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1.
Carcinogenesis ; 43(11): 1071-1082, 2022 12 25.
Artículo en Inglés | MEDLINE | ID: mdl-36179220

RESUMEN

Alpha-synuclein (SNCA) is a pathological hallmark of Parkinson's disease, known to be involved in cancer occurrence and development; however, its specific effects in breast cancer remain unknown. Data from 150 patients with breast cancer were retrieved from tissue microarray and analyzed for SNCA protein level using immunohistochemistry. Functional enrichment analysis was performed to investigate the potential role of SNCA in breast cancer. SNCA-mediated inhibition of epithelial-mesenchymal transition (EMT) was confirmed with western blotting. The effects of SNCA on invasion and migration were evaluated using transwell and wound-healing experiments. Furthermore, the potential influence of SNCA expression level on drug sensitivity and tumor infiltration by immune cells was analyzed using the public databases. SNCA is lowly expressed in breast cancer tissues. Besides, in vitro and in vivo experiments, SNCA overexpression blocked EMT and metastasis, and the knockdown of SNCA resulted in the opposite effect. A mouse model of metastasis verified the restriction of metastatic ability in vivo. Further analysis revealed that SNCA enhances sensitivity to commonly used anti-breast tumor drugs and immune cell infiltration. SNCA blocks EMT and metastasis in breast cancer and its expression levels could be useful in predicting the chemosensitivity and evaluating the immune microenvironment in breast cancer.


Asunto(s)
Transición Epitelial-Mesenquimal , Neoplasias , Animales , Ratones , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Sinucleínas , Pronóstico , Movimiento Celular/genética , alfa-Sinucleína/farmacología
2.
Neurosci Bull ; 40(8): 1037-1052, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39014176

RESUMEN

Posttraumatic stress disorder (PTSD) is a complex mental disorder notable for traumatic experience memory. Although current first-line treatments are linked with clinically important symptom reduction, a large proportion of patients retained to experience considerable residual symptoms, indicating pathogenic mechanism should be illustrated further. Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation. However, its role in PTSD remains to be elucidated. In this study, we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus. Fluoxetine, but not risperidone or sertraline, has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities. Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling. Our data demonstrated the correlation between PTSD and abnormal myelination, suggesting that the oligodendroglial lineage could be a target for PTSD treatment.


Asunto(s)
Modelos Animales de Enfermedad , Fluoxetina , Ratones Endogámicos C57BL , Vaina de Mielina , Trastornos por Estrés Postraumático , Animales , Trastornos por Estrés Postraumático/tratamiento farmacológico , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Vaina de Mielina/efectos de los fármacos , Vaina de Mielina/patología , Vaina de Mielina/metabolismo , Masculino , Ratones , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , Lóbulo Parietal/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología
3.
Front Pharmacol ; 14: 1269096, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38313074

RESUMEN

Breast cancer is one of the most common female malignant tumors today and represents a serious health risk for women. Although the survival rate and quality of life of patients with breast cancer are improving with the continuous development of medical technology, metastasis, recurrence, and drug resistance of breast cancer remain a significant problem. Huaier, a traditional Chinese medicine (TCM) fungus, is a type of Sophora embolism fungus growing on old Sophora stems. The polysaccharides of Trametes robiniophila Murr (PS-T) are the main active ingredient of Huaier. There is increasing evidence that Huaier has great potential in breast cancer treatment, and its anti-cancer mechanism may be related to a variety of biological activities, such as the inhibition of cell proliferation, metastasis, tumor angiogenesis, the promotion of cancer cell death, and regulation of tumor-specific immunity. There is growing evidence that Huaier may be effective in the clinical treatment of breast cancer. This review systematically summarizes the basic and clinical studies on the use of Huaier in the treatment of breast cancer, providing useful information to guide the clinical application of Huaier and future clinical studies.

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