AbstractIntestinal microbiota contributes to host defense against pathogens while avoiding the induction of inflammation in homeostatic conditions, but the mechanism is not fully understood. To investigate the potential role of the bacterial metabolite desaminotyrosine (DAT) in regulating host defense and inflammation, we pretreated mouse bone marrow‐derived macrophages (BMDMs) with DAT for 12 hours and then challenged with bacterial lipopolysaccharide (LPS). We found that DAT priming‐enhanced type I interferon response while selectively inhibiting proinflammatory interleukin (IL)‐6 production after exposure to LPS. This is related to the fact that DAT is a natural antioxidant determined by radical scavenging assay in a cell‐free system. DAT‐primed cells had increased levels of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) upon LPS stimulation. Countering the increased NADPH by supplementing extra oxidized NADP+ to cells reversed DAT's effect on LPS‐induced Il‐6 and interferon‐stimulated gene expressions. DAT‐primed cells also were more resistant to oxidative stress‐induced generation of reactive oxygen species and cell death. DAT promoted the production of antimicrobial effector nitric oxide in a cellular redox‐dependent manner, leading to enhanced macrophage antimicrobial activity during Salmonella enterica infection. Our data suggest that DAT acts as a host‐microbiota crosstalk signal in shaping host immune defense and inflammatory response.

2024-06-03·European journal of paediatric dentistry

Dog-Assisted Therapy (DAT) for the management of anxiety during paediatric dental care. A scoping review.

Review

作者: Pozos-Guillén, F ; Ríos-Méndez, D ; Garrocho-Rangel, A ; Pozos-Guillén, A ; Flores-Velázquez, J ; Trejo-Herbert, D ; Rosales-Bérber, M

AIMDistraction techniques in paediatric dentistry can be effective in decreasing the child's attention span from an unpleasant or stressful procedure. Distraction is achieved through imagination, audio, and/or visual stimuli. It has been shown that the accompaniment and participation of animals or pets, specifically dogs (Dog-Assisted Therapy or DAT), during medical, oral, and therapeutic activities can improve the physical and mental health of patients, especially children. However, there is limited information available regarding the impact of incorporating a certified therapy dog into the paediatric dental environment as a distraction strategy to alleviate anxiety levels during dental procedures.METHODSThis scoping review aimed to identify and review published articles concerning the use of DAT in paediatric dentistry. The article discusses indications, benefits, and potential risks to human health and safety in clinical settings. Eligible sources encompass clinical trials, observational studies, and narrative reviews written in either English or Spanish and published over the last two decades, sourced from four electronic databases. Ultimately, seven pertinent studies were included in the review.CONCLUSIONDAT presents itself as a promising alternative in managing anxiety and stress among children during dental visits. The integration of a therapy dog and its handler into the paediatric oral care team should be thoughtfully considered by clinicians as a means to enhance the comfort and compliance of apprehensive patients.

2023-10-01·Biochemical and Biophysical Research Communications

In vivo anti-cancer activity of 10-methyl-aplog-1, a simplified analog of aplysiatoxin, and its possible signaling pathway associated with G1 arrest

Article

作者: Kikumori, Masayuki ; Shikata, Yuki ; Dan, Shingo ; Imoto, Masaya ; Okamura, Mutsumi ; Irie, Kazuhiro ; Hanaki, Yusuke

Naturally occurring protein kinase C (PKC) activators such as phorbol esters, teleocidins, and aplysiatoxins, have the potential to become anti-cancer agents, since they are anti-proliferative against specific cancer cell lines in vitro. However, their potent tumor-promoting and proinflammatory activities have hampered their clinical uses. Recently, we developed 10-methyl-aplog-1 (1), a simplified analog of tumor-promoting debromoaplysiatoxin (DAT), which retained anti-proliferative activity comparable to DAT, but induced neither tumorigenesis nor inflammation on mouse skin. Our previous study suggested that PKCα and δ were involved in the cell line-selective anti-proliferative activity of 1, but the downstream signaling of PKC isozymes remained unknown. In this study, we confirmed that 1 inhibited the growth of three aplog-sensitive cancer cell lines (NCI-H460, HCC-2998, and HBC-4) without severe side effects in mice xenograft models. In addition, in vitro analysis using A549, one of the aplog-sensitive cell lines in vitro, revealed that PKCα induced PP2A-mediated attenuation of the Akt/S6 signaling axis. Since S6 inhibition in A549 was reported to result in G1 arrest, this pathway could be involved in the PKCα-dependent anti-proliferative activity of 1.

100 项与 DAT antagonists(University of Vienna) 相关的药物交易

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