Luteolin promotes neuronogenesis in hippocampus of chronic unpredictable mild stress rats and primary hippocampus of fetal rats.

OBJECTIVE: To investigate the effects of luteolin on chronic unpredictable mild stress (CUMS)-induced depressive rats and corticosterone (CORT)-induced depressive primary hippocampal neurons, and to elucidate the mechanism behind the action. METHODS: The antidepressant mechanism of luteolin was studied by using CUMS rat model and primary hippocampal neurons in fetal rats. In vivo, novelty suppressed feeding, open-field and sucrose preference tests as well as Morris water maze were evaluated. The content of brain derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in serum were detected by enzyme-linked immunosorbent assay. The mechanisms of luteolin were explored based on neurotrophin and hippocampal neurogenesis, and proliferation. Survival of the septo-temporal axis in hippocampus was assayed using the 5-bromo-2-deoxyuridine (BrdU), the expression of BDNF, neurotrophin-3 (NT-3), and nerve growth factor (NGF) in hippocampus dentate gyrus region were measured by Western-blotting. In vitro, BDNF, NT-3, tropomyosin receptor kinase B (TrkB), and phosphorylated cyclic adenosine monophosphate responsive element binding protein (p-CREB) were detected through the high content analysis (HCA) to investigate neurotrophin and apoptosis. RESULTS: Induction of CUMS in rats induced depressive symptoms, while luteolin significantly enhanced sucrose consumption, decreased feeding latency, increased locomotor activity, escape latency, distance of target quadrant and regulated the content of depressive-like biomarkers. Histology analysis revealed that luteolin increased the abundance of new born neurons that had been labeled with BrdU, BrdU + neuronal nuclear antigen, and BrdU + doublecortin in septo-temporal axis of S2 (mid-septal) and T3 (mid-temporal). Moreover, expression of BDNF, NT-3, and NGF increased significantly in the septo-temporal axis of S2 and T3. HCA showed increased expression of BDNF, NT-3, TrkB and p-CREB in primary hippocampal neurons. CONCLUSION: The results provided direct evidence that luteolin has an antidepressant effect and could effectively promote the regeneration of the septotemporal axis nerve and hippocampal neuronutrition, which suggested that the antidepressant effect of luteolin may be related to hippocampal neurogenesis.

The efficiency of neoadjuvant chemotherapy in colon cancer with mismatch repair deficiency.

Colon cancers with mismatch repair deficiency (dMMR) have specific clinicopathologic characteristics compared with mismatch repair proficiency (pMMR); however, the effect of MMR status on the efficiency of neoadjuvant chemotherapy (NCT) remains unclear. In our study, 439 dMMR and 26 pMMR colon cancer patients with or without NCT from 2010 to 2017 were retrospectively collected. Clinicopathological features, treatment response, and survival were compared between different groups. In the dMMR group, patients with NCT were likely to have higher CEA (abnormal CEA: 51.6% vs. 17.4%, p < 0.001), more multiorgan resection (38.7% vs. 16.8%, p = 0.006), and larger postoperative tumor diameter (7.26 vs. 6.21, p = 0.033) than those without NCT, but nearly half of cT4b patients who had NCT (42.9%, 9/21) avoid multiorgan resection. pT4 stage (HR, 14.97; 95% CI, 1.88-118.92; p = 0.010), number of positive lymph nodes (HR, 1.17; 95% CI, 1.09-1.26; p < 0.001), and tumor deposit (HR, 6.73; 95% CI, 2.08-21.74; p = 0.001) were independent prognosis factors of disease-free survival (DFS). For the advanced tumor subset, there is no significant difference between patients with or without NCT for OS (p = 0.13) and DFS (p = 0.11), although the survival rate of NCT was higher than non-NCT patients. Moreover, tumor regression grade was similar between dMMR and pMMR patients who had NCT. This study showed that NCT was more likely to be employed in dMMR patients with advanced tumors and may reduce the rate of multiorgan resection for cT4b dMMR patients. More large-scaled researches are needed to further explore if MMR status could predict the efficacy of neoadjuvant chemotherapy in patients with colon cancer.

Epigallocatechin-3-Gallate Reduces Neuronal Apoptosis in Rats after Middle Cerebral Artery Occlusion Injury via PI3K/AKT/eNOS Signaling Pathway.

BACKGROUND/AIMS: Epigallocatechin-3-gallate (EGCG) has neuroprotective effects and the ability to resist amyloidosis. This study observed the protective effect of EGCG against neuronal injury in rat models of middle cerebral artery occlusion (MCAO) and investigated the mechanism of action of PI3K/AKT/eNOS signaling pathway. METHODS: Rat models of permanent MCAO were established using the suture method. Rat behavior was measured using neurological deficit score. Pathology and apoptosis were measured using HE staining and TUNEL. Oxidative stress and brain injury markers were examined using ELISA. Apoptosis-related proteins and PI3K/AKT/eNOS signaling pathway were determined using western blot assay and immunohistochemistry. RESULTS: EGCG decreased neurological function score, protected nerve cells, inhibited neuronal apoptosis, and inhibited oxidative stress injury and brain injury markers level after MCAO. EGCG reduced the apoptotic rate of neurons, increased the expression of Bcl-2, and decreased the expression of Caspase-3 and Bax. After LY294002 suppressed the PI3K pathway, the protective effect of EGCG decreased after administration of PI3K inhibitors. CONCLUSION: EGCG has a protective effect on rat brain injury induced by MCAO, possibly by modulating the PI3K/AKT/eNOS signaling pathway.

A mRMRMSRC feature selection method for radiomics approach.

Radiomics can convert digital images to mineable data by extracting a huge number of image features. Because of the high dimensions of radiomics features, feature selection is a very important step which affects the performance of the final prediction or classification. In this paper, we propose a feature selection criterion for radiomics analysis of glioma based on Magnetic Resonance Image (MRI). The proposed method named as minimum Redundancy, Maximum Relevance and Maximum Sparse Representation Coefficient (mRMRMSRC) criterion, which take three factors into consideration at the same time: relevance between features and labels with or without the influence of all other features, and redundancy between each couple of features. Different from traditional feature selection method, the mRMRMSRC manifests the best performance compared with the methods based on sparse representation coefficient (SRC), minimum redundancy maximum relevance (mRMR), F_score and ReliefF. We conducted our methods on glioma Isocitrate Dehydrogenase 1 (IDH1) estimation. The experiment showed that mRMRMSRC produced area under the ROC curve (AUC) of 90% compared with 77%-89% of state-of-art methods.