SETBP1 mutation determines sensitivity to immune checkpoint inhibitors in melanoma and NSCLC.

SET binding protein 1 (SETBP1) plays crucial roles in various biological processes; however, its involvement in cancer immune checkpoint inhibitor (ICI) treatments has never been studied. In this study, we collected a total of 631 melanoma and 109 non-small cell lung cancer (NSCLC) samples treated with ICI agents (i.e., anti-CTLA-4, anti-PD-1/PD-L1, or combination therapy). Additionally, we obtained their corresponding somatic mutational profiles. We observed that SETBP1 mutated (SETBP1-MUT) melanoma patients exhibited significantly prolonged ICI survival outcomes compared to wild-type patients (HR: 0.56, 95% CI: 0.38-0.81, P = 0.002). Consistently, an elevated ICI response rate was also noticed in the SETBP1-MUT group (42.9% vs. 29.1%, P = 0.016). The Association of SETBP1 mutations with favorable immunotherapeutic prognosis and response was further supported by an independent NSCLC cohort (both P < 0.05). Additional immunological analyses revealed that favorable immune infiltration, tumor immunogenicity, and immune response circuits were enriched in SETBP1-MUT patients. Overall, our findings suggest that SETBP1 mutations may serve as a new biomarker for stratifying beneficiaries of ICI treatments in melanoma and NSCLC, which provides possible evidence for tailoring clinical immunotherapeutic strategies.

Quinoa husk peptides reduce melanin content via Akt signaling and apoptosis pathways.

To improve the treatment of pigmentation disorders, looking for natural and safe inhibitors of melanin synthesis has become an area of research interest. The quinoa husk peptides reportedly elicit various biological activities (e.g., anti-cancer, antioxidant, anti-hypertensive, and so forth), but its effects on melanin inhibition remain unknown. In the current study, we purified quinoa husk peptides with 30 and 80% ethanol using a macroporous adsorption resin (DA201-C). Component screening revealed that the 80%-ethanol fraction (i.e., QHP fraction) contained numerous short peptides (84.41%) and hydrophobic amino acids (45.60%), while eliciting a superior tyrosinase [TYR]-inhibition rate, 2,2-diphenyl-1-picryhydrazil-scavenging rate, reducing activity, and chelating capacity compared to the 30% fraction and was thus applied in subsequent analyses. Differentially expressed genes in the QHP fraction were primarily enriched in the Akt-signaling pathways based on transcriptomics. Thus, we assessed the expression of related proteins and genes in A375 cells and rat skin cells following treatment with QHP.

Extractable and non-extractable polyphenols from blueberries modulate LPS-induced expression of iNOS and COX-2 in RAW264.7 macrophages via the NF-κB signalling pathway.

BACKGROUND: Plant polyphenols are rich in blueberries that have a wide range of properties beneficial to human health. There are two types, according to the solubility of polyphenols, which were defined as extractable polyphenols (EPP) and non-extractable polyphenols (NEPP), respectively. At present, in most of reports, 'total polyphenol' refers only to EPP excluding NEPP. In this paper, the effects of EPP and NEPP on lipopolysaccharides (LPS) induced production of nitric oxide (NO) and gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 cells via nuclear factor-κB (NF-κB) signalling pathway were compared. RESULTS: The results showed that EPP and NEPP from blueberries significantly inhibited the LPS-induced production of NO and gene expression of iNOS and COX-2 in cells. The constitutive level of p65 sub-unit of NF-κB was obviously detected after the treatments with EPP or NEPP. By contrast, the level of phosphorylated p65 (P-p65) was strongly inhibited by EPP or NEPP. EPP had a stronger inhibition on the gene expression of iNOS and COX-2 than that of NEPP. CONCLUSION: These findings of inhibition of iNOS and COX-2 mRNA expression through the suppression of NF-κB suggest that EPP and ENPP from blueberries have significant anti-inflammatory effect and may be a potential medicine. © 2015 Society of Chemical Industry.

Polyphenols from blueberries modulate inflammation cytokines in LPS-induced RAW264.7 macrophages.

Polyphenols including 3-glucoside/arabinoside/galactoside-based polymers of delphinidins, petunidins, peonidins, malvidins and cyanidins are one type of biological macromolecules, which are extraordinarily rich in blueberries. Anti-inflammatory activity of blueberry polyphenols (BPPs) was investigated by using lipopolysaccharide (LPS) induced RAW264.7 macrophages. The results showed that BPPs suppressed the gene expression of IL-1ß (interleukin-1ß), IL-6 and IL-12p35. The inhibition effect on IL-1ß and IL-6 mRNA was most obvious at the concentration of 10-200µg/mL BPPs. But the inhibition effect on IL-12p35 mRNA was increased with the increasing concentration of BPPs. When fixed at 100µg/mL BPPs, the most significant inhibition on IL-1ß, IL-6 and IL-12p35 mRNA expression was detected at 12-48h. In conclusion, BPPs exhibit anti-inflammation activity by mediating and modulating the balances in pro-inflammatory cytokines of IL-1ß, IL-6, and IL-12.