Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived immunostimulatory factor, which activates several immune cells such as dendritic cells, T cells, and mast cells. Recently, epithelial cell-derived TSLP has gained immense attention as a cytokine that induces allergic immune responses. Therefore, understanding the regulation of TSLP production is an important step in uncovering the pathophysiology of allergic diseases. Moreover, the compounds that regulate TSLP production can be used as therapeutic drugs for the treatment of allergic diseases. We aim to elucidate the detailed regulation of TSLP production from epithelial cells, and in doing so discovered new regulating factors and an inhibitor of TSLP production. This review article explains the role of TSLP in allergic diseases, its regulation, and our research results.

Organocatalysts, which are less toxic than metal catalysis, as well as inexpensive, environmentally benign, and stable against moisture and oxygen compared to metal-based catalysts, have received considerable attention for being efficient and clean catalysts. With respect to green chemistry, the development of organocatalysis is a significant research subject for a sustainable society. This article reviews studies on the development of novel organocatalysts and the reactions achieved from using them. Focusing on the push-pull ethylene moiety, in which two electron-withdrawing groups (EWGs) were introduced, we proposed that the vinylogous amide proton (N-H) will lead to the design of organocatalysts. We have developed the diaminomethylenemalononitrile (DMM) organocatalysts, which are push-pull ethylenes having two cyano groups as EWGs, and proved that they are effective for highly stereoselective hydrophosphonylation with aldehydes. The catalytic ability of the DMM organocatalyst was demonstrated in the development of the first asymmetric hydrophosphonylation of ketones using organocatalysts. The DMM organocatalyst can be applied to the selective 1,4-addition asymmetric hydrophosphonylation of enones. In addition, we designed and synthesized novel organocatalysts bearing squaramide-sulfonamide motif as multiple hydrogen bond donors. Squaramide-sulfonamide organocatalysts efficiently catalyzed the asymmetric direct vinylogous aldol reactions of furan-2(5H)-one with aldehydes. Successively, we achieved the synthesis of γ,γ-disubstituted-δ-hydroxy-γ-butenolide via asymmetric direct vinylogous aldol reaction of furanone derivatives using the squaramide-sulfonamide organocatalysts.

The oxidation of p-methoxybenzyl (PMB) ethers was achieved using a nitroxyl radical catalyst 1, which contains electron-withdrawing ester groups adjacent to the nitroxyl group. The oxidative deprotection of the PMB moieties on the hydroxy groups was observed upon treatment of 1 with one equivalent of the co-oxidant phenyl iodonium bis(trifluoroacetate) (PIFA). This system showed an excellent chemoselectivity profile for the deprotection of PMB ethers from a broad range of functional groups including diverse oxidation-sensitive moieties. The corresponding carbonyl compounds were obtained by treating the PMB-protected alcohols with 1 and an excess amount of PIFA.

Opsins (also called animal rhodopsins) are universal photoreceptive proteins that provide the molecular basis of visual and nonvisual photoreception in animals, including humans. Opsins consist of seven helical α-transmembrane domains and use retinal, a derivative of vitamin A, as a chromophore. In many opsins, light absorption triggers photo-isomerization from 11-cis retinal to all-trans retinal, resulting in activation via dynamic structural changes in the protein moiety. Activated opsins stimulate cognate trimeric G proteins to induce signal transduction cascades in cells. Recently, molecular and physiological analyses of diverse opsins have progressively advanced. This review introduces the molecular basis and physiological functions of opsins. Based on the functions of opsins, I will discuss the potential of opsins as target molecules to treat and prevent visual and nonvisual diseases such as sleep disorder and depression.

Japan is currently a super-aging society, and lifestyle-related diseases that increase in incidence with age and the related rise in national medical expenses are major social problems. Preventive medicine and self-medication are becoming more important. Recently, various in vitro and in vivo studies have shown that food-derived natural compounds may contribute to the prevention and treatment of obesity-related diseases, such as diabetes mellitus. This report reviews our previous studies on the usefulness of the citrus flavonoid naringenin for obesity-related diseases. We showed that naringenin exerts an anti-diabetic effect by regulating inflammation pathways involving adipocytes and adipose tissue, and also showed an interaction between naringenin and anti-diabetic drugs. Because natural compounds are generally inexpensive and safe, they have the advantage of being easily applied to clinical applications. However, more detailed studies, such as clinical trials in humans, are required. Further research and scientific evidence will be required for the proper use of food factors in disease prevention and treatment.

Medication adherence is an important factor in the success or failure of drug treatment. No matter how good a drug is, if a patient cannot or does not want to take it, the therapeutic effect of the drug will not be sufficient and as expected. Therefore, we have been developing formulations with “clinical functionality”, namely, formulation characteristics that enhance the likelihood of obtaining the expected therapeutic effect. We researched formulations that are easy to take and deliver expected results; these formulations include gummy drugs as confectionery-like formulations and orally disintegrating (OD) tablets that can be easily swallowed. In particular, OD tablets have been jointly developed with pharmaceutical companies and have been commercialized. Clinical trials with gummy drugs and OD tablets have been conducted to verify the impact of these formulations with clinical functionality on improving medication adherence.

Plasma medicine is a rapidly expanding new field of interdisciplinary research that combines physics, chemistry, biology, and medicine. Non-thermal atmospheric pressure plasma (NTAPP) has recently been applied to living cells and tissues, and has emerged as a novel technology for medical applications, such as wound healing, blood coagulation, and cancer treatment. NTAPP was found to affect cells indirectly through the treatment of cells with previously prepared medium irradiated by NTAPP, termed plasma-activated medium (PAM). The treatment of culture media with NTAPP results in the generation of a large amount of reactive oxygen species and reactive nitrogen species, and their derived species. We found that PAM triggered a spiral apoptotic cascade in the mitochondrial-nuclear network in A549 cancer cells. This process induced the depletion of total cellular NAD⁺ and elevations in intracellular calcium ion, ultimately leading to cell death. We also detected the production of hydroxyl radical and elevations in intracellular ferrous ions in PAM-treated cells. The elevations observed in ferrous ions may have been due to their release from the intracellular iron store, ferritin. However, difficulties are associated with applying PAM to the clinical phase because culture media cannot be used for medical treatments. The anti-tumor activity of plasma-activated Ringer's solution was significantly stronger than that of PAM. At the end, we herein demonstrated the advantages of the combined application of plasma-activated acetate Ringer's solution and hyperthermia, a heat treatment at 42℃, for A549 cancer cell death and elucidated the underlying mechanisms.

Patients with sleep-disordered breathing exhibit intermittent hypoxia that causes increased oxidative stress, accelerates atherosclerosis, and pulmonary hypertension, resulting in life-threatening arrhythmias and congestive heart failure. Hypoxic stress caused by intermittent hypoxia might be involved in the pathophysiology of many cardiovascular diseases, especially those involving atrial fibrillation, for which anti-coagulant therapy may be recommended. In this study, the inhibition of proteinase-activated receptor (PAR) 1/2 significantly reduced oxidative stress and fibrosis while suppressing the activation of MAPK or Smad pathways and the gene expression of molecules responsible for the pathways in the myocardium, consequently attenuating hypoxia-mediated cardiomyocyte hypertrophy. These findings suggest that the inhibition of PAR 1/2 could be a novel potential treatment option to prevent cardiac remodeling in patients with sleep apnea syndrome and atrial fibrillation or chronic thromboembolic pulmonary hypertension.

In order to understand the actual state of residual solvents contained in commercial supplements, we performed a simultaneous analysis of residual solvents by headspace (HS)-GC-MS with reference to the Japanese Pharmacopoeia's “Residual Solvents”, for 29 products selected from among commercial supplements (e.g., revitalizers, weight loss pills) that are deeply colored or contain coating agents and extract powder. As a result, benzene (class 1) was detected in eight black-colored supplements, and hexane (class 2B) was also detected in one of those products. On the other hand, methanol (class 2A) was detected in four products containing coating agents and extract powders, such as citrus peel extract. None of these residual solvents exceeded the concentration limits set by the Japanese Pharmacopoeia. Benzene was detected at 1.7 μg/g, which was near the concentration limit, in some products. As raw materials used for the manufacture of the black-colored supplements from which benzene was detected commonly included activated carbon, we analyzed the residual solvents contained in activated carbon commercially available for use as food additive and in food production and medicine. As a result, benzene was detected at high concentrations in activated carbon made from hemp (approximately 29 μg/g) and bamboo (approximately 140 μg/g).