PubMed

BMC Bioinformatics. 2024 Dec 26;25(1):391. doi: 10.1186/s12859-024-06016-w.ABSTRACTAs a heterogeneous disease, prostate cancer (PCa) exhibits diverse clinical and biological features, which pose significant challenges for early diagnosis and treatment. Metabolomics offers promising new approaches for early diagnosis, treatment, and prognosis of PCa. However, metabolomics data are characterized by high dimensionality, noise, variability, and small sample sizes, presenting substantial challenges for classification. Despite the wide range of applications of deep learning methods, the use of deep learning in metabolomics research has not been extensively explored. In this study, we propose a hybrid model, TransConvNet, which combines transformer and convolutional neural networks for the classification of prostate cancer metabolomics data. We introduce a 1D convolution layer for the inputs to the dot-product attention mechanism, enabling the interaction of both local and global information. Additionally, a gating mechanism is incorporated to dynamically adjust the attention weights. The features extracted by multi-head attention are further refined through 1D convolution, and a residual network is introduced to alleviate the gradient vanishing problem in the convolutional layers. We conducted comparative experiments with seven other machine learning algorithms. Through five-fold cross-validation, TransConvNet achieved an accuracy of 81.03% and an AUC of 0.89, significantly outperforming the other algorithms. Additionally, we validated TransConvNet's generalization ability through experiments on the lung cancer dataset, with the results demonstrating its robustness and adaptability to different metabolomics datasets. We also proposed the MI-RF (Mutual Information-based random forest) model, which effectively identified key biomarkers associated with prostate cancer by leveraging comprehensive feature weight coefficients. In contrast, traditional methods identified only a limited number of biomarkers. In summary, these results highlight the potential of TransConvNet and MI-RF in both classification tasks and biomarker discovery, providing valuable insights for the clinical application of prostate cancer diagnosis.PMID:39725937 | DOI:10.1186/s12859-024-06016-w

BMC Pregnancy Childbirth. 2024 Dec 26;24(1):868. doi: 10.1186/s12884-024-07097-4.ABSTRACTBACKGROUND: Delivery mode has been linked to child health, e.g., allergic disease. However, it remains unclear whether protein and metabolite differences across different delivery modes may underlie child development.METHODS: A cohort comprising 16 spontaneous onset vaginal delivery (VD), 16 prelabor cesarean delivery on maternal request (CS), and 8 intrapartum cesarean section (Intra_CS) women were analyzed using label-free proteomic and untargeted metabolomics assays on amniotic fluid and cord blood samples, respectively. We used weighted gene co-expression network analyses (WGCNA) to identify modules of highly correlated proteins or metabolites that associated with delivery modes and related clinical traits. KEGG enrichment analyses were performed to investigate the biological function of the identified modules. Integrative multiomics analysis was employed to examine the biological interplay between proteomic and metabolic interactions.RESULTS: Compared to the CS group, the proteomic and metabolomic profiles were similar between the Intra_CS and VD groups in our study. We did not identify any enriched protein or metabolite pathways related to immune development that could influence the risk of allergic diseases in offspring across different delivery modes. However, we identified seven protein modules correlated with the duration from the rupture of the membranes to full dilation of the cervix, with the actin cytoskeleton module significantly enriched. A metabolic module in cord blood that correlated with VD was enriched in subclasses including C21 steroids, steroid sulfates, and oxysterols. Integrative analysis of proteomic and metabolomic data suggested pathways related to mode of delivery and duration of labor, encompassing the actin cytoskeleton, NADP metabolic process, nicotinate, and nicotinamide metabolism in amniotic fluid, and the steroid hormone biosynthesis pathway in cord blood.CONCLUSIONS: Differences in steroid hormones and the actin cytoskeleton pathway according to proteomics and metabolomics in amniotic fluid and cord blood were more indicative of the labor process. These findings could guide future studies on delivery-associated biochemical pathways.PMID:39725908 | DOI:10.1186/s12884-024-07097-4

Invest New Drugs. 2024 Dec 27. doi: 10.1007/s10637-024-01489-1. Online ahead of print.ABSTRACTAntiangiogenic drugs may cause vascular normalization and correct hypoxia in tumors, shifting cells to mitochondrial respiration as the primary source of energy. In turn, the addition of an inhibitor of mitochondrial respiration to antiangiogenic therapy holds potential to induce synthetic lethality. This study evaluated the mitochondrial inhibitor ME-344 in combination with bevacizumab in patients with refractory metastatic colorectal cancer (mCRC). Patients were eligible if they had disease progression after standard therapies, adequate hematologic, hepatic and renal function, and no contraindications to bevacizumab. ME-344 was administered intravenously on days 1, 8 and 15 and bevacizumab on days 1 and 15 of 28-day cycles until disease progression or intolerance. The primary efficacy endpoint was progression-free survival (PFS) at week 16. In the 23 patients enrolled, the median age was 58 years, median number of prior lines of therapy was 4, and median interval from last therapy was 3 months. The most common adverse events (all grades/grade ≥ 3) were fatigue (48%/13%), abdominal pain (35%/4%), diarrhea (30%/4%) and constipation (30%/0%). No patient had an objective response; 9 patients (39%) achieved stable disease. The 16-week PFS was 30.6% (95% confidence interval [CI]: 12.2-51.3), the median PFS was 1.9 months (95% CI: 1.6-4.7), and the median overall survival was 6.7 months (95% CI: 3.4-not reached). ME-344 plus bevacizumab was well tolerated. Disease control was limited in this heavily pretreated patient population. Additional investigations in earlier lines are indicated, and extended-release ME-344 formulations may provide longer drug exposure to maximize benefit. (Trial registration number ClinicalTrials.gov NCT05824559. Registration date 22 March 2022).PMID:39725778 | DOI:10.1007/s10637-024-01489-1

Gut Microbes. 2025 Dec;17(1):2446391. doi: 10.1080/19490976.2024.2446391. Epub 2024 Dec 26.ABSTRACTResveratrol (RSV), a natural polyphenol, has been suggested to influence glucose and lipid metabolism. However, the underlying molecular mechanism of its action remains largely unknown due to its multiple biological targets and low bioavailability. In this study, we demonstrate that RSV supplementation ameliorates high-fat-diet (HFD)-induced gut microbiota dysbiosis, enhancing the abundance of anti-obesity bacterial strains such as Akkermansia, Bacteroides and Blautia. The critical role of gut microbiota in RSV-mediated anti-obesity effects was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation (FMT), which showed that RSV treatment effectively mitigates body weight, histopathological damage, glucose dysregulation and systematic inflammation associated with HFD. Metabolomics analysis revealed that RSV supplementation significantly increases the levels of the gut microbial flavonoid catabolite 4-hydroxyphenylacetic acid (4-HPA). Notably, 4-HPA was sufficient to reverse obesity and glucose intolerance in HFD-fed mice. Mechanistically,4-HPA treatment markedly regulates SIRT1 signaling pathways and induces the expression of beige fat and thermogenesis-specific markers in white adipose tissue (WAT). These beneficial effects of 4-HPA are partially abolished by EX527, a known SIRT1 inhibitor. Collectively, our findings indicate that RSV improve obesity through a gut microbiota-derived 4-HPA-SIRT1 axis, highlighting gut microbiota metabolites as a promising target for obesity prevention.PMID:39725607 | DOI:10.1080/19490976.2024.2446391

Lett Appl Microbiol. 2024 Dec 26:ovae116. doi: 10.1093/lambio/ovae116. Online ahead of print.ABSTRACTLactic acid bacteria are considered the safest alternative to antibiotics and have a broad range of applications in animal husbandry. Enterococcus faecalis is a primary component of the chicken gut microbiota; it is known for its ability to regulate intestinal microbial balance and its probiotic functions. In this study, E. faecalis strain AQ10 from isolated from was the chicken cecum and used a combination of whole-genome sequencing and phenotypic analyses to investigate its probiotic properties. Whole-genome sequencing revealed that the genome length of E. faecalis AQ10 is 2.98 Mbp, with an average guanine-cytosine content of 38.12%, and includes 2832 protein-coding genes. Genome mining tools were used to identify an antimicrobial compound gene cluster. Additionally, E. faecalis AQ10 exhibited probiotic characteristics in vivo and antibacterial effects in vitro, with organic acids potentially contributing to its anti-Klebsiella pneumoniae activity. Metabolomics analyses revealed that the supernatant of E. faecalis AQ10 contained seven organic acids. In conclusion, E. faecalis AQ10 demonstrates significant probiotic potential and may be a suitable candidate for use in livestock and poultry breeding.PMID:39725445 | DOI:10.1093/lambio/ovae116

J Ethnopharmacol. 2024 Dec 24:119284. doi: 10.1016/j.jep.2024.119284. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Pachysandra axillaris Franch., a traditional herbal medicine in Yunnan, has been used to treat traumatic injuries and stomach ailments, some of which were related to microbial infections in conventional applications, but, to the best of our knowledge, the antifungal bioactivity of this plant and its main antifungal components have not been previously reported.AIM OF THE STUDY: To identify the antifungal compounds of P. axillaris against fluconazole-resistant C. albicans in vitro and in vivo, and then elucidate the underlying mechanism of action.MATERIALS AND METHODS: The antifungal compounds were obtained by bioguided isolation, and then they were investigated in vitro by MIC, growth curves, time-kill assay, and drug resistance induction. The antifungal mechanism was explored using combined network pharmacology and metabolomic analysis, and further supported by analyzing sterol composition using LC-MS/MS, scanning and transmission electron microscopy observation of fungal cell morphology, examining its effects on cell membranes using the fluorescent probes and RT-qPCR. Additionally, the antifungal effect in vivo was evaluated by a murine C. albicans skin infection model.RESULTS: Three bioactive compounds from P. axillaris efficiently inhibited fluconazole-resistant C. albicans (MIC = 4 μg/mL), in which the major compound, pachysamine M, affected the ergosterol biosynthesis pathway by inhibiting ERG genes (ERG1, ERG4, ERG7, ERG9, and ERG24), leading to the accumulation of squalene, lanosterol, and zymosterol. So, pachysamine M targeted cell membranes in vitro by reducing the ergosterol level, to avoid drug resistance. In addition, it promoted wound healing, reduced fungal load, and alleviated inflammation in vivo.CONCLUSIONS: Pachysamine M, an antifungal compound without reported before, inhibited fluconazole-resistant C. albicans efficiently in vitro and in vivo, and its mechanism targeted cell membranes, reducing the risk of drug resistance, which validated the traditional use of P. axillaris for the treatment of fungal skin infections.PMID:39725364 | DOI:10.1016/j.jep.2024.119284

Bioresour Technol. 2024 Dec 24:132019. doi: 10.1016/j.biortech.2024.132019. Online ahead of print.ABSTRACTLow-temperature plasma (LTP) has gained significant attention recently due to its unique properties and potentially wide applications in agriculture, pharmaceuticals, medicine, cosmetics, and the food industries. Microalgae have become important to human life since they provide raw materials and bioactive products to industries. This review especially examines how LTP technology can be utilized to enhance microalgae growth and production of various metabolites and bioactive compounds such as astaxanthin, biofuel, lipid, protein, and polysaccharides through mutagenesis and/or stimulation ways, and suggests that LTP may be combined with multi-omics tools such as proteomics, transcriptome, metabolomics and advanced methods such as single-cell analysis techniques to provide a promising strategy for acquiring desirable strains in algal mutant breeding and for enhancing the production of bioactive compounds in the microalgae. By shedding light on the benefits and applications of LTP, we hope to inspire new solutions to the challenges of commercial-scale microalgae development.PMID:39725362 | DOI:10.1016/j.biortech.2024.132019

J Hazard Mater. 2024 Dec 25;486:136958. doi: 10.1016/j.jhazmat.2024.136958. Online ahead of print.ABSTRACTFlorfenicol (FF), a third-generation chloramphenicol antibiotic widely used in food-producing animals, has become a "pseudopersistent" environmental contaminant, raising concerns about its potential ecological and human health impacts. However, its bioaccumulation behavior and hepatotoxic mechanisms remain poorly understood. This study aims to address these gaps with a 28-day exposure experiment in adult zebrafish at 0.05 and 0.5 mg/L FF. Multiomic analyses (metabolomics, lipidomics, and transcriptomics), combined with histological and mitochondrial function assessments, were employed. Higher bioaccumulation was observed at 0.05 mg/L, potentially due to metabolic saturation at higher concentrations. Histological analysis revealed significant hepatic steatosis (>5 % steatosis area), indicative of moderate nonalcoholic fatty liver disease (NAFLD). Multiomic data demonstrated global dysregulation in energy metabolism, including marked alterations in lipids (accumulation of toxic sphingolipids, excessive fatty acids, and acylglycerol), amino acids, tricarboxylic acid cycle intermediates, and nucleotides. Crucially, mitochondrial dysfunction was identified as a central mechanism, with impaired respiratory chain activities, adenosine triphosphate depletion, elevated reactive oxygen species, and oxidative stress promoting NAFLD progression. These findings highlight mitochondrial impairment and oxidative stress as key drivers of FF-induced hepatotoxicity, providing novel insights into its toxicological mechanisms and emphasizing the ecological risks posed by antibiotic pollution in aquatic systems.PMID:39724715 | DOI:10.1016/j.jhazmat.2024.136958

Food Chem. 2024 Dec 19;469:142584. doi: 10.1016/j.foodchem.2024.142584. Online ahead of print.ABSTRACTSilkworm pupae are highly valuable as edible insects due to their nutritional and bioactive properties. Investigating the bioactive compounds within silkworm pupae can provide useful information for advanced processing and utilization of this resource. In this study, untargeted metabolomics analysis was employed to characterize the bioactive compounds present in silkworm pupae (Bombyx mori). A total of 93 bioactive compounds were putatively annotated, including 23 amino acids and their derivatives or metabolites, 21 lipids and their analogues, 17 phenolics, and others. Bioactive compounds in male and female silkworm pupae were analyzed using chemometrics. In the process, 34 bioactive compounds were screened as differential bioactive compounds. Bioinformatics analysis was then conducted on the differential bioactive compounds to gain a deeper understanding of these disparities. Based on the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, 34 metabolic pathways related to these differential metabolites were putatively annotated.PMID:39724699 | DOI:10.1016/j.foodchem.2024.142584

J Exp Bot. 2024 Dec 26:erae507. doi: 10.1093/jxb/erae507. Online ahead of print.ABSTRACTOur current agricultural system faces a perfect storm-climate change, burgeoning population, and unpredictable outbreaks like COVID-19 disrupt food production, particularly for vulnerable populations in developing countries. A paradigm shift in agriculture practices is needed to tackle these issues. One solution is the diversification of crop production. While ~56% of the protein consumed from plants stems from three major cereal crops (rice, wheat and maize), underutilized crops such as millets, legumes and other cereals are highly neglected by farmers and the research community. Millets are one of the most ancient and versatile orphan crops with attributes like fast-growing, high-yielding, withstanding harsh environments, and rich in micronutrients such as iron and zinc, making them appealing to achieve agronomic sustainability. Here, we highlight the contribution of millet to agriculture and pay attention to the latest research on the genetic diversity of millet, genomic resources, and next-generation omics and their applications under various stress conditions. Additionally, integrative omics technologies could identify and develop millets with desirable phenotypes having high agronomic value and mitigating climate change. Here, we emphasize that biotechnological interventions, such as genome-wide association, genomic selection, genome editing, and artificial intelligence/machine learning, can improve and breed millets more effectively.PMID:39724286 | DOI:10.1093/jxb/erae507

Perfusion. 2024 Dec 26:2676591241311726. doi: 10.1177/02676591241311726. Online ahead of print.ABSTRACTINTRODUCTION: Cardioplegia (CP) is integral to myocardial protection during cardiac surgery. Two standard cardioplegic solutions viz. Del Nido solution (DNS) and St Thomas solution (STS) are widely used in cardiac surgeries. The DNS is a single-dose CP that offers superior myocardial protection in adults, and studies have claimed myocardial injury in STS patients. The elevated circulatory level of citric acid cycle intermediate, succinate is a metabolic hallmark of ischemia. Its rapid oxidation after reperfusion causes ischemia-reperfusion (IR) injury through mitochondrial reactive oxygen species production. Succinate has been identified as an early marker of IR injury through blood plasma/serum-based clinical metabolomics studies. The primary objective of the study was metabolomic profiling of succinate from the coronary sinus and venous blood.METHODS: Two blood samples each were obtained from coronary sinus (CS) & venous reservoir from patients before the application of aortic cross-clamp and after the release of aortic cross-clamp from 22 patients divided into two groups. The blood-serum metabolic profiles were measured by 800 MHz NMR spectrometer and compared using univariate statistical analysis methods. The study also compared the two groups' cardiopulmonary bypass variables and left ventricle functions.RESULT: DNS leads to increased serum levels of succinate in the coronary sinus blood after the reperfusion compared to STS. The results of our study are consistent with a previous study that found DNS administration (90 minutes) increases the inflammatory response in the myocardium.CONCLUSION: NMR-based serum metabolomics revealed significantly increased circulatory succinate in coronary sinus blood of patients administered with DNS cardioplegia in comparison to STS cardioplegia. URL- https://ctri.nic.in/Clinicaltrials/login.php.PMID:39724051 | DOI:10.1177/02676591241311726

J Agric Food Chem. 2024 Dec 26. doi: 10.1021/acs.jafc.4c08160. Online ahead of print.ABSTRACTSalicylic acid (SA) exhibits positive effects against Citrus Huanglongbing (HLB), but how SA affects citrus resistance to HLB is currently unknown. This study conducted integrated transcriptome and metabolome analyses on SA-treated Citrus sinensis (HLB-sensitive) and Poncirus trifoliata (HLB-tolerant). The results indicated that the syntheses of flavones and flavonols were induced by SA, while the expression levels of associated genes and the contents of corresponding metabolites varied significantly between the two species after SA treatment or HLB infection. These differences may underpin the enhanced HLB management through SA treatment and the inherent HLB tolerance of P. trifoliata. Furthermore, two insertions of miniature inverted-repeat transposable element (MITE) were identified within the promoter of PtrF3'H in P. trifoliata, whereas none were found in the promoter of CsF3'H in C. sinensis. These MITE insertions notably enhanced the promoter activity of PtrF3'H in an SA-dependent manner. Our findings deepen the understanding of the correlation between SA response and HLB tolerance in Citrus.PMID:39723904 | DOI:10.1021/acs.jafc.4c08160

Phytochem Anal. 2024 Dec 26. doi: 10.1002/pca.3493. Online ahead of print.ABSTRACTINTRODUCTION: The roots and rhizomes of Curcuma longa L. serve as distinct traditional Chinese medicines with varying therapeutic effects, likely attributed to differences in the accumulation and distribution of metabolites in these parts.OBJECTIVE: The study aims to investigate the differences and spatial distribution patterns of metabolites in C. longa L. roots and rhizomes.METHODS: Metabolite analysis of roots and rhizomes was conducted using ultra-high-performance liquid chromatography-quadruple orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) combined with desorption electrospray ionization mass spectrometry imaging (DESI-MSI). Using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to screen for differential metabolites. The relative contents of differential metabolites were visualized using heat maps. Additionally, the spatial distribution of differential metabolites was analyzed based on DESI-MSI.RESULTS: A total of 49 main chemical components were identified in roots and rhizomes using UHPLC-Q-Orbitrap HRMS. Through nontargeted metabolomics analysis combining UHPLC-Q-Orbitrap HRMS with PCA and OPLS-DA, 24 differential markers were identified; Additionally, using DESI-MSI alongside PCA and OPLS-DA, 18 differential markers were selected. Based on the DESI-MSI results, curcuminoids and sesquiterpenoids, including bisdemethoxycurcumin, demethoxycurcumin, furanodienone, furanogermenone, furanodiene, β-elemene, and curzerene, were more abundant in the rhizomes compared to the roots. And these differential compounds exhibited spatial distribution differences in the epidermis, phloem, and xylem between the roots and rhizomes.CONCLUSION: The metabolomics analysis using UHPLC-Q-Orbitrap HRMS combined with DESI-MSI suggest differences in the accumulation and spatial distribution of metabolites in C. longa L. roots and rhizomes, possibly related to the biosynthesis of secondary metabolites.PMID:39723548 | DOI:10.1002/pca.3493

Arterioscler Thromb Vasc Biol. 2024 Dec 26. doi: 10.1161/ATVBAHA.124.322112. Online ahead of print.ABSTRACTBACKGROUND: To explore the association of social isolation with venous thromboembolism (VTE) risk and the mediating role of metabolomics on this association.METHODS: Overall, 236 026 participants free of VTE and with complete metabolomics data at baseline from the UK Biobank were included. Social isolation was constructed based on the frequency of friend/family visits, weekly group activities, and living alone. The study outcome was incident VTE, including deep vein thrombosis or pulmonary embolism. Least absolute shrinkage and selection operator regression was applied to create a social isolation-associated metabolic signature. We estimated hazard ratios of study outcomes in relation to social isolation/metabolic signature and calculated the proportion of social isolation-VTE association mediated by the metabolic signature.RESULTS: During a median follow-up of 12.5 years, 6681 VTE cases were recorded. Social isolation was positively associated with VTE risk (versus without social isolation; hazard ratio, 1.17 [95% CI, 1.09-1.27]). A metabolic signature for social isolation was constructed using 28 metabolites. This metabolic signature showed significant association with VTE risk (per SD increment; hazard ratio, 1.16 [95% CI, 1.13-1.19]) and mediated 11.0% (95% CI, 7.0-19.8) of the increased VTE risk associated with social isolation. 11 metabolites in the metabolic signature also significantly mediated the association between social isolation and VTE risk, with mediation proportions ranging from 0.5% to 2.6%. Similar results were found for incident deep vein thrombosis and pulmonary embolism, respectively.CONCLUSIONS: Social isolation was positively associated with VTE risk. The metabolic signature for social isolation, especially the 11 major metabolites included, significantly mediated the association between social isolation and VTE risk.PMID:39723538 | DOI:10.1161/ATVBAHA.124.322112

Pest Manag Sci. 2024 Dec 26. doi: 10.1002/ps.8618. Online ahead of print.ABSTRACTBACKGROUND: Casuarina equisetifolia, a crucial species of coastal windbreaks, is highly susceptible to infestation by Anoplophora chinensis. This stem-boring pest poses a significant threat to the health and sustainability of Casuarina equisetifolia forests. Understanding the molecular mechanisms underlying the host preference of A. chinensis to Casuarina equisetifolia is essential for developing effective pest management strategies.RESULTS: Through field surveys, we identified two cultivars of Casuarina equisetifolia that exhibited differing levels of host preference for A. chinensis. Further analysis of multi-omics data (phenomics, transcriptomics, and metabolomics) from these cultivars revealed that longifolene plays a significant role in attracting A. chinensis to Casuarina equisetifolia. Additionally, the jasmonic acid (JA) signaling pathway was found to suppress longifolene accumulation, primarily through the interaction between the jasmonate ZIM-domain (JAZ) proteins and the terpene synthase (TPS) gene. Moreover, we identified a critical JAZ component, CeJAZ3, whose overexpression led to the down-regulation of TPS expression levels and, consequently, a reduced release of longifolene.CONCLUSION: We confirmed that the negative regulator of host preference, CeJAZ3, in the JA signaling pathway can suppress the expression of TPSs, thereby down-regulating the accumulation of longifolene in Casuarina equisetifolia and indirectly suppressing the attraction of host plants to A. chinensis, which provides a basis for the integrated management of A. chinensis. © 2024 Society of Chemical Industry.PMID:39723485 | DOI:10.1002/ps.8618

J Pineal Res. 2025 Jan;77(1):e70023. doi: 10.1111/jpi.70023.ABSTRACTLight environment in the Arctic differs widely with the seasons. Studies of relationships between objectively measured circadian phase and amplitude of light exposure and melatonin in community-dwelling Arctic residents are lacking. This investigation combines cross-sectional (n = 24-62) and longitudinal (n = 13-27) data from week-long actigraphy (with light sensor), 24-h salivary melatonin profiles, and proxies of metabolic health. Data were collected within the same week bracketing spring equinox (SE), and winter/summer solstices (WS/SS). Drastic seasonal differences in blue light exposure (BLE) corresponded to seasonal changes in the 24-h pattern of melatonin, which was phase delayed and reduced in normalized amplitude (NA) during WS/SS compared to SE. The extent of individual melatonin's acrophase and Dim Light Melatonin Onset (DLMO) change from SE to WS correlated with that from SE to SS. Although similar in extent and direction, melatonin phase changes versus SE were linked to morning BLE deficit in WS, contrasting to evening BLE excess in SS. Seasonal changes in sleep characteristics were closely associated with changes in the phases of BLE and melatonin. Proxies of metabolic health included triglycerides (TG), high-density lipoprotein cholesterol (HDL), TG/HDL ratio, and cortisol. Adverse seasonal changes in these proxies were associated with delayed acrophases of BLE and melatonin during WS and SS. TG and TG/HDL were higher in WS and SS than in SE, and cross-sectionally correlated with later melatonin and BLE acrophases, while lower HDL was associated with later BLE onset and later melatonin acrophase. Overall, this study shows that optimal 24-h patterns of light exposure during SE is associated with an earlier acrophase and a larger 24-h amplitude of melatonin, and that both features are linked to better metabolic health. Improving light hygiene, in particular correcting winter morning light deficit and summer evening light excess may help maintain metabolic health at high latitudes. Novel solutions for introducing proper circadian light hygiene such as human-centric light technologies should be investigated to address these issues in future studies.PMID:39723449 | DOI:10.1111/jpi.70023

Clin Cosmet Investig Dermatol. 2024 Dec 21;17:2999-3011. doi: 10.2147/CCID.S495217. eCollection 2024.ABSTRACTBACKGROUND: The onset of atopic dermatitis (AD) is complex, and its specific pathological mechanisms have not yet been fully elucidated.METHODS: Using circulating multi-omics as the exposure factors and AD as the outcome, we conducted univariable MR analysis. The circulating multi-omics data included immunomics (731 immune cell types), proteomics (4907 plasma proteins), metabolomics (1400 metabolites and 486 additional metabolites), and 91 inflammatory factors. MR analysis was conducted using IVW, WM, Simple Mode, Weighted Mode, and MR-Egger methods, with IVW as the primary analysis tool. To address horizontal pleiotropy, we utilized MR-Egger intercept tests and MR-PRESSO for correction, alongside the Cochrane Q statistic for heterogeneity assessment. Sensitivity analysis was performed using a leave-one-out strategy. To control for false positives due to multiple testing, we set a standard of a 5% false discovery rate. Additionally, we conducted F-statistics on the included SNPs to eliminate the impact of weak instrumental variables.RESULTS: IL-18R1 on AD (OR = 1.12, 95% CI: 1.08-1.17, P FDR < 0.01). Mannonate levels on AD (OR = 0.88, 95% CI: 0.83-0.94, P FDR = 0.03). Retinol (Vitamin A) to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) on AD (OR = 1.12, 95% CI: 1.06-1.18, PFDR = 0.03). HVEM on CM CD4+ cells on AD (OR = 0.81, 95% CI: 0.75-0.88, P FDR < 0.01). CR2 on AD (OR = 0.81, 95% CI: 0.72-0.90, P FDR = 0.04). MANSC1 on AD (OR = 0.87, 95% CI: 0.81-0.93, P FDR = 0.04). IL18R1 (4097 inflammatory markers) on AD (OR = 1.11, 95% CI: 1.06-1.17, P FDR = 0.01). HNRNPAB on AD (OR = 1.44, 95% CI: 1.23-1.70, P FDR < 0.01).CONCLUSION: This study further explored the correlations between multi-omics data and AD. We identified seven previously unreported circulating substances with causal relationships to AD, filling a current theoretical gap.PMID:39723341 | PMC:PMC11669345 | DOI:10.2147/CCID.S495217

Cureus. 2024 Nov 25;16(11):e74381. doi: 10.7759/cureus.74381. eCollection 2024 Nov.ABSTRACTSalivaomics has emerged as a ground-breaking field in the detection and management of oral cancer (OC), offering a non-invasive, efficient, and patient-friendly alternative to traditional diagnostic methods. This innovative approach leverages the comprehensive molecular insights provided by genomics, transcriptomics, proteomics, metabolomics, and microbiomics. The potential of salivaomics lies in its ability to enable early detection, predict malignant transformation, and monitor treatment outcomes and disease recurrence. Advancing salivary diagnostics necessitates the standardization of saliva collection and processing protocols, identification and validation of robust biomarkers, and development of cutting-edge detection technologies. A single biomarker is unlikely to fulfill all diagnostic requirements; thus, research should focus on developing a panel of biomolecules to enhance diagnostic accuracy and management of OC. Salivaomics stands at the forefront of non-invasive diagnostic methods, with the promise to revolutionize early detection and management of OC. Future research directions should emphasize the integration of multi-omics data for superior biomarker discovery, the development of portable and cost-effective point-of-care devices, and the fostering of interdisciplinary collaborations to drive innovation. Overcoming these challenges will facilitate the translation of salivaomics into routine clinical practice, significantly improving early diagnosis, treatment, and prognosis of OC. This review provides a comprehensive overview of salivaomics, detailing the use of saliva as a diagnostic fluid. It covers saliva collection, preparation, transportation, storage methods, and various analytical techniques. Additionally, the review discusses the current challenges and future directions of this transformative technology, emphasizing its potential to enhance clinical outcomes in OC.PMID:39723315 | PMC:PMC11669377 | DOI:10.7759/cureus.74381

Front Cell Dev Biol. 2024 Dec 11;12:1500474. doi: 10.3389/fcell.2024.1500474. eCollection 2024.ABSTRACTDiabetic retinopathy (DR) is a leading global cause of vision impairment, with its prevalence increasing alongside the rising rates of diabetes mellitus (DM). Despite the retina's complex structure, the underlying pathology of DR remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) and recent advancements in multi-omics analyses have revolutionized molecular profiling, enabling high-throughput analysis and comprehensive characterization of complex biological systems. This review highlights the significant contributions of scRNA-seq, in conjunction with other multi-omics technologies, to DR research. Integrated scRNA-seq and transcriptomic analyses have revealed novel insights into DR pathogenesis, including alternative transcription start site events, fluctuations in cell populations, altered gene expression profiles, and critical signaling pathways within retinal cells. Furthermore, by integrating scRNA-seq with genetic association studies and multi-omics analyses, researchers have identified novel biomarkers, susceptibility genes, and potential therapeutic targets for DR, emphasizing the importance of specific retinal cell types in disease progression. The integration of scRNA-seq with metabolomics has also been instrumental in identifying specific metabolites and dysregulated pathways associated with DR. It is highly conceivable that the continued synergy between scRNA-seq and other multi-omics approaches will accelerate the discovery of underlying mechanisms and the development of novel therapeutic interventions for DR.PMID:39723239 | PMC:PMC11668801 | DOI:10.3389/fcell.2024.1500474

Phenomics. 2024 Mar 6;4(5):487-521. doi: 10.1007/s43657-023-00153-7. eCollection 2024 Oct.ABSTRACTHigh-throughput technologies for multiomics or molecular phenomics profiling have been extensively adopted in biomedical research and clinical applications, offering a more comprehensive understanding of biological processes and diseases. Omics reference materials play a pivotal role in ensuring the accuracy, reliability, and comparability of laboratory measurements and analyses. However, the current application of omics reference materials has revealed several issues, including inappropriate selection and underutilization, leading to inconsistencies across laboratories. This review aims to address these concerns by emphasizing the importance of well-characterized reference materials at each level of omics, encompassing (epi-)genomics, transcriptomics, proteomics, and metabolomics. By summarizing their characteristics, advantages, and limitations along with appropriate performance metrics pertinent to study purposes, we provide an overview of how omics reference materials can enhance data quality and data integration, thus fostering robust scientific investigations with omics technologies.PMID:39723231 | PMC:PMC11666855 | DOI:10.1007/s43657-023-00153-7