Metabolites最新文献

Background/objectives: Bone marrow adipose tissue (BMAT) has been described as an important biomechanic and lipotoxic factor with negative impacts on skeletal and hematopoietic system regeneration. BMAT undergoes metabolic and cellular adaptations with age and disease, being a source of potential biomarkers. However, there is no evidence on the lipid profile and cellularity at different skeletal locations in osteoarthritis patients undergoing primary hip arthroplasty.

Methods: Acetabular and femoral bone marrow (BM) and gluteofemoral subcutaneous adipose tissue (gfSAT) were obtained from matched patients undergoing hip replacement surgery. BM, BMAT, and gfSAT were explored at the levels of total lipids, fatty acids, and cells by using thin-layerand gas chromatography, ex vivo cellular assays, and flow cytometry.

Results: BMAT content was significantly higher in femoral than in acetabular BM. Total lipid analyses revealed significantly lower triglyceride content in femoral than in acetabular BMAT and gfSAT. Frequencies of saturated palmitic, myristic, and stearic acids were higher in femoral than in acetabular BMAT and gfSAT. The content of CD45⁺CD34⁺ cells within femoral BMAT was higher than in acetabular BMAT or gfSAT. This was associated with a higher incidence of total clonogenic hematopoietic progenitors and late erythroid colonies CFU-E in femoral BMAT when compared to acetabular BMAT, similar to their BM counterparts.

Conclusions: Collectively, our results indicate that the lipid profiles of hip bone and femoral BMAT impose significantly different microenvironments and distributions of cells with hematopoietic potential. These findings might bring forth new inputs for defining BMAT biology and setting novel directions in OA disease investigations.

Background: The influence of serum uric acid (SUA) on bone metabolism, as suggested by previous studies, remains a contentious issue. SUA plays a complex role in bone health and hypertension, making it challenging to discern its impact on the skeletal status of middle-aged and elderly hypertensive patients. This study aims to elucidate the effects of SUA on bone health, with a particular focus on its association with osteoporosis and the risk of fractures.

Methods: Multiple linear regression analyzed SUA levels against bone mineral density (BMD) and future fracture risk. Additionally, multivariate logistic regression was used to examine the association between SUA and osteoporosis. Dose-response relationship analysis was conducted using generalized smooth curve fitting (GSCF) and restricted cubic spline (RCS) methods.

Results: With the exception of the total femur region, SUA and BMD showed a positive connection. GSCF analysis revealed an inverted U-shaped relationship between SUA and BMD, alongside a U-shaped trend with FRAX scores. Moreover, RCS analysis indicated a U-shaped relationship between osteoporosis risk and SUA levels, with higher risks identified in the first and third tertiles compared to the second tertile.

Conclusions: In individuals with middle-aged and older hypertension, SUA is substantially linked to bone health. The identification of an inverted U-shaped relationship with BMD and U-shaped relationships with FRAX scores and osteoporosis risk highlights the nuanced influence of SUA. These findings suggest that both low and high SUA levels may adversely affect bone health, emphasizing the need for further research.

Background/Objectives: Metabolic profiling of human milk (HM) is indispensable for elucidating mother-milk-infant relationships. Methods: We evaluated the Biocrates MxP^® Quant 500 assay for HM-targeted metabolomics (106 small molecules, 524 lipids) and analyzed in a feasibility test HM from apparently healthy Brazilian mothers (A: 2-8, B: 28-50, C: 88-119 days postpartum, n_total = 25). Results: Of the 630 possible signatures detectable with this assay, 506 were above the limits of detection in an HM-pool (10 µL) used for assay evaluation, 12 of them above the upper limit of quantitation. Analyzing five different HM-pool volumes (2-20 µL) revealed acceptable linearity for 458 metabolites. Intraday accuracy of 80-120% was attained by 469 metabolites after spiking and for 342 after a 1:2 dilution. Analyzing HM from Brazilian mothers revealed significantly lower concentrations in colostrum vs. mature milk for many flow-injection analyses (FIA) and only a few LC-MS metabolites, including triglycerides, sphingomyelins, and phosphatidylcholines. Higher concentrations at the later lactation stages were found predominantly for amino acids and related compounds. Conclusions: The MxP Quant^® 500 assay is a useful tool for HM metabolic profiling, minimizing analytical bias between matrices, and enhancing our ability to study milk as a biological system.

Background/Objectives: This study explores the allelopathic effects of volatile organic compounds (VOCs) emitted by the invasive species Ailanthus altissima (Mill.) Swingle on the seed germination of Bidens pilosa. A. altissima is known for releasing allelopathic VOCs that suppress the growth of neighbouring plants, contributing to its invasive potential. Methods: To examine these effects, we exposed B. pilosa seeds to varying concentrations of A. altissima VOCs, assessing germination rates and metabolic changes through untargeted metabolomics. Results: Our findings revealed that VOCs from A. altissima significantly inhibited the germination speed and overall germination rates of B. pilosa in a dose-dependent manner. Metabolomic profiling showed disruptions in energy and amino acid metabolism pathways, specifically involving delayed breakdown of starch and key metabolites, indicating inhibition of critical metabolic processes during early germination stages. This metabolic delay likely impairs B. pilosa's establishment and competitiveness, enhancing A. altissima's ecological dominance. Conclusions: The results underscore the potential of VOC-based allelopathy as a mechanism of plant invasion, offering insights into the role of VOCs in interspecies plant competition and ecosystem dynamics.

Background/objectives: Silybum marianum extract, obtained via microwave-enhanced extraction, was evaluated for its antioxidant, antidiabetic, and antimicrobial activities to explore its therapeutic potential.

Methods: The extraction was performed using microwave-enhanced techniques, and LC-MS/MS was employed to profile the metabolites in the extract. Total phenolic and flavonoid contents were quantified using spectrophotometric methods. Antioxidant activity was assessed using DPPH, ABTS, CUPRAC, Phenanthroline, and FRAP assays. Enzyme inhibition assays were conducted to evaluate antidiabetic activity against α-glucosidase and α-amylase. Antimicrobial activity was determined using the disc diffusion method, and in silico ADMET and drug-likeness analyses were performed for key metabolites.

Results: The extract contained 251.2 ± 1.2 mg GAE/g of total phenolics and 125.1 ± 1.6 mg QE/g of total flavonoids, with 33 metabolites identified, including phenolic acids, tannins, flavonoids, and flavolignans. Strong antioxidant activity was observed, with IC₅₀ values of 19.2 ± 2.3 μg/mL (DPPH), 7.2 ± 1.7 μg/mL (ABTS), 22.2 ± 1.2 μg/mL (CUPRAC), 35.2 ± 1.8 μg/mL (Phenanthroline), and 24.1 ± 1.2 μg/mL (FRAP). Antidiabetic effects were significant, with IC₅₀ values of 18.1 ± 1.7 μg/mL (α-glucosidase) and 26.5 ± 1.3 μg/mL (α-amylase). Antimicrobial activity demonstrated inhibition zones of 8.9 ± 1.1 mm (Bacillus subtilis), 12.6 ± 1.6 mm (Escherichia coli), 8.2 ± 1.2 mm (Fusarium oxysporum), and 9.2 ± 1.1 mm (Aspergillus niger). In silico analyses showed high absorption, favorable metabolism and excretion, and minimal toxicity, with no hERG channel inhibition or hepatotoxicity.

Conclusions: The comprehensive results highlight the significant antioxidant, antidiabetic, and antimicrobial activities of S. marianum extract, suggesting its potential for therapeutic and preventive applications.

Background: Huntington's disease (HD) is a multifaceted neurological disorder characterized by the progressive deterioration of motor, cognitive, and psychiatric functions. Despite a limited understanding of its pathogenesis, research has implicated abnormal trinucleotide cytosine-adenine-guanine CAG repeat expansion in the huntingtin gene (HTT) as a critical factor. The development of innovative strategies is imperative for the early detection of predictive biomarkers, enabling timely intervention and mitigating irreversible cellular damage. Lipidomics, a comprehensive analytical approach, has emerged as an indispensable tool for systematically characterizing lipid profiles and elucidating their role in disease pathology.

Method: A MedLine search was performed to identify studies that use lipidomics for the characterization of HD. Search terms included "Huntington disease"; "lipidomics"; "biomarker discovery"; "NMR"; and "Mass spectrometry".

Results: This review highlights the significance of lipidomics in HD diagnosis and treatment, exploring changes in brain lipids and their functions. Recent breakthroughs in analytical techniques, particularly mass spectrometry and NMR spectroscopy, have revolutionized brain lipidomics research, enabling researchers to gain deeper insights into the complex lipidome of the brain.

Conclusions: A comprehensive understanding of the broad spectrum of lipidomics alterations in HD is vital for precise diagnostic evaluation and effective disease management. The integration of lipidomics with artificial intelligence and interdisciplinary collaboration holds promise for addressing the clinical variability of HD.

Chronic kidney disease (CKD) is a prevalent global health concern affecting approximately 850 million people worldwide, with a significant and rising mortality rate. CKD often coexists with hyperuricemia (HSUA), which is also increasingly common due to its association with hypertension, obesity, and diabetes. The interplay between hyperuricemia and CKD is complex; while in vitro studies and animal models support a role for uric acid mediating glomerular and tubule-interstitial damage, and HSUA has been shown to predict the onset and progression of CKD, the expectations of renal protection by the use of urate lowering treatment (ULT) are inconsistent. A significant challenge in managing asymptomatic HSUA in CKD patients lies in determining the appropriate SUA threshold values. Recent research, including the URRAH project, has sought to identify SUA cut-offs predictive of cardiovascular mortality, but these thresholds may vary depending on the severity of CKD. This variability complicates the establishment of universal guidelines for treating asymptomatic HSUA, leading to a lack of specific recommendations in clinical practice. In conclusion, while hyperuricemia is recognized as a prognostic factor for CKD and cardiovascular risk, more research is needed to refine the threshold values for SUA and to identify which patients may benefit from ULT. Stratification based on glomerular filtration rate may be necessary to tailor the treatments and improve outcomes in this population.

Background: Polysaccharides produced by the edible fungus Cordyceps cicadae can regulate blood sugar levels and may represent a suitable candidate for the treatment of diabetes and its complications. However, there is limited information available about the mechanism of how C. cicadae polysaccharide (CCP) might improve diabetic conditions. Methods: This study investigated its effects on the intestinal microbiota, intestinal mucosal barrier, and inflammation in mice with type 2 diabetes mellitus (T2DM) induced by streptozotocin, and its potential mechanisms. Results: Compared with the DC (diabetes model control group), CCPH oral treatment significantly increased the number of beneficial bifidobacteria, bifidobacteria, and lactobacilli (p < 0.01), restored the diversity of intestinal microorganisms in diabetic mice, and the proportions of Firmicutes and Bacteroidetes (34.36%/54.65%) were significantly lower than those of the DC (52.15%/32.09%). Moreover, CCPH significantly reduced the content of endotoxin (lipopolysaccharide, LPS) and D-lactic acid(D-LA) (p < 0.05), the activities of antioxidant enzymes and total antioxidant capacity were significantly increased (p < 0.01), and the content of proinflammatory cytokines TNF-α, IL-6, and IL-1β were reduced by 42.05%, 51.28%, and 52.79%, respectively, compared with the DC. The TLR4/NF-κB signaling pathway, as a therapeutic target for diabetic intestinal diseases, plays a role in regulating the inflammatory response and protecting the intestinal barrier function. Molecular mechanism studies showed that oral treatment with CCPH down-regulated the expression of NF-κB, TLR-4, and TNF-α genes by 18.66%, 21.58%, and 34.87%, respectively, while up-regulating the expression of ZO-1 and occludin genes by 32.70% and 25.11%, respectively. CCPH regulates the expression of short-chain fatty acid levels, increases microbial diversity, and ameliorates mouse colon lesions by inhibiting the TLR4/NF-κB signaling pathway. Conclusions: In conclusion, it is demonstrated that in this murine model, the treatment of diabetes with C. cicadae polysaccharide can effectively regulate intestinal microbiota imbalance, protect intestinal mucosal barrier function, and reduce inflammation in vivo, suggesting this natural product can provide a suitable strategy for the treatment of T2D-induced gut dysbiosis and intestinal health.

Background: Untreated hyperprolactinemia and autoimmune thyroiditis (Hashimoto's disease) seem to increase cardiometabolic risk. The cardiometabolic effects of cabergoline were less significant in young women with concurrent euthyroid Hashimoto's illness. This study sought to investigate if the detrimental effects of this condition on cabergoline efficacy are also evident in postmenopausal women. Methods: The study comprised 50 postmenopausal women exhibiting increased prolactin levels, with half qualifying for euthyroid Hashimoto's illness. The subjects with thyroid autoimmunity were matched with those without thyroid disease according to age, body mass index, and prolactin levels. In addition to prolactin, we assessed thyroid-stimulating hormone (TSH), thyroid antibodies, and glucose homeostasis markers: fasting glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), and glycated hemoglobin (HbA1c). Furthermore, we assessed plasma lipids, plasma uric acid levels, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and the urine albumin-to-creatinine ratio (UACR). The decadal cardiovascular risk was assessed with the Framingham Risk Score (FRS). Results: Before therapy, disparities existed among groups in HOMA1-IR, HDL cholesterol, antibody titers, uric acid, hsCRP, fibrinogen, homocysteine, UACR, and FRS. After six months of treatment, cabergoline successfully corrected prolactin levels (both total and monomeric) in women without thyroid disorders. This normalization correlated with decreases in HOMA1-IR, triglycerides, uric acid, hsCRP, fibrinogen, homocysteine, UACR, and FRS, as well as an elevation in HDL cholesterol. In women diagnosed with Hashimoto's disease, cabergoline's effects were limited to a reduction in prolactin levels, HOMA1-IR, and UACR, as well as an elevation in HDL cholesterol, with these alterations being less pronounced compared to women without thyroid illness. Conclusions: The cardiometabolic benefits of cabergoline were associated with the degree of prolactin concentration reduction. In women diagnosed with Hashimoto's disease, connections were noted between baseline levels and treatment-induced alterations in hsCRP. These data indicate that concurrent euthyroid autoimmune thyroiditis mitigates the cardiometabolic consequences of cabergoline.

Background: Sarcoidosis is a granulomatous disease affecting multiple organ systems and poses a diagnostic challenge due to its diverse clinical manifestations and absence of specific diagnostic tests. Currently, blood biomarkers such as ACE, sIL-2R, CD163, CCL18, serum amyloid A, and CRP are employed to aid in the diagnosis and monitoring of sarcoidosis. Metabolomics holds promise for identifying highly sensitive and specific biomarkers. This study aimed to leverage metabolomics for the early diagnosis of sarcoidosis and to identify metabolic phenotypes associated with disease progression. Methods: Serum samples from patients with sarcoidosis (n = 40, including stage 1 to stage 4), were analyzed for metabolite levels by semi-untargeted liquid chromatography-mass spectrometry (LC-MS). Metabolomics data from patients with sarcoidosis were compared with those from patients with COVID-19 and healthy controls to identify distinguishing metabolic biosignatures. Univariate and multivariate analyses were applied to obtain diagnostic and prognostic metabolic phenotypes. Results: Significant changes in metabolic profiles distinguished stage 1 sarcoidosis from healthy controls, with potential biomarkers including azelaic acid, itaconate, and glutarate. Distinct metabolic phenotypes were observed across the stages of sarcoidosis, with stage 2 exhibiting greater heterogeneity compared with stages 1, 3, and 4. Conclusions: we explored immunometabolic phenotypes by comparing patients with sarcoidosis with patients with COVID-19 and healthy controls, revealing potential metabolic pathways associated with acute and chronic inflammation across the stages of sarcoidosis.