A natural acylphloroglucinol exerts anti-erythroleukemia effects via targeting STAT3 and p38-MAPK, and inhibiting PI3K/AKT/mTOR signaling pathway.

Erythroleukemia, a subtype of acute myeloid leukemia (AML), is a life-threatening malignancy that affects the blood and bone marrow. Despite the availability of clinical treatments, the complex pathogenesis of the disease and the severe side effects of chemotherapy continue to impede therapeutic progress in leukemia. In this study, we investigated the antitumor activity of L76, an acylphloroglucinol compound derived from Callistemon salignus DC., against erythroleukemia, along with its underlying mechanisms. MTT assays were performed to evaluate the inhibitory effects of L76 on cancer cell viability, while flow cytometry was used to analyze apoptosis and cell cycle arrest in HEL cells. The molecular mechanisms of L76 were further explored using Western blotting, microscopic analysis, and cellular thermal shift assays (CETSA). Our in vitro experiments demonstrated that L76 inhibits proliferation, induces G1/S cell cycle arrest, and promotes apoptosis in human leukemia cells. Mechanistically, L76 exerts its effects by targeting STAT3 and p38-MAPK, and by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, this study highlights the potential of L76 as an anti-erythroleukemia agent, demonstrating its ability to target STAT3 and p38-MAPK, and to inhibit the PI3K/AKT/mTOR signaling pathway. These findings suggest that L76 could be a promising candidate for the treatment of erythroleukemia.

Synergistic combination of isogarcinol isolated from edible fruits of Garcinia multiflora and dexamethasone to overcome leukemia glucocorticoid resistance.

Isogarcinol (ISO), a cytotoxic polycyclic polyprenylated acylphloroglucinol isolated from the edible fruits of Garcinia multiflora. However, synergistic combination of ISO and dexamethasone (DEX) to overcome leukemia glucocorticoid resistance has never been investigated. Therefore, in this study, the effects of ISO in combination with DEX was conducted on leukemia in vivo and glucocorticoid resistance in vitro. As a result, the combination of the two compounds could efficiently inhibit leukemia progression in mice and reverse DEX resistance in acute lymphoblastic leukemia (ALL) Jurkat cells. Significantly, our findings indicated that c-Myc may be a potential target of ISO, as it is involved in cell cycle arrest and apoptosis by the combination of ISO and DEX in Jurkat cells. Furthermore, western blot analysis revealed that ISO and DEX inhibits the PI3K/Akt/mTOR signaling pathway and promotes the nuclear translocation of glucocorticoid receptor (GR), which activates target genes NR3C1 and TSC22D3, leading to apoptosis in Jurkat cells. Hence, our results suggest that ISO, as a safe and effective food-derived agent, can enhance the anti-leukemia effects of DEX.

Thermal effect on the fecundity and longevity of Bactrocera dorsalis adults and their improved oviposition model.

The oriental fruit fly, Bactrocera dorsalis, is a destructive polyphagous pest that causes damage to various fruit crops, and their distribution is currently expanding worldwide. Temperature is an important abiotic factor that influences insect population dynamics and distribution by affecting their survival, development, and reproduction. We examined the fecundity, pre-oviposition and oviposition periods, and longevity of adult B. dorsalis at various constant temperatures ranging from13°C to 35°C. The longevity of female B. dorsalis ranged from 116.8 days (18.8°C) to 22.4 days (34.9°C), and the maximum fecundity per female was 1,684 eggs at 28.1°C. Females were only able to lay eggs at 16.7°C to 34.9°C, and both the pre-oviposition and oviposition periods were different depending on the temperature. We modeled female reproduction in two oviposition models (OMs): 1) the current model developed by Kim and Lee, an OM composed of a fecundity model, age-specific survival model, and age-specific cumulative oviposition rate model, and 2) a two-phase OM modified the logic structure of the current model by separating pre-oviposition, so that oviposition was estimated with the female in oviposition phase who had complete pre-oviposition phase. The results of the two-phase OM provided more realistic outputs at lower and higher temperatures than those of the current model. We discussed the usefulness of the two-phase OM for the reproduction of insects with long pre-oviposition periods.

Monitoring resistance to spinosad in the melon fly (Bactrocera cucurbitae) in Hawaii and Taiwan.

Spinosad is a natural insecticide with desirable qualities, and it is widely used as an alternative to organophosphates for control of pests such as the melon fly, Bactrocera cucurbitae (Coquillett). To monitor the potential for development of resistance, information about the current levels of tolerance to spinosad in melon fly populations were established in this study. Spinosad tolerance bioassays were conducted using both topical applications and feeding methods on flies from field populations with extensive exposure to spinosad as well as from collections with little or no prior exposure. Increased levels of resistance were observed in flies from the field populations. Also, higher dosages were generally required to achieve specific levels of mortality using topical applications compared to the feeding method, but these levels were all lower than those used for many organophosphate-based food lures. Our information is important for maintaining effective programs for melon fly management using spinosad.