Ursodeoxycholic acid alleviates atopic dermatitis-associated inflammatory responses in HaCaT and RBL-2H3 cells and DNCB/DFE-treated mice.

AIMS: Ursodeoxycholic acid (UDCA) is a hydrophilic dihydroxy bile acid used for cholestatic liver disease and exhibits antioxidant, antitumor, and anti-inflammatory effects. However, its potential effects on atopic dermatitis (AD) have not been elucidated. This study aimed to evaluate the efficacy of UDCA in inhibiting the inflammatory response and alleviating lesions in AD-like mice. MAIN METHODS: To investigate the efficacy of UDCA in AD-like inflammatory responses, tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-stimulated HaCaT cells and anti-dinitrophenyl immunoglobulin E (DNP-IgE)- and human serum albumin (HSA)-stimulated RBL-2H3 cells were used to investigate the levels of inflammatory factors and their mechanisms. AD-like lesions were induced by applying DNCB/DFE to mice. The effect of UDCA administration in AD-like mice was analyzed by assessing organ weight, serum IgE and inflammatory cytokine levels, and histopathological changes using immunohistochemical and immunofluorescent staining. KEY FINDINGS: In HaCaT cells, UDCA significantly diminished TARC, MDC, MCP-1, and IL-6 expression by inhibiting the phosphorylation of nuclear NF-κB and cytoplasmic IκB, and also increased the levels of skin barrier protein. In RBL-2H3 cells, UDCA reduced ß-hexosaminidase and IL-4 levels. In AD-like mice, UDCA suppressed organ hypertrophy, ear edema, SCORAD index, DFE-specific IgE levels, inflammatory cytokine levels, skin hypertrophy, mast cell invasion, skin barrier loss, and thymic stromal lymphopoietin-positive areas. SIGNIFICANCE: UDCA suppressed the expression of pro-inflammatory cytokines by keratinocytes and mast cells. It also alleviated atopy by suppressing symptoms without organ toxicity in AD-like mice. UDCA may be an effective and safe treatment for AD.

Exploring the Anti-Osteoporotic Potential of Daucosterol: Impact on Osteoclast and Osteoblast Activities.

Osteoporosis is a debilitating condition characterized by reduced bone mass and density, leading to compromised structural integrity of the bones. While conventional treatments, such as bisphosphonates and selective estrogen receptor modulators (SERMs), have been employed to mitigate bone loss, their effectiveness is often compromised by a spectrum of adverse side effects, ranging from gastrointestinal discomfort and musculoskeletal pain to more severe concerns like atypical fractures and hormonal imbalances. Daucosterol (DC), a natural compound derived from various plant sources, has recently garnered considerable attention in the field of pharmacology. In this study, we investigated the anti-osteoporosis potential of DC by characterizing its role in osteoclasts, osteoblasts, and lipopolysaccharide (LPS)-induced osteoporosis. The inhibitory effect of DC on osteoclast differentiation was determined by tartrate-resistant acid phosphatase (TRAP) staining, F-actin ring formation by fluorescent staining, and bone resorption by pit formation assay. In addition, the calcification nodule deposition effect of osteoblasts was determined by Alizarin red S staining. The effective mechanisms of both cells were verified by Western blot and reverse transcription polymerase chain reaction (RT-PCR). To confirm the effect of DC in vivo, DC was administered to a model of osteoporosis by intraperitoneal administration of LPS. The anti-osteoporosis effect was then characterized by micro-CT and serum analysis. The results showed that DC effectively inhibited osteoclast differentiation at an early stage, promoted osteoblast activity, and inhibited LPS-induced bone density loss. The results of this study suggest that DC can treat osteoporosis through osteoclast and osteoblast regulation, and therefore may be considered as a new therapeutic alternative for osteoporosis patients in the future.

Importance of detection of capitellar cartilage injuries concomitant with isolated radial head fractures: A retrospective clinical study.

OBJECTIVE: This study aimed to analyze the injury pattern and clinical importance of concomitant capitellar cartilage defects (CCDs) among patients treated surgically for radial head fracture (RHF). METHODS: A total of 74 patients who were treated surgically for isolated RHFs were retrospectively reviewed. Of these, 12 patients with CCDs (16.2%) were classified as Group I (10 men; mean age, 41.3±12.8 years) and the remaining 62 patients without CCD as Group II (control group) (48 men; mean age, 50.8±13 years). The mean follow-up was 21.3±3.2 months in Group I and 18.7±6.4 in Group II. In Group I, 11 patients underwent open reduction and internal fixation, whereas 1 patient was treated by radial head resection. The preoperative range of motion (ROM) was recorded; the severity of RHF was assessed using the Mason classification. The location, size, and thickness of CCD injuries at the time of surgery were also documented. At the final follow-up, radiological assessment was performed to determine the bone union, and clinical measurements, including ROM and the Mayo elbow performance score (MEPS), were performed. The clinical features of the 2 groups were statistically analyzed. RESULTS: In Group I, 10 patients showed limited forearm rotation. CCD was located posterolaterally in 11 patients and anterolaterally in 1 patient. At the final follow-up, 11 patients from Group I who underwent open reduction and internal fixation showed complete union of RHF and full recovery of pronation and supination. According to the MEPS, 9 patients exhibited excellent results, and 3 patients exhibited good results. In Group I, RHFs were classified as Mason type II in 7 patients (58.3%) and type III in 4 patients (58.3%). In Group II, RHFs were type II in 45 patients (72.6%) and type III in 17 patients (27.4%). In comparative analyses, there was a significant difference in age (41.3±12.8 versus 50.8±13.0, p=0.041) between the 2 groups. Preoperative pronation/supination was higher in Group II (131.7±36.2) than in Group I (106.3±31.6) (p=0.021). There were no significant differences in sex (p=0.097), follow-up period (p=0.326), Mason type (p=0.482), preoperative extension/flexion (102.3±43.3 [Group I] versus 107.6±44.9 [Group II]) (p=0.584), final follow-up extension/flexion (133.3±10.7 [Group I] versus 126.9±21.2 [Group II]) (p=0.384), pronation/supination (151.2±9.1 [Group I] versus 151.2±13.3 [Group II]) (p=0.558), and the MEPSs (92.9±6.6 [Group I] versus 93.3±7.5 [Group II]) (p=0.701). CONCLUSION: If a thorough physical examination of a patient with RHF reveals limited forearm rotation, effort must be made to identify the cause, and the possibility of CCD must be considered. Moreover, there is a need for careful observation during RHF surgery for not only fracture reduction or fixation but also possible CCD. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

Near infrared dye-conjugated oxidative stress amplifying polymer micelles for dual imaging and synergistic anticancer phototherapy.

The recent advances in nanotechnology have led to the development of smart nanomaterials that combine diagnostic and therapeutic functions and provide synergistic anticancer effects through the combination of different treatment modalities. Here, we report a promising theranostic nanoconstruct that can translate into multiple functionalities: fluorescence/photoacoustic imaging, acid-triggered generation of ROS (reactive oxygen species), heat and singlet oxygen production under near infrared (NIR) laser irradiation, and coupling oxidative anticancer therapy to dual imaging-guided photothermal/photodynamic therapy. An NIR dye-conjugated hydroxyl radical generating biodegradable polymer (HRGP-IR) is employed as a theranostic nanoplatform. HRGP-IR could self-assemble to form micelles and elevate oxidative stress by generating hydrogen peroxide and hydroxyl radical. Under the NIR (808 nm) laser irradiation, HRGP-IR micelles also generate heat and singlet oxygen to induce cancer cell death. In mouse xenograft models, HRGP-IR micelles accumulated in tumors preferentially and the tumor could be detected by dual imaging. Effective tumor ablation was achieved by HRGP-IR micelles (5 mg/kg) combined with NIR laser irradiation, demonstrating the synergistic anticancer effects of oxidative stress with photothermal heating. Given their dual imaging capability, anticancer phototherapy and highly potent synergistic anticancer activity with NIR laser irradiation, HRGP-IR micelles hold great potential as a nanotheranostic agent for cancer treatment.