Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC 50 of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC 50 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.

ObjectiveSepsis-induced acute lung injury (ALI) and acute kidney injury (AKI) are major causes of mortality. Menthol is a natural compound that has anti-inflammatory and antioxidative actions. Since exaggerated inflammatory and oxidative stress are characteristics of sepsis, the aim of this study was to evaluate the effect of menthol against sepsis-induced mortality, ALI, and AKI.MethodsThe cecal ligation and puncture (CLP) procedure was employed as a model of sepsis. Rats were grouped into sham, sham-Menthol, CLP, and CLP-Menthol (100 mg/kg, p.o).Key FindingsA survival study showed that menthol enhanced the survival after sepsis from 0% in septic group to 30%. Septic rats developed histological evidence of ALI and AKI. Menthol markedly suppressed sepsis induced elevation of tissue TNF-a, ameliorated sepsis-induced cleavage of caspase-3 and restored the antiapoptotic marker Bcl2.SignificanceWe introduced a role of the proliferating cell nuclear antigen (PCNA) in these tissues with a possible link to the damage induced by sepsis. PCNA level was markedly reduced in septic animals and menthol ameliorated this effect. Our data provide novel evidence that menthol protects against organ damage and decreases mortality in experimental sepsis.

Background: 2,3-dimethylquinoxaline (DMQ) is a naturally occurring compound with documented antifungal activity. It showed also good in vitro physicochemical and pharmacokinetic characteristics. Methods: The wound healing activity of 1% DMQ hydrogel in healthy adult male Wister rats were evaluated using the excision wound model. On day 7, the mean percentage closure of the wound area was determined. The animals were sacrificed on day 7 and skin was isolated for histology research and assessment of some inflammatory & oxidative markers, hydroxyproline and tissue growth factor. Results and Discussion: Almost complete wound healing was observed after treatment with DMQ 1 % Jell for 7 days. The histological study confirmed marked attenuation of wound-induced histological changes. There was a marked reduction in TNF-α, IL-6 IL-β1 and NF-κB. levels. These data suggest the potential anti-inflammatory effect of DMQ. Conclusion: DMQ has potential skin wound healing ability likely due to its anti-inflammatory mechanism. Further study is needed to confirm these preliminary findings and explore the molecular mechanism

Aims: To explore the antifungal activity of 2,3-dimethylquinoxaline. Study Design: A preclinical study of a compound against 10 fungal species. Backgrounds: Severe fungal infections cause significant clinical problem and need more effort to search for new antifungals. Methodology: We evaluated the susceptibility of 2,3-dimethylquinoxaline in vitro against a wide range of pathogenic fungi, including six Candida species, two Aspergillus species, one Cryptococcus species, and one Trichophyton species. Also, we evaluated the susceptibility of 2,3-dimethylquinoxaline in vivo against oral candidiasis using a mice model. Results: The highest score of the minimum inhibitory concentration was 9 µg/ml against Cryptococcus neoformans. While, the lowest score was 1125 µg/ml against Candida tropicalis. The oral candidiasis in a mouse model was resolved using 2,3-dimethylquinoxaline 1% gel. Conclusion: The 2,3-Dimethyquinoxaline has interesting antifungal activity. Quinoxalines in general need to be further developed as a promising antifungal candidate.

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