Inflammatory bowel disease (IBD) is characterized by recurrent abdominal pain, diarrhea, and mucopurulent bloody stools as its main clinical manifestations. In recent years, its parenteral manifestations have received increasing attention. Fatigue, as one of the extraintestinal manifestations of IBD, affects the quality of life of patients, and results in considerable distress for patients. The influencing factors of fatigue symptoms in IBD patients include inflammation, psychological comorbidities, sleep disorders, anemia, micronutrient deficiency, changes in microbiota, and metabolomics. The pathogenesis is currently unclear and may be related to disorders in tryptophan metabolism. This article will review the influencing factors and pathogenesis of fatigue symptoms in IBD patients, aiming to provide a basis for the prevention and treatment of IBD fatigue.
ObjectiveTo explore the metabolic changes during the differentiation of 3T3-L1 adipocytes caused by the treatment of the transient receptor potential vanilloid 4 (TRPV4)-specific agonist GSK1016790A basing on ultra-performance liquid chromatography-mass spectrometry technology. MethodsMouse 3T3-L1 cells were treated with GSK1016790A at different concentrations (0.1, 1, and 10 μmol/L), and the effect of drugs on cell proliferation was detected by cell counting kit-8 method. A mature adipocyte model was constructed, and GSK1016790A was used to activate TRPV4 channel protein activity and verify the expression levels of TRPV4 and triglycerides. Cell metabolites were collected for metabolomic studies, differential metabolites were screened between groups, and related metabolic pathways were analyzed. Results After GSK1016790A intervened in mature adipocytes, the expression levels of TRPV4 mRNA and triglycerides in cells were significantly upregulated (P<0.05). Metabolomics detection found that GSK1016790A screened a total of 45 differential metabolites such as 2-amino-1,3,4-octadecanetriol, linoleic acid, sphingosine, sphinganine, sn-glycerol-3-phosphate and uridine, mainly involving 13 possible metabolic pathways such as sphingolipid metabolism and biosynthesis of unsaturated fatty acids. Conclusion GSK1016790A may promote adipogenesis in adipocytes by activating TRPV4 channel protein activity, and at the same time participate in regulating metabolic pathways such as the biosynthesis of unsaturated fatty acids pathway and sphingolipid metabolism pathway, affecting lipid metabolism in adipocytes.
ObjectiveTo summarize the research results of metabolites of breast cancer based on metabonomics technology, and systematically reviews them in order to provide a new direction for the research of metabolism of breast cancer.MethodBy searching the relevant literatures in recent years, the application of metabonomics in identifying high-risk breast cancer population, monitoring the progress of tumor and evaluating the response of radiotherapy and chemotherapy were analyzed and summarized.ResultsWith the development of high-resolution, high-sensitivity and high-throughput bioanalysis platform technology, metabolomics had been widely used in breast cancer research field by virtue of its unique perspective and technical advantages to more accurately, systematically and dynamically monitor the changes of host metabolites.ConclusionMetabolomics technology provides a new research direction for primary prevention, early screening and diagnosis of breast cancer and optimal treatment strategy selection.
Objective To explore the effect of corn oligopeptide (COP) on dexamethasone-induced muscle atrophy. Methods Forty-nine male Sprague-Dawley rats aged 8 weeks were divided into blank group (n=10) and model group (n=39). The rats in the model group were intraperitoneally injected with dexamethasone (1.0 mg/kg), and the rats in the blank group were injected with normal saline. After 19 days, one rat in the blank group and three rats in the model group were taken to observe whether the model was successfully constructed. After successful modeling, the rats in the model group were randomly divided into model control group, COP low-dose group (COP-L group, 0.5 g/kg), COP medium-dose group (COP-M group, 1.0 g/kg) and COP high-dose group (COP-H group, 2.0 g/kg), with 9 rats in each group. After 33 days, the grip strength of the rats was measured, and then the gastrocnemius, soleus, tibialis anterior and metatarsal muscles were separated and weighed, and muscle fiber diameter, relative expression of Atrogin-1 and MuRF-1 mRNA were measured. Non-targeted metabolomics of gastrocnemius muscle were measured. Results Compared with that in the blank group, the body weight of rats in the model group reduced (P<0.05), and myofibril rupture was observed, indicating that the model was successful. Compared with those in the model control group, the grip strength increased in the COP-L and COP-M groups (P<0.05); the muscle coefficients of gastrocnemius and soleus in the COP-L and COP-H groups increased (P<0.05), and the muscle coefficients of plantaris in the COP-L and COP-M groups increased (P<0.05); the muscle fiber diameter of the tibial anterior muscle increased in the three doses of COP groups (P<0.05), and the muscle fiber diameter of the plantaris muscle increased in the COP-M and COP-H groups (P<0.05); the relative expression of Atrogin-1 mRNA decreased in the three doses of COP groups (P<0.05), while the relative expression of MurF-1 mRNA in the COP-L and COP-H groups decreased (P<0.05). The amino acid synthesis pathway, glycolysis pathway, and acid metabolism pathway were activated in gastrocnemius muscle. Conclusions COP can significantly improve the muscle atrophy induced by dexamethasone. The mechanism may be related to the decrease of Atrogin-1 and MuRF-1 expression in ubiquitin-proteasome pathway and the increase of amino acid biosynthesis.
Objective To investigates the metabolic changes in serum between patients with normal cognition of cerebral small vessel disease (CSVD) and those with cognitive impairment of CSVD. It aims to identify distinct metabolic pathways of CSVD-related cognitive impairment, which can provide new research directions for the diagnosis and treatment of this disease. Methods Serum samples from CSVD patients diagnosed in the Department of Neurology, West China Hospital of Sichuan University between July 2021 and December 2023 were used in this study. According to the patients’ Montreal Cognitive Assessment scores, they were divided into cognitively unimpaired CSVD group and cognitively impaired CSVD group. Untargeted metabolomic detection was performed using ultra-high performance liquid chromatography-tandem mass spectrometry. Quality control of the metabolomic data was conducted through correlation analysis of quality control samples. This study constructed an orthogonal partial least squares-discriminant analysis model to examine the relationship between metabolites and sample groups. Different metabolites were selected based on the criteria of P<0.05 and variable importance in projection >1, which were then subjected to metabolic pathway enrichment analysis. Results A total of 157 CSVD patients were included, including 51 cognitively unimpaired CSVD patients and 106 cognitively impaired CSVD patients. Untargeted metabolomics analysis, conducted in both positive and negative ion modes, identified a total of 68 significantly different metabolites between the cognitively unimpaired and cognitively impaired CSVD groups. These metabolites primarily consisted of lipids and lipid-like molecules, amino acids and their metabolites, and steroid hormones. Among these, the serum levels of 21 metabolites were increased in patients with CSVD-related cognitive impairment, while the levels of 47 metabolites were decreased. Further enrichment analysis revealed that these differential metabolites were predominantly enriched in 11 metabolic pathways, which included signaling pathways such as sphingolipid metabolism, protein digestion and absorption, and amino acid biosynthesis. Conclusions Compared with cognitively unimpaired CSVD patients, those with cognitive impairment showed increased levels of endogenous sphingolipids, such as phytosphingosine, and decreased levels of essential amino acids, including valine and leucine, in their serum. This suggests that lipid metabolism reprogramming and energy metabolism disturbances may be the main metabolic features in CSVD-related cognitive impairment. These different metabolites not only serve as promising biomarker candidates for CSVD-related cognitive impairment, but also offer new directions for investigating its pathological mechanisms.
ObjectiveTo explore the differences in metabolomic changes and metabolic pathways between the vitreous humor and serum of patients with early-onset proliferative diabetic retinopathy (PDR). MethodsA prospective observational study. From January to June 2025, 30 patients with PDR who underwent pars plana vitrectomy (PPV) in the Department of Ophthalmology, Peking University People's Hospital were included in the study. Patients were categorized into an early-onset PDR group (diagnosis age ≤40 years, n=10) and a late-onset PDR group (diagnosis age ＞40 years, n=20) based on the age at diabetes diagnosis. Fasting serum samples collected preoperatively and vitreous humor samples obtained intraoperatively were analyzed using untargeted metabolomics via ultra-high-performance liquid chromatography coupled with electrostatic field orbitrap tandem mass spectrometry. Differential metabolites were screened with thresholds of P＜0.05, variable importance in projection＞1, and fold change＞1.200 or ＜0.833. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). The Mann-Whitney U test was used to compare clinical data between the two groups. ResultsSignificant differences were observed between the early-onset and late-onset PDR groups in the age at diabetes diagnosis and diabetes duration (Z=?4.41, ?2.62; P＜0.05). Metabolomic analysis identified 37 differential metabolites in the vitreous humor (34 upregulated, 3 downregulated) and 42 in the serum (10 upregulated, 32 downregulated). The two most abundant classes of differential metabolites common to both sample types were carboxylic acids and derivatives (16.2% in vitreous, 16.7% in serum) and fatty acyls (13.5% in vitreous, 11.9% in serum). KEGG enrichment analysis revealed the tryptophan metabolism pathway was significantly enriched in the vitreous humor (enrichment factor=0.024, P＜0.05), with L-kynurenine and indole-3-acetamide as key differential metabolites. In the serum, the taurine and hypotaurine metabolism pathway was significantly enriched (enrichment factor=0.042, P＜0.05), with hydroxyethanesulfonic acid identified as a differential metabolite. ConclusionsEarly-onset PDR has characteristic metabolic disorders. The dual activation of the kynurenine and indole branches of tryptophan metabolism in the vitreous humor, alongside increased consumption in the taurine pathway in serum, may underlie its pathophysiology. Additionally, abnormalities in serum steroids and steroid derivatives suggest that dysregulated steroid hormone metabolism might contribute to disease progression.
