Cacao beans contain various bioactive phytochemicals that could modify the pathogeneses of certain diseases. Here, we report that oral administration of cacao powder (CP) attenuates UVB-induced skin wrinkling by the regulation of genes involved in dermal matrix production and maintenance. Transcriptome analysis revealed that 788 genes are down- or upregulated in the CP supplemented group, compared with the UVB-irradiated mouse skin controls. Among the differentially expressed genes, cathepsin G and serpin B6c play important roles in UVB-induced skin wrinkle formation. Gene regulatory network analysis also identified several candidate regulators responsible for the protective effects of CP supplementation against UVB-induced skin damage. CP also elicited antiwrinkle effects via inhibition of UVB-induced matrix metalloproteinases-1 expression in both the human skin equivalent model and human dermal fibroblasts. Inhibition of UVB-induced activator protein-1 via CP supplementation is likely to affect the expression of matrix metalloproteinases-1. CP supplementation also downregulates the expression of cathepsin G in human dermal fibroblasts. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone, a major in vivo metabolite of CP, showed effects similar to CP supplementation. These results suggest that cacao extract may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, which leads to an overall reduction in wrinkle formation.
Patients with cleft lip and/or palate (CLP), who undergo numerous medical interventions from infancy, can suffer from lifelong debilitation caused by underdeveloped maxillae. Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse. While such relapse has been a long-standing battle in craniofacial care of patients, currently there are no available strategies to address this pervasive problem. Estrogen, 17β-estradiol (E2), is a powerful therapeutic agent that plays a critical role in bone homeostasis. However, E2's clinical application is less appreciated due to several limitations, including its pleiotropic effects and short half-life. Here, we developed a treatment strategy using an injectable system with photo-crosslinkable hydrogel (G) and nanodiamond (ND) technology to facilitate the targeted and sustained delivery of E2 to promote bone formation. In a preclinical expansion/relapse model, this functionalized E2/ ND/G complex substantially reduced postexpansion relapse by nearly threefold through enhancements in sutural remodeling compared with unmodified E2 administration. The E2/ND/G group demonstrated greater bone volume by twofold and higher osteoblast number by threefold, compared with the control group. The E2/ND/G platform maximized the beneficial effects of E2 through its extended release with superior efficacy and safety at the local level. This broadly applicable E2 delivery platform shows promise as an adjuvant therapy in craniofacial care of patients.nanomedicine | cleft palate | craniofacial medicine | nanodiamond | drug delivery
BackgroundCalcaneal insufficiency avulsion (CIA) fractures often present with neuropathic etiology, such as Charcot neuroarthropathy (CN). Under the same surgical procedures, the outcomes of CIA fractures are less desirable, compared to the outcomes of the traumatic calcaneal avulsion fractures. Here, the study suggests Achilles tenodesis technique using suture anchor after resection of the CIA fracture fragments could provide satisfactory clinical results in the cases of surgically indicated CIA fractures.Materials and methodsThis retrospective study included seven patients of calcaneal avulsion fracture who had underlying diabetes mellitus (DM) and no specific traumatic event. The patients were treated with Achilles tenodesis techniques for their CIA fractures. Achilles tenodesis was performed using suture anchor with removal of the fracture fragments. The patients were evaluated with the Foot and Ankle Outcome Score (FAOS), visual analogue scale (VAS), single-heel rise test, and X-ray images on their final follow-ups.ResultsInitially, three of the CIA fracture cases treated with traditional open reduction and internal fixation reported pullout failure. Consequently, all patients received Achilles tenodesis using suture anchor after bone fragment resection and had good clinical outcomes. Only one subject with low compliance reported poor outcome.The FAOS of each patient were obtained at a mean of 16.3 months after surgery. The results are as follows: pain 80.6 (SD = 6.2), symptom 83.8 (SD = 4.9), activities of daily living 80.5 (SD = 8.0), sport and recreation function 75.6 (SD = 11.93), and foot- and ankle-related quality of life 77.9 (SD = 6.7). On their final follow-ups, the average VAS was 2.6 (range, 1 to 4).ConclusionAchilles tenodesis using suture anchor after bone fragment resection achieved competent clinical results in the patients with CIA fractures. The study proposes that this surgical procedure could be an appropriate treatment option for patients with CIA fractures.Trial registrationThe study was approved by the institutional review board (IRB) of our medical center (IRB File No. 2016-07-043), retrospectively registered.
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