Search Results (29)

Aminoglycoside antibiotics are critical in clinical use for treating severe infections, but they can occasionally cause irreversible sensorineural hearing loss. To establish a rational pathway for otoprotectant discovery, we provide an integrated, three-tier methodology—comprising cell-model selection, transcriptomic analysis, and a gentamicin–Texas Red (GTTR) uptake assay—to guide the development of otoprotective strategies. We first utilized two murine auditory cell lines—UB/OC-2 and HEI-OC1. We focused on TMC1 and OCT2 and further explored the underlying mechanisms of ototoxicity. UB/OC-2 exhibited a higher sensitivity to gentamicin, which correlated with elevated OCT2 expression confirmed via RT-PCR and Western blot. Transcriptomic analysis revealed upregulation of PI3K-Akt, calcium, and GPCR-related stress pathways in gentamicin-treated HEI-OC1 cells. Protein-level analysis further confirmed that gentamicin suppressed phosphorylated Akt while upregulating ER stress markers (GRP78, CHOP) and apoptotic proteins (cleaved caspase 3, PARP). Co-treatment with PI3K inhibitors (LY294002, wortmannin) further suppressed Akt phosphorylation, supporting the role of PI3K-Akt signaling in auditory cells. To visualize drug entry, we used GTTR to evaluate its applicability as a fluorescence-based uptake assay in these cell lines, which were previously employed mainly in cochlear explants. Sodium thiosulfate (STS) and N-acetylcysteine (NAC) significantly decreased GTTR uptake, suggesting a protective effect against gentamicin-induced hair cell damage. In conclusion, our findings showed a complex ototoxic cascade involving OCT2- and TMC1-mediated drug uptake, calcium imbalance, ER stress, and disruption of PI3K-Akt survival signaling. We believe that UB/OC-2 cells serve as a practical in vitro model for mechanistic investigations and screening of otoprotective compounds. Additionally, GTTR may be a simple, effective method for evaluating protective interventions in auditory cell lines. Overall, this study provides molecular-level insights into aminoglycoside-induced ototoxicity and introduces a platform for protective strategies. Full article

Background/Objectives: VitroScreenORA^® (by VitroScreen srl) Dermo Papilla spheroids, based on two micro-physiological systems (non-vascularized DP and vascularized VASC-DP), were used to study the molecular mechanisms behind hair cycle regression. Methods: Dermal papilla cells (HFDPC) were cultured to develop both models. Hair cycle regression was induced by exposing DP spheroids to TGF-β1 for 72 h and/or FGF-18 for an additional 24 h. Catagen phase entrance was evaluated by modulating specific genes (FGF7, CCND1, and WNT5B). The VASC-DP model was obtained by sequentially co-culturing HFDPC and primary dermal microvascular endothelial cells (HMDEC), mimicking the surrounding capillary loop. The vascular system’s impact was assessed at 5 and 10 days using IF on CD31 (micro-vessels) and Fibronectin (FN). Nanostring nCounter^® technology was applied to investigate the transcriptional signature based on the WNT pathway. Extended culture time up to 11 days simulated natural hair cycle regression, monitored by versican and FN expression (IF). Minoxidil, Doxorubicin, and Retinol-based products were used to modify physiological aging over time. Results: Data shows that the vascular system improves tissue physiology by modulating the associated genes. Extended culture time confirms progressive DP structure degeneration that is partially recoverable with Retinol-based treatments. Conclusions: Both models provide a reliable platform to investigate the hair cycle, paving the way for new testing systems for personalized therapies. Full article

Hair luster, a key component of visual hair quality, depends largely on the integrity of the cuticle. While cosmetic products offer temporarily enhanced luster, their effects are limited due to a poor understanding of the underlying molecular mechanisms. In this study, we employed a UVB-induced mouse model of hair luster loss to identify differentially expressed genes via quantitative real-time reverse transcription PCR. Key candidate genes were subsequently validated in vitro using human hair follicle dermal papilla cells and in ex vivo human scalp hair follicle tissue models. Subsequently, we evaluated the effects of minoxidil, caffeine, and biotin on gene expression and luster restoration. UVB exposure suppressed several luster-related genes, with COL7A1 consistently downregulated across all models. Treatment with minoxidil, caffeine, and biotin restored the expression of COL7A1 along with KRTAP5-5, KRTAP5-4, TGM3, and PTK7. These findings highlight COL7A1 as a novel molecular marker for hair luster and support its modulation as a potential therapeutic strategy. Full article

Background/Objectives: Treatment options for androgenic alopecia are still very limited and lack long-term efficacy. Dutasteride (DUT) has gained interest as a potent inhibitor of 5α-reductase, allowing for spaced applications, but DUT oral intake can cause serious adverse effects. Herein, we developed, characterized, and assessed the potential of DUT-loaded ethosomes with increasing ethanolic concentrations for hair follicle (HF) targeting to treat androgenic alopecia, hypothesizing that ethanol’s interaction with HFs’ sebum might increase DUT targeting to the HFs. Methods: Ethosomes were obtained using the water-dropping method. After a hydrodynamic size screening, a 30% ethanol concentration was fixed. Ethosomes with 30% ethanol were also prepared and had their ethanolic content removed by rotary evaporation for the evaluation of ethanol in targeting DUT to the HFs. The targeting factor (Tf) was calculated as the ratio between the DUT amount in HFs and the total DUT amount recovered from all skin layers after in vitro porcine skin penetration tests for 12 and 24 h. Results: The ethanolic concentration affected the vesicles’ size and the targeting potential. While the dried ethosomes could not increase DUT accumulation in the HFs at both time points (Tf: 0.27 in 12 h and Tf: 0.28 in 24 h), the presence of 30% ethanol in the vesicles increased the Tf from 0.28 (12 h) to 0.34 (24 h), significantly superior (p < 0.05) than the dried ethosome and control (Tf: 0.24) in 24 h. Conclusion: Ethosomes with a 30% ethanolic concentration were slightly more efficient in targeting HFs for dutasteride delivery. Full article

Cisplatin (Cis) is a commonly used chemotherapeutic agent for the clinical management of malignant tumors, but its toxic side effects could cause hearing loss, and there is an urgent need to find drugs that ameliorate Cis ototoxicity. Previous studies have found that ferulic acid (FA), a phenolic compound derived from natural plants, exerts antioxidant and anti-inflammatory effects by scavenging free radicals, preventing lipid peroxidation and cell death. Combination therapy, the use of multiple drugs to improve clinical outcomes, has multiple advantages compared to monotherapy. Another small-molecule ascorbic acid (AA) shows robust antioxidant function. However, the optimal route of administration, dosage, concentration, and effective time must be determined. More importantly, whether the combination of FA and AA can improve Cis ototoxicity and reduce the risk of large doses of AA is unclear. This study aims to evaluate the therapeutic potential of FA combined with AA in Cis-induced hearing impairment. In vitro and in vivo experiments were performed to observe the effects of FA, AA, and FA+AA on Cis-induced apoptosis. Compared with the Cis-only group, FA combined with AA ameliorated the Cis-induced decrease in cell viability, production of reactive oxygen species (ROS), and apoptosis of cells to varying degrees, respectively, and the improvement in cell viability, ROS, and apoptosis was even more pronounced with the combination of the two treatments. Network pharmacology combined with transcriptomics and molecular docking results showed that FA and AA could inhibit the Cis-induced apoptosis of cochlear hair cells through Matrix Metalloproteinase 9(MMP9)via the p38 Mitogen-Activated Protein Kinase (p38 MAPK) signaling pathway. In this study, we discovered that FA+AA reduced Cis ototoxicity by suppressing MMP9 in the MAPK signaling pathway. Full article

Introduction: Hair damage from chemical treatments, mechanical stress, and environmental factors can lead to significant degradation in hair quality, necessitating effective solutions for restoration. The aim of this study was to develop and evaluate novel compounds for repairing hair damage through the chemical regeneration of disulfide bridges. Materials and Methods: Three novel thiol-reactive cross-linking agents (APA, STA, SAA) were synthesized and characterized. Their efficacy in repairing hair damage was evaluated through in vitro tensile strength tests on human hair fibers, comparing treated and untreated samples. Cysteine reactivity tests were also performed to assess the capability of these agents to restore disulfide bridges in hair keratin. Results: The tensile strength tests revealed significant improvements in the mechanical properties of treated hair fibers compared to untreated samples. APA demonstrated the highest efficacy in restoring tensile strength and elasticity, showing higher performance in mechanical strengthening. The cysteine reactivity tests confirmed that APA could effectively re-establish disulfide bonds, particularly at higher temperatures. STA, while less effective than APA, showed substantial efficiency in restoring disulfide bonds. When compared to the reference agent, both APA and STA exhibited higher performance in tensile strength and cysteine reactivity, with APA showing the greatest improvement in mechanical properties. Conclusions: Our study successfully revealed the potential of the synthesized thiol-reactive cross-linking agents in repairing hair damage by chemically regenerating disulfide bridges. These findings offer a promising new direction for the development of advanced hair repair treatments in the cosmetic industry. Full article

Hair loss, a prevalent condition affecting individuals across various demographics, is associated with hormonal imbalances, oxidative stress, inflammation, and environmental factors. This study evaluated the anti-hair loss potential of the water-soluble fraction of Rhus semialata gall extract (WRGE) and its primary component, Penta-O-Galloyl-β-D-Glucose (PGG), through both in vitro and clinical studies. WRGE was obtained using a standardized extraction process, and PGG was identified via HPLC-DAD and HRESIMS/MS techniques. Human dermal papilla cells (HDPCs) are specialized fibroblasts that can regulate the hair growth cycle and hair follicle growth. HDPCs are widely used in research focused on anti-hair loss. In this study, the anti-hair loss effects of WRGE and PGG on HDPCs were confirmed. WRGE and PGG enhance cell proliferation in HDPCs. These results are associated with the activation of the Wnt/β-catenin signaling pathway and the upregulation of hair growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and fibroblast growth factor (FGF). Furthermore, WRGE and PGG significantly inhibited dihydrotestosterone (DHT)-mediated DKK-1 secretion and H₂O₂-medicated cytotoxicity. Clinical trials further validated these results, demonstrating significant improvements in hair density and visual hair appearance scores in participants treated with WRGE compared to a placebo group. These results collectively suggest that WRGE and PGG may serve as promising natural agents for the prevention and treatment of hair loss by targeting multiple biological pathways, including the regulation of hair growth factors, oxidative stress, and hormonal imbalances. Full article

Background/Objectives: Acne vulgaris is a skin disorder that affects millions worldwide, with Cutibacterium acnes playing a key role in its inflammation. Antibiotics reduce C. acnes and inflammation, but growing antibiotic resistance has limited their efficacy. Additionally, other common acne treatments with bactericidal activity, like benzoyl peroxide, cause irritation, dryness, and peeling. To fulfill the unmet need for alternative therapies, our strategy focused on identifying potent phage lysins and/or their derived cationic peptides. Methods: The C-terminal cationic antimicrobial peptide of the Prevotella intermedia phage lysin PlyPi01 was synthesized along with several sequence-engineered variants in an attempt to enhance their bactericidal efficacy. In vitro bacterial killing assays evaluated the potency of the lysin-derived peptide derivatives against C. acnes and Staphylococcus aureus, another skin bacterium associated with acne. Antibacterial activity was assessed both in conditions simulating the human skin and in combination with retinoids. Results: The variant peptide P156 was engineered by adding arginine residues at both the N- and C-terminal ends of the parental peptide PiP01. P156 was highly potent and eradicated all tested strains of C. acnes and S. aureus. P156 acted rapidly (>5-log kill in 10 min), further reducing the potential of resistance development. Additionally, P156 maintained its potency under conditions (e.g., temperature, pH, and salt concentration) observed on the skin surface and in hair follicles, as well as in combination with retinoid—all without being toxic to human cells. Conclusions: These collective findings position P156 as a promising topical drug for clinical applications to control acne vulgaris. Full article

Introduction: Mesenchymal stem cells (MSCs) have been introduced as a promising treatment for diabetic wounds. The effects of stem cell therapy are thought to be caused by bioactive molecules secreted by stem cells. Stem cell-based gene therapies can target bioactive molecules. Therefore, treatment using conditioned medium (CM) derived from genetically engineered stem cells has been proposed as an alternative option for diabetic ulcer care. Methods: MSCs derived from human umbilical cords were obtained and engineered to overexpress the angiogenin-1 gene (MSCs^Ang1) through plasmid transfection. This study extracted conditioned medium from MSCs (MSC-CM) or MSCs^Ang1(MSC^Ang1-CM) for wound treatment applications. Via in vitro experiments, the proangiogenic effects of MSC^Ang1-CM were assessed via the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Furthermore, the efficacy of MSC^Ang1-CM in promoting wound healing, re-epithelialization, hair follicle, and angiogenesis was evaluated via a diabetic mouse skin defect model. Results: In vitro assays demonstrated that MSC^Ang1-CM significantly enhanced HUVECs’ functions, including migration and tube formation. In vivo assays revealed that MSC^Ang1-CM exhibited notable advancements in healing speed, re-epithelialization, hair follicle, and angiogenesis. Conclusion: These results indicate that MSC^Ang1-CM can promote wound healing in diabetic mice and make the vascular structure in regenerated tissues more stable without inducing tissue fibrosis, providing a new therapeutic strategy for treating diabetic skin wounds. This provides a valuable theoretical basis for further research on regenerative medicine and cell therapy. Full article

Background/Objectives: Although androgenic alopecia is the most prevalent among non-cicatricial alopecia, it still lacks an effective and safe treatment. Dutasteride (DUT) shows promising results in hair regrowth; however, oral DUT intake causes serious sexual adverse events. Hence, we produced liposomes with different bilayer structures and evaluated the capability of such systems in increasing DUT accumulation in the hair follicles. Methods: In vitro skin penetration tests were performed with porcine ear skin, and the follicular targeting factor (Tf) was calculated as the ratio between DUT amount in HFs and DUT recovered from the sum of all skin layers. Results: While the stiffer DUT-loaded liposome was not able to target the hair follicles in 12 h (Tf = 0.15), a DUT-loaded liposome with an edge activator in its composition, i.e., transfersomes, promoted better control over DUT release and a higher Tf (0.32) (p < 0.005). Conclusions: Transfersomes present higher affinity with DUT providing a better controlled release; hence, they are a better option for DUT follicle targeting compared to liposomes. Further formulation optimizations are needed aiming to prolong such targeting effect. 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

This review aims to provide a detailed overview of the botanical, phytochemical, and dermatological properties of Juglans regia (J. regia). The entire tree contains a wealth of chemical compounds, including phenols, tannins, alkaloids, saponins, reducing sugars, and amino acids, which contribute to its significant nutritional and pharmacological value. Extracts and oils from all parts of J. regia have been studied for their effects on various skin conditions, demonstrating antioxidant, antimicrobial, anti-inflammatory, UV-protective, and chemoprotective properties. Additionally, these substances have shown potential in promoting wound healing, anti-aging, skin hydration, anti-tyrosinase activity, and hair dyeing. These benefits have been evaluated in various in vitro and in vivo studies. The therapeutic potential of J. regia suggests that its components could be integrated into treatment protocols and skincare routines. However, to optimize effectiveness and safety, future research should focus on in vivo studies in human subjects to determine the ideal concentrations and formulations of J. regia active compounds for specific skin conditions. Full article

Chemotherapy-induced hair loss is a distressing side effect of cancer treatment, and medical interventions are often needed to address this problem. The objectives of this study were to evaluate the bioactivity of goat placenta (GP) extract on both normal and chemotherapy-induced hair cells and to develop PEGylated liposomes (PL) and microspicule (MS) formulations for promoting hair growth in patients with chemotherapy-induced hair loss. The bioactivities of GP extract on human follicle dermal papilla (HFDP) cells and cells damaged by chemotherapy were assessed. GP extract was incorporated into PLs and MS gel (PL-MS) and then investigated in vitro skin permeation and in vivo studies on the scalps of patients with chemotherapy-induced hair loss. GP extract stimulated HFDP cell proliferation in both normal and cisplatin-damaged cells. PL nanovesicles and MS gel worked synergistically to deliver macromolecular proteins into the skin and hair follicles. The application of GP extract-loaded PL-MS to the scalps of chemotherapy-treated patients for 12 weeks significantly enhanced the hair growth rate, without causing skin irritation. In conclusion, GP extract promoted the proliferation of hair cells damaged by chemotherapy, when this extract, combined with PL-MS, effectively delivered bioactive macromolecules across the skin and hair follicles, resulting in successful regrowth of hair post-chemotherapy. Full article

Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% (p < 0.01), APN + 6.20% (p < 0.001)) and thickness (MNX + 5.14% (p < 0.001), APN + 10.32% (p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development. Full article

Treatment of chronic wounds is challenging, and the development of different formulations based on insulin has shown efficacy due to their ability to regulate oxidative stress and inflammatory reactions. The formulation of insulin with polysaccharides in biohybrid hydrogel systems has the advantage of synergistically combining the bioactivity of the protein with the biocompatibility and hydrogel properties of polysaccharides. In this study, a hydrogel formulation containing insulin, chitosan, and hydroxypropyl methyl cellulose (Chi/HPMC/Ins) was prepared and characterized by FTIR, thermogravimetric, and gel point analyses. The in vitro cell viability and cell migration potential of the Chi/HPMC/Ins hydrogel were evaluated in human keratinocyte cells (HaCat) by MTT and wound scratch assay. The hydrogel was applied to excisional full-thickness wounds in diabetic mice for twenty days for in vivo studies. Cell viability studies indicated no cytotoxicity of the Chi/HPMC/Ins hydrogel. Moreover, the Chi/HPMC/Ins hydrogel promoted faster gap closure in the scratch assay. In vivo, the wounds treated with the Chi/HPMC/Ins hydrogel resulted in faster wound closure, formation of a more organized granulation tissue, and hair follicle regeneration. These results suggest that Chi/HPMC/Ins hydrogels might promote wound healing in vitro and in vivo and could be a new potential dressing for wound healing. Full article