Search

Objectives: Breast cancer is a common malignancy in women. More than 90% of breast cancer deaths are caused by metastasis. Epimedii Folium (EF) is a commonly used herb with anti-tumor benefits, but its underlying mechanisms and active components for breast cancer prevention are little understood. This study assessed the therapeutic role of Icariside I (ICS I) in Epimedium flavonoids (EF) on lung metastasis of breast cancer, including the underlying mechanism. Methods: Western blot, RT-qPCR, wound healing assay, colony formation assay, and flow cytometry were used to investigate the inhibition of breast cancer cells growth and migration by EF and ICS I through disrupting the IL-6/STAT3 pathway. Combined with 4T1 breast cancer model in mice, Western blot, RT-qPCR, Hematoxylin and Eosin staining, immunohistochemistry were used to evaluate the therapeutic role of ICS I in proliferation, apoptosis, invasion, and metastasis of breast cancer. Key findings: EF can inhibit STAT3 phosphorylation and reduce the colony formation and migration of breast cancer cells. Detecting the active ingredients in EF, we found ICS I can reduce the activation of STAT3 in 4T1 breast cancer cells, impair colony formation and migration. Moreover, ICS I induced cells G1 phase arrest and modulated Cyclin D1, CDK4, bcl-2, and bax to inhibit proliferation and survival of breast cancer cells. Similarly, the in vivo studies demonstrated that ICS I significantly suppressed tumor development and lung metastasis in the 4T1 mouse model. Tumor cells in vehicle group were arranged in a spoke-like pattern with obvious heterogeneity, and multinucleated tumor giant cells were seen. But, the tumor cells in the ICS I group were disorganized and necrotic lysis was seen in some areas. In ICS I-treated group, tumors' STAT3 phosphorylation level, IL-6, Cyclin D1, CDK4, bcl-2, and vimentin expression were downregulated, bax and cleaved caspase 3 expression were upregulated. In the lung tissue, we could find less metastasis of breast cancer cells and less lung injury in the ICS I group. Besides, the expression of metastasis-related genes MMP9 and vimentin was decreased in the lung tissue of ICS I group. Conclusions: These findings suggest that ICS I can inhibit breast cancer proliferation, apoptosis, invasion and metastasis probably via targeting IL-6/STAT3 pathway. Therefore, ICS I has the potential to become an innovative therapeutic candidate to breast cancer prevention and treatment. [ABSTRACT FROM AUTHOR]

Objective: Glucosylceramidase (GBA) variants and onset age significantly affect clinical phenotype and progression in Parkinson's disease (PD). The current study compared clinical characteristics at baseline and cognitive and motor progression over time among patients having GBA‐related PD (GBA‐PD), early‐onset idiopathic PD (early‐iPD), and late‐onset idiopathic PD (late‐iPD). Methods: We recruited 88 GBA‐PD, 167 early‐iPD, and 488 late‐iPD patients in this study. A subset of 50 GBA‐PD, 81 early‐iPD, and 223 late‐iPD patients was followed up at least once, with a 3.0‐year mean follow‐up time. Linear mixed‐effects models helped evaluate the rate of change in the Unified Parkinson's Disease Rating Scale motor and Montreal Cognitive Assessment scores. Results: At baseline, the GBA‐PD group showed more severe motor deficits and non‐motor symptoms (NMSs) than the early‐iPD group and more NMSs than the late‐iPD group. Moreover, the GBA‐PD group had more significant cognitive and motor progression, particularly bradykinesia and axial impairment, than the early‐iPD and late‐iPD groups at follow‐up. However, the early‐onset GBA‐PD (early‐GBA‐PD) group was similar to the late‐onset GBA‐PD (late‐GBA‐PD) group in baseline clinical features and cognitive and motor progression. Conclusion: GBA‐PD patients exhibited faster cognitive and motor deterioration than early‐iPD and late‐iPD patients. Thus, subtype classification based on genetic characteristics rather than age at onset could enhance the prediction of PD disease progression. [ABSTRACT FROM AUTHOR]

Growing evidence supports that depression in Parkinson's disease (PD) depends on disruptions in specific neural networks rather than regional dysfunction. According to the resting‐state functional magnetic resonance imaging data, the study attempted to decipher the alterations in the topological properties of brain networks in de novo depression in PD (DPD). The study also explored the neural network basis for depressive symptoms in PD. We recruited 20 DPD, 37 non‐depressed PD and 41 healthy controls (HC). The Graph theory and network‐based statistical methods helped analyse the topological properties of brain functional networks and anomalous subnetworks across these groups. The relationship between altered properties and depression severity was also investigated. DPD revealed significantly reduced nodal efficiency in the left superior temporal gyrus. Additionally, DPD decreased five hubs, primarily located in the temporal‐occipital cortex, and increased seven hubs, mainly distributed in the limbic cortico‐basal ganglia circuit. The betweenness centrality of the left Medio Ventral Occipital Cortex was positively associated with depressive scores in DPD. In contrast to HC, DPD had a multi‐connected subnetwork with significantly lower connectivity, primarily distributed in the visual, somatomotor, dorsal attention and default networks. Regional topological disruptions in the temporal‐occipital region are critical in the DPD neurological mechanism. It might suggest a potential network biomarker among newly diagnosed DPD patients. [ABSTRACT FROM AUTHOR]

Due to the depletion of fossil energy and environmental pollution, renewable clean energy has been paid more and more attention. This paper researches a multi-objective wind-solar-hydro-thermal scheduling model (MOSWS), whose objectives are to minimize the economic cost and minimize the environmental pollution caused by thermal power generation. The region search evolutionary algorithm (RSEA) with constraint handling method is proposed to solve the constrained multi-objective problems and applied to MOSWS model. From the experimental results, we find that RSEA with constraint handling is able to solve the constrained multi-problems and outperforms MODE-ACM in terms of both convergence and diversity. The RSEA is also applied to hydro-thermal system. The results show that wind-solar-hydro-thermal system can not only increase economic benefits, but also reduce the impact of thermal power generation on the atmospheric environment.

The polysaccharide extract from Isatidis Radix exhibits potent antiinflammatory and antiviral activities, but the mechanism of Isatidis Radix polysaccharide (IRP) remains obscure. Herein, we reported that IRP blocked the activation of nod‐like receptor pyrin domain‐containing 3 (NLRP3) inflammasome, leading to the inhibiting of caspase‐1 cleavage and IL‐1β secretion. Mechanistically, IRP did not inhibit NLRP3 inflammasome through suppressing mitochondrial reactive oxygen species (mtROS) production. However, IRP can significantly suppress the oligomerization of apoptosis‐associated speck‐like protein (ASC) and subsequently block the formation of inflammasome. Next, we evaluate the role of IRP in monosodium urate (MSU)‐induced gout in vivo which is a NLRP3‐associated disease. We also observed that oral administration of IRP can reduce the increased ankle thickness and the secretion of IL‐1β, IL‐18, IL‐6, TNF‐α and MPO of the mouse ankle joints caused by MSU crystals. Furthermore, flow cytometry analysis highlighted a significant modulation of T helper 17 cells (Th17)/regulatory T cells (Treg) following IRP treatment in MSU induced gout. Overall, our findings suggest that IRP has comprehensive and potent antiinflammatory effects and provide a reasonable therapeutic strategy in preventing inflammasome‐associated diseases, such as inflammatory gouty arthritis. [ABSTRACT FROM AUTHOR]