Pyroptosis is a type of regulated cell death, and its dysregulation is detrimental and implicated in various diseases. The authors screened chemical compounds and identified azalamellarin N (AZL-N), a hexacyclic pyrrole alkaloid, as an inhibitor of pyroptosis induced by the intracellular multiprotein complex NLRP3 inflammasome. The inhibitory effects of AZL-N differed depending on the type of stimulus, which was different from those of MCC950, a well-established NLRP3 inhibitor. Considering that many studies have been focusing on the general mechanisms of NLRP3 inflammasome-dependent pyroptosis, AZL-N is a unique tool for uncovering the differential mechanisms of pyroptosis depending on the type of inflammatory stimulus.
The article by Oyama et al. suggested a novel mechanism of radiation-induced acquisition of malignant profile in lung cancer. Authors have shown that activation of adenosine A2B receptor and cannabinoid receptors (CB1, CB2 and GPR55) are involved in enhancement of cell migration after g-irradiation in A549 cells. And authors have shown that enhancement of cell migration by activation of adenosine A2B receptor is mediated by activation of CB2 and GPR55 receptor. These findings proposed that the A2B-CB2 and A2B-GPR55 pathways contributes to the radiation-induced acquisition of malignant profile in lung cancer and could be a novel molecular target to improve the efficiency of radiation therapy for lung cancer.
The authors revealed that changes in gastrointestinal fluid volume due to solution osmolality can explain the differences in the magnitude of beverage-drug interactions depending on the type of beverage. Osmolality-dependent fluid secretion and consequent decrease in luminal concentrations and absorption of drugs were observed in the rat intestine after administration of apple juice, orange juice, and grapefruit juice. Further, in vivo oral experiments showed that plasma concentrations of atenolol, a low-permeability drug, after oral administration decreased in dependence upon the magnitude of osmolality of ingested beverages, while the plasma concentrations of antipyrine, a high-permeability drug, did not change.
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Chronic cerebral hypoperfusion can cause
white matter lesions, leading to vascular dementia. Recently, these diseases
have been reported to be associated with lipid peroxidation. In this research,
the authors revealed that ethoxyquin, a lipid-soluble antioxidant, had a
protective effect against a glutamate-stimulated mouse hippocampal cell line
and was comparable to the ferroptosis inhibitor. Additionally, when applied to
a mouse model of chronic cerebral hypoperfusion, ethoxyquin suppressed white
matter lesions and inflammatory responses. Overall, the authors demonstrated
that inhibiting lipid peroxidation could be a helpful therapy for chronic
cerebrovascular disease.
Lecithin reverse wormlike micelles (LRWs) are highly viscoelastic bodies
and
potentially useful for transdermal applications. The authors prepared LRWs with
6-carboxyfluorescein (CF) as a model for a hydrophilic drug, and investigated
the effect of the rheological properties and composition of LRWs on the skin
permeation of CF. The highest skin permeability of CF was observed when IPM was
used as the oil, and the penetration of CF into hair follicles is influenced
not only by the rheology of the formulation but also by the interaction between
IPM and sebum in the hair follicles.