Aberrant reactivation of the Sonic Hedgehog (SHH) signaling pathway promotes prostate cancer (PC) growth and progression by regulating cancer-related genes through its downstream effectors GLI1 and GLI2. Therefore, targeting the SHH-GLI pathway provides an alternative approach to avoid cancer progression. The aim of this study was to delineate the underlying molecular mechanisms by which GDC-0449 (a SMO receptor inhibitor) and GANT-61 (a GLI transcription factor inhibitor) regulate cellular proliferation and self-renewal in human PC stem cells (ProCSCs). Inhibition of the SHH signaling pathway by GANT-61 induced apoptosis with more efficacy than by GDC-0449 in ProCSCs and PC cell lines. GLI1 and GLI2 expression, promoter-binding activity and GLI-responsive luciferase reporter activity were all decreased with either GDC-0449 or GANT-61 treatment. Expression of Fas, DR4, DR5, and cleavage of caspase-3 and PARP were increased, whereas levels of PDGFR-α and Bcl-2 were reduced. Double knockout of GLI1 and GLI2 using shRNA abolished the effects observed with either GDC-0449 or GANT-61 treatment. Collectively, our results showed that GANT-61 and GDC-0449 induced ProCSC apoptosis by directly or indirectly inhibiting the activities of the GLI family transcription factors, may enhance the efficacy of PC treatment.

Background As one of the vital crops globally, sugarcane (Saccharum officinarum L.) has been one of model crops for conducting metabolome research. Although many studies have focused on understanding bioactive components in specific sugarcane tissues, crucial questions have been left unanswered about the response of metabolites to niche differentiation such as different sugarcane tissues (leaf, stem and root), and soil regions (rhizosphere and bulk) under silicon (Si) amended soils. Here, nontargeted metabolite profiling method was leveraged to assess the similarities and differences in the abundance and community composition of metabolites in the different sugarcane and soil compartments. Identify the compartment-specific expression patterns of metabolites, and their association with cane agronomic traits and edaphic factors. We also investigated the response of sugarcane agronomic traits and edaphic factors to Si amended soil. Results We found that Si fertilizer exhibited the advantages of overwhelmingly promoting the height and theoretical production of cane, and profoundly increased soil Si content by 24.8 and 27.0%, while soil available potassium (AK) was enhanced by 3.07 and 2.67 folds in the bulk and rhizosphere soils, respectively. It was also noticed that available phosphorus (AP) in the rhizosphere soil tremendously increased by 105.5%. We detected 339 metabolites in 30 samples using LC–MS/MS analyses, 161 of which were classified and annotated, including organooxygen compounds (19.9%), carboxylic acids and derivatives (15.5%), fatty acyls (15.5%), flavonoids (4.4%), phenols (4.4%), and benzene and substituted derivatives (3.7%). In addition, the total percentages covered by these core metabolites in each compartment ranged from 94.0% (bulk soil) to 93.4% (rhizosphere soil), followed by 87.4% (leaf), 81.0% (root) and 80.5% (stem), suggesting that these bioactive compounds may have migrated from the belowground tissues and gradually filtered in various aboveground niches of the plant. We also observed that the variations and enrichment of metabolites abundance and community were compartment-specific. Furthermore, some key bioactive compounds were markedly associated with plant growth parameters and soil edaphic. Conclusion Taken together, we hypothesized that Si utilization can exhibit the advantage of enhancing edaphic factors and cane agronomic traits, and variations in metabolites community are tissue-specific.

The microbiomes of plant are potential determinants of plant growth, productivity, and health. They provide plants with a plethora of functional capacities, namely, phytopathogens suppression, access to low-abundance nutrients, and resistance to environmental stressors. However, a comprehensive insight into the structural compositions of the bacterial abundance, diversity, richness, and function colonizing various microenvironments of plants, and specifically their association with bioactive compounds and soil edaphic factors under silicon (Si) amendment remains largely inconclusive. Here, high-throughput sequencing technology and nontargeted metabolite profiling method were adopted to test the hypotheses regarding microbiome niche abundance, diversity, richness, function, and their association with bioactive compounds and soil edaphic factors within different ecological niches (leaf, stem, root, rhizosphere, and bulk soils) under Si amendment during cane growth were we addressed. Our results demonstrated that Si correspondingly increased sugarcane theoretical production and yield, and remarkably enhanced soil nutrient status, especially Si, AP, and AK. It was also observed that bacterial diversity demonstrated tissue-dependent distribution patterns, with the bulk soil, rhizosphere soil, and root endosphere revealing the highest amount of bacterial diversity compared with the stem and leaf tissues. Moreover, Si exhibited the advantage of considerably promoting bacterial abundance in the various plant compartments. Co-occurrence interactions demonstrated that Si application has the potential to increase bacterial diversity maintenance, coexistence, and plant–soil systems bacteria connections, thereby increasing the functional diversity in the various plant tissues, which, in turn, could trigger positive growth effects in plants. Network analysis further revealed that metabolite profiles exhibited a strong association with bacterial community structures. It was also revealed that Si content had a considerable positive association with bacterial structures. Our findings suggest that the dynamic changes in microbe’s community composition in different plant and soil compartments were compartment-specific. Our study provides comprehensive empirical evidence of the significance of Si in agriculture and illuminated on differential metabolite profiles and soil microbe’s relationship.

Polysaccharide (PF40) has been recognized as a main bioactive substances inPseudostellaria heterophylla (Miq.). The current study explored the potential protective effects of PF40 on immune system in mice with cyclophosphamide-induced immunosuppression. The mice were intragastric administered PF40 at the dosage of 100, 200 or 400 mg/kg once daily for 30 days, On the 24th and 25th day, the additional intraperitoneal injection of PF40 (50 mg/kg) were administered. The results showed that PF40 enhanced the cell-mediated immunity via improvements in macrophage phagocytosis, splenocyte proliferation, NK cell activity and delayed type hypersensitivity. Equally, it improves humoral immunity through promoting the formation of serum hemolysin.Moreover, PF40 maintain the immune balance of splenic lymphocytes and altered the intestinal physiological status in Cyp-induced mice. PF40 regulates the intestinal microbiota by restoring the relative abundance of Odoribacter and Mucispirillum and reducing the relative abundance of Sporosarcina, Yaniella, and Jeotgalicoccus in Cypintervened mice. The findings suggested that PF40 might be a promising natural functional foods for reducing chemotherapy-induced immunosuppression.

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