Novel Phenylethanoid Glycosides Improve Hippocampal Synaptic Plasticity via the Cyclic Adenosine Monophosphate-CREB-Brain-Derived Neurotrophic Growth Factor Pathway in APP/PS1 Transgenic Mice.

INTRODUCTION: Alzheimer's disease (AD) is a major public health concern worldwide, but there are still no drugs available that treat it effectively. Previous studies have shown that phenylethanoid glycosides have pharmacological effects, which include anti-AD properties, but the underlying mechanisms by which they ameliorate AD symptoms remain unknown. METHODS: In this study, we used an APP/PS1 AD mouse model to explore the function and mechanisms underlying savatiside A (SA) and torenoside B (TB) in the treatment of AD. SA or TB (100 mg·kg-1·d-1) was orally administered to 7-month-old APP/PS1 mice for 4 weeks. Cognitive and memory functions were measured using behavioral experiments (including the Morris water maze test and the Y-maze spontaneous alternation test). Molecular biology experiments (including Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays) were used to detect any corresponding changes in signaling pathways. RESULTS: The results showed that SA or TB treatment could significantly reduce cognitive impairment in APP/PS1 mice. We also showed that chronic treatment with SA/TB could prevent spine loss, synaptophysin immunoreactivity, and neuronal loss in mice, thereby improving synaptic plasticity and moderating learning and memory deficits. SA/TB administration also promoted the expression of synaptic proteins in APP/PS1 mouse brains and upregulated phosphorylation of proteins in the cyclic adenosine monophosphate (cAMP)/CREB/brain-derived neurotrophic growth factor (BDNF) pathway that are responsible for synaptic plasticity. Additionally, chronic SA/TB treatment increased the levels of BDNF and nerve growth factor (NGF) in the brains of APP/PS1 mice. Both astrocyte and microglia volumes, as well as the generation of amyloid ß, were also decreased in SA/TB-treated APP/PS1 mice compared to control APP/PS1 mice. CONCLUSION: In summary, SA/TB treatment was associated with activation of the cAMP/CREB/BDNF pathway and increased BDNF and NGF expression, indicating that SA/TB improves cognitive functioning via nerve regeneration. SA/TB is a promising candidate drug for the treatment of AD.

Inhibition of KIF20A by transcription factor IRF6 affects the progression of renal clear cell carcinoma.

BACKGROUND: Renal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, whose incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, although there is yet no report on its expression in ccRCC. METHODS: The expression of IRF6 and KIF20A in ccRCC was predicted by GEPIA and HAP databases. In addition, GEPIA database predicted the relationship between IRF6 and KIF20A expressions and the pathological staging, overall survival, and disease-free survival of ccRCC. The possible binding sites of IRF6 and KIF20A promoters were predicted by JASPAR database and verified by luciferase and ChIP assays. The specific effects of IRF6 on ccRCC cell proliferation, invasion and apoptosis were subsequently examined at both cellular level and animal level. RESULTS: The database predicted down-regulated IRF6 expression in renal carcinoma tissues and its correlation with poor prognosis. IRF6 overexpression inhibited cRCC cell proliferation, invasion and migration. In addition, up-regulated KIF20A expression in renal carcinoma tissues and its association with prognosis were also predicted. Interference with KIF20A inhibited the proliferation, invasion, and migration of ccRCC cells. Finally, we confirmed that KIF20A is a functional target of IRF6 and can partially reverse the effects of IRF6 on the proliferation, invasion and migration of ccRCC cells. CONCLUSION: Inhibition of KIF20A by transcription factor IRF6 affects cell proliferation, invasion and migration in renal clear cell carcinoma.

CT-based peritumoral radiomics signatures for malignancy grading of clear cell renal cell carcinoma.

OBJECTIVE: To evaluate the efficiency of CT-based peritumoral radiomics signatures of clear cell renal cell carcinoma (ccRCC) for malignancy grading in preoperative prediction. MATERIALS AND METHODS: 203 patients with pathologically confirmed as ccRCC were retrospectively enrolled in this study. All patients were categorized into training set (n = 122) and validation set (n = 81). For each patient, two types of volumes of interest (VOI) were masked on CT images. One type of VOIs was defined as the tumor mass volume (TMV), which was masked by radiologists delineating the outline of all contiguous slices of the entire tumor, while the other type defined as the peritumoral tumor volume (PTV), which was automatically created by an image morphological method. 1760 radiomics features were calculated from each VOI, and then the discriminative radiomics features were selected by Pearson correlation analysis for reproducibility and redundancy. These selected features were investigated their validity for building radiomics signatures by mRMR feature ranking method. Finally, the top ranked features, which were used as radiomics signatures, were input into a classifier for malignancy grading. The prediction performance was evaluated by receiver operating characteristic (ROC) curve in an independent validation cohort. RESULTS: The radiomics signatures of PTV showed a better performance on malignancy grade prediction of ccRCC with AUC of 0.807 (95% CI 0.800-0.834) in train data and 0.848 (95% CI 0.760-0.936) in validation data, while the radiomics signatures of TMV with AUC of 0.773 (95% CI 0.744-0.802) in train data and 0.810 (95% CI 0.706-0.914) in validation data. CONCLUSION: The CT-based peritumoral radiomics signature is a potential way to be used as a noninvasive tool to preoperatively predict the malignancy grades of ccRCC.