Comparative analysis of medicinal attributes between Lignosus cameronensis and its sister species.

Lignosus cameronensis holds promise for exploration given its morphological likeness to the renowned Lignosus rhinocerus, or tiger milk mushroom. Investigating its potential medicinal and industrial applications addresses a significant knowledge gap in this field. A comparative analysis with other Lignosus species and cultivars provides insights into biopharmacological potential. L. cameronensis cold water extract (LC-CWE) displayed moderate antioxidant activity, demonstrating promising Trolox equivalent antioxidant -capacity. Variable cytotoxicity was observed in different cell lines, with an IC50 of 215 µg/ml against breast cancer cells (MCF-7) cells. LC-CWE exhibited anti-inflammatory potential with an ED50 of 60 mg/kg in a λ-carrageenan-induced rat paw oedema model. Comparison with other Lignosus species and cultivars emphasised LC-CWE's distinct attributes, including high phenolic content and moderate antioxidant capacity. LC-CWE displayed potential in selectively inhibiting MCF-7 cells and reducing inflammation, highlighting its medicinal promise. This research expands our understanding of L. cameronensis and underscores the need for further mechanistic exploration.

Activation function 1 of progesterone receptor is required for progesterone antagonism of oestrogen action in the uterus.

BACKGROUND: Progesterone receptor (PGR) is a master regulator of uterine function through antagonistic and synergistic interplays with oestrogen receptors. PGR action is primarily mediated by activation functions AF1 and AF2, but their physiological significance is unknown. RESULTS: We report the first study of AF1 function in mice. The AF1 mutant mice are infertile with impaired implantation and decidualization. This is associated with a delay in the cessation of epithelial proliferation and in the initiation of stromal proliferation at preimplantation. Despite tissue selective effect on PGR target genes, AF1 mutations caused global loss of the antioestrogenic activity of progesterone in both pregnant and ovariectomized models. Importantly, the study provides evidence that PGR can exert an antioestrogenic effect by genomic inhibition of Esr1 and Greb1 expression. ChIP-Seq data mining reveals intermingled PGR and ESR1 binding on Esr1 and Greb1 gene enhancers. Chromatin conformation analysis shows reduced interactions in these genes' loci in the mutant, coinciding with their upregulations. CONCLUSION: AF1 mediates genomic inhibition of ESR1 action globally whilst it also has tissue-selective effect on PGR target genes.

Activation function 1 of progesterone receptor is required for mammary development and regulation of RANKL during pregnancy.

Progesterone receptor (PGR) is a member of the nuclear receptor superfamily of transcription factors. It is critical for mammary stem cells expansion, mammary ductal branching and alveologenesis. The transcriptional activity of PGR is mainly mediated by activation functions AF1 and AF2. Although the discovery of AF1 and AF2 propelled the understanding of the mechanism of gene regulation by nuclear receptors, their physiological roles are still poorly understood. This is largely due to the lack of suitable genetic models. The present study reports gain or loss of AF1 function mutant mouse models in the study of mammary development. The gain of function mutant AF1_QQQ exhibits hyperactivity while the loss of function mutant AF1_FFF shows hypoactivity on mammary development. However, the involvement of AF1 is context dependent. Whereas the AF1_FFF mutation causes significant impairment in mammary development during pregnancy or in response to estrogen and progesterone, it has no effect on mammary development in nulliparous mice. Furthermore, Rankl, but not Wnt4 and Areg is a major target gene of AF1. In conclusion, PGR AF1 is a pivotal ligand-dependent activation domain critical for mammary development during pregnancy and it exerts gene specific effect on PGR regulated genes.

Nutrient composition, antioxidant properties, and anti-proliferative activity of Lignosus rhinocerus Cooke sclerotium.

BACKGROUND: Lignosus rhinocerus (tiger milk mushroom) is an important medicinal mushroom used in Southeast Asia and China, and its sclerotium can be developed into functional food/nutraceuticals. The nutrient composition, antioxidant properties, and anti-proliferative activity of wild type and a cultivated strain of L. rhinocerus sclerotia were investigated. RESULTS: The sclerotial powder has high carbohydrate but low fat content. Interestingly, the cultivated strain contains higher amounts of protein and water-soluble substances than the wild type. Phenolic content of hot-water, cold-water, and methanol extracts of the sclerotial powders ranged from 19.32 to 29.42 mg gallic acid equivalents g⁻¹ extract, while the ferric reducing antioxidant power values ranged from 0.006 to 0.016 mmol min⁻¹ g⁻¹ extract. The DPPH• , ABTS•⁺ , and superoxide anion radical scavenging activities of the extracts ranged from 0.52 to 1.12, 0.05 to 0.20, and -0.98 to 11.23 mmol Trolox equivalents g⁻¹ extract, respectively. Both strains exhibited strong superoxide anion radical scavenging activity comparable to rutin. The cold-water extracts exhibited anti-proliferative activity against human breast carcinoma (MCF-7) cells, with IC50 values of 206 µg mL⁻¹ and 90 µg mL⁻¹ for the wild type and cultivated strains, respectively. CONCLUSION: The cultivated L. rhinocerus sclerotium has the potential to be developed into functional food/nutraceuticals.