Glucocorticoids are steroid hormones that bind to the glucocorticoid receptor (GR), a member of the steroid hormone receptor superfamily of transcription factors. Excessive glucocorticoid secretion induces obesity, metabolic disturbances, and liver steatosis in patients with Cushing's syndrome. We investigated the metabolic role of adipocyte GR in Cushing's syndrome using adipocyte-specific GR knockout (AGRKO) mice and clinical samples from patients with Cushing's syndrome. AGRKO mice showed healthy adipose tissue expansion with diminished ectopic lipid deposition and improved insulin sensitivity after chronic corticosterone treatment. These changes were associated with adipose triglyceride lipase (Atgl)-mediated lipolysis. Additionally, integrated analysis with RNA sequencing of white adipose tissue from AGRKO mice and patients with Cushing's syndrome revealed that the healthy adipose tissue expansion was associated with the dysregulation of tissue remodeling and preadipocyte proliferation. Therefore, our study revealed the role of adipocyte GR in healthy adipose tissue expansion and its multiple mechanisms of action in Cushing's syndrome.

Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, called incretin modulators, are key drugs for managing type 2 diabetes that are widely recognized for their effectiveness. These drugs contribute to the regulation of glucose metabolism by mimicking or enhancing the function of a gastrointestinal hormone known as incretins, including GLP-1 and gastric inhibitory peptide (GIP). Incretins uniquely stimulate insulin secretion in a glucose concentration-dependent manner only when blood glucose is elevated. Among the incretin modulators, GLP-1 receptor agonists have shown multiple benefits: they delay gastric emptying, reduce glucagon secretion, enhance glycogen synthase in the liver, suppress appetite in the central nervous system, and decrease body weight. Additionally, they have been recently shown to protect cardiovascular and kidney functions. These findings have led to their recommendation for use in patients with type 2 diabetes mellitus complicated by chronic kidney disease or heart failure. Currently, these incretin modulators are prescribed only for type 2 diabetes; however, some GLP-1 receptor agonists are expected to be approved for obesity treatment soon in Japan. Their clinical use exemplified successful translational research.

The pathological condition of atopic dermatitis is formed by three factors: decreased skin barrier function, type 2 immune response, and itching. In recent years, elucidation of the pathological condition of atopic dermatitis has progressed from the immunological aspect. Type 2 cytokines, such as interleukin (IL) -4 and IL-13, produced from cells such as Th2 cells and type 2 innate lymphocytes, play a crucial role in the lesion areas of atopic dermatitis. These type 2 cytokines decrease the antibacterial peptide levels and the barrier of epidermal keratinocytes, and induce inflammation. Currently, antibody preparations that suppress targeted cytokines, Janus kinase (JAK) inhibitors that inhibit the JAK-signal transducer and activator of transcription (STAT) pathway and system, and anti-phosphodiesterase4 (PDE4) inhibitors, developed based on the pathological condition of atopic dermatitis, are on the market. The existing topical drug therapies are the anticipated treatment methods for refractory atopic dermatitis affecting children and adults.

The discovery of natriuretic peptides represents one of the most crucial discoveries in cardiovascular medicine, shedding light on the endocrine properties of the heart. Natriuretic peptides are activated in heart failure (HF), and they play an important role in cardioprotection. Atrial natriuretic peptide and brain natriuretic peptide are abundantly expressed and secreted in the atria and ventricles, respectively. They induce diuretic/natriuretic effects, vasodilation, and counteract the actions of angiotensin II by inhibiting aldosterone secretion. The identification of natriuretic peptides has spurred a growing research field dedicated to characterizing their physiological roles in cardiovascular homeostasis and disease. Furthermore, their potential as biomarkers and therapeutic agents is under active investigation. Carperitide and sacubitril/valsartan are effective HF treatments that utilize the physiological effects of natriuretic peptides. Understanding the roles of the different members within the natriuretic peptide family in maintaining cardiovascular homeostasis, along with recognizing their pathophysiological implications in the development and progression of HF, forms the fundamental basis for the clinical significance of natriuretic peptides in the development of diagnostic and therapeutic agents for HF.

In recent years, osteoporosis has become a serious concern in developed countries. Romosozumab, launched in 2019, is a relatively new osteoporosis medication that enhances bone mineral density and inhibits development of new fractures. Contraindications to romosozumab administration include hypocalcemia. It should also be administered with caution to patients at a high risk of cardiovascular disorders. To maximize its effects, it is preferable to administer romosozumab before initiation of other osteoporosis medications. Currently, no clinical reports have discussed the ability of romosozumab to promote fracture healing. Combination therapy using romosozumab and other drugs may be useful in patients with osteoporosis.

Allergic rhinitis and chronic rhinosinusitis (CRS) are both upper airway diseases with high prevalence rates in Japan. Because these diseases significantly reduce patients' quality of life, new treatments are being researched every day. In this paper, we focused on allergic rhinitis, eosinophilic chronic rhinosinusitis (ECRS), and CRS with IgG4-related disease (CRS with IgG4-RD), their underlying pathogenic mechanisms, and treatments that have been recently attracting attention.

Allergic rhinitis is a type 1 hypersensitivity reaction that induces chemical mediators, such as histamine, and type 2 cytokines, such as IL-5. The effectiveness of biologic agents, such as Omalizumab, an anti-IgE antibody, and sublingual immunotherapy have already been assessed and approved.

ECRS, caused by type 2 inflammation, is a refractory disease. Its pathogenic conditions are formed mainly by type 2 cytokines, such as IL-4, IL-5, and IL-13. Dupilumab, an anti-IL-4α receptor antibody, inhibits the function of IL-4 and IL-13, has recently been reported to improve disease-control of ECRS.

IgG4-RD has been reported to complicate CRS. In this study, activation-induced cytidine deaminase (AID) -positive cells and regulatory T cells were found to increase in the sinus mucosa of CRS with IgG4-RD. The results implied that the pathogenesis of CRS with IgG4-RD and IgG4-RD are possibly of the same mechanism.

Clarifying the pathogenesis of these refractory diseases is necessary to improve disease-control and gain insights from which better treatments can be developed.

In recent years, rhythmic fluctuations in life, organized by biological clocks, have been found to maintain health and prevent aging and certain diseases. Circadian signals are transmitted from the central clock in the suprachiasmatic nuclei located in the hypothalamus to the local clocks in the brain and most peripheral tissues, which coordinate the function of nerves, hormone secretion, and sleep-wake rhythms. Clock genes regulate the biological clock, and if their expression level decreases, the movement of the clock deteriorates, which harms health. Humans have an internal cycle of more than 24 h, and the appropriate timing is maintained according to external daily stimuli, such as morning light. Local clocks in the peripheral tissues have a strong direct response to external stimuli of stress, exercise, and/or food, that are independent of the central clock. Therefore, light exposure, diet, and exercise at the appropriate times of the day lead to a healthy lifestyle. Melatonin, a sleep hormone, begins to be secreted at night due to morning light, increases at night, and decreases at dawn, which is disrupted by light exposure at night; therefore, it is important to limit light exposure at night to maintain sleep.