Coumarin osthole is a dominant bioactive ingredient of the natural plant commonly used for traditional Chinese herbal medicines for therapies and treatments including antipruritus and antidermatitis. However, the molecular mechanism underlying the action of osthole remains unclear. In this study, we report that osthole exerts an antipruritic effect through selective inhibition of Ca-permeable and thermosensitive transient receptor potential vanilloid 3 (TRPV3) cation channels that are primarily expressed in the keratinocytes of the skin. Coumarin osthole was identified as an inhibitor of TRPV3 channels transiently expressed in HEK293 cells in a calcium fluorescent assay. Inhibition of the TRPV3 current by osthole and its selectivity were further confirmed by whole-cell patch clamp recordings of TRPV3-expressing HEK293 cells and mouse primary cultured keratinocytes. Behavioral evaluation demonstrated that inhibition of TRPV3 by osthole or silencing by knockout of the 3 gene significantly reduced the scratching induced by either acetone-ether-water or histamine in localized rostral neck skin in mice. Taken together, our findings provide a molecular basis for use of natural coumarin osthole from the plant in antipruritic or skin care therapy, thus establishing a significant role of the TRPV3 channel in chronic itch signaling or acute histamine-dependent itch sensation.

The temperature-sensitive and calcium-permeable transient receptor potential vanilloid 3 (TRPV3) channel abundantly expressed in keratinocytes plays important functions in skin physiology. Dysfunctional gain-of-function TRPV3 gene mutations cause genetic Olmsted syndrome characterized by periorificial keratoderma, palmoplantar keratoderma, inflammation, and severe itching, which suggests that pharmacological inhibition of overactive TRPV3 function may be beneficial in treating pruritus or skin disorders. To test this hypothesis, we identified natural compound forsythoside B as a TRPV3 inhibitor through screening of human embryonic kidney 293 (HEK293) cells expressing human TRPV3 channels in a calcium fluorescent assay. Whole-cell patch-clamp recordings of HEK293 cells expressing TRPV3 confirmed that forsythoside B selectively inhibited the channel current activated by agonist 2-aminoethoxydiphenyl borate (50 mM) in a dose-dependent fashion, with an IC 50 value of 6.7 6 0.7 mM. In vivo evaluation of scratching behavior demonstrated that pharmacological inhibition of TRPV3 by forsythoside B significantly attenuated acute itch induced by either the TRPV3 agonist carvacrol or the pruritogen histamine, as well as chronic itch induced by acetone-ether-water in a mouse model of dry skin. Furthermore, forsythoside B was able to prevent the death of HEK293 cells or native human immortalized nontumorigenic keratinocyte cells from human keratinocytes expressing a gain-offunction TRPV3 G573S mutant or in the presence of the TRPV3 agonist carvacrol. Taken together, our findings demonstrate the crucial role of TRPV3 in pruritus and keratinocyte toxicity; thus, specific inhibition of overactive TRPV3 by natural forsythoside B may possess therapeutic potential for treatment of chronic pruritus, skin allergy, or inflammation-related skin diseases.

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NNEO and PAA showed high efficacy in foodborne pathogen removal from fresh produce. Produce surface texture plays an important role in pathogen removal. NNEO and PAA effectively prevented cross-contamination during the crisping process.

Introduction To reassess the prevalence of fallopian tube endometriosis (EM), and its associated clinicopathologic characteristics and risk factors. Methods Cross-sectional study was conducted from June 2016 to August 2017. Unpregnant premenopausal women who underwent unilateral or bilateral salpingectomy due to gynecologic diseases were recruited. Patient clinical data and fallopian tube specimens were collected. Hematoxylin-eosin (H&E) staining and CD10 immunohistochemistry were used to diagnose tubal EM. Results Tubal EM prevalence was 14.48% (161/1112, 95% confidence interval [CI] 12.41%–16.55%). Prevalence of tubal EM in patients with EM was 37.37% (95%CI 30.58%–44.17%) which is higher in patients without EM (9.52%, 95%CI 7.61%–11.42%) and even higher in those with multi-organ EM (43.94%, 95%CI 35.36%–52.52%). At unilateral or bilateral salpingectomy, tubal EM was more likely located in the left fallopian tube (52.17%) than the right one (40.37%) and presence of hydrosalpinx/ hematosalpinx increased in women with tubal EM than without tubal EM (43.47% versus 23.79%). With increasing severity of pelvic EM (r = 0.26, P< 10 −4 ) and adhesion (r = 0.25, P< 10 −4 ), the tubal EM prevalence also increased. Pathological examination found that tubal EM was more likely located in the mucosa of the proximal tube with significantly more surrounding inflammation and fibrotic lesions than the serosa/sub-serosa in the distal tube (r = 0.90, P< 10 −4 ). Multivariate analysis showed that abnormal uterine bleeding (AUB) (AOR = 3.10), previous EM surgery (AOR = 4.22) and tubal ligation (AOR = 2.33) were risk factors for tubal EM. Conclusions These data provide clinicians with important information that the prevalence of tubal EM among premenopausal unpregnant patients was higher than previous investigators, especially higher among women with EM diseases. Identifying its clinicopathologic characteristics and predictors may facilitate clinical decision making.