Search Results (130)

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Background/Objectives: Oxidative stress plays a pivotal role in skin aging and carcinogenesis. Phytochemicals such as sulforaphane (SF, from broccoli sprouts or seeds) or curcumin (CUR, from turmeric) can be highly protective against this stress. They each induce a suite of cytoprotective and antioxidant enzymes that are coordinately transcribed via the Keap1-Nrf2-ARE pathway in mammals, such as the prototypical cytoprotective enzyme NAD(P)H dehydrogenase 1 (NQO1). Methods: Eighteen healthy human volunteers (9 males, 9 females, aged 18–69. were randomized to receive daily glucoraphanin (GR), which is converted to SF upon ingestion (450 mg; 1 mmol), CUR (1000 mg; 2.7 mmol), or both (450 mg GR + 1000 mg CUR), as oral supplements. After 8 days of a diet low in both compounds, blood and urine were collected for compliance and biomarker measurements. Randomized spots on the buttock’s skin were exposed to 2 x M.E.D. of UVB, and punch biopsies were obtained 1 and 3 days later for biomarker and histological measurement. Erythema was measured with a chromameter daily for 3 consecutive days following UVB. The process was repeated after receiving oral supplements, both with and without UVB exposure. Results: Compared to baseline, each treatment (n = 6 for each) induced NQO1 mRNA levels in skin biopsies: 3.1-fold with GR, 3.3-fold with CUR, and 3.6-fold with the combination of GR and CUR. Across all treatments (n = 18), expression of the pro-inflammatory cytokines IL-1β and TNF-α were reduced, as were IL-6, IL-17, STING, and CYR61, though less robustly. Modulation of these biomarkers persisted, but was less pronounced, in biopsies taken following UV exposure. The presence of SF and its metabolites in the skin post-treatment was confirmed by examining 6 of 12 subjects who ingested GR. Supplement effects on erythema following UV exposure were not significant, and no significant changes were measured in the same biomarkers in blood cells (PBMC), or by counting dyskeratotic keratinocytes. Supplements were well tolerated and compliance was excellent. Conclusions: Oral GR and CUR are well tolerated and have for the first time been shown to result in increased expression of cytoprotective genes and reduced expression of inflammatory cytokine genes in human skin in vivo. This mechanism-based clinical study suggests that an antioxidant, anti-inflammatory, and cytoprotective benefit from these oral supplements is delivered to the skin in humans. Full article

Atopic dermatitis (AD), a chronic inflammatory skin condition, is a common allergic disorder. The human skin, the largest organ, serves as the first barrier in protecting the body against various external threats. Human epidermal keratinocytes (HEKs) in the epidermal layer and human dermal fibroblasts (HDFs) in the dermis of the skin are implicated in AD-associated skin inflammation through the secretion of diverse inflammatory mediators, including chemokines. Sigesbeckia pubescens Makino (SP), a traditional Korean and Chinese herbal remedy, is used for treating inflammatory conditions. While several pharmacological effects of SP extract (SPE) have been documented, its specific inhibitory effect on AD-related skin inflammation remains unexplored. Hence, oral administration of SPE to NC/Nga mice reduced the severity of house dust mite extract-induced dermatitis, accompanied by lowered levels of serum inflammatory mediators, decreased epidermal thickness, reduced mast cell infiltration, and restoration of skin barrier function within skin lesions. In conclusion, SPE has demonstrated the ability to alleviate skin inflammation and protect the skin barrier and shows potential as a therapeutic option for AD. SPE inhibited proinflammatory chemokine production by modulating the Janus kinase (JAK) 2/signal transducer and activator of transcription proteins (STAT) 1/STAT3 signaling pathway in IFN-γ- and TNF-α-stimulated skin cells. Full article

Background/Objectives: The essential trace element zinc (Zn) has a pivotal role in wound healing and can show antibacterial activity, but its application in oral implant materials is underexplored. Customized healing abutments can modulate the peri-implant tissue health when appropriate bioactive materials promoting mucosal healing are used. The present study investigated a novel Zn-containing polymer for its potential in soft-tissue engineering applications. Methods: Four traditional materials—titanium, glass ionomer, a composite, and the novel Zn-containing polymer—were tested in vitro for bacterial growth using a multispecies oral bacterial model compared to hydroxyapatite. The biocompatibility of the materials was also evaluated by evaluating the adhesion, proliferation, and cytotoxicity of human oral keratinocytes (HOK-18A) onto these materials, compared to tissue culture plastic. Results: The Zn-containing polymer exhibited a significantly lower biofilm formation compared to conventional materials as it was composed of less pathogenic bacteria. The Zn-containing material also demonstrated a superior biocompatibility towards HOK-18A, approximating the adhesion and proliferation of the keratinocytes to optimal tissue culture conditions. Moreover, these properties did not seem to degrade and were maintained over a period of 31 days. The cytotoxicity assessment revealed no significant reduction in metabolic activity for any material. Conclusions: This study highlights the potential of the novel Zn-containing polymer in soft-tissue engineering, owing to its antimicrobial and biocompatible assets. These properties, combined with the ease of chairside modeling, position the material as a promising alternative for creating customized healing abutments. Further research is needed to explore its mechanism of wound healing modulation and its clinical performance. Full article

Cisplatin (CDDP) is an anticancer drug that is frequently used to treat head and neck cancers; however, it may cause oral mucositis. The discontinuation of CDDP may be required for some patients with a severe status, and the control of oral mucositis is extremely important. β-Cryptoxanthin (β-cry), a carotenoid, exerts anti-inflammatory effects. Its inhibition of 5-FU-induced inflammatory responses was recently demonstrated. However, the effects of β-cry on CDDP-induced oral mucositis remain unclear. In the present study, we stimulated human oral mucosa-derived keratinocytes (hOMK) and fibroblasts (hOMF) with CDDP, added β-cry, and examined its effects, with a focus on the production of inflammatory cytokines, matrix metalloproteinase (MMPs), and reactive oxygen species (ROS). CDDP increased the mRNA expression and production of inflammatory cytokines and MMPs both in hOMK and hOMF. However, increases in IL-6 and MMP-9 mRNA expression levels and IL-6 production in CDDP-treated hOMK and hOMF were inhibited by β-cry. Furthermore, the production of ROS and the rate of SA-β-gal-positive cells were increased by CDDP, but were not affected by β-cry. CDDP may induce oral mucositis by increasing the levels of inflammatory cytokines, MMPs, and ROS. β-cry partially inhibited CDDP-induced increases in inflammatory cytokines and MMPs, suggesting its potential to attenuate the symptoms of chemotherapy-related oral mucositis. Full article

Background: Hypertension (HTN) is recognized as a major risk factor for cardiovascular disease, chronic kidney disease, and peripheral artery disease. Valsartan (VAL), an angiotensin receptor blocker drug for hypertension, has been limited due to its poor solubility and poor absorption from the GIT, which leads to low oral bioavailability. Objectives/Method: In the present research, firstly, VAL-loaded nanoliposomes were formulated and optimized using the Box–Behnken design (BBD). Optimized VAL-nanoliposomes were physically characterized and their fate was examined by scanning and transmission microscopy, DSC, FTIR, XRD, and ex vivo studies using rat skin. In vitro studies using human keratinocyte (HaCaT) cells showed a decrease in cell viability as the liposome concentration increased. Secondly, the formulation of VAL-loaded nanoliposomes was integrated into dissolvable microneedles (DMNs) to deliver the VAL transdermally, crossing the skin barrier for better systemic delivery. Results: The optimized nanoliposomes showed a vesicle size of 150.23 (0.47) nm, a ZP of −23.37 (0.50) mV, and an EE% of 94.72 (0.44)%. The DMNs were fabricated using a ratio of biodegradable polymers, sodium alginate (SA), and hydroxypropyl methylcellulose (HPMC). The resulting VAL-LP-DMNs exhibited sharp pyramidal microneedles, adequate mechanical properties, effective skin insertion capability, and rapid dissolution of the microneedles in rat skin. In the ex vivo analysis, the transdermal flux of VAL was significantly (5.36 (0.39) μg/cm²/h) improved by VAL-LP-DMNs. The enhancement ratio of the VAL-LP-DMNs was 1.85. In conclusion, liposomes combined with DMNs have shown high potential and bright prospects as carriers for the transdermal delivery of VAL. Conclusions: These DMNs can be explored in studies focused on in vivo evaluations to confirm their safety, pharmacokinetics profile, and pharmacodynamic efficacy. Full article

The distinctive clinicopathologic characteristics of OLP indicated that both microbial dysbiosis and neurogenic inflammation may be jointly involved in its progression, and transient receptor potential vanilloid receptor-1 (TRPV1) may be a crucial element. The purpose of this study was to explore how TRPV1 mediated P. melaninogenica-induced inflammation. Meanwhile, we aimed to unravel how IL-36γ dysregulated the barrier function in oral keratinocytes. Here, the expression of TRPV1, calcitonin gene-related peptide (CGRP), and its receptor receptor activity-modifying protein 1 (RAMP1) in OLP patients were detected. Prevotella melaninogenica (P. melaninogenica) was used to build a mouse model of oral chronic inflammation. Normal human oral keratinocytes (NHOKs) stimulated by P. melaninogenica were used to examine TRPV1 activation and CGRP release. To investigate the effect of exogenous CGRP on Interleukin-36 gamma (IL-36γ) expression in NHOKs and bacterial viability, P. melaninogenica and NHOKs were treated with it, respectively. Recombinant IL-36γ protein was used to probe its regulation of oral epithelial barrier function. TRPV1, CGRP, and RAMP1 were substantially expressed in OLP. P. melaninogenica increased TRPV1 expression in mice and caused the release of CGRP and an increase in pro-inflammatory cytokines via activating TRPV1 in NHOKs. Blockade of TRPV1 suppressed P. melaninogenica-induced inflammation. CGRP boosted the production of IL-36γ released by NHOKs, resulting in lower expression of zonula occludens-1 (ZO-1). Also, CGRP can decrease the viability of P. melaninogenica. Together, these findings provide fresh insight into the vital role performed by P. melaninogenica-induced functional changes in oral epithelial cells and neurons in an intricate OLP inflammatory process. Full article

The evaluation of chlorhexidine-carrier nanosystems based on iron oxide magnetic nanoparticles (IOMNPs), has gained significant attention in recent years due to the unique properties of the magnetic nanoparticles (NPSs). Chlorhexidine (CHX), a well-established antimicrobial agent, has been widely used in medical applications, including oral hygiene and surgical antisepsis. This study aims to report an in vitro and in ovo toxicological screening of the synthesized CHX-NPS nanosystem, of the carrier matrix (maghemite NPSs) and of the drug to be delivered (CHX solution), by employing two types of cell lines—HaCaT immortalized human keratinocytes and JB6 Cl 41-5a murine epidermal cells. After the characterization of the CHX-NPS nanosystem through infrared spectroscopy and electronic microscopy, the in vitro results showed that the CHX antimicrobial efficacy was enhanced when delivered through a nanoscale system, with improved bioavailability and reduced toxicity when this was tested as the newly CHX-NPS nanosystem. The in ovo screening exhibited that the CHX-NPS nanosystem did not cause any sign of irritation on the chorioallantoic membrane vasculature and was classified as a non-irritant substance. Despite this, future research should focus on optimizing this type of nanosystem and conducting comprehensive in vivo studies to validate its therapeutic efficacy and safety in clinical settings. Full article

Little is known about the anti-graying effects of antioxidants on hair. The anti-graying effects of three antioxidants (luteolin, hesperetin, and diosmetin) on hair were investigated according to the sequential processes of hair graying that were previously clarified in model mice [Ednrb(+/−);RET-mice]. External treatment with luteolin, but not that with hesperetin or diosmetin, alleviated hair graying in Ednrb(+/−);RET-mice. Internal treatment with luteolin also mitigated hair graying in the mice. Although both luteolin treatments had very limited effects on hair cycles, the treatments suppressed the increase in p16^ink4a-positive cells in bulges [senescent keratinocyte stem cells (KSCs)]. Both of the treatments also suppressed decreases in the expression levels of endothelins in KSCs and their receptor (Ednrb) in melanocyte stem cells (MSCs) and alleviated hair graying in the mice. Luteolin is a special antioxidant with an anti-graying potency through improvement of age-related dysfunction in signaling between endothelins in KSCs and their receptor in MSCs. Luteolin for topical and oral use is commercially available to people in the form of supplements. Similar processes of hair graying in Ednrb(+/−);RET-mice and humans have been reported. These results are encouraging for the practical application of luteolin as a medicine with an anti-graying effect on hair in humans. Full article

Background/Objectives: The tumor protein D52 (TPD52) family includes TPD52, TPD53, TPD54, and TPD55. The balance between TPD52 and TPD54 expression plays an important role in high-malignant oral squamous cell carcinoma (OSCC) cells. However, the relationship between TPD53 and OSCC cells (particularly low-malignant OSCC cells) remains unclear. In the present study, we investigated the role of TPD53 in the malignant transformation of low-malignant OSCC cells. Methods: Temporal changes in the expression of TPD52 family members at the protein and mRNA levels in OSCC cells and normal human epidermal keratinocytes (NHEK) were examined. Results: The mRNA expression of TPD53 increased in HSC-3 and HSC-4 cells in a time-dependent manner. Similar results for protein expression were observed. The effects of TPD53 on anchorage-dependent and anchorage-independent proliferation, cell cycle, invasion and migration, epithelial-mesenchymal transition (EMT), and matrix metalloproteinase (MMP) activities in HSC-3 and HSC-4 cells were assayed. Finally, using the HSC-3-xenograft-nude-mice model, these effects were examined in vivo. Overexpression of TPD53 increased cell viability and the percentage of cells in the S phase. Furthermore, overexpression of TPD53 increased cell invasion, migration, and MMP activities, regardless of its effect on EMT. Notably, these effects were more pronounced in HSC-3 than in HSC-4 cells. Overexpression of TPD53 enhanced tumor formation and growth in mouse xenografts, corroborating the results of in vitro experiments. Conclusions: The present study revealed novel and important functions of TPD53 in the proliferation and invasion of low-malignant OSCC cells. Full article

Background/Objectives: Ivermectin gained widespread attention as the “miracle drug” during the coronavirus disease 2019 (COVID-19) pandemic. Its inclusion in the 21st World Health Organization (WHO) List of Essential Medicines is attributed to its targeted anti-helminthic response, high efficacy, cost-effectiveness and favorable safety profile. Since the late 2000s, this bio-inspired active pharmaceutical ingredient (API) gained renewed interest for its diverse therapeutic capabilities. However, producing ivermectin formulations does remain challenging due to its poor water solubility, resulting in low bioavailability after oral administration. Therefore, the transdermal drug delivery of ivermectin was considered to overcome these challenges, which are observed after oral administration. Methods: Ivermectin was incorporated in a nano-emulsion, nano-emulgel and a colloidal suspension as ivermectin-loaded nanoparticles. The nano-drug delivery vehicles were optimized, characterized and evaluated through in vitro membrane release studies, ex vivo skin diffusion studies and tape-stripping to determine whether ivermectin was successfully released from its vehicle and delivered transdermally and/or topically throughout the skin. This study concluded with cytotoxicity tests using the methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on both human immortalized epidermal keratinocytes (HaCaT) and human immortalized dermal fibroblasts (BJ-5ta). Results: Ivermectin was successfully released from each vehicle, delivered transdermally and topically throughout the skin and demonstrated little to no cytotoxicity at concentrations that diffused through the skin. Conclusions: The type of nano-drug delivery vehicle used to incorporate ivermectin influences its delivery both topically and transdermally, highlighting the dynamic equilibrium between the vehicle, the API and the skin. Full article

Background/Objectives: Ibrutinib (IBR) is a tyrosine kinase inhibitor under investigation in preclinical and clinical settings as an alternative treatment for melanoma. Nevertheless, the limited oral bioavailability of IBR and the need for high doses of the drug to kill melanoma cells are major drawbacks for this purpose. Considering that melanoma is restricted to the skin at early stages, the topical application of IBR might constitute an effective and safer administration route. In this study, we determined IBR’s toxicity and dermatokinetics using human primary cells and human organotypic skin explant cultures (hOSECs). Methods: After demonstrating that human primary fibroblasts and keratinocytes present IBR target genes, the cytotoxicity of the drug was determined using the MTT and annexin V/PI staining assays. IBR toxicity in the skin was assessed using the TTC assay, and the irritation potential was established using histological assessment. Finally, IBR cutaneous permeation was assessed ex vivo to determine the drug dermatokinetics. Results: Our findings reveal that IBR exerts dose-dependent toxicity towards skin cells, presenting an IC₅₀ in the same range as melanoma cells. The topical application of the drug successfully reduced irritation and toxicity in the skin, and the drug was shown to successfully permeate the stratum corneum and reach the viable skin layers in therapeutic concentrations. Conclusions: Overall, our data encourage the topical application of IBR to treat melanoma, paving the way for future studies in this theme. Full article

The purpose of this study is to evaluate Lactobacillus paracasei SMB092 as a prophylactic agent for oral pathogens. We examined the physical interaction of SMB092 with a host by identifying the presence of mucus-binding (MuB) protein domains and the capacity of the mucin binding. We determined the role of heat-killed SMB092 in host oral immunity by quantifying the mRNA levels of β-defensins (BDs), Toll-like receptors (TLRs), and their cofactors (CD14/CD36) in normal human oral keratinocytes (HOK-16B cells). To assess the clinically relevant oral health effects of heat-killed SMB092, the growth of Porphyromonas (P.) gingivalis and the production of a volatile sulfur compound (H₂S) were also measured in the filtered condition media (FCM) obtained from its cultures with HOK-16B cells. SMB092 possessed 14 putative MuB protein domains and was attached to mucin. Significant amounts of hBD1/2 and TLR2/6 were expressed in heat-killed SMB092-treated HOK-16B cells. The specific neutralization of TLR2 attenuated the expression of hBD1/2 and CD14/CD36. The FCM inhibited the growth of P. gingivalis and the production of H₂S. Our data indicate that heat-killed SMB092 may contribute to a healthy oral microbiome as an immune stimulant in the production of BDs via the activation of the TLR2/6 signaling pathway. Full article

Actinic keratosis (AK) is characterized by a reddish or occasionally skin-toned rough patch on sun-damaged skin, and it is regarded as a precursor to squamous cell carcinoma (SCC). Photodynamic therapy (PDT), utilizing 5-aminolevulinic acid (ALA) along with red light, is a recognized treatment option for AK that is limited by the penetration depth of light and the distribution of the photosensitizer into the skin. Cold atmospheric plasma (CAP) is a partially ionized gas with permeability-enhancing and anti-cancer properties. This study analyzed, in vitro, whether a combined treatment of CAP and ALA-PDT may improve the efficacy of the treatment. In addition, the effect of the application sequence of ALA and CAP was investigated using in vitro assays and the molecular characterization of human oral SCC cell lines (SCC-9, SCC-15, SCC-111), human cutaneous SCC cell lines (SCL-1, SCL-2, A431), and normal human epidermal keratinocytes (HEKn). The anti-tumor effect was determined by migration, invasion, and apoptosis assays and supported the improved efficacy of ALA-PDT in combination with CAP. However, the application sequence ALA-CAP–red light seems to be more efficacious than CAP-ALA–red light, which is probably due to increased intracellular ROS levels when ALA is applied first, followed by CAP and red light treatment. Furthermore, the expression of apoptosis- and senescence-related molecules (caspase-3, -6, -9, p16^INK4a, p21^CIP1) was increased, and different genes of the junctional network (ZO-1, CX31, CLDN1, CTNNB1) were induced after the combined treatment of CAP plus ALA-PDT. HEKn, however, were much less affected than SCC cells. Overall, the results show that CAP may improve the anti-tumor effects of conventional ALA-PDT on SCC cells. Whether this combined application is successful in treating AK in vivo has to be carefully examined in follow-up studies. Full article

With the escalating prevalence of hair loss, the demand for effective hair loss treatment has surged. This study evaluated the effects of hot water extract of Hydrangea serrata (Thunb.) Ser. leaf (WHS) on hair growth, employing cell cultures, mice, and human skin organoid models. Both WHS and hydrangenol were found to enhance 5α-reductase inhibitory activity. WHS and hydrangenol have been shown to stimulate dermal papilla cell (DPC) growth, potentially through factors like keratinocyte growth factor (KGF), fibroblast growth factor 10 (FGF10), and transforming growth factor-β1 (TGF-β1). They also elevated the expression levels of keratin genes (K31 and K85) and the ceramide synthase (CerS3) gene, crucial clinical indicators of hair health. Furthermore, they exhibited notable anti-inflammatory and anti-androgenic properties by reducing the levels of tumor necrosis factor-α (TNF-α) and androgen signaling molecules, including androgen receptor (AR) and dickkopf-1 (DKK-1) gene expression. Oral administration of WHS to C57BL/6 mice for 3 weeks confirmed its hair growth-promoting effects, improving hair growth parameters and gene expression without significant changes in hair weight. Additionally, in a human skin organoid model, WHS was found to stimulate hair formation and augment the expression of follicle markers. These findings position WHS as a promising nutraceutical for promoting hair health, as evidenced by its efficacy in both in vitro and in vivo models. Full article