Recent progress of TP/NIR fluorescent probes for metal ions.

Metal ions are of significance in various pathological and physiological processes. As such, it is crucial to monitor their levels in organisms. Two-photon (TP) and near-infrared (NIR) fluorescence imaging has been utilized to monitor metal ions because of minimal background interference, deeper tissue depth penetration, lower tissue self-absorption, and reduced photodamage. In this review, we briefly summarize recent progress from 2020 to 2022 of TP/NIR organic fluorescent probes and inorganic sensors in the detection of metal ions. Additionally, we present an outlook for the development of TP/NIR probes for bio-imaging, diagnosis of diseases, imaging-guided therapy, and activatable phototherapy.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 2. Management of H1-Antihistamine-Refractory Chronic Urticaria.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H1-antihistamines, even though the dose of H1-antihistamines is increased up to 4-fold. CSU that is not controlled with H1-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H1-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.

Phototherapy May be a Useful Adjuvant Therapy for Retractable Chronic Spontaneous Urticaria: A Systematic Review.

The recent guideline on the management of urticaria recommends second-generation H1 antihistamine as the first-line therapy, with dose increases of up to fourfold and the addition of omalizumab or cyclosporine if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing. Therefore, a safe and effective treatment option is needed for refractory CSU. To evaluate whether phototherapy can relieve urticarial symptoms and serve as an additional treatment for CSU uncontrolled with antihistamine, we performed a qualitative systematic review. Our result suggests that NBUVB could be an effective complementary treatment modality to manage refractory CSU.

The Clinical Profile of Patients with Psoriasis in Korea: A Nationwide Cross-Sectional Study (EPI-PSODE).

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting multiple aspects of patients' lives. Its epidemiology varies regionally; however, nationwide epidemiologic data on psoriasis depicting profile of Korean patients has not been available to date. OBJECTIVE: To understand nationwide epidemiologic characteristics and clinical features of adult patients with psoriasis visited university hospitals in Korea. METHODS: This multicenter, non-interventional, cross-sectional study recruited 1,278 adult patients with psoriasis across 25 centers in Korea in 2013. Various clinical data including PASI, BSA, DLQI, SF-36 and PASE were collected. RESULTS: A total of 1,260 patients completed the study (male:female=1.47:1). The mean age was 47.0 years with a distribution mostly in the 50s (24.9%). Early onset (<40 years) of psoriasis accounted for 53.9% of patients. The mean disease duration was 109.2 months; mean body mass index was 23.9 kg/m2; and 12.7% of patients had a family history of psoriasis. Plaque and guttate types of psoriasis accounted for 85.8% and 8.4%, respectively. Patients with PASI ≥10 accounted for 24.9%; patients with body surface area ≥10 were 45.9%. Patients with DLQI ≥6 accounted for 78.8%. Between PASI <10 and PASI ≥10 groups, significant difference was noted in age at diagnosis, disease duration, blood pressure, waist circumference of female, and treatment experiences with phototherapy, systemic agents, and biologics. CONCLUSION: This was the first nationwide epidemiologic study of patients with psoriasis in Korea and provides an overview of the epidemiologic characteristics and clinical profiles of this patient population.

Secondary Cutaneous Amyloidosis in a Patient with Mycosis Fungoides.

Secondary cutaneous amyloidosis refers to clinically unapparent amyloid deposits within the skin in association with a pre-existing skin condition or skin tumors, such as basal cell carcinoma, porokeratosis, solar elastosis, Bowen's disease, and mycosis fungoides. A 70-year-old woman presented with a 6-month history of asymptomatic multiple yellowish plaques on both legs. She had been diagnosed with mycosis fungoides 7 years ago and was treated with psoralen and ultraviolet A radiation (PUVA) therapy, narrow-band ultraviolet B (UVB) therapy, and acitretin for 5 years. Finally, she reached complete remission of mycosis fungoides. However, new yellowish lesions started to appear 1 year after discontinuing the phototherapy. A physical examination revealed multiple yellowish plaques on both extremities. The plaques were well circumscribed and slightly elevated. All laboratory tests were normal. A biopsy specimen showed multiple nodular deposits of eosinophilic amorphous material in papillary dermis and upper reticular dermis. The deposits represented apple green birefringence on Congo red stain viewed under polarized light. Acellular small nodules in the upper dermis consisted of randomly oriented, non-branching, 6.67~12.7 nm thick amyloid fibrils on electron microscopy. We report an interesting and rare case of secondary cutaneous amyloidosis after narrow-band UVB therapy and PUVA therapy in a patient with mycosis fungoides.

The Efficacy and Safety of 660 nm and 411 to 777 nm Light-Emitting Devices for Treating Wrinkles.

BACKGROUND: Low-level light therapy (LLLT) using light-emitting diodes (LEDs) is considered to be helpful for skin regeneration and anti-inflammation. OBJECTIVE: To evaluate the efficacy and safety of 2 types of LLLTs using 660 nm-emitting red LEDs and 411 to 777 nm-emitting white LEDs in the treatment of facial wrinkles. MATERIALS AND METHODS: A prospective, randomized, double-blinded, comparative clinical trial involving 52 adult female subjects was performed. The faces of the subjects were irradiated daily with 5.17 J of red or white LEDs for 12 weeks. RESULTS: In both groups treated with red and white LEDs, the wrinkle measurement from skin replica improved significantly from baseline at Week 12. The red LED group showed slightly better improvement, but there were no statistical differences. In assessments by blinded dermatologists, no significant differences were observed in both groups. In the global assessment of the subjects, the mean improvement score of the red LED group was higher than that of the white LED group. CONCLUSION: Low-level light therapy using 660 nm LEDs or 411 to 777 nm LEDs significantly improved periocular wrinkles. Especially, 660 nm LEDs could be an effective and tolerable treatment option for wrinkles.

Effects of Allium victorialis leaf extracts and its single compounds on aldose reductase, advanced glycation end products and TGF-ß1 expression in mesangial cells.

BACKGROUND: Accumulating evidences suggest that aldose reductase (AR) inhibitors and advanced glycation end product (AGE) formation inhibitors may prevent chronic hyperglycemia-induced long-term complication in diabetes. Transforming growth factor-beta1 (TGF-ß1) plays an important role in the development of diabetic nephropathy. Allium species have been utilized in folk medicine throughout the world for the treatment of various physical disorders. However, the benefits of Allium victorialis (A. victorialis) against diabetic complications, especially nephropathy, have yet to be explored. In the present study, we investigated the protective effect of the compounds isolated from A. victorialis leaf on diabetic nephropathy. METHODS: In vitro AR activity, AGEs formation, and AGE-receptor for AGEs (RAGE) binding in human RAGE (hRAGE)-overexpressing cells were tested. High glucose-induced transforming growth factor-beta1 (TGF-ß1) expression was also examined in mouse kidney mesangial cells (MMCs) cultured under high glucose. RESULTS: Of the isolated eight compounds from A. victorialis leaf extracts tested, quercitrin exhibited the most pronounced inhibitory effects on AR activity (IC50 value of 0.17 µM) and AGEs formation (IC50 value of 4.20 µM). Furthermore, quercitrin disrupted AGE-RAGE binding in a concentration-dependent manner in hRAGE-overexpressing cells. Additionally, of the eight compounds tested, ferulic acid significantly reduced high glucose-induced TGF-ß1 expression and secretion in MMCs. CONCLUSIONS: Our results suggest that active compounds isolated from A. victorialis leaf exhibit inhibitory effects on AR activity in rat lenses and AGE formation. Further, ferulic acid reduces TGF-ß1 mRNA expression and secretion in MMCs under diabetic conditions. Thus, A. victorialis is a good candidate for the development of treatments for diabetic nephropathy.

Development of a cellular tau enzyme-linked immunosorbent assay method for screening GSK-3ß inhibitors.

Glycogen synthase kinase-3ß (GSK-3ß), a serine/threonine kinase also known as tau protein kinase I, has been implicated in the pathogenic conditions of Alzheimer's disease. Many investigators have focused on GSK-3 inhibitor as a therapeutic drug. In this study, we established a cell-based assay for the screening of novel GSK-3ß inhibitors. For this purpose, four-repeat tau cDNAs were stably expressed in human embryonic kidney 293 (HEK293) cells (HEK293-Tau). The proliferation of HEK293-Tau cells was no different from that of HEK293 cells, as measured by the bromodeoxyuridine enzyme-linked immunosorbent assay (BrdU ELISA). The concentration-dependent reduction of tau phosphorylation by GSK-3 inhibitors, LiCl, Chir98023, and SB415286, was examined by immunoblot analysis and Tau ELISA (in situ ELISA). Highly consistent data were obtained, suggesting that this novel ELISA method is highly reproducible. Using this ELISA strategy, we isolated a few candidate compounds, including compounds 114 and 149, from several hundreds of synthetic agents and demonstrated that such candidates protect nerve growth factor-differentiated PC12 cells against amyloid-ß-induced cell death. These data indicate that this Tau ELISA method in HEK293-Tau cells may be a suitable cell-based assay system to screen for GSK-3ß inhibitors.

Discovery of thiochroman and chroman derivatives as pure antiestrogens and their structure-activity relationship.

In order to develop pure antiestrogens, a series of 7-hydroxy-3-(4-hydroxyphenyl)-3-methylchroman and 7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman derivatives with sulfoxide containing side chains at the 4-position were designed, synthesized, and evaluated. Among them, compounds 14b and 24b functioned as pure antiestrogens with the ability to downregulate ER, and their in vitro and in vivo antiestrogen activities were similar to those of ICI182,780. In addition, the structure-activity relationship indicated that the (3RS,4RS)-configuration between the 3- and 4-position, the methyl group at the 3-position, the 9-methylene chain between the scaffold and the sulfoxide moiety, and the terminal perfluoroalkyl moiety play an important role in increasing estrogen receptor binding and oral antiestrogen activities.