blocked the cell cycle, and promoted apoptosis. KCF was also found to regulate the contents of three metabolites (D-maltose, citric acid, and fumaric acid).CONCLUSION: The present study was the first to report that KCF exhibited therapeutic effects against BPH by regulating energy metabolism and inhibiting epithelial-mesenchymal transition in prostate tissues. Hence, KCF presents a viable treatment option for BPH.PMID:37651753 | DOI:10.1016/j.phymed.2023.155048

J Agric Food Chem. 2023 Aug 31. doi: 10.1021/acs.jafc.3c03948. Online ahead of print.ABSTRACTInsoluble dietary fiber (IDF) was recently revealed to have an antiobesity impact. However, the impact and potential mechanism of high-purity IDF derived from okara (HPSIDF) on obesity caused by a high-fat diet (HFD) remain unclear. Except for dietary supplementation, intermittent fasting (IF) has attracted extensive interest as a new dietary strategy against obesity. Thus, we hypothesize that HPSIDF combined with IF treatment may be more effective in preventing obesity. In this study, HPSIDF combined with IF treatment synergistically alleviated HFD-induced dyslipidemia, impaired glucose homeostasis, systemic inflammation, and fat accumulation. Furthermore, gut microbiota dysbiosis and lowered short-chain fatty acid synthesis were recovered by HPSIDF combined with IF treatment. Meanwhile, metabolomic analysis of feces revealed that HPSIDF combined with IF treatment obviously reversed the alterations of metabolic pathways and differential metabolites induced by HFD, which were linked to the modulations of the gut microbiota. Collectively, our findings indicated that HPSIDF combined with IF treatment has great potential to substantially enhance antiobesity efficacy by modulating the gut microbiota and its metabolites.PMID:37651598 | DOI:10.1021/acs.jafc.3c03948

PLoS Genet. 2023 Aug 31;19(8):e1010909. doi: 10.1371/journal.pgen.1010909. Online ahead of print.ABSTRACTTrichoderma spp. are ubiquitous rhizosphere fungi capable of producing several classes of secondary metabolites that can modify the dynamics of the plant-associated microbiome. However, the bacterial-fungal mechanisms that mediate these interactions have not been fully characterized. Here, a random barcode transposon-site sequencing (RB-TnSeq) approach was employed to identify bacterial genes important for fitness in the presence of Trichoderma atroviride exudates. We selected three rhizosphere bacteria with RB-TnSeq mutant libraries that can promote plant growth: the nitrogen fixers Klebsiella michiganensis M5aI and Herbaspirillum seropedicae SmR1, and Pseudomonas simiae WCS417. As a non-rhizosphere species, Pseudomonas putida KT2440 was also included. From the RB-TnSeq data, nitrogen-fixing bacteria competed mainly for iron and required the siderophore transport system TonB/Exb for optimal fitness in the presence of T. atroviride exudates. In contrast, P. simiae and P. putida were highly dependent on mechanisms associated with membrane lipid modification that are required for resistance to cationic antimicrobial peptides (CAMPs). A mutant in the Hog1-MAP kinase (Δtmk3) gene of T. atroviride showed altered expression patterns of many nonribosomal peptide synthetase (NRPS) biosynthetic gene clusters with potential antibiotic activity. In contrast with exudates from wild-type T. atroviride, bacterial mutants containing lesions in genes associated with resistance to antibiotics did not show fitness defects when RB-TnSeq libraries were exposed to exudates from the Δtmk3 mutant. Unexpectedly, exudates from wild-type T. atroviride and the Δtmk3 mutant rescued purine auxotrophic mutants of H. seropedicae, K. michiganensis and P. simiae. Metabolomic analysis on exudates from wild-type T. atroviride and the Δtmk3 mutant showed that both strains excrete purines and complex metabolites; functional Tmk3 is required to produce some of these metabolites. This study highlights the complex interplay between Trichoderma-metabolites and soil bacteria, revealing both beneficial and antagonistic effects, and underscoring the intricate and multifaceted nature of this relationship.PMID:37651474 | DOI:10.1371/journal.pgen.1010909

PLoS Pathog. 2023 Aug 31;19(8):e1011566. doi: 10.1371/journal.ppat.1011566. Online ahead of print.ABSTRACTAs an obligate intracellular parasite, Toxoplasma gondii must import essential nutrients from the host cell into the parasitophorous vacuole. We previously reported that the parasite scavenges cholesterol from host endocytic organelles for incorporation into membranes and storage as cholesteryl esters in lipid droplets. In this study, we have investigated whether Toxoplasma utilizes cholesterol as a precursor for the synthesis of metabolites, such as steroids. In mammalian cells, steroidogenesis occurs in mitochondria and involves membrane-bound type I cytochrome P450 oxidases that are activated through interaction with heme-binding proteins containing a cytochrome b5 domain, such as members of the membrane-associated progesterone receptor (MAPR) family. Our LC-MS targeted lipidomics detect selective classes of hormone steroids in Toxoplasma, with a predominance for anti-inflammatory hydroxypregnenolone species, deoxycorticosterone and dehydroepiandrosterone. The genome of Toxoplasma contains homologs encoding a single type I CYP450 enzyme (we named TgCYP450mt) and a single MAPR (we named TgMAPR). We showed that TgMAPR is a hemoprotein with conserved residues in a heme-binding cytochrome b5 domain. Both TgCYP450 and TgMAPR localize to the mitochondrion and show interactions in in situ proximity ligation assays. Genetic ablation of cyp450mt is not tolerated by Toxoplasma; we therefore engineered a conditional knockout strain and showed that iΔTgCYP450mt parasites exhibit growth impairment in cultured cells. Parasite strains deficient for mapr could be generated; however, ΔTgMAPR parasites suffer from poor global fitness, loss of plasma membrane integrity, aberrant mitochondrial cristae, and an abnormally long S-phase in their cell cycle. Compared to wild-type parasites, iΔTgCYP450mt and ΔTgMAPR lost virulence in mice and metabolomics studies reveal that both mutants have reduced levels of steroids. These observations point to a steroidogenic pathway operational in the mitochondrion of a protozoan that involves an evolutionary conserved TgCYP450mt enzyme and its binding partner TgMAPR.PMID:37651449 | DOI:10.1371/journal.ppat.1011566

Cell Rep. 2023 Aug 30;42(9):113034. doi: 10.1016/j.celrep.2023.113034. Online ahead of print.ABSTRACTMetabolic rewiring is essential for cancer onset and progression. We previously showed that one-carbon metabolism-dependent formate production often exceeds the anabolic demand of cancer cells, resulting in formate overflow. Furthermore, we showed that increased extracellular formate concentrations promote the in vitro invasiveness of glioblastoma cells. Here, we substantiate these initial observations with ex vivo and in vivo experiments. We also show that exposure to exogeneous formate can prime cancer cells toward a pro-invasive phenotype leading to increased metastasis formation in vivo. Our results suggest that the increased local formate concentration within the tumor microenvironment can be one factor to promote metastases. Additionally, we describe a mechanistic interplay between formate-dependent increased invasiveness and adaptations of lipid metabolism and matrix metalloproteinase activity. Our findings consolidate the role of formate as pro-invasive metabolite and warrant further research to better understand the interplay between formate and lipid metabolism.PMID:37651228 | DOI:10.1016/j.celrep.2023.113034

Crit Rev Food Sci Nutr. 2023 Aug 31:1-9. doi: 10.1080/10408398.2023.2251616. Online ahead of print.ABSTRACTGut microbiota modulates host physiology and pathophysiology through the production of microbial metabolites. Diet is a crucial factor in shaping the microbiome, and gut microbes interact with the host by producing beneficial or detrimental diet-derived microbial metabolites. Evidence from our lab and others indicates that the interaction between diet and gut microbes plays a pivotal role in modulating vascular health. Diet-derived microbial metabolites such as short-chain fatty acids and metabolites of phenolic acids improve vascular health, whereas trimethylamine oxide and certain amino acid-derived microbial metabolites impair the vasculature. These metabolites have been shown to regulate blood pressure, vascular inflammation, and atherosclerosis by acting on multiple targets. Nonetheless, there are substantial gaps in knowledge within this field. The microbial enzymes essential for the production of diet-derived metabolites, the role of the food matrix in regulating the bioavailability of metabolites, and the structure-activity relationships between metabolites and biomolecules in the vasculature are largely unknown. Potential diet-derived metabolites to improve vascular health can be identified through future studies that investigate the causal relationship between dietary components, gut microbes, diet-derived metabolites, and vascular health by using radiolabeled compounds, metabolomics, transcriptomics, and proteomics techniques.PMID:37651204 | DOI:10.1080/10408398.2023.2251616

J Agric Food Chem. 2023 Aug 31. doi: 10.1021/acs.jafc.3c02653. Online ahead of print.ABSTRACTKiwifruit canker is caused by Pseudomonas syringae pv. actinidiae and is one of the most destructive diseases of kiwifruit worldwide. Sulfur can improve the deposit of lignin in kiwifruit stems and induce disease resistance, but the action mechanism at the molecular level remains unclear. This omics-based study revealed that sulfur-induced S lignin synthesis contributes to disease resistance. Histological staining verified sulfur-enhanced total lignin deposition in kiwifruit stems. High-performance liquid chromatography and confocal Raman microscopy showed that sulfur-activated S lignin was mainly deposited in the cell corner. Metabolome and transcriptome analysis revealed that the levels of phenylpropanoid pathway S lignin precursors sinapic acid and sinapyl alcohol were significantly increased and 16 laccase genes were upregulated. Sulfur-induced resistance defense promoted elevated laccase activity by activating the laccase genes, participating in sinapic acid and sinapyl alcohol substance synthesis, and ultimately polymerizing S lignin at cell corner against kiwifruit canker disease.PMID:37651104 | DOI:10.1021/acs.jafc.3c02653

Mar Biotechnol (NY). 2023 Aug 31. doi: 10.1007/s10126-023-10238-z. Online ahead of print.ABSTRACTMicroplastics (MP) and microcystins (MCs) are two co-occurring pollutants in freshwater ecosystems that pose significant risks to aquatic organisms and human health. This study investigates the interactions between MP and MCs and their effects on the metabolic responses of freshwater aquaculture. Asian clams have been used as an indicator of microplastic pollution in freshwater ecosystems. The present study investigates metabolic responses of Asian clams during microplastic and microcystin-LR stress to identify health impacts and elucidate mechanistic effects of external stressors on Asian clams. A liquid chromatography/mass spectrometry (LC-MS)-based metabolomics approach was used to identify metabolic perturbations and histological section technique was used to assess changes of tissues from different Asian clam treatment groups. The results showed significantly pathological changes in the gills and hepatopancreas in experimental clam compared to control (healthy) clam. Metabolomics revealed alterations of many metabolites in the hepatopancreas of six Asian clam comparison groups, reflecting perturbations in several molecular pathways, including energy metabolism, amino acid metabolism, protein degradation/tissue damage, and oxidative stress. Overall, this study emphasizes the importance of understanding the interactions between MP and MCs and the need for proactive measures to safeguard freshwater ecosystems and human health.PMID:37651025 | DOI:10.1007/s10126-023-10238-z

Inflamm Bowel Dis. 2023 Aug 31:izad185. doi: 10.1093/ibd/izad185. Online ahead of print.ABSTRACTBACKGROUND: Stress reactivity (SR) is associated with increased risk of flares in ulcerative colitis (UC) patients. Because both preclinical and clinical data support that stress can influence gut microbiome composition and function, we investigated whether microbiome profiles of SR exist in UC.METHODS: Ninety-one UC subjects in clinical and biochemical remission were classified into high and low SR groups by questionnaires. Baseline and longitudinal characterization of the intestinal microbiome was performed by 16S rRNA gene sequencing and fecal and plasma global untargeted metabolomics. Microbe, fecal metabolite, and plasma metabolite abundances were analyzed separately to create random forest classifiers for high SR and biomarker-derived SR scores.RESULTS: High SR reactivity was characterized by altered abundance of fecal microbes, primarily in the Ruminococcaceae and Lachnospiraceae families; fecal metabolites including reduced levels of monoacylglycerols (endocannabinoid-related) and bile acids; and plasma metabolites including increased 4-ethyl phenyl sulfate, 1-arachidonoylglycerol (endocannabinoid), and sphingomyelin. Classifiers generated from baseline microbe, fecal metabolite, and plasma metabolite abundance distinguished high vs low SR with area under the receiver operating characteristic curve of 0.81, 0.83, and 0.91, respectively. Stress reactivity scores derived from these classifiers were significantly associated with flare risk during 6 to 24 months of follow-up, with odds ratios of 3.8, 4.1, and 4.9. Clinical flare and intestinal inflammation did not alter fecal microbial abundances but attenuated fecal and plasma metabolite differences between high and low SR.CONCLUSIONS: High SR in UC is characterized by microbial signatures that predict clinical flare risk, suggesting that the microbiome may contribute to stress-induced UC flares.PMID:37650887 | DOI:10.1093/ibd/izad185

Curr Opin Clin Nutr Metab Care. 2023 Aug 30. doi: 10.1097/MCO.0000000000000977. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: Artificial intelligence has reached the clinical nutrition field. To perform personalized medicine, numerous tools can be used. In this review, we describe how the physician can utilize the growing healthcare databases to develop deep learning and machine learning algorithms, thus helping to improve screening, assessment, prediction of clinical events and outcomes related to clinical nutrition.RECENT FINDINGS: Artificial intelligence can be applied to all the fields of clinical nutrition. Improving screening tools, identifying malnourished cancer patients or obesity using large databases has been achieved. In intensive care, machine learning has been able to predict enteral feeding intolerance, diarrhea, or refeeding hypophosphatemia. The outcome of patients with cancer can also be improved. Microbiota and metabolomics profiles are better integrated with the clinical condition using machine learning. However, ethical considerations and limitations of the use of artificial intelligence should be considered.SUMMARY: Artificial intelligence is here to support the decision-making process of health professionals. Knowing not only its limitations but also its power will allow precision medicine in clinical nutrition as well as in the rest of the medical practice.PMID:37650706 | DOI:10.1097/MCO.0000000000000977

Mol Nutr Food Res. 2023 Aug 31:e2300329. doi: 10.1002/mnfr.202300329. Online ahead of print.ABSTRACTSCOPE: Mild cognitive impairment is associated with a high prevalence of dementia. The study examines the benefits of a modified Korean MIND (K-MIND) diet and explores biomarkers using multi-omics analysis.METHODS AND RESULTS: The K-MIND diet, tailored to the elderly Korean population, includes perilla oil, milk, or fermented milk, and avoids alcohol consumption. As a result, the K-MIND diet significantly improves subjects "orientation to place" in the Korean version of the Mini-Mental State Examination, 2nd edition test. According to multi-omics analysis, the K-MIND diet upregulates genes associated with mitochondrial respiration, including ubiquinone oxidoreductase, cytochrome C oxidase, and ATP synthase, and immune system processes, and downregulates genes related to nuclear factor kappa B activity and inflammatory responses. In addition, K-MIND affects the metabolic pathways of glycine, serine, threonine, tryptophan, and sphingolipids, which are closely linked to cognitive function through synthesis of neurotransmitters and structures of brain cell membranes.CONCLUSION: The findings imply that the K-MIND diet improves cognitive function by upregulating key genes involved in oxidative phosphorylation and downregulating pro-inflammatory cytokines.PMID:37650267 | DOI:10.1002/mnfr.202300329

Mol Nutr Food Res. 2023 Aug 31:e2300044. doi: 10.1002/mnfr.202300044. Online ahead of print.ABSTRACTSCOPE: This study aims to discover metabolites of dietary carbohydrate, soy and milk protein supplements and evaluate their roles in blood pressure (BP) regulation in the protein and blood pressure (ProBP), a cross-over trial.METHODS AND RESULTS: Plasma metabolites are profiled at pre-trial baseline and after 8 weeks of supplementation with carbohydrate, soy protein, and milk protein, respectively, among 80 ProBP participants. After Bonferroni correction (α = 6.49 × 10-4 ), dietary interventions significantly changed 40 metabolites. Changes of erucate (22:1n9), an omega-9 fatty acid, are positively associated with systolic BP changes (Beta = 1.90, p = 6·27 × 10-4 ). This metabolite is also associated with higher odds of hypertension among 1261 participants of an independent cohort (odds ratio per unit increase = 1.34; 95% confidence interval: 1.07-1.68). High levels of acylcholines dihomo-linolenoyl-choline (p = 4.71E-04) and oleoylcholine (p = 3.48E-04) at baseline predicted larger BP lowering effects of soy protein. Increasing cheese intake during the trial, as reflected by isobutyrylglycine and isovalerylglycine, reduces the BP lowering effect of soy protein.CONCLUSIONS: The study identifies molecular signatures of dietary interventions. Erucate (22:1n9) increases systolic BP. Acylcholine enhances and cheese intake reduces the BP lowering effect of soy protein supplement.PMID:37650262 | DOI:10.1002/mnfr.202300044

Chembiochem. 2023 Aug 31:e202300537. doi: 10.1002/cbic.202300537. Online ahead of print.ABSTRACTMale Heliconius butterflies possess two pheromone emitting structures, wing androconia and abdominal clasper scent glands. The composition of the clasper scent gland of males of 17 Heliconius and Eueides species from an overlapping area in Ecuador, comprising three mimicry groups, was investigated by GC/MS. The chemical signal serves as an anti-aphrodisiac signal that is transferred from males to females during mating, indicating the mating status of the female to prevent them from harassment by other males. In addition, the odour may also serve in predator defence. There is potential for convergence driven by mimicry, although, such convergence might be detrimental for species recognition of the butterflies within the mimicry ring, making mating more difficult. More than 500 compounds were detected, consisting of volatile, semi-volatile or non-volatile compounds, including terpenes, fatty acid esters or aromatic compounds. Several novel esters were identified by GC/MS and GC/IR data, microderivatisation and synthesis, including butyl (Z)-3-dodecenoate and other (Z)-3-alkenoates, 3-oxohexyl citronellate and 5-methylhexa-3,5-dienyl (E)-2,3-dihydrofarnesoate. The secretions were found to be species specific, potentially allowing for species differentiation. Statistical analysis of the more than 500 compounds showed differentiation by phylogenetic clade and species, but not by mimicry group.PMID:37650217 | DOI:10.1002/cbic.202300537

ERJ Open Res. 2023 Aug 29;9(4):00143-2023. doi: 10.1183/23120541.00143-2023. eCollection 2023 Jul.ABSTRACTBACKGROUND: Asthma and COPD are among the most common respiratory diseases. To improve the early detection of exacerbations and the clinical course of asthma and COPD new biomarkers are needed. The development of noninvasive metabolomics of exhaled air into a point-of-care tool is an appealing option. However, risk factors for obstructive pulmonary diseases can potentially introduce confounding markers due to altered volatile organic compound (VOC) patterns being linked to these risk factors instead of the disease. We conducted a systematic review and presented a comprehensive list of VOCs associated with these risk factors.METHODS: A PRISMA-oriented systematic search was conducted across PubMed, Embase and Cochrane Libraries between 2000 and 2022. Full-length studies evaluating VOCs in exhaled breath were included. A narrative synthesis of the data was conducted, and the Newcastle-Ottawa Scale was used to assess the quality of included studies.RESULTS: The search yielded 2209 records and, based on the inclusion/exclusion criteria, 24 articles were included in the qualitative synthesis. In total, 232 individual VOCs associated with risk factors for obstructive pulmonary diseases were found; 58 compounds were reported more than once and 12 were reported as potential markers of asthma and/or COPD in other studies. Critical appraisal found that the identified studies were methodologically heterogeneous and had a variable risk of bias.CONCLUSION: We identified a series of exhaled VOCs associated with risk factors for asthma and/or COPD. Identification of these VOCs is necessary for the further development of exhaled metabolites-based point-of-care tests in these obstructive pulmonary diseases.PMID:37650089 | PMC:PMC10463028 | DOI:10.1183/23120541.00143-2023

Front Plant Sci. 2023 Aug 15;14:1203284. doi: 10.3389/fpls.2023.1203284. eCollection 2023.ABSTRACTINTRODUCTION: Waxy maize, mainly consumed at the immature stage, is a staple and vegetable food in Asia. The pigmentation in the kernel of purple waxy maize enhances its nutritional and market values. Light, a critical environmental factor, affects anthocyanin biosynthesis and results in pigmentation in different parts of plants, including in the kernel. SWL502 is a light-sensitive waxy maize inbred line with purple kernel color, but the regulatory mechanism of pigmentation in the kernel resulting in purple color is still unknown.METHODS: In this study, cyanidin, peonidin, and pelargonidin were identified as the main anthocyanin components in SWL502, evaluated by the ultra-performance liquid chromatography (UPLC) method. Investigation of pigment accumulation in the kernel of SWL502 was performed at 12, 17, and 22 days after pollination (DAP) under both dark and light treatment conditions via transcriptome and metabolome analyses.RESULTS: Dark treatment affected genes and metabolites associated with metabolic pathways of amino acid, carbohydrate, lipid, and galactose, biosynthesis of phenylpropanoid and terpenoid backbone, and ABC transporters. The expression of anthocyanin biosynthesis genes, such as 4CL2, CHS, F3H, and UGT, was reduced under dark treatment. Dynamic changes were identified in genes and metabolites by time-series analysis. The genes and metabolites involved in photosynthesis and purine metabolism were altered in light treatment, and the expression of genes and metabolites associated with carotenoid biosynthesis, sphingolipid metabolism, MAPK signaling pathway, and plant hormone signal transduction pathway were induced by dark treatment. Light treatment increased the expression level of major transcription factors such as LRL1, myc7, bHLH125, PIF1, BH093, PIL5, MYBS1, and BH074 in purple waxy maize kernels, while dark treatment greatly promoted the expression level of transcription factors RVE6, MYB4, MY1R1, and MYB145.DISCUSSION: This study is the first report to investigate the effects of light on waxy maize kernel pigmentation and the underlying mechanism at both transcriptome and metabolome levels, and the results from this study are valuable for future research to better understand the effects of light on the regulation of plant growth.PMID:37649997 | PMC:PMC10465178 | DOI:10.3389/fpls.2023.1203284

Front Pharmacol. 2023 Aug 15;14:1215861. doi: 10.3389/fphar.2023.1215861. eCollection 2023.ABSTRACTBackground: Psoriasis is a common chronic inflammatory skin disease characterized by an external red rash that is caused by abnormal proliferation and differentiation of keratinocytes and immune T cells. This study aimed to elucidate the role of aminooxy acetic acid (AOA) in alleviating psoriasis from the perspective of immunology and metabolomics. Therefore, contributing to the development of new drugs as candidates for psoriasis treatment. Methods: To investigate the symptom-alleviating effects and the related mechanisms of AOA on the treatment of psoriasis, we used a 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin mouse model and interleukin (IL)-17-stimulated human keratinocytes. Results: The results showed that AOA ameliorated psoriasis-related symptoms and decreased inflammation-associated antimicrobial peptides and T-helper 17 (Th17)-associated cytokines in a mouse model of psoriasis. Furthermore, AOA inhibited the activation of mechanistic target of rapamycin (mTOR) by suppressing serine metabolism-related genes. Importantly, mTOR inhibition ameliorated psoriatic disease by affecting the differentiation of various T cells and normalizing the Th17/regulatory T (Treg) cell balance. In addition, IL-17-stimulated human keratinocytes showed the same results as in the in vivo experiments. Conclusion: Taken together, these results suggest that targeting the serine metabolism pathway in the treatment of psoriasis is a novel strategy, and that AOA could be utilized as a novel biologic to treat psoriasis.PMID:37649889 | PMC:PMC10464615 | DOI:10.3389/fphar.2023.1215861

Front Pharmacol. 2023 Aug 15;14:1224239. doi: 10.3389/fphar.2023.1224239. eCollection 2023.ABSTRACTIntroduction: Osteoarthritis (OA) is a prevalent joint disorder worldwide. Sodium hyaluronate (SH) and mesenchymal stem cells (MSCs) are promising therapeutic strategies for OA. Previous studies showed they could improve knee function and clinical symptoms of OA. However, the mechanism of the therapeutic effects on the improvement of OA has not been clearly explained. Methods: In our study, we used a technique called 5-(diisopropylamino)amylamine derivatization liquid chromatography coupled with mass spectrometry to find the metabolites in OA synovial fluid under different treatments. Results and Discussion: After looking into the metabolomics, we discovered that SH and MSC treatment led to the downregulation of ω-6 polyunsaturated fatty acids (PUFAs) and the upregulation of ω-3 PUFAs. Significantly, the contents of 5(S)-HETE, PGA2, PGB2, and PGJ2 were lower in the MSC group than in the SH group after quantification using 5-(diisopropylamino)amylamine derivatization-UHPLC-QQQ-MS. This is the first report on the relationship of 11(S)-HETE, PGA2, PGB2, PGF2β, 11β-PGF2α, and DK-PGE2 with OA. Moreover, the correlation analysis of metabolites and inflammation factors showed the positive association of ω-6 PUFAs with pro-inflammation cytokines, and of ω-3 PUFAs with anti-inflammation cytokines. Our results indicated the therapeutic effect of SH and MSCs in patients with OA. In addition, this reliable metabolic approach could uncover novel biomarkers to treat OA.PMID:37649888 | PMC:PMC10462907 | DOI:10.3389/fphar.2023.1224239

Front Microbiol. 2023 Aug 15;14:1238737. doi: 10.3389/fmicb.2023.1238737. eCollection 2023.ABSTRACTFuture sustainable energy production can be achieved using mass cultures of photoautotrophic microorganisms such as cyanobacteria, which are engineered to synthesize valuable products directly from CO2 and sunlight. For example, strains of the model organism Synechocystis sp. PCC 6803 have been generated to produce ethanol. Here, we performed a study to prove the hypothesis that carbon flux in the direction of pyruvate is one bottleneck to achieve high ethanol titers in cyanobacteria. Ethanol-producing strains of the cyanobacterium Synechocystis sp. PCC 6803 were generated that bear mutation in the gene pirC aiming to increase carbon flux towards pyruvate. The strains were cultivated at different nitrogen or carbon conditions and the ethanol production was analysed. Generally, a clear correlation between growth rate and ethanol production was found. The mutation of pirC, however, had only a positive impact on ethanol titers under nitrogen depletion. The increase in ethanol was accompanied by elevated pyruvate and lowered glycogen levels indicating that the absence of pirC indeed increased carbon partitioning towards lower glycolysis. Metabolome analysis revealed that this change in carbon flow had also a marked impact on the overall primary metabolism in Synechocystis sp. PCC 6803. Deletion of pirC improved ethanol production under specific conditions supporting the notion that a better understanding of regulatory mechanisms involved in cyanobacterial carbon partitioning is needed to engineer more productive cyanobacterial strains.PMID:37649635 | PMC:PMC10465007 | DOI:10.3389/fmicb.2023.1238737

Front Microbiol. 2023 Aug 15;14:1219763. doi: 10.3389/fmicb.2023.1219763. eCollection 2023.ABSTRACTINTRODUCTION: Obesity and diabetes are common chronic metabolic disorders which can cause an imbalance of the intestinal flora and gut-liver metabolism. Several studies have shown that probiotics, including Escherichia coli Nissle 1917 (EcN), promote microbial balance and metabolic health. However, there are no studies on how EcN outer membrane vesicles (EcN-OMVs) influence the intestinal microflora and affect the metabolic disorders of obesity and diabetes.METHODS: In this study, we evaluated the effects of EcN-OMVs on high-fat diet (HFD)-induced obesity and HFD + streptozotocin (STZ)-induced diabetes.RESULTS: EcN-OMVs could reduce body weight, decrease blood glucose, and increase plasma insulin in obese mice. Similarly, EcN-OMVs treatment could modify the ratio of Firmicutes/Bacteroidetes in the gut, elevate intestinal short-chain fatty acid (SCFA)-producing flora, and influence the SCFA content of the intestine. Furthermore, the intestinal metabolites ornithine and fumaric acid, hepatic ω-6 unsaturated fatty acids, and SCFAs were significantly increased after administering EcN-OMVs.DISCUSSION: Overall, this study showed that EcN-OMVs might act as post-biotic agents that could modulate gut-liver metabolism and ameliorate the pathophysiology of obesity and diabetes.PMID:37649633 | PMC:PMC10465304 | DOI:10.3389/fmicb.2023.1219763

Front Immunol. 2023 Aug 15;14:1228795. doi: 10.3389/fimmu.2023.1228795. eCollection 2023.ABSTRACTAntiretroviral therapy (ART) induces persistent suppression of HIV-1 replication and gradual recovery of T-cell counts, and consequently, morbidity and mortality from HIV-related illnesses have been significantly reduced. However, in approximately 30% of people living with HIV (PLHIV) on ART, CD4+ T-cell counts fail to normalize despite ART and complete suppression of HIV viral load, resulting in severe immune dysfunction, which may represent an increased risk of clinical progression to AIDS and non-AIDS events as well as increased mortality. These patients are referred to as "immune inadequate responders", "immunodiscordant responders" or "immune nonresponders (INR)". The molecular mechanisms underlying poor CD4+ T-cell recovery are still unclear. In this sense, the use of omics sciences has shed light on possible factors involved in the activity and metabolic dysregulation of immune cells during the failure of CD4+ T-cell recovery in INR. Moreover, identification of key molecules by omics approaches allows for the proposal of potential biomarkers or therapeutic targets to improve CD4+ T-cell recovery and the quality of life of these patients. Hence, this review aimed to summarize the information obtained through different omics concerning the molecular factors and pathways associated with the INR phenotype to better understand the complexity of this immunological status in HIV infection.PMID:37649488 | PMC:PMC10465175 | DOI:10.3389/fimmu.2023.1228795