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Journal: Food Science and Human Wellness, Vol. 12, No. 5, pp. 1526-1537

Studies have shown that cannabinoid CB2 receptors are involved in wound repair, however, its physiological roles in fibrogenesis remain to be elucidated. In the present study, the capacity of cannabinoid CB2 receptors in the regulation of skin fibrogenesis during skin wound healing was investigated. To assess the function of cannabinoid CB2 receptors, skin excisional BALB/c mice were treated with either the cannabinoid CB2 receptor selective agonist, GP1a, or antagonist, AM630. Skin fibrosis was assessed by histological analysis and profibrotic cytokines were determined by immunohistochemistry, immunofluorescence staining, reverse transcription?quantitative polymerase chain reaction and immunoblotting in these animals. GP1a decreased collagen deposition, reduced the levels of transforming growth factor (TGF)?β1, TGF?β receptor I (TβRI) and phosphorylated small mothers against decapentaplegic homolog 3 (P?Smad3), but elevated the expression of its inhibitor, Smad7. By contrast, AM630 increased collagen deposition and the expression levels of TGF?β1, TβRI and P?Smad3. These results indicated that cannabinoid CB2 receptors modulate fibrogenesis and the TGF?β/Smad profibrotic signaling pathway during skin wound repair in the mouse.

Blocking glioma cell invasion has been challenging due to cancer cells that can swiftly switch their migration mode, and agents that can block more than one migration mode are sought after. We found that small molecule 2-(1H-indole-3-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous aryl hydrocarbon receptor (AHR) agonist, can block more than one mode of glioma cell migration, based on cultured cell behavior captured by videos. Data from wound-healing assays and mouse xenograft glioma models corroborated ITE’s migration-inhibiting effects while knocking down AHR by siRNA abolished these effects. To identify genes that mediated ITE-AHR’s effect, we first collected gene expression changes upon ITE treatment by RNA-seq, then compared them against literature reported migration-related genes in glioma and that were potentially regulated by AHR. MYH9, a component of nonmuscle myosin IIA (NMIIA), was confirmed to be reduced by ITE treatment. When MYH9 was overexpressed in the glioma cells, a good correlation was observed between the expression level and the cell migration ability, determined by wound-healing assay. Correspondingly, overexpression of MYH9 abrogated ITE’s migration-inhibiting effects, indicating that ITE-AHR inhibited cell migration via inhibiting MYH9 expression. MYH9 is essential for cell migration in 3D confined space and not a discovered target of AHR; the fact that ITE affects MYH9 via AHR opens a new research and development avenue.

Dietary proteins play a critical role in maintaining the health of elderly people. Although experts recommend that elderly people consume more protein, a high-protein diet may add to the burden of elderly people with degraded digestion and absorption functions. The effects of a normal or high-protein diet and those of a whole or hydrolyzed protein diet on bone and muscle health and gastrointestinal function were evaluated in aged female C57BL/6J mice. The hydrolyzed protein diet with 14.7% protein energy ratio (HNP) contributed to the maintenance of weight and an increase in bone and muscle mass. Further, the overall aging situation was improved by the consumption of this diet. However, the hydrolyzed protein diet with 21.3% protein energy ratio (HHP) increased the levels of LPS, IL-6, IL-10, and TNF-α in serum. Additionally, the small intestine structure was damaged, and the goblet cell number was decreased in the HHP and whole protein with 21.3% protein energy ratio (HP) groups. The relative abundances of Streptococcus and Peptococcuswere decreased while that of Bifidobacterium was increased in HNP group compared with the whole protein with 14.7% protein energy ratio (NP) and HP groups. Undigested proteins entering the intestine may cause undesirable changes in gut microbiota, which adversely affect the aging body in NP and HP groups. In summary, hydrolyzed proteins are more advisable than untreated dietary protein in aged mice. This study aimed to provide guidance for daily diet for elderly people, and provide additional information to industry in order to guide their future food development.