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Objective: To evaluate the synergistic effects and underlying mechanisms of WNT974 and artesunate (ART) combination therapy in the treatment of colorectal cancer (CRC). Methods: We conducted an initial assessment of the synergistic impact of WNT974 and ART on cell viability using the MTT assay across eight CRC cell lines with diverse mutation statuses.Subsequently, a 3D in vitro model was utilized to confirm the synergistic effect of the combination. Flow cytometry was employed to analyze cell cycle distribution. The molecular mechanisms were further investigated by examining the expression levels of cell cycle-related proteins (p21, p27, and CDK2) and AKT activity through PCR and Western blot analyses. The in vivo efficacy of the combination therapy was evaluated using a xenograft mouse model of CRC. Results: The combination of WNT974 and ART significantly reduced cell viability in all eight CRC cell lines, demonstrating a synergistic effect. Additionally, the combination exhibited synergy in inhibiting 3D spheroid growth. Cell cycle analysis revealed that the combination therapy induced a marked G1/G0 arrest through CDK2 inhibition, surpassing the efficacy of individual treatments. Molecular analysis indicated that the combination therapy upregulated p21 and p27 expression and reduced AKT activity. In vivo, the combination therapy significantly inhibited tumor growth in the xenograft mouse model, notably outperforming 5FU, the standard first-line drug for CRC. Conclusion: The study highlights the synergistic anti-CRC effects of combining WNT974 and ART. This combination induces G1/G0 phase cell cycle arrest by cooperatively regulating p21, p27, and AKT, presenting a promising alternative to current CRC treatments. These findings elucidate the molecular basis of this interaction and provide a scientific foundation for advancing ART combined with WNT94 as a novel therapy for CRC, offering a potential new avenue.

Comprehending the mechanisms governing metacommunity assembly holds pivotal importance for effective conservation strategies. Amidst diverse theories in explaining metacommunity assembly processes, ecologists are progressively delving into the interplay between ecological stochasticity and determinism in shaping species assemblages. Given the ease of measurement, three null model-based methodologies have been widely employed to measure the stochastic and deterministic process, i.e., dispersal-niche continuum index (DNCI), elements of metacommunity structure (EMS), and zeta diversity calculations. However, it is still in doubt which approach can better detect the dominant ecological process governing metacommunity assembly. In this study, we concurrently utilized these three approaches to reveal the fish metacommunity assembly processes in a transitional floodplain among different habitats between high- and low-water levels. In general, our results recognized functional zeta diversity as indicative measurement in this study case since it uniquely unveiled the significant assembly transitions from stochasticity to determinism in response to water receding. Specifically, fish metacommunity in high-water periods was governed by stochastic processes, which can be ascribed to connectivity and easier dispersal in the flooding period. In contrast, the deterministic process shaped fish metacommunity in low-water phase since the stringent environmental loading enhance environmental filtering. This phenomenon is more pronounced in lotic habitats due to the more intricate environments there. It is worth noting that EMS and DNCI approaches showed blind response to this shift. In consequence, our findings advocate for favoring zeta diversity in resolving stochastic and deterministic contributions in governing metacommunity assembly. In addition, our findings also highlight the superiority of functional diversity over traditional taxonomic diversity, since we recorded a more reasonable metacommunity assembly process revealed by the functional group approach, which emphasizes the significance of incorporating functional traits in community ecology.

Elephantopus scaber, globally acknowledged for its edible and medicinal uses, remains underexplored despite the identification of active compounds. This research explores Elephantopus scaber extract's therapeutic capabilities in hepatocellular carcinoma (HCC). Initial in vitro screenings using the MTT assay revealed that ethanol extract (EEES) inhibited HCC cell proliferation while exhibiting low toxicity to normal cells. Further explorations showed EEES induced cell cycle arrest, apoptosis, and inhibited cell metastasis. A bioinformatics analysis using a network pharmacology approach identified the PI3K/Akt pathway as a key modulation for EEES's anti-HCC activities, validated through western blot analysis. In animal studies, EEES demonstrated the ability to inhibit HCC tumor growth in vivo with a high level of safety. In summary, our research positions Elephantopus scaber as a potent herb with anti-HCC activities and remarkable safety, offering promising prospects for the prevention and treatment of liver diseases, including HCC.

Objective: To evaluate the anticancer activity of the natural diterpenoid lasiokaurin (LAS) against nasopharyngeal carcinoma (NPC) both in vitro and in vivo, along with investigating its underlying mechanism. Methods: MTT and colony formation assays were used to assess cell viability. Flow cytometry was utilized for the analysis of cell cycle arrest and apoptosis. Additionally, wound healing and transwell invasion assays were conducted separately to investigate cell migration and invasion. To uncover potential targets and pathways of LAS within NPC, a network pharmacological study based on RNA-sequencing (RNA-seq) was performed. Immunoblotting was subsequently used to determine protein levels. Furthermore, the anti-NPC activity of LAS was evaluated in vivo using a xenograft mouse model. Results: Based on in vitro investigations, it is evident that LAS exerted substantial inhibitory effects on NPC cells. Notably, LAS demonstrated significant reductions in cell viability, migration, and invasion capabilities, while simultaneously inducing apoptosis and G2/M cell cycle arrest. Furthermore, LAS suppressed the activation of MAPK, mTOR, STAT3, and NF-κB pathways within NPC cells. Additionally, in vivo experiments underscored LAS's capacity to attenuate NPC tumor growth without eliciting any discernible impact on body weight. Conclusion: Our data clearly demonstrate the anticancer activity of LAS against NPC, both in vitro and in vivo. These findings firmly position LAS as a potential candidate for the treatment of NPC.

Tumor-associated macrophage (TAM) affects the intrinsic properties of tumor cells and the tumor microenvironment (TME), which can stimulate tumor cell proliferation, migration, and genetic instability, and macrophage diversity includes the diversity of tumors with different functional characteristics. Macrophages are now a central drug target in various diseases, especially in the TME, which, as “tumor promoters” and “immunosuppressors”, have different responsibilities during tumor development and accompany by significant dynamic alterations in various subpopulations. Remodelling immunosuppression of TME and promotion of pre-existing antitumor immune responses is critical by altering TAM polarization, which is relevant to the efficacy of immunotherapy, and uncovering the exact mechanism of action of TAMs and identifying their specific targets is vital to optimizing current immunotherapies. Hence, this review aims to reveal the triadic interactions of macrophages with programmed death and oncotherapy, and to integrate certain relationships in cancer treatment.