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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]

Participants in mixed-species bird flocks (MSFs) have been shown to associate with species that are similar in body size, diet, and evolutionary history, suggesting that facilitation structures these assemblages. In addition, several studies have suggested that species in MSFs resemble each other in their plumage, but this question has not been systematically investigated for any MSF system. During the nonbreeding season of 2020 and 2021, we sampled 585 MSFs on 14 transects in 2 habitats of Tongbiguang Nature Reserve in western Yunnan Province, China. We performed social network analysis and the Multiple Regression Quadratic Assignment Procedure to evaluate the effect of 4 species traits (body size, overall plumage color, distinctive plumage patterns, and diet) and evolutionary history on species association strength at the whole-MSF and within-MSF levels. All 41 significant relationships showed that species with stronger associations were more similar in their various traits. Body size had the strongest effect on association strength, followed by phylogeny, plumage patterns, and plumage color; diet had the weakest effect. Our results are consistent with the hypotheses that the benefits of associating with phenotypically similar species outweigh the potential costs of interspecific competition, and that trait matching can occur in plumage characteristics, albeit more weakly than in other traits. Several explanations exist as to why similarities in plumage may occur in MSFs, including that they could reduce predators' ability to target phenotypically "odd" individuals. Whether trait matching in plumage occurs through assortative processes in ecological time or is influenced by co-evolution requires further study. [ABSTRACT FROM AUTHOR]

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]

The activation of the nucleotide oligomerization domain (NOD)‐like receptor (NLR) family, pyrin domain‐containing protein 3 (NLRP3) inflammasome is related to the pathogenesis of a wide range of inflammatory diseases, but drugs targeting the NLRP3 inflammasome are still scarce. In the present study, we demonstrated that Licochalcone B (LicoB), a main component of the traditional medicinal herb licorice, is a specific inhibitor of the NLRP3 inflammasome. LicoB inhibits the activation of the NLRP3 inflammasome in macrophages but has no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, LicoB directly binds to NEK7 and inhibits the interaction between NLRP3 and NEK7, thus suppressing NLRP3 inflammasome activation. Furthermore, LicoB exhibits protective effects in mouse models of NLRP3 inflammasome‐mediated diseases, including lipopolysaccharide (LPS)‐induced septic shock, MSU‐induced peritonitis and non‐alcoholic steatohepatitis (NASH). Our findings indicate that LicoB is a specific NLRP3 inhibitor and a promising candidate for treating NLRP3 inflammasome‐related diseases. Synopsis: Licochalcone B, a main component of the medicinal herb licorice, specifically inhibits the NLRP3 inflammasome by disrupting NEK7‐NLRP3 interaction and exhibits protective effects in mouse models of NLRP3 inflammasome‐mediated diseases. Licochalcone B specifically inhibits both canonical and non‐canonical NLRP3 inflammasome activation.Licochalcone B blocks NLRP3‐dependent ASC oligomerization.Licochalcone B binds to NEK7 and disrupts the NEK7‐NLRP3 interaction.Licochalcone B effectively protects against NLRP3‐mediated diseases. [ABSTRACT FROM AUTHOR]

The genus Sinocyclocheilus , comprising a large radiation of freshwater cavefishes, are well known for their presence of regressive features (e.g. variable eye reduction). Fewer constructive features are known, such as the expansion of the lateral line system (LLS), which is involved in detecting water movements. The precise relationship between LLS expansion and cave adaptation is not well understood. Here, we examine morphology and LLS-mediated behaviour in Sinocyclocheilus species characterized by broad variation in eye size, habitat and geographical distribution. Using live-staining techniques and automated behavioural analyses, we examined 26 Sinocyclocheilus species and quantified neuromast organ number, density and asymmetry within a phylogenetic context. We then examined how these morphological features may relate to wall-following, an established cave-associated behaviour mediated by the lateral line. We show that most species demonstrated laterality (i.e. asymmetry) in neuromast organs on the head, often biased to the right. We also found that wall-following behaviour was distinctive, particularly among eyeless species. Patterns of variation in LLS appear to correlate with the degree of eye loss, as well as geographical distribution. This work reveals that constructive LLS evolution is convergent across distant cavefish taxa and may mediate asymmetric behavioural features that enable survival in stark subterranean microenvironments.