The antiproliferative activities on tumoral cells, namely, human breast cancer (MCF-7 and MDA-MB-231), hepatoma (HepG2) and myeloid leukemia (HL-60), of ethanolic extracts from two species of Ganoderma, G. lucidum and G. sinense, were investigated. Though both extracts had certain antiproliferative activities, their chemical characteristics, including nucleosides, triterpenoids and sterols, were significantly different. Their effects on MDA-MB-231 cells were further studied using apoptotic detection and cell cycle analyses. As a result, both had apoptosis induction through the alternation of mitochondrial transmembrane depolarization, though no triterpenoids were detected in ethanolic extract of G. sinense. Furthermore, the two extracts from G. lucidum and G. sinense could arrest cell cycle at different phases. This study showed that ethanol extracts of both G. lucidum and G. sinense have antitumoral proliferation effect through both apoptosis pathway and cell cycle arrest effect, and some other compounds such as sterols and/or nucleosides may contribute to their activity besides triterpenoids.

Inflammatory diseases decrease the extracellular environmental pH. However, whether proton-activated G protein-coupled receptors (GPCRs) can regulate the development of osteoarthritis (OA) is largely unknown. In this study, we report that proton-activated GPR4 is essential for OA development. We found a marked increase in expression of the proton-activated GPR4 in human and mouse OA cartilage. Lentivirus-mediated overexpression of GPR4 in mouse joints accelerated the development of OA, including promotion of articular cartilage damage, synovial hyperplasia, and osteophyte formation, while Gpr4 knockout effectively attenuated the development of posttraumatic and aging-associated OA in mice. We also found that inhibition of GPR4 with the antagonist NE52-QQ57 ameliorated OA progression in mice, promoted extracellular matrix (ECM) production, and protected cartilage from degradation in human articular cartilage explants. Moreover, GPR4 overexpression upregulated matrix-degrading enzymes’ expression and inflammation factors under pro-inflammatory and slightly acidic conditions. Mechanistically, GPR4 suppressed chondrocyte differentiation and upregulated cartilage homeostasis through NF-κB/MAPK signaling activation by regulating CXCR7/CXCL12 expression. Together, our results take the lead to illustrate that proton-activated GPCR acts as a key regulator for OA pathogenesis in vivo, and support that GPR4 could be a promising therapeutic target for OA treatment.

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The economy and zoonoses have recently been significantly threatened by aquatic diseases. Yet, our knowledge of the diversity and abundance of fish viruses is still limited.

The gut flora is a treasure house of diverse bacteriophages maintaining a harmonious and coexistent relationship with their hosts. The giant panda ( Ailuropoda melanoleuca ), as a vulnerable endemic species in China, has existed for millions of years and is regarded as a flagship species for biodiversity conservation. And yet, limited studies have analyzed the phage communities in the gut of giant pandas. Using viral metagenomic analysis, the phageomes of giant pandas and other relative species were investigated. Our study explored and compared the composition of phage communities from different animal sources. Giant pandas possessed more diverse and abundant phage communities in the gut compared with other relevant animals. Phylogenetic analyses based on the phage terminase large subunit (TerL) showed that the Caudovirales phages in giant pandas also presented highly genetic diversity. Our study revealed the diversity of phage communities in giant pandas and other relative species, contributing to the health maintenance of giant pandas and laying the groundwork for molecular evolution research of bacteriophages in mammals. IMPORTANCE Gut phageome plays an important role in shaping gut microbiomes by direct interactions with bacteria or indirect influences on the host immune system, potentially regulating host health and disease status. The giant panda ( Ailuropoda melanoleuca ) is a vulnerable and umbrella species for biodiversity conservation. Our work explored and compared the gut phageome of giant pandas and relative species, contributing to the health maintenance of giant pandas.