Ras-related C3 botulinum toxin substrate 1 (rac1) has been implicated in tumor epithelial-mesenchymal transition (EMT); however, limited information is available regarding the role of rac1 in epithelial ovarian cancer (EOC). This study aimed to evaluate the correlation of rac1 expression with EMT and EOC prognosis. Rac1 protein levels of 150 EOC specimens were evaluated by immunohistochemical staining. Survival analysis was performed to determine the correlation between rac1 expression and survival. Cellular and molecular changes were also examined after rac1 in ovarian cancer cells was silenced in vitro and in vivo. The mechanism of rac1 on EMT was investigated by Western blot analysis. Rac1 was highly expressed in EOC. Rac1 overexpression was closely associated with advanced stage based on International Federation of Gynecology and Obstetrics, poor grade, serum Ca-125, and residual tumor size. Survival analyses demonstrated that patients with high rac1 expression levels were more susceptible to early tumor recurrence with very poor prognosis. This study revealed that rac1 downregulation decreased cell EMT and proliferation capability in vitro and in vivo. Rac1 expression possibly altered cell EMT by interacting with p21-activated kinase 1 and p38 mitogen-activated protein kinase signaling pathways. The present study showed that rac1 overexpression is associated with cell EMT and poor EOC prognosis. Rac1 possibly plays an important role in predicting EOC metastasis.
This study aimed to explore the molecular mechanism by which mesenchymal stem cells (MSCs) mediate lung cancer progression. Extracellular vesicles (EVs) were isolated from transfected or untransfected MSCs, and were co-cultured with lung cancer cells with/without microRNA-130b-3p (miR-130b-3p) inhibitor, mimic, overexpression plasmids of FOXO3/NFE2L2, or shRNAs. CCK-8 assay, colony formation, transwell assay, and flow cytometry were carried out to determine the biological functioning of lung cancer cells. Furthermore, FOXO3, Keap1, NFE2L2, and TXNRD1 expression was determined by qRT-PCR and western blot analysis. A tumor xenograft mouse model was used to determine role of EVs-miR-130b-3p and its target FOXO3 in lung cancer progression in vivo . miR-130b-3p was highly expressed in lung cancer tissues and MSC-derived EVs. Moreover, the MSC-derived EVs transferred miR-130b-3p to lung cancer cells to promote cell proliferation, migration, and invasion while repress cell apoptosis. miR-130b-3p directly targeted FOXO3, and FOXO3 elevated Keap1 expression to downregulate NFE2L2, thus inhibiting TXNRD1. FOXO3 overexpression or silencing of NFE2L2 or TXNRD1 diminished lung cancer cell proliferation, invasion, and migration but enhanced apoptosis. EV-delivered miR-130b-3p or FOXO3 silencing promoted lung cancer progression in vivo . In summary, MSC-derived EVs with upregulated miR-130b-3p suppressed FOXO3 to block the NFE2L2/TXNRD1 pathway, thus playing an oncogenic role in lung cancer progression.
Fatty liver hemorrhage syndrome (FLHS), a nutritional and metabolic disease that frequently occurs in laying hens, causes serious losses to the poultry industry. Nowadays, the traditional clinical diagnosis of FLHS still has its limitations. Therefore, searching for some metabolic biomarkers and elucidating the metabolic pathway in vivo are useful for the diagnosis and prevention of FLHS. In the present study, a model of FLHS in laying hens induced by feeding a high-energy, low-protein diet was established. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) was used to analyze the metabolites in serum at days 40 and 80. The result showed that, in total, 40 differential metabolites closely related to the occurrence and development of FLHS were screened and identified, which were mainly associated with lipid metabolism, amino acid metabolism, and energy metabolism pathway disorders. Further investigation of differential metabolites showed 10 potential biomarkers such as 3-hydroxybutyric acid, oleic acid, palmitoleic acid, and glutamate were possessed of high diagnostic values by analyzing receiver operating characteristic (ROC) curves. In conclusion, this study showed that the metabolomic method based on GC-TOF-MS can be used in the clinical diagnosis of FLHS in laying hens and provide potential biomarkers for early risk evaluation of FLHS and further insights into FLHS development.
To assess relationships between xanthine oxidase (XOD) and nephropathogenic infectious bronchitis virus (NIBV) infection, 240 growing layers (35 days old) were randomly divided into two groups (infected and control) of 120 chickens each. Each chicken in the control and infected group was intranasally inoculated with 0.2 mL sterile physiological saline and virus, respectively, after which serum antioxidant parameters and renal XOD mRNA expression in growing layers were evaluated at 8, 15 and 22 days post-inoculation (dpi). The results showed that serum glutathione peroxidase and superoxide dismutase activities in the infected group were significantly lower than in the control group at 8 and 15 dpi (p < 0.01), while serum malondialdehyde concentrations were significantly higher (p < 0.01). The serum uric acid was significantly higher than that of the control group at 15 dpi (p < 0.01). In addition, the kidney mRNA transcript level and serum activity of XOD in the infected group was significantly higher than that of the control group at 8, 15 and 22 dpi (p < 0.05). The results indicated that NIBV infection could cause the increases of renal XOD gene transcription and serum XOD activity, leading to hyperuricemia and reduction of antioxidants in the body.
Infectious bronchitis is a highly contagious, acute viral respiratory disease of chickens, regardless of the strain, and its infection may lead to considerable economic losses to the poultry industry. New nephropathogenic infectious bronchitis virus (NIBV) strains have increasingly emerged in recent years; hence, evaluating their infection-influenced immune function changes and the alteration of metabolite profiling is important. Initially, chickens were randomly distributed into two groups: the control group (Con) and the disease group (Dis). Here, the partial cytokines were examined, and the metabolome alterations of the bursa of Fabricius (BF) in NIBV infections in chickens were profiled by gas chromatography time-of-flight/mass spectrometry (GC-TOF/MS). The results revealed that the NIBV infection promotes the mRNA expression of inflammatory cytokines. Metabolic profile analysis indicated that clustering differed between the two groups and there were 75 significantly different metabolites detected between the two groups, suggesting that the host metabolism was significantly changed by NIBV infection. Notably, the following 12 metabolites were identified as the potential biomarkers: 3-phenyllactic acid, 2-deoxytetronic acid, aminomalonic acid, malonamide 5, uric acid, arachidonic acid, 2-methylglutaric acid, linoleic acid, ethanolamine, stearic acid, N-alpha-acetyl-l-ornithine, and O-acetylserine. Furthermore, the results of the correlation analysis showed that a strong correlation existed between metabolic biomarkers and inflammatory cytokines. Our results describe an immune and metabolic profile for the BF of chickens when infected with NIBV and provide new biomarkers of NIBV infection as potential targets and indicators of indicating therapeutic efficacy.
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