RESUMEN
Aortic aneurysm is a life-threatening disease with limited interventions that is closely related to vascular smooth muscle cell (VSMC) phenotypic switching. SLC44A2, a member of the solute carrier series 44 (SLC44) family, remains undercharacterized in the context of cardiovascular diseases. Venn diagram analysis based on microarray and single-cell RNA sequencing identified SLC44A2 as a major regulator of VSMC phenotypic switching in aortic aneurysm. Screening for Slc44a2 among aortic cell lineages demonstrated its predominant location in VSMCs. Elevated levels of SLC44A2 were evident in the aorta of both patients with abdominal aortic aneurysm and angiotensin II-infused (Ang II-infused) Apoe-/- mice. In vitro, SLC44A2 silencing promoted VSMCs toward a synthetic phenotype, while SLC44A2 overexpression attenuated VSMC phenotypic switching. VSMC-specific SLC44A2-knockout mice were more susceptible to aortic aneurysm under Ang II infusion, while SLC44A2 overexpression showed protective effects. Mechanistically, SLC44A2's interaction with NRP1 and ITGB3 activates TGF-ß/SMAD signaling, thereby promoting contractile gene expression. Elevated SLC44A2 in aortic aneurysm is associated with upregulated runt-related transcription factor 1 (RUNX1). Furthermore, low-dose lenalidomide (LEN; 20 mg/kg/day) suppressed aortic aneurysm progression by enhancing SLC44A2 expression. These findings reveal that the SLC44A2-NRP1-ITGB3 complex is a major regulator of VSMC phenotypic switching and provide a potential therapeutic approach (LEN) for aortic aneurysm treatment.
Asunto(s)
Aneurisma de la Aorta Abdominal , Glicoproteínas de Membrana , Proteínas de Transporte de Membrana , Músculo Liso Vascular , Miocitos del Músculo Liso , Animales , Humanos , Masculino , Ratones , Angiotensina II/farmacología , Aneurisma de la Aorta/genética , Aneurisma de la Aorta/metabolismo , Aneurisma de la Aorta/patología , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/genética , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Ratones Noqueados , Ratones Noqueados para ApoE , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Fenotipo , Transducción de Señal , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismoRESUMEN
This study aimed to compare the nutritive value and obesity prevention of ordinary Cordyceps militaris (CM) and selenium-enriched CM (SeCM). The results indicated that Se enrichment significantly increased the total carbohydrate and soluble dietary fiber content, while the protein and insoluble dietary fiber content decreased. Although the fat content was not affected, the medium and long-chain fatty acids content significantly changed. Moreover, Se enrichment significantly elevated the secondary metabolites belonging to terpenoids and alkaloids, which are linked with the enhanced biosynthesis of secondary metabolites. Both CM and SeCM reduced body weight, adipose accumulation, impaired glucose tolerance, and lipid levels in high-fat diet (HFD)-fed mice, and there was no significant difference between them. Network pharmacological analysis revealed that dietary CM and SeCM prevented HFD-induced obesity and associated metabolic diseases with multi-ingredients acting on multi-targets. Overall, Se enrichment improved the nutritive value of CM without altering its role in preventing obesity.
RESUMEN
BACKGROUND: Peptide drugs provide promising regimes in bladder cancer. In order to identify potential bioactive peptides involved in bladder cancer, we performed the present study. METHODS: Liquid chromatography/mass spectrometry assay was used to compare the endogenous peptides between bladder cancer and normal control. The potential biological functions of these dysregulated peptides are assessed by GO analysis and KEGG pathway analysis of their precursors. The SMART and UniProt databases are used to identify the sequences of the dysregulated peptides located in the functional domains. The Open Targets Platform database was used to investigate the precursors related to metabolic diseases. RESULTS: A total of 9 up-regulated peptides and 110 down-regulated peptides in bladder cancer compared with normal control were identified (fold change > 1.2, P < 0.05). The MW of these dysregulated peptides ranged from 500 Da to 2500 Da and the MW of all identified peptides was below 3500 Da. The GO and KEGG pathway analysis indicated that these dysregulated peptides could play an important role in bladder cancer. Our further analysis revealed that 45HFNPRFNAHGDAN 57 derived from LGALS1 and those peptides derived from P4HB and SERPINA1 might be the promising diagnostic biomarkers and therapeutic targets of bladder cancer. CONCLUSION: In the present study, we have identified the profile of the peptides significantly dysregulated in bladder cancer. Moreover, using bioinformatic analysis, we found the peptides derived from LGALS1, P4HB and SERPINA1 could be the promising diagnostic biomarkers and therapeutic targets of bladder cancer.
RESUMEN
Bladder cancer (BC) brings a heavy burden to afflicted patients worldwide. In order to find new diagnostic markers and therapeutic targets for this disease, we investigated the role of a novel lncRNA, AC114812.8, in bladder cancer progression. Clone formation and CCK-8 assays were used to detect the proliferative capacity of the cells, and the transwell assay was used to explore their invasion and migration abilities. Wound healing experiments were also used to detect cell migration. Luciferase reporter assays were used to investigate the interactions between lncRNA, target gene and miRNA. The expression of FUT4 and marker genes related to epithelial-mesenchymal transition was explored through western blot analysis. Our findings revealed that AC114812.8 was significantly upregulated in BC and could markedly facilitate the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Furthermore, duel-luciferase reporter assay revealed that AC114812.8 could regulate the FUT4 expression level by sponging miR-371b-5p to facilitate BC progression. We detected the levels of EMT-related biomarkers in AC114812.8-overexpressing BC cells by western blot analysis and found that AC114812.8 could promote EMT process. Rescue experiments showed that miR-371b-5p could rescue the effect of AC114812.8 on proliferation and metastasis of BC. Our results suggest that AC114812.8 could be a novel prognostic biomarker and therapeutic target for bladder cancer.
Asunto(s)
Progresión de la Enfermedad , Fucosiltransferasas/biosíntesis , MicroARNs/biosíntesis , ARN Largo no Codificante/biosíntesis , Neoplasias de la Vejiga Urinaria/metabolismo , Animales , Línea Celular Transformada , Línea Celular Tumoral , Fucosiltransferasas/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , ARN Largo no Codificante/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
Bladder cancer (BC) is one of the most common malignant tumors in males globally. Its progression imposes a heavy burden on patients; however, the expression profile of circular (circ)RNAs in BC progression remains unclear. This study explored changes in circRNA expression during BC progression by sequencing different grade BC samples and normal controls to reveal the circRNA expression profiles of different BC grades. Gene Ontology (GO) and Kyoto Encyclopedia of Gens and Genomes (KEGG) pathway analyses, and proteinprotein interaction network construction were used to predict pathways that the differentially expressed circRNAs may participate in. circRNA expression levels were detected using reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and dualluciferase reporter assays were used to investigate the interactions between circRNA and microRNA (miR). Cell Counting Kit8 and Transwell assays were also performed to detect cell proliferation, migration, and invasion. In total, 244 circRNAs were found to be differentially expressed in highgrade BC compared to lowgrade BC, whilst 316 dysregulated circRNAs were detected in highgrade BC compared with normal urothelium. Furthermore, 42 circRNAs overlapped between the two groups, seven of which were randomly selected and detected by RTqPCR to validate the sequencing results. GO analysis and KEGG pathway analyses revealed that the differentially expressed circRNAs may participate in BC via 'GTPase activity regulation', 'cell junction', and 'focal adhesion' pathways. Of note, we proposed that a novel circRNA in BC progression, hsa_circ_0137606, could suppress BC proliferation and metastasis by sponging miR1231. Through bioinformatics analysis, we predicted that PH domain and leucine rich repeat protein phosphatase 2 could be a target of the hsa_circ_0137606/miR1231 axis in BC progression. Using highthroughput sequencing, this study revealed the circRNA expression profiles of different grades of BC and proposed that the novel circRNA, hsa_circ_0137606, suppresses BC proliferation and metastasis by sponging miR1231. Our findings may provide novel insight into potential therapeutic targets for treating BC.
Asunto(s)
MicroARNs/genética , ARN Circular/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Anciano , Proliferación Celular/genética , Biología Computacional/métodos , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Transducción de Señal/genética , Vejiga Urinaria/patologíaRESUMEN
Poplar(Pupulus x Xiao zhannica, cv. "balizhuang-yang") transferred with mtl-D gene was used as an experimental material. Through tissue culture, aquaculture and pot culture transgenic poplars are tested with variant Nacl salt gradient. In it transgenic poplar raises its initial days for differentiation, differentiation rate, bud intensity, bud height and growth potential than control plant. At the same time, the transgenic poplar has higher rooting rate and more top roots, side roots and higher root length than control under the same salt stress. The result shows that the transgenic poplar has better tolerance ability than control plant in the salt 4@1000 contensity mediums.