Efficacy of Phototherapy With 308-nm Excimer Light for Skin Microbiome Dysbiosis and Skin Barrier Dysfunction in Canine Atopic Dermatitis.

The management of canine atopic dermatitis, an allergic skin disorder, is challenging. To investigate the effect of phototherapy using a 308-nm excimer light as a topical treatment for canine atopic dermatitis, 10 dogs with canine atopic dermatitis and 10 with non-allergic skin were enrolled in this study. Phototherapy was applied every 7 days for a total of 2 months. The skin microbiome, skin barrier function, and clinical outcomes were evaluated after phototherapy. Phototherapy significantly changed the composition of the skin microbiome of dogs with atopic dermatitis and significantly increased the relative abundance of the phyla Actinobacteria and Cyanobacteria. It significantly alleviated the clinical signs of canine atopic dermatitis without serious adverse effects. Transepidermal water loss, as a measure of skin barrier function, significantly decreased after phototherapy. In addition, phototherapy increased microbial diversity and decreased the relative abundance of Staphylococcus pseudintermedius associated with the severity of canine atopic dermatitis. These results suggest that the excimer light therapy is a suitable and safe therapeutic option for canine atopic dermatitis, which is also a spontaneous animal model of atopic dermatitis.

Donepezil for mild cognitive impairment in Parkinson's disease.

We investigated the efficacy of donepezil for mild cognitive impairment in Parkinson's disease (PD-MCI). This was a prospective, non-randomized, open-label, two-arm study. Eighty PD-MCI patients were assigned to either a treatment or control group. The treatment group received donepezil for 48 weeks. The primary outcome measures were the Korean version of Mini-Mental State Exam and Montreal Cognitive Assessment scores. Secondary outcome measures were the Clinical Dementia Rating, Unified Parkinson's Disease Rating Scale part III, Clinical Global Impression scores. Progression of dementia was assessed at 48-week. Comprehensive neuropsychological tests and electroencephalography (EEG) were performed at baseline and after 48 weeks. The spectral power ratio of the theta to beta2 band (TB2R) in the electroencephalogram was analyzed. There was no significant difference in the primary and secondary outcome measures between the two groups. However, the treatment group showed a significant decrease in TB2R at bilateral frontotemporoparietal channels compared to the control group. Although we could not demonstrate improvements in the cognitive functions, donepezil treatment had a modulatory effect on the EEG in PD-MCI patients. EEG might be a sensitive biomarker for detecting changes in PD-MCI after donepezil treatment.

Attractor landscape analysis of the cardiac signaling network reveals mechanism-based therapeutic strategies for heart failure.

Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure (HF), a global leading cause of death, and are regulated through the complicated intracellular signaling network, limiting the development of effective treatments due to its complexity. To identify effective therapeutic strategies for HF at a system level, we develop a large-scale comprehensive mathematical model of the cardiac signaling network by integrating all available experimental evidence. Attractor landscape analysis of the network model identifies distinct sets of control nodes that effectively suppress apoptosis and hypertrophy of cardiomyocytes under ischemic or pressure overload-induced HF, the two major types of HF. Intriguingly, our system-level analysis suggests that intervention of these control nodes may increase the efficacy of clinical drugs for HF and, of most importance, different combinations of control nodes are suggested as potentially effective candidate drug targets depending on the types of HF. Our study provides a systematic way of developing mechanism-based therapeutic strategies for HF.

Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network.

Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure and are known to be regulated by complex interactions in the underlying intracellular signaling network. Previous experimental studies were successful in identifying some key signaling components, but most of the findings were confined to particular experimental conditions corresponding to specific cellular contexts. A question then arises as to whether there might be essential regulatory interactions that prevail across diverse cellular contexts. To address this question, we have constructed a large-scale cardiac signaling network by integrating previous experimental results and developed a mathematical model using normalized ordinary differential equations. Specific cellular contexts were reflected to different kinetic parameters sampled from random distributions. Through extensive computer simulations with various parameter distributions, we revealed the five most essential context-independent regulatory interactions (between: (1) αAR and Gαq, (2) IP3 and calcium, (3) epac and CaMK, (4) JNK and NFAT, and (5) p38 and NFAT) for hypertrophy and apoptosis that were consistently found over all our perturbation analyses. These essential interactions are expected to be the most promising therapeutic targets across a broad spectrum of individual conditions of heart failure patients.