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To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.
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Neoplasias Colorrectales , Enterotoxinas , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Mapas de Interacción de ProteínasRESUMEN
BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory reaction, which is rare and life-threatening. According to the pathogen, HLH is divided into genetic and acquired. The most common form of acquired HLH is infection-associated HLH, of which Herpes viruses, particularly Epstein-Barr virus (EBV), are the leading infectious triggers. However, it is difficult to distinguish between simple infection with EBV and EBV-induced infection-associated HLH since both can destroy the whole-body system, particularly the liver, thereby increasing the difficulty of diagnosis and treatment. CASE SUMMARY: This paper elaborates a case about EBV-induced infection-associated HLH and acute liver injury, aiming to propose clinical guides for the early detection and treatment of patients with EBV-induced infection-associated HLH. The patient was categorized as acquired hemophagocytic syndrome in adults. After the ganciclovir antiviral treatment combined with meropenem antibacterial therapy and methylprednisolone inhibition to inflammatory response, gamma globulin enhanced immunotherapy, the patient recovered. CONCLUSION: From the diagnosis and treatment of this patient, attention should be paid to routine EBV detection and a further comprehensive understanding of the disease as well as early recognition and early initiation are keys to patients' survival.
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BACKGROUND: The "one-to-multiple" phenomenon is prevalent in medicinal herbs. Accurate species identification is critical to ensure the safety and efficacy of herbal products but is extremely challenging due to their complex matrices and diverse compositions. PURPOSE: This study aimed to identify the determinable chemicalome of herbs and develop a reasonable strategy to track their relevant species from herbal products. METHODS: Take Astragali Radix-the typical "one to multiple" herb, as a case. An in-house database-driven identification of the potentially bioactive chemicalome (saponins and flavonoids) in AR was performed. Furthermore, a pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data. Then based on the data matrix, the random forest algorithm was trained to predict Astragali Radix species from commercial products. RESULTS: The pseudotargeted metabolomics method was first developed and validated to obtain high-quality semi-quantitative data (including 56 saponins and 49 flavonoids) from 26 batches of AR. Then the random forest algorithm was well-trained by importing the valid data matrix and showed high performance in predicting Astragalus species from ten commercial products. CONCLUSION: This strategy could learn species-special combination features for accurate herbal species tracing and could be expected to promote the traceability of herbal materials in herbal products, contributing to manufacturing standardization.
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Planta del Astrágalo , Medicamentos Herbarios Chinos , Saponinas , Astragalus propinquus , Medicamentos Herbarios Chinos/farmacología , Bosques Aleatorios , Flavonoides , Saponinas/farmacologíaRESUMEN
Liver toxicity induced by Triptolide (TP) has limited its clinical application on rheumatoid arthritis (RA). Saponins have been proved as an efficacious remedy to mitigate hepatotoxicity. However, the mechanism of reducing hepatotoxicity by saponins intervention remains incompletely characterized. Tryptophan (Trp) metabolites activate transcriptional regulators to mediate host detoxification responses. Our study aimed to investigate whether Clematichinenoside AR (C-AR) could attenuate TP-induced liver damage by regulating Trp metabolism. We used targeted metabolomics to quantify Trp metabolites in the serum and liver samples of collagen-induced arthritis rats treated by TP. Multiple comparison analyses helped the evaluation of promising biomarkers. The pronounced changed levels of Trp, indole acetic acid, and indole-3-carboxaldehyde in the serum and indole acetic acid, indole, and tryptamine in the liver are relevant to TP-induced liver injury. Intervention with C-AR could relieve TP-induced hepatotoxicity evidenced by ameliorative serum parameters and hepatic histology. In addition, C-AR regulated the levels of these indoles biomarker candidates to normal. Therapeutic modulation with natural compounds might be a useful clinical strategy to ameliorate toxicity induced by TP. Deciphering Trp metabolism will facilitate a better understanding of the pathogenesis of diseases and drug responding.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Diterpenos , Fenantrenos , Saponinas , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Diterpenos/toxicidad , Compuestos Epoxi/toxicidad , Hígado , Fenantrenos/toxicidad , Ratas , Triterpenos , TriptófanoRESUMEN
Neurotransmitter (NT) abnormalities in the enteric nervous system have been reported as crucial roles to regulate the intestinal inflammation and gut immune homeostasis. Capturing quantitative changes at the NT metabolome provides an opportunity to develop an understanding of neuroimmune-mediated inflammation. Given the wide diversity of chemical characterizations in the NTs, only partial coverage of the NT metabolome can be simultaneously quantified in a single-run analysis. Herein, we summarized the distribution of functional groups of compound entries in the NT metabolome. Based on this information, an orthogonal dansyl-labeling and label-free dual pretreatment approach was separately designed to target phenol and amine NTs and tertiary amine and choline NTs. By combining the dansyl-labeled and unlabeled NTs within a single vial, a comprehensive and practical approach was optimized for quantifying high coverage of NT metabolome in a single-run analysis on the reversed-phase C18 column. Method validation indicated good linearity with correlation coefficients (R2) > 0.99, intra- and interday accuracy with relative error < ±20%, and precision with relative standard deviations of ≤15%. With this method, we could simultaneously monitor the alterations of cholines, amines, amino acids, tryptophan and phenylalanine biological pathways in dextran sulphate sodium-induced colitis mice. The measured levels of NT metabolome ranged from 0.0007 to 3.540 µg/mg in intestinal contents and 0.013-154.54 µg/mL in serum samples. The NT metabolism was disrupted by colitis, characterized by the changed NT levels in serum and excessive amino acid NTs accumulation in the intestinal contents. We envisage that the orthogonal approach is of great significance for the comprehensive determination of targeted metabolomics. NTs have the potential to be biomarkers for clinical metabolomics.
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Sistema Nervioso Entérico , Metabolómica , Animales , Biomarcadores/metabolismo , Sistema Nervioso Entérico/metabolismo , Metaboloma , Ratones , NeurotransmisoresRESUMEN
Oxidative stress and neuroinflammation play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced cognitive impairment. This study aims to observe the effect of electroacupuncture (EA) on the cognitive function in LPS-induced mice, and its regulation on hippocampal α7 nicotinic acetylcholine receptors (α7nAChR), oxidative and proinflammatory factors. Adult male C57BL/6 nice were used to establish animal model of LPS-induced cognitive impairment, and were randomly divided into three groups (nâ¯=â¯16): control group, model group (LPS: 5â¯mg/kg), and EA group. The cognitive function was measured by Morris water-maze test, and protein expression of α7nAChR in hippocampus was detected by immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to measure hippocampal proinflammatory cytokines. The results showed that LPS significantly impaired working and spatial memory of mice, which could be attenuated by EA treatment. EA prevented LPS-induced decrease of α7nAChR protein, acetylcholine (ACh) content and choline acetyltransferase (ChAT) activity, and prevented LPS-induced increase of acetylcholinesterase (AChE) activity (Pâ¯<â¯0.05). EA significantly decreased malondialdehyde (MDA) and hydrogen peroxide (H2O2), and increased the contents of catalase (CAT) and glutathione (GSH) in hippocampus of LPS-treated Mice (Pâ¯<â¯0.05). EA also prevented LPS-induced increase of proinflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in hippocampus (Pâ¯<â¯0.05). In conclusion, electroacupuncture can improve the learning and memory in LPS-treated mice, and its mechanism may be related to enhanced expression of α7-nAChR and cholinergic factors, and suppression of oxidative stress and neuroinflammation in hippocampus.