PubMed

Microbiol Spectr. 2024 Oct 30:e0152124. doi: 10.1128/spectrum.01521-24. Online ahead of print.ABSTRACTVulvovaginal candidiasis (VVC) is a common vaginal infectious disease caused by Candida. The high recurrence rate of VVC is a great clinical challenge, with recurrent VVC (RVVC) defined as four or more episodes within a year. In this study, we recruited 31 RVVC patients, 28 VVC patients, and 29 healthy women. Vaginal samples were collected for metagenomic and metabolic analysis. RVVC and VVC groups presented similar clinical symptoms, with only a significantly increased incidence of swelling in the VVC group. Vaginal microbiota in VVC/RVVC exhibited a decreased abundance of Lactobacillus and increased bacterial vaginosis-associated bacteria, such as Gardnerella, Prevotella, and Atopobium. Notably, Lactobacillus iners was higher in RVVC, suggesting not all Lactobacillus species are protective. Healthy women showed lower overall microbiota diversity, emphasizing single-species dominance for stability. Glycogen metabolism pathways were enriched in RVVC/VVC, and were correlated with Atopobium vaginae, Prevotella bivia, and Lactobacillus jensenii. Peptidoglycan synthesis pathways, associated with P. bivia, were enriched, with the substrate L-glutamate elevated in RVVC, possibly promoted by L. iners. These findings shed light on potential therapeutic targets for recurrent VVC, contributing to the understanding of the intricate interplay between the metabolism of vaginal microbiome and disease.IMPORTANCE: This study enhances our knowledge of the vaginal microbiota dynamics and the role of associated metabolites in individuals with vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis through shotgun sequencing and multi-omics analysis. The relationship between metabolites and vaginal microbiota and disease state was revealed. The accumulation of L-glutamate generated in glycogen metabolism, which is governed by Lactobacillus iners or bacterial vaginosis-associated bacteria, may contribute to the incidence and recurrence of VVC. Such insights have the potential to impact the treatment and prevention strategies for these common yet distressing conditions, potentially leading to targeted therapies and improved patient outcomes.PMID:39475249 | DOI:10.1128/spectrum.01521-24

Nucleic Acids Res. 2024 Oct 30:gkae961. doi: 10.1093/nar/gkae961. Online ahead of print.ABSTRACTMetabolomic microbiome research has become an important topic for understanding agricultural, ecological as well as health correlations. Only the determination of both the non-volatile and the volatile organic compound (mVOC) production by microorganisms allows a holistic view for understanding the complete potential of metabolomes and metabolic capabilities of bacteria. In the recent past, more and more bacterial headspaces and culture media were analyzed, leading to an accumulation of about 3500 mVOCs in the updated mVOC 4.0 database, including compounds synthesized by the newly discovered non-canonical terpene pathway. Approximately 10% of all mVOCs can be assigned with a biological function, some mVOCs have the potential to impact agriculture in the future (e.g. eco-friendly pesticides) or animal and human health care. mVOC 4.0 offers various options for exploring extensively annotated mVOC data from different perspectives, including improved mass spectrometry matching. The mVOC 4.0 database includes literature searches with additional relevant keywords, making it the most up-to-date and comprehensive publicly available mVOC platform at: http://bioinformatics.charite.de/mvoc.PMID:39475188 | DOI:10.1093/nar/gkae961

Proteomics Clin Appl. 2024 Oct 30:e202400048. doi: 10.1002/prca.202400048. Online ahead of print.ABSTRACTLiquid chromatography, when used in conjunction with mass spectrometry (LC/MS), is a powerful tool for conducting accurate and reproducible investigations of numerous metabolites in natural products (NPs). LC/MS has gained prominence in metabolomic research due to its high throughput, the availability of multiple ionization techniques and its ability to provide comprehensive metabolite coverage. This unique method can significantly influence various scientific domains. This review offers a comprehensive overview of the current state of LC/MS-based metabolomics in the investigation of NPs. This review provides a thorough overview of the state of the art in LC/MS-based metabolomics for the investigation of NPs. It covers the principles of LC/MS, various aspects of LC/MS-based metabolomics such as sample preparation, LC modes, method development, ionization techniques and data pre-processing. Moreover, it presents the applications of LC/MS-based metabolomics in numerous fields of NPs research such as including biomarker discovery, the agricultural research, food analysis, the study of marine NPs and microbiological research. Additionally, this review discusses the challenges and limitations of LC/MS-based metabolomics, as well as emerging trends and developments in this field.PMID:39474988 | DOI:10.1002/prca.202400048

Physiol Plant. 2024 Nov-Dec;176(6):e14585. doi: 10.1111/ppl.14585.ABSTRACTK+ accumulation in plant tissues is a crucial factor for plant growth and development. The tomato high-affinity K+ transporter SlHAK5 is essential for root K+ acquisition from low external concentrations. It is also involved in K+ accumulation in pollen and plant fertility as slhak5 KO plants show a low rate of pollen germination, impaired pollen tube growth and parthenocarpic fruits. Here, we present a thorough analysis of slhak5 flowers, which showed relevant defects at the anatomic, ionomic, metabolomic and transcriptomic levels. First, slhak5 flowers exhibited shorter styles and enlarged ovaries that, together with a low number of seeds in fruits from slhak5 X WT crosses, indicated an effect of the slhak5 mutation on female fertility. Second, a lower accumulation of Ca2+, as well as of several metabolites such as amino acids, citric acid and sugars, was observed in mutant flowers, whereas indole-3-acetic acid content was increased when compared to the wild-type. Third, RNAseq conducted on pistils and stamens of wild-type and slhak5 plants revealed that transport and signalling pathways are significantly enriched in the gene expression analyses of stamens. Thus, it can be concluded that a functional SlHAK5 transporter is required to maintain appropriate Ca2+, metabolite and gene expression levels in flowers, and its absence leads to important reductions in both male and female fertility.PMID:39474665 | DOI:10.1111/ppl.14585

Environ Health (Wash). 2023 May 30;1(1):32-40. doi: 10.1021/envhealth.3c00002. eCollection 2023 Jul 21.ABSTRACTLecithotrophic fish embryos rely on finite maternally deposited yolk resources for early development. Toxicant exposure can disrupt the uptake of yolk resources with consequences for development. In this study, we investigate the impacts of altered yolk utilization on fish embryos using the cardiotoxic compound phenanthrene. Zebrafish embryos were exposed to a cardiotoxic concentration of phenanthrene beginning at 6 hpf (hours post-fertilization) until a maximum of 72 hpf. Embryos were stained with Oil Red O to visualize neutral lipids. We then used a nontargeted approach to profile lipids in 24 and 72 hpf embryos after phenanthrene treatment. To assess changes in lipid movement within the embryo, the yolk sac was dissected from the body at 24 and 72 hpf and analyzed separately from the body at 72 hpf. Overall, total metabolites were significantly reduced in the yolk sac, and staining for neutral lipids was reduced in the embryo body at 72 hpf. This result is consistent with significant reductions in triglycerides in both the embryo body and yolk, indicating a limited contribution of impaired cardiac function to lipid mobilization at the dose tested. Additionally, lysophosphatidylcholines and lysophosphatidylethanolamines were significantly increased in the 72 hpf embryo body. Bioinformatic pathway analysis indicated that changes to these lysophospholipids could be linked to a disease model associated with inflammation and neuron demyelination consistent with previously observed injuries to neuronal and eye development in fish embryos and larvae.PMID:39474628 | PMC:PMC11504619 | DOI:10.1021/envhealth.3c00002

Front Pharmacol. 2024 Oct 15;15:1444439. doi: 10.3389/fphar.2024.1444439. eCollection 2024.ABSTRACTINTRODUCTION: Due to the high mortality rate and increasing severity of antibiotic resistance, there is a growing interest in new treatments for Klebsiella pneumoniae (KP)-induced pneumonia. Research has shown that the single herbs of SiHuangQingXinWan (SHQXW) are effective in treating pneumonia caused by KP. The PI3K/AKT signaling pathway has garnered attention for its potential role in the management of bacterial infections. This study aimed to evaluate the anti-pneumonia effect of SHQXW and to investigate its mechanism of action.MATERIALS AND METHODS: The potential plant metabolites and molecular targets of SHQXW in the context of pneumonia were determined through ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) and bioinformatics analysis. The therapeutic effect of SHQXW was evaluated in a KP-induced pneumonia murine model with imipenem/cilastatin as a positive control. Transcriptomics and non-targeted metabolomics were carried out to unveil potential mechanisms and targets for anti-pneumonia effects. Additionally, an in-depth exploration on the PI3K/AKT signaling pathway was conducted in this study.RESULTS: A total of 24 potential plant metabolites and 285 SHQXW-pneumonia-related targets selected by Homo sapiens were identified in this study. The tested doses of SHQXW significantly reduced mortality, improved body weight, decreased the lung index, reduced the bacterial load, and alleviated lung pathological damage in the KP-induced pneumonia murine model (p < 0.05). Notably, 1.3 g/kg/day of SHQXW provided the most effective protective outcome. Furthermore, SHQXW demonstrated the ability to suppress the production of inflammatory factors such as IL-1α, IL-1β, IL-3, IL-6, IL-12p70, G-CSF, GM-CSF, MCP-1, KC, and TNF-α. Analysis of transcriptomic and metabolomic data revealed that SHQXW could modulate inflammation-related signaling pathways (TNF, HIF-1, NF-κB, and PI3K/AKT) and metabolites to regulate pulmonary inflammation. Additional experiments using RT-qPCR and western blotting indicated that SHQXW may exert anti-inflammatory effects by activating the PI3K/AKT pathway.DISCUSSION: The findings indicate that SHQXW effectively reduces inflammation in mice with KP-induced pneumonia by modulating inflammatory signaling pathways and metabolites, rather than by directly inhibiting the growth of KP. This study introduces a novel treatment approach for KP-induced pneumonia and presents a new outlook on drug development.PMID:39474608 | PMC:PMC11519414 | DOI:10.3389/fphar.2024.1444439

World J Hepatol. 2024 Oct 27;16(10):1208-1212. doi: 10.4254/wjh.v16.i10.1208.ABSTRACTIn this letter, we comment on a recent publication by Mei et al, in the World Journal of Hepatology, investigating the hepatoprotective effects of the modified Xiaoyao San (MXS) formula in a male rat model of non-alcoholic steatohepatitis (NASH). The authors found that MXS treatment mitigated hepatic steatosis and inflammation in the NASH model, as evidenced by the reduction in lipid droplets (LDs), fibrosis markers and lipogenic factors. Interestingly, these hepatoprotective effects were associated with androgen upregulation (based on metabolomics analysis of male steroid hormone metabolites), adenosine 5'-monophosphate-activated protein kinase (AMPK) activation, and restoration of phosphatase and tensin homolog (PTEN) expression. However, the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model, and androgen upregulation, AMPK activation, and restoration of PTEN expression. This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model. As a perspective, we propose additional mechanisms (such as autophagy/lipophagy activation in hepatocytes) for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model. A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.PMID:39474573 | PMC:PMC11514612 | DOI:10.4254/wjh.v16.i10.1208

Environ Epidemiol. 2024 Oct 28;8(6):e352. doi: 10.1097/EE9.0000000000000352. eCollection 2024 Dec.ABSTRACTBACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a class of persistent synthetic chemicals that are found in human milk and are associated with negative health effects. Research suggests that PFAS affect both lactation and the human metabolome.METHODS: We measured perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in the milk of 425 participants from the New Hampshire Birth Cohort Study using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A nontargeted metabolomics assay was performed using LC with high-resolution MS, and metabolites were identified based on in-house database matching. We observed six metabolic profiles among our milk samples using self-organizing maps, and multinomial logistic regression was used to identify sociodemographic and perinatal predictors of these profiles, including infant sex, parity, participant body mass index, participant age, education, race, smoking status, gestational weight gain, and infant age at time of milk collection.RESULTS: Elevated PFOA was associated with profiles containing higher amounts of triglyceride fatty acids, glycerophospholipids and sphingolipids, and carnitine metabolites, as well as lower amounts of lactose and creatine phosphate. Lower concentrations of milk PFOS were associated with lower levels of fatty acids.CONCLUSION: Our findings suggest that elevated PFOA in human milk is related to metabolomic profiles consistent with enlarged milk fat globule membranes and altered fatty acid metabolism. Further, our study supports the theory that PFAS share mammary epithelial membrane transport mechanisms with fatty acids and associate with metabolic markers of reduced milk production.PMID:39474471 | PMC:PMC11521063 | DOI:10.1097/EE9.0000000000000352

Environ Health (Wash). 2024 Jul 1;2(10):729-738. doi: 10.1021/envhealth.4c00066. eCollection 2024 Oct 18.ABSTRACTAmbient ozone (O3) exposure may be associated with a reduction of semen quality, yet the potential biological mechanisms remain unclear. We investigated the effects of certain seminal plasma metabolites on mediating the links between O3 exposure and the deterioration of semen quality. The untargeted metabolomics analysis was performed on semen samples of 200 Chinese adult men to determine candidate metabolites associated with characteristics of semen quality. Mediation analysis was adopted to examine whether these metabolites modulated the links between O3 exposure and semen quality. We found a significant reduction in sperm concentration by -28.1% (95% CI: -41.7%, -11.3%), and sperm count by -29.2% (95% CI: -43.7%, -11.0%) associated with each 10 μg/m3 increase in ambient O3 concentration during the period of sperm development. We delineated 7 metabolites in seminal fluid that substantially mediated the links between O3 exposure and declined semen quality, including myristoleic acid, aspartyl-isoleucine, phenylethyl primeveroside, ACar (18:2), ACar (18:1), FAHFA (22:6/22:3), and LPS (22:5). Among these, myristoleic acid exhibited the most pronounced mediation effects, with its indirect effect of which accounts for 46.4% of the overall association. Our findings suggested that exposure to ozone decreased sperm quality by disrupting fatty acid metabolism, particularly myristoleic acid.PMID:39474432 | PMC:PMC11504433 | DOI:10.1021/envhealth.4c00066

Environ Health (Wash). 2024 Feb 14;2(4):221-232. doi: 10.1021/envhealth.3c00168. eCollection 2024 Apr 19.ABSTRACTEpidemiology has associated fine particulate matter (PM2.5) exposure with an increased cardiovascular risk. However, the underlying mechanism, particularly from the liver perspective, remains unclear. Here, the influence of chronic PM2.5 exposure on cardiovascular risk in mice fed a high-fat and high-cholesterol diet (HFCD) was studied by using a real-world PM2.5 exposure system. Results showed that PM2.5 exposure elevated the serum levels of nonhigh-density lipoprotein cholesterol (non-HDL-C) and oxidized low-density lipoprotein (oxLDL) in HFCD-fed mice, demonstrating increased cardiovascular risk. To investigate the molecular mechanism, lipidomics and metabolomics analyses were conducted and revealed that PM2.5 exposure enhanced lipid accumulation and disturbed purine metabolism and glutathione metabolism in the liver of HFCD-fed mice, contributing to the elevated non-HDL-C levels and intensified oxidative stress. Moreover, PM2.5 exposure increased total cholesterol levels by upregulating Hmgcr expression and downregulating Cyp7a1 expression in the livers of HFCD-fed mice. The HDL-C level was reduced by inhibiting the hepatic Abca1 and Abcg1 expression and decreasing the levels of ApoA-I and LCAT. Additionally, the PM2.5-induced pro-oxidative environment impeded the oxLDL clearance and further triggered inflammation, in turn exacerbating oxidative stress and oxLDL production. This study demonstrated a synergy of PM2.5 and HFCD on cardiovascular risk and illuminated the molecular mechanism in PM2.5-susceptible populations.PMID:39474144 | PMC:PMC11503791 | DOI:10.1021/envhealth.3c00168

iScience. 2024 Sep 11;27(10):110917. doi: 10.1016/j.isci.2024.110917. eCollection 2024 Oct 18.ABSTRACTThe portrayed effects of olanzapine on brain development and neuronal response remain unclear under the genetic background of Homo sapiens. Here, we constructed therapeutic-dosage olanzapine-treated cerebral organoid (CO) models using induced pluripotent stem cells from human samples. We found that the activation of NODAL/FOXH1 axis mediated the early response to olanzapine up to day 15, which subsequently caused thicker cortical-like structures, cell identity maturation, higher stemness of neural progenitor cells (NPCs), and mature neuronal firing of early neurons in day 24. Transcriptomics and targeted metabolomics confirmed the upregulation of neurodevelopmental-related terms and glutamate production on day 24. Gene enrichment of transcriptomics into large-scale genome-wide association studies (GWAS) showed possible relationships with intelligence, major depressive disorder, schizophrenia. We did not observe the negative effects of in-utero exposure to olanzapine in mice. Collectively, we tended to conclude that olanzapine treatment had beneficial effects instead of harmful on early brain development.PMID:39474064 | PMC:PMC11519431 | DOI:10.1016/j.isci.2024.110917

Front Cell Infect Microbiol. 2024 Oct 15;14:1397735. doi: 10.3389/fcimb.2024.1397735. eCollection 2024.ABSTRACTUlcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammatory tissue damage to the intestinal mucosa and forming intestinal epithelial ulcers. It is one of the most intractable diseases in the world. To date, the mechanism is unclear. Causonis japonica (Thunb.) Raf. (Wu Lianmei in Chinese; WLM), a traditional Chinese medicine, which has a long history as an anti-inflammatory, but its effect on UC was unconfirmed yet. Therefore, we established a dextran sodium sulfate (DSS)-induced UC mice model and evaluated the therapeutic effect of WLM extract. The results indicated that WLM inhibits DSS-induced inflammatory response in colitis in vivo, decrease DSS-induced clinical manifestations, reverses colon length shortening, and reduces tissue damage. The results of ELISA kits suggested that WLM could reverse the levels of DSS-induced inflammatory factors. To explore the mechanism of WLM in treating DSS-induced UC, 1H NMR and UHPLC-Q/Orbitrap MS were used to perform non-targeted metabolomics analysis; 21 differential metabolites in colon tissues were closely related to UC. Meanwhile, the pseudo-targeted lipidomics based on UHPLC-Q/Trap MS was used to analyze lipid metabolism disorders, and 60 differential lipid compounds were screened. These differential compounds were mainly involved in glycerophospholipid, arachidonic acid, glycerolipid, citric acid, tyrosine, and ether lipid metabolisms. The analysis of gut microbial showed that WLM may improve the symptoms of UC mice by reducing the abundance of Helicobacter and Streptococcus and increasing the abundance of Limosilactobacillus and Akkermansia. Moreover, the real-time qPCR results showed that WLM extract could decrease the mRNA levels of inflammatory factors and may be associated with protecting the integrity of intestinal mucosal barrier by destroying in vivo metabolic pathways, especially by regulating energy and lipid metabolisms and reducing inflammatory reactions. It provides a beneficial reference for studying WLM to elucidate the therapeutic mechanism of UC.PMID:39473926 | PMC:PMC11518848 | DOI:10.3389/fcimb.2024.1397735

Infect Drug Resist. 2024 Oct 25;17:4665-4683. doi: 10.2147/IDR.S475164. eCollection 2024.ABSTRACTINTRODUCTION: Our study investigated the disparities and correlations between oral microbiota and metabolites in pregnant patients with and without periodontitis.METHODS: Subgingival plaque samples from all subjects were collected for shotgun metagenomic sequencing and broad-target metabolomics analysis.RESULTS: Forty pathogens, including Porphyromonas gingivalis, Fusobacterium nucleatum, Eubacterium saphenum, Gemella morbillorum, Tannerella forsythia, Streptococcus anginosus group, Selenomonas sputigena etc, were significantly enriched in pregnant patients with periodontitis (PPP). Conversely, symbiotic species such as Morococcus cerebrosus, Streptococcus vestibularis, S. salivarius, S. mitis, and S. pneumoniae were significantly more abundant in healthy controls (HCs). A total of 87 predicted functional modules (PFMs) exhibited significant differences between the two groups; eight PFMs showed high enrichment in PPP with involvement of PPP-enriched species within these pathways. The remaining 79 PFMs encompassing ribonucleotide biosynthesis, carbohydrate, and amino acid metabolism were highly abundant in HCs. For oral microbial metabolome, a total of 105 metabolites related to 150 KEGG pathways displayed significant differences between the two groups. Pathways such as pyruvate metabolism, folate biosynthesis, vascular smooth muscle contraction, and AMPK/mTOR signaling pathway along with their associated metabolites were found to be enriched in PPP, while carbohydrate metabolism predominated among HCs. Spearman's rank correlation analysis revealed significant positive associations between species enriched in PPP and metabolites enriched in PPP, but significant negative associations between species enriched in PPP and metabolites enriched in HCs.DISCUSSION: Our findings provide potential biomarkers for distinguishing periodontitis during pregnancy while offering valuable insights into mechanisms exploration and clinical intervention.PMID:39473909 | PMC:PMC11520917 | DOI:10.2147/IDR.S475164

Front Microbiol. 2024 Oct 15;15:1456087. doi: 10.3389/fmicb.2024.1456087. eCollection 2024.ABSTRACTBACKGROUND: Low birth weight (LBW; <2,500 g) affects approximately 15 to 20 percent of global births annually and is associated with suboptimal child development. Recent studies suggest a link between the maternal gut microbiome and poor obstetric and perinatal outcomes. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings.METHODS: This was a secondary analysis of the Women First trial conducted in a semi-rural region of Guatemala. Maternal weight was measured at 12 and 34 weeks (wk) of gestation. Infant anthropometry measures were collected within 48 h of delivery. Maternal fecal samples at 12 and 34 weeks were used for microbiome (16S rRNA gene amplicon sequencing) and metabolomics analysis (34 wk). Linear mixed models using the MaAslin2 package were utilized to assess changes in microbiome associated with LBW. Predictive models using gradient boosted machines (XGBoost) were developed using the H2o.ai engine.RESULTS: No differences in β-diversity were observed at either time point between mothers with LBW infants relative to normal weight (NW) infants. Simpson diversity at 12 and 34 weeks was lower in mothers with LBW infants. Notable differences in genus-level abundance between LBW and NW mothers (p < 0.05) were observed at 12 weeks with increasing abundances of Barnesiella, Faecalibacterium, Sutterella, and Bacterioides. At 34 weeks, there were lower abundances of Magasphaera, Phascolarctobacterium, and Turicibacter and higher abundances of Bacteriodes, and Fusobacterium in mothers with LBW infants. Fecal metabolites related to bile acids, tryptophan metabolism and fatty acid related metabolites changed in mothers with LBW infants. Classification models to predict LBW based on maternal anthropometry and predicted microbial functions showed moderate performance.CONCLUSION: Collectively, the findings indicate that alterations in the maternal microbiome and metabolome were associated with LBW. Future research should target functional and predictive roles of the maternal gut microbiome in infant birth outcomes including birthweight.PMID:39473842 | PMC:PMC11518777 | DOI:10.3389/fmicb.2024.1456087

Adv Mater. 2024 Oct 30:e2409102. doi: 10.1002/adma.202409102. Online ahead of print.ABSTRACTCancer nanomedicine has emerged as a promising approach to overcome the limitations of conventional cancer therapies, offering enhanced efficacy and safety in cancer management. However, the inherent heterogeneity of tumors presents increasing challenges for the application of cancer nanomedicine in both diagnosis and treatment. This heterogeneity necessitates the integration of advanced and high-throughput analytical techniques to tailor nanomedicine strategies to individual tumor profiles. Omics technologies, encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and more, provide unparalleled insights into the molecular and cellular mechanisms underlying cancer. By dissecting tumor heterogeneity across multiple levels, these technologies offer robust support for the development of personalized and precise cancer nanomedicine strategies. In this review, the principles, techniques, and applications of key omics technologies are summarized. Especially, the synergistic integration of omics and nanomedicine in cancer therapy is explored, focusing on enhanced diagnostic accuracy, optimized therapeutic strategies and the assessment of nanomedicine-mediated biological responses. Moreover, this review addresses current challenges and outlines future directions in the field of omics-enhanced nanomedicine. By offering valuable insights and guidance, this review aims to advance the integration of omics with nanomedicine, ultimately driving improved diagnostic and therapeutic strategies for cancer.PMID:39473316 | DOI:10.1002/adma.202409102

Mol Nutr Food Res. 2024 Oct 30:e2400500. doi: 10.1002/mnfr.202400500. Online ahead of print.ABSTRACTSCOPE: This multi-omic study investigates the bidirectional interactions between gut microbiota and silymarin metabolism, highlighting the differential effects across various age groups. Silymarin, the extract from Silybum marianum (milk thistle), is commonly used for its hepatoprotective effects.METHODS AND RESULTS: An in vitro fermentation colon model was used with microbiota from 20 stool samples obtained from healthy donors divided into two age groups. A combination of three analytical advanced techniques, namely proton nuclear magnetic resonance (1H NMR), next-generation sequencing (NGS), and liquid chromatography-mass spectrometry (LC-MS) was used to determine silymarin microbial metabolites over 24 h, overall metabolome, and microbiota composition. Silymarin at a low diet-relevant dose of 50 µg mL-1 significantly altered gut microbiota metabolism, reducing short-chain fatty acid (acetate, butyrate, propionate) production, glucose utilization, and increasing alpha-diversity. Notably, the study reveals age-related differences in silymarin catabolism. Healthy elderly donors (70-80 years) exhibited a significant increase in a specific catabolite associated with Oscillibacter sp., whereas healthy young donors (12-45 years) showed a faster breakdown of silymarin components, particularly isosilybin B, which is associated with higher abundance of Faecalibacterium and Erysipelotrichaceae UCG-003.CONCLUSION: This study provides insights into microbiome functionality in metabolizing dietary flavonolignans, highlighting implications for age-specific nutritional strategies, and advancing our understanding of dietary (poly)phenol metabolism.PMID:39473280 | DOI:10.1002/mnfr.202400500

J Neurochem. 2024 Oct 30. doi: 10.1111/jnc.16244. Online ahead of print.ABSTRACTAlzheimer's disease (AD) pathogenesis involves dysregulation in diverse biochemical processes. Nevertheless, plasma tau phosphorylated at threonine 181 (P-tau181), a recognised AD biomarker, has been described to reflect early-stage cortical amyloid-β (Aβ) deposition in cognitively normal (CN) adults. Therefore, identifying changes in plasma metabolites associated with plasma P-tau181 at the pre-clinical stage may provide insights into underlying biochemical mechanisms to better understand initial AD pathogenesis. In the current study, plasma P-tau181, quantified via single molecule array (Simoa) technology, and plasma metabolites, quantified via targeted-mass spectrometry, were investigated for associations in CN older adults and upon stratification by positron emission tomography (PET)-Aβ load. In addition, the P-tau181-linked metabolites were evaluated for cognitive performance and neuroimaging markers of AD and the potential to distinguish between CN Aβ- and CN Aβ+ individuals. Significant positive associations of medium- and long-chain acylcarnitines (ACs) were observed with P-tau181 in the entire cohort, CN Aβ- and CN Aβ+, suggesting a link between initial Aβ pathology and fatty acid oxidation-mediated energy metabolism pathways. However, in CN Aβ-, additional linear associations of P-tau181 were observed with muscle metabolism and nitric oxide homeostasis-associated metabolites. Upon investigating the P-tau181-linked metabolites for cognitive performance, significant inverse correlations of the verbal and visual episodic memory and the global composite score were noted in CN Aβ+ with medium- and long-chain ACs, suggesting prognostic value of ACs accompanying weaker cognitive performance. While investigating neuroimaging markers, ACs had positive associations with PET-Aβ load and inverse associations with hippocampal volume in CN Aβ+, indicating connections of ACs with initial AD pathogenesis. Furthermore, based on receiver operating characteristics analysis, the associated ACs potentially classified PET-Aβ status in older adults. Therefore, plasma P-tau181-linked circulating ACs may serve as potential prognostic markers for initial AD pathogenesis in CN older adults. However, further cross-sectional and longitudinal research in highly characterised AD cohorts is needed to validate current findings.PMID:39473263 | DOI:10.1111/jnc.16244

Curr Mol Med. 2024 Oct 28. doi: 10.2174/0115665240296536240603112525. Online ahead of print.ABSTRACTBACKGROUND: Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. According to Traditional Chinese Medicine (TCM) syndromes theory, moist heat arthralgia spasm syndrome is the most prevalent syndrome of RA patients in the active period. However, the mechanism of alteration of gut microbiota in RA with moist heat arthralgia spasm syndrome has not been reported until now.OBJECTIVE: This study focused on the alteration of gut microbiota in adjuvant-induced arthritis rats with moist heat arthralgia spasm syndrome, elaborated its regulation mechanism, and analyzed the associations between gut microbiota and microbial metabolites.METHODS: The disease-syndrome combination rat model of RA with moist heat arthralgia spasm syndrome was constructed with Adjuvant-Induced Arthritis (AIA) under damp-heat stimulating. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure serum biochemical indicators. Damages of ankle joints were observed using hematoxylin and eosin (H&E). 16 small ribosomal subunit RNA (16S rRNA) gene sequencing was conducted to assess the gut microbiota composition and function on feces from rats. Alterations in fecal metabolites profiling were evaluated by fecal metabolomics through Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography-Mass Spectrometry (GC-MS). Pearson correlation analysis was performed to explore the associations of altered gut microbiota and microbial metabolites in Model rats.RESULTS: The imbalance of gut microbiota in Model rats was accompanied by metabolic disorders. Lactobacillus, Prevotellaceae_NK3B31_group, Allobaculum, Prevotellaceae_UCG_001, Alloprevotella, and Dubosiella were found to be dominant genera in Model rats. In total, 357 metabolites were significantly altered in Model rats and predominantly enriched into fatty acid degradation and glycerophospholipid metabolism. Pearson correlation analysis showed that TNF-α and IL-1β were associated with Prevotellaceae_Ga6A1_group and 3R-hydroxy-docosan-5S-olide, alpha-N-(3-hydroxy-14-methyl-pentadecanoyl)-ornithine, 17-methyl-trans-4,5- methylenenona-decanoic acid, Semiplenamide F.CONCLUSION: The key differential microbiota genera and differential microbial metabolites may become important targets for the treatment of RA and provide the theoretical basis for exploring the pathogenesis of RA.PMID:39473257 | DOI:10.2174/0115665240296536240603112525

Gut Microbes. 2024 Jan-Dec;16(1):2416928. doi: 10.1080/19490976.2024.2416928. Epub 2024 Oct 29.ABSTRACTBACKGROUND: The importance of gut microbes in mediating the benefits of lifestyle intervention is increasingly recognized. However, compared to the bacterial microbiome, the role of intestinal fungi in exercise remains elusive. With our established randomized controlled trial of exercise intervention in Chinese males with prediabetes (n = 39, ClinicalTrials.gov:NCT03240978), we investigated the dynamics of human gut mycobiome and further interrogated their associations with exercise-elicited outcomes using multi-omics approaches.METHODS: Clinical variations and biological samples were collected before and after training. Fecal fungal composition was analyzed using the internal transcribed spacer 2 (ITS2) sequencing and integrated with paired shotgun metagenomics, untargeted metabolomics, and Olink proteomics.RESULTS: Twelve weeks of exercise training profoundly promoted fungal ecological diversity and intrakingdom connection. We further identified exercise-responsive genera with potential metabolic benefits, including Verticillium, Sarocladium, and Ceratocystis. Using multi-omics approaches, we elucidated comprehensive associations between changes in gut mycobiome and exercise-shaped metabolic phenotypes, bacterial microbiome, and circulating metabolomics and proteomics profiles. Furthermore, a machine-learning algorithm built using baseline microbial signatures and clinical characteristics predicted exercise responsiveness in improvements of insulin sensitivity, with an area under the receiver operating characteristic (AUROC) of 0.91 (95% CI: 0.85-0.97) in the discovery cohort and of 0.79 (95% CI: 0.74-0.86) in the independent validation cohort (n = 30).CONCLUSIONS: Our findings suggest that intense exercise training significantly remodels the human fungal microbiome composition. Changes in gut fungal composition are associated with the metabolic benefits of exercise, indicating gut mycobiome is a possible molecular transducer of exercise. Moreover, baseline gut fungal signatures predict exercise responsiveness for diabetes prevention, highlighting that targeting the gut mycobiome emerges as a prospective strategy in tailoring personalized training for diabetes prevention.PMID:39473051 | DOI:10.1080/19490976.2024.2416928

J Biol Eng. 2024 Oct 29;18(1):61. doi: 10.1186/s13036-024-00457-w.ABSTRACTType 2 diabetes mellitus (T2DM) is a major public health concern with significant cardiovascular complications (CVD). Despite extensive epidemiological data, the molecular mechanisms relating hyperglycemia to CVD remain incompletely understood. We here investigated the impact of chronic hyperglycemia on human aortic smooth muscle cells (HASMCs) cultured under varying glucose conditions in vitro, mimicking normal (5 mmol/L), pre-diabetic (10 mmol/L), and diabetic (20 mmol/L) conditions, respectively. Normal HASMC cultures served as baseline controls, and patient-derived T2DM-SMCs served as disease controls. Results showed significant increases in cellular proliferation, area, perimeter, and F-actin expression with increasing glucose concentration (p < 0.01), albeit not exceeding the levels in T2DM cells. Atomic force microscopy analysis revealed significant decreases in Young's moduli, membrane tether forces, membrane tension, and surface adhesion in SMCs at higher glucose levels (p < 0.001), with T2DM-SMCs being the lowest among all the cases (p < 0.001). T2DM-SMCs exhibited elevated levels of selected pro-inflammatory markers (e.g., ILs-6, 8, 23; MCP-1; M-CSF; MMPs-1, 2, 3) compared to glucose-treated SMCs (p < 0.01). Conversely, growth factors (e.g., VEGF-A, PDGF-AA, TGF-β1) were higher in SMCs exposed to high glucose levels but lower in T2DM-SMCs (p < 0.01). Pathway enrichment analysis showed significant increases in the expression of inflammatory cytokine-associated pathways, especially involving IL-10, IL-4 and IL-13 signaling in genes that are up-regulated by elevated glucose levels. Differentially regulated gene analysis showed that compared to SMCs receiving normal glucose, 513 genes were upregulated and 590 genes were downregulated in T2DM-SMCs; fewer genes were differentially expressed in SMCs receiving higher glucose levels. Finally, the altered levels in genes involved in ECM organization, elastic fiber synthesis and formation, laminin interactions, and ECM proteoglycans were identified. Growing literature suggests that phenotypic switching in SMCs lead to arterial wall remodeling (e.g., change in stiffness, calcific deposits formation), with direct implications in the onset of CVD complications. Our results suggest that chronic hyperglycemia is one such factor that leads to morphological, biomechanical, and functional alterations in vascular SMCs, potentially contributing to the pathogenesis of T2DM-associated arterial remodeling. The observed differences in gene expression patterns between in vitro hyperglycemic models and patient-derived T2DM-SMCs highlight the complexity of T2DM pathophysiology and underline the need for further studies.PMID:39473010 | DOI:10.1186/s13036-024-00457-w