RESUMO
Alzheimer's disease (AD) is one of the acute degenerative diseases of the brain that occurs in the central nervous system. This disease is caused by the abnormal deposition of insoluble plaques and peptide amyloid beta (Aß), the formation of nodules, and synaptic disorder. The formation of these nodes disrupts the functioning of neural circuits and changes in behavioral response due to the activation of neurotransmitter receptors. Research in recent years has shown that microRNAs play an effective role in Alzheimer's disease and neurotransmitter factors. Recently, miR-107 is effective in the pathology of Alzheimer's disease (AD) through the regulation of NF-κB signaling pathway. Experiments conducted using the dual luciferase method and western blot analysis also showed that miR-107 in primary neurons affects neurotransmitter factors in Alzheimer's disease through the regulation of the NF-κB signaling pathway. The results showed that the reduction of miR-107 expression through the regulation of the NF-κB signaling pathway leads to the suppression of cell apoptosis in Alzheimer's patients. On the other hand, increasing the expression of miR-107 leads to increasing the breaking process of Amyloid precursor protein (APP). This factor increases the production of amyloid beta (Aß) peptide plaques and increases the expression of the BACE1 gene, which ultimately leads to the induction of apoptosis and induction of Alzheimer's disease.
Assuntos
Doença de Alzheimer , MicroRNAs , Humanos , Doença de Alzheimer/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Peptídeos beta-Amiloides/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genéticaRESUMO
Emerging evidence suggests that myo-inositol (MI) has a critical role in reducing renal inflammatory processes and improving podocyte function and preventing diabetes-related renal damage. We aimed to explore the function and underlying workings of MI in renal interstitial fibrosis (RIF). Based on a mouse model, we explored the effect of MI in unilateral ureteral obstruction (UUO) and in transforming growth factor-ß1 (TGF-ß1)-treated HK-2 cells. Pathological changes of the kidney tissues were examined following staining of the tissues with hematoxylin, eosin, and Masson's trichrome. The mRNA quantities of fibrosis markers, fibronectin, α-smooth muscle actin (α-SMA), and collagen I, were analyzed by means of real-time polymerase chain reaction, whereas those of protein levels were assessed with Western blotting. We also determined the expression of collagen I by immunofluorescence, and the levels of phosphorylated phosphotidylinositol-3-kinase and protein kinase B (PI3K/AKT) by Western blot. In vivo, histopathological examination in the UUO mice revealed renal tubular epithelial cell necrosis, inflammatory cell infiltration, and RIF. UUO mice showed higher expression levels of collagen I, fibronectin, α-SMA, pPI3K, and pAKT compared with sham-operated mice. However, MI treatment diminished the pathological alterations of RIF in UUO mice and downregulated the expression of fibrosis markers and phosphorylated PI3K/AKT. In vitro, TGF-ß1 positively influenced the propagation and differentiation of HK-2 cells and upregulated the levels of α-SMA, fibronectin, collagen I, pPI3K, and pAKT, but these became significantly reversed by MI treatment. In conclusion, MI ameliorates RIF, possibly by negatively regulating TGF-ß1-induced epithelial transdifferentiation and PI3K/AKT activation.
Assuntos
Nefropatias , Obstrução Ureteral , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Transformador beta1/genética , Fibronectinas/genética , Fibronectinas/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/etiologia , Nefropatias/metabolismo , Obstrução Ureteral/complicações , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/metabolismo , Fibrose , ColágenoRESUMO
OBJECTIVE: Previous investigations indicated the anticancer activity of puerarin. The current study aimed to evaluate the effect and molecular mechanisms of puerarin in chemotherapy-resistant ovarian cancer cells. METHODS: We examined the effects of puerarin in platinum-resistant epithelial ovarian cancer cells in vitro and in vivo. We also analyzed the molecular mechanism underlying Wnt/ß-catenin inhibition and sirtuin 1 (SIRT1) regulation following puerarin treatment. RESULTS: Our study demonstrated that puerarin effectively inhibited cell growth in vitro and in vivo by increasing apoptosis in ovarian cancer cells. More importantly, puerarin sensitized cisplatin-resistant ovarian cancer cells to chemotherapy. Puerarin treatment decreased SIRT1 expression, which attenuated the nuclear accumulation of ß-catenin to inhibit Wnt/ß-catenin signaling. In addition, SIRT1 overexpression diminished the effects of puerarin treatment on cisplatin-resistant ovarian cancer cells. Further analysis supported SIRT1/ß-catenin expression as a candidate biomarker for the disease progression of epithelial ovarian cancer. CONCLUSIONS: Puerarin increased the apoptosis of platinum-resistant ovarian cancer cells. The mechanism is partly related to the downregulation of SIRT1 and subsequent inhibition of Wnt/ß-catenin signaling.