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Background: Prostate cancer (PCa) is the leading cause of death in men and has poor therapeutic outcomes. Methods: A novel endostatin 33 peptide was synthesized by adding a specific QRD sequence on the basis of the endostatin 30 peptide (PEP06) with antitumor activity. Then, bioinformatic analysis and subsequent experiments were performed to validate the antitumor function of this endostatin 33 peptide. Results: We found that the 33 polypeptides significantly inhibited growth, invasion and metastasis and promoted the apoptosis of PCa in vivo or vitro, which is more significant than PEP06 under the same conditions. According to 489 cases from the TCGA data portal, the α6β1 high expression group was closely associated with the poor prognosis (Gleason score, pathological N stage, etc.) of PCa and was mainly enriched in the PI3K-Akt pathway. Subsequently, we demonstrated that endostatin 33 peptide can down-regulate the PI3K-Akt pathway via the targeted inhibition of α6β1, thereby inhibiting the epithelial–mesenchymal transition and matrix metalloproteinase in C42 cell lines. Conclusion: The endostatin 33 peptide can exert antitumor effects by inhibiting the PI3K-Akt pathway, especially in tumors with a high expression of the integrin α6β1 subtype, such as prostate cancer. Therefore, our study will provide a new method and theoretical basis for the treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Amygdalin is the essential component of the traditional Chinese medicinal drug peach kernel. The early studies of amygdalin are mainly focused on antitussive and tumor anti-tumor, but there are few studies on the treatment of neuroinflammation. Objectives: The purpose of this study was to explore the anti-inflammatory effect of amygdalin on lipopolysaccharide (LPS)-induced neuron–microglia and its protective mechanism for toll-like receptors (TLRs) signaling pathways. Materials and Methods: Griess, quantitative PCR, and flow cytometry were used to detect the influence of amygdalin on the release of inflammatory factors from BV2 mouse microglia (BV2 cells). The anti-inflammatory pathway of amygdalin was further explored by western blotting. At the same time, the effect of amygdalin on LPS-induced oxidative stress damage in BV2 cells was detected by WST-8 and fluorescence probe. Results: After LPS induction, the pro-inflammatory factors such as nitric oxide, interleukin-6, tumor necrosis factor-alpha, interleukin-1β, and recombinant NLR Family, Pyrin Domain Containing Protein3 were significantly increased. However, the levels were reversed significantly after treatment with amygdalin. In addition, amygdalin significantly inhibited the increase of TLR4, TLR2, and its downstream signal myeloid differentiation primary response gene 88 and P-NF-κB p65 in BV2 cells induced by LPS. Amygdalin can also reverse the abnormal expression of LPS-induced oxidative stress indexes such as cyclooxygenase-2, reactive oxygen species, and superoxide dismutase. Conclusion: Amygdalin may reduce the LPS-induced accumulation of pro-inflammatory substances via the down-regulating of the TLR2/TLR4-nuclear factor kappa-B signaling pathway. [ABSTRACT FROM AUTHOR]

Abnormal microRNA (miR) expressions were implicated in prostate cancer progression. We identified a novel miR-495, which was downregulated in prostate cancer, but not normal prostate cell lines. MiR-495 directly targeted the 3′-UTR of Akt and mTOR mRNAs. Expression of miR-495 in prostate cancer cells significantly downregulated Akt and mTOR, which further inhibited cancer cell proliferation, migration, and invasionin vitro. Function of miR-495in vivowas examined in mouse xenograft model and was found to significantly inhibit the growth of tumors, mediated by repressing Akt and mTOR. Our report supported miR-495 as a novel tumor suppressor microRNA in prostate cancer. [ABSTRACT FROM PUBLISHER]

Danhong injection (DHI) is a traditional Chinese medicine injection that promotes blood circulation and removes blood stasis and has been widely used in the treatment of stroke. Many studies have focused on the mechanism of DHI in acute ischemic stroke (IS); however, few studies have thoroughly explored its role during recovery. In this study, we aimed to determine the effect of DHI on long-term neurological function recovery after cerebral ischemia and explored the related mechanisms. Middle cerebral artery occlusion (MCAO) was used to establish an IS model in rats. The efficacy of DHI was assessed using neurological severity scores, behaviors, cerebral infarction volume and histopathology. Immunofluorescence staining was performed to assess hippocampal neurogenesis. An in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was constructed and western-blot analyses were performed to verify the underlying mechanisms. Our results showed that DHI treatment greatly reduced the infarct volume, promoted neurological recovery and reversed brain pathological changes. Furthermore, DHI promoted neurogenesis by increasing the migration and proliferation of neural stem cells, and enhancing synaptic plasticity. Moreover, we found that the pro-neurogenic effects of DHI were related to an increase in brain-derived neurotrophic factor (BDNF) expression and the activation of AKT/CREB, which were attenuated by ANA-12 and LY294002, the inhibitors of the BDNF receptor and PI3K. These results suggest that DHI improves neurological function by enhancing neurogenesis and activating the BDNF/AKT/CREB signaling pathways. [Display omitted] • We focus on the effects of DHI on long-term neurological function after stroke. • DHI improves neurological functional rehabilitation by enhancing neurogenesis. • DHI promotes neurogenesis by activating BDNF/AKT/CREB signaling pathway. [ABSTRACT FROM AUTHOR]