Objective: Platinum- and anthracycline-based chemotherapy regimens cause nausea and vomiting in clinical practice, resulting in the deterioration of patients’ QoL, discontinuation of chemotherapy, and reduced therapeutic outcomes. Using pica behavior as an indicator, we aimed to clarify whether anamorelin, an orally active ghrelin receptor agonist, exerts antiemetic effects against cisplatin-induced nausea and vomiting in rats. Materials and Methods: Sprague–Dawley rats were treated with cisplatin (5 mg/kg, i.p.), three-drug or four-drug antiemetics (granisetron [0.3 mg/kg, p.o.], dexamethasone [1.5 mg/kg, p.o.], fosaprepitant [12.5 mg/kg, i.p.], with or without anamorelin [30 mg/kg, p.o.]). Data on kaolin intake, normal food intake, and spontaneous motor activity (SMA) were recorded 1 d before and 5 d after cisplatin administration. Body weight (BW) was measured daily, and the percentage change in BW from baseline was calculated. Results: At the primary endpoint, kaolin intake was significantly higher in the cisplatin-only group than in the pretreatment and vehicle groups (p < 0.05). Additionally, kaolin food intake was not significantly low in cisplatin-treated mice treated with three-drug antiemetics with or without anamorelin. At the secondary endpoints, normal food intake, SMA, and percentage change in BW were significantly lower in the cisplatin-only group than in the vehicle group. Conclusion: Our findings suggest that the prophylactic administration of standard three-drug antiemetics, besides anamorelin, may not improve cisplatin-induced nausea and vomiting. Further studies using methods suitable for evaluating anamorelin levels are required.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants, and their harmful effects on humans and animals are a major concern. Although the mechanisms of PCB toxicity have been studied, and they are known to largely accumulate in adipose tissue and liver, no therapy for PCB exposure has been established. To develop excretion-enhancing methods or antidotes for PCBs, animal models reflecting actual PCB bioaccumulation should be used. To establish such a model, we administered four levels of [³H]-labeled PCB-126 (710.4 × 10⁴, 142.1 × 10⁴, 28.4 × 10⁴, and 5.7 × 10⁴ dpm) to mice and investigated their excretion and tissue distribution. Lindane was used as a readily excreted comparator. 28.4 × 10⁴ or 5.7 × 10⁴ dpm [³H]PCB-126 resulted in excretion and tissue-distribution levels that were close to the detection limit. Administration of the maximum dose of [³H]PCB-126 resulted in continual excretion in feces and urine over the 8-day experimental period. In the mouse administered 142.1 × 10⁴ dpm [³H]PCB-126, the fecal and urinary excretion were reduced to a constant low level by day 8 after exposure, suggesting that the distribution of [³H]PCB-126 into the tissues had almost been completed. Our results suggest that mice administered 142.1 × 10⁴ dpm [³H]PCB-126 could be suitable as a PCB-126 bioaccumulation model for research to facilitate methods to enhance PCBs excretion and to develop therapies for PCBs toxicity.

Atrophic age-related macular degeneration (AMD) is a progressive form with macular atrophy. Unfortunately, the mechanism of atrophic AMD progression is not fully revealed, and the effective remedy to improve patient’s visual acuity is none today. This study aims to explore a new therapeutic target for atrophic AMD. Microarray analysis of the retinal pigment epithelium (RPE)-choroid-sclera complex from sodium iodate (NaIO₃)-administered retinal degeneration model mice revealed that the expression of G protein-coupled receptor 35 (Gpr35) mRNA was markedly increased. This result was similar to that of an analysis using the NCBI Gene Expression Omnibus database, which showed a trend toward increased expression of Gpr35 in the macular RPE-choroid of atrophic AMD patients. NaIO₃-induced retinal degeneration model mice showed different severities depending on the dose of NaIO₃. Gpr35 mRNA level was markedly upregulated in RPE-choroid-sclera complexes treated with 40 mg/kg NaIO₃, whereas those treated with 20 mg/kg NaIO₃ showed an increasing but non-significant trend. Immunostaining images showed that GPR35 expression was observed around the RPE layer after treatment with 40 mg/kg NaIO₃ and was merged with macrophage/microglia marker F4/80. Interestingly, the GPR35 agonist cromolyn suppressed NaIO₃-induced RPE cell death. These findings suggest that GPR35 might be a novel potential therapeutic target for the pathological progression of atrophic AMD.

PD-L1 molecules on a tumor have attracted attention because PD-L1 on a tumor plays an important role in escape for host immune responses. It has been shown that genistein attenuates immune checkpoint therapy for B16F1 melanoma in mice. We examined the effect of genistein on expression of PD-L1 in B16F1 melanoma cells and found that genistein increases the expression of IFN-γ-induced PD-L1 molecules at both protein and mRNA levels. Genistein increased the mRNA expression of STAT1 and STAT3 in IFN-γ-treated B16F1 cells. We compared the effects of ten types of flavonoids on PD-L1 expression and found that genistein is a strong inducer of PD-L1 expression among the flavonoids.