BACKGROUND: Psoriasis refers to a highly prevalent and immunologically mediated dermatosis with considerable deterioration in life quality. Wogonin, a sort of flavonoid, has been mentioned to elicit protective activities in skin diseases. However, whether Wogonin is implicated in the treatment of psoriasis and its specific mechanisms are not fully understood.
OBJECTIVE: The present work attempted to elaborate the role of Wogonin during the process of psoriasis and to concentrate on the associated action mechanism.
METHODS: Cell counting kit-8 (CCK-8) method was initially applied to assay the viability of human keratinocyte HaCaT cells treated by varying concentrations of Wogonin. To mimic psoriasis in vitro, HaCaT cells were exposed to M5 cytokines. CCK-8 and 5-Ethynyl-2\'-deoxyuridine  assays were adopted for the measurement of cell proliferation. Inflammatory levels were examined with enzyme-linked immunosorbent assay. Immunofluorescence staining tested nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) and Caspase-1 expressions. Western blot examined the protein expressions of proliferation-, inflammation-, pyroptosis-associated factors, and NLRP3.
RESULTS: Wogonin treatment antagonized the proliferation, inflammatory response, and NLRP3/caspase-1/Gasdermin-D (GSDMD)-mediated pyroptosis in M5-challenged HaCaT cells. Besides, NLRP3 elevation partially abrogated the effects of Wogonin on M5-induced proliferation, inflammatory response, and NLRP3/caspase-1/GSDMD-mediated pyroptosis in HaCaT cells.
CONCLUSIONS: In a word, Wogonin might exert anti-proliferation, anti-inflammatory and anti-pyroptosis activities in M5-induced cell model of psoriasis and the blockade of NLRP3/Caspase-1/GSDMD pathway might be recognized as a potential mechanism underlying the protective mechanism of Wogonin in psoriasis, suggesting Wogonin as a prospective anti-psoriasis drug.

In the present study, pyroligneous acid, also known as wood vinegar, has been employed as reducing and stabilizing agent in the synthesis of silver nanoparticles (AgNPs) anchored on nanocellulose (NC). The idea is to confer the latter bactericidal properties for its typical uses such as in cosmetics and food-packing. It has been demonstrated that AgNPs can be directly produced onto NC in one-pot fashion while dramatically enhancing the kinetics of AgNPs synthesis (2 h for reaction completion) in comparison to the NC-less counterpart (10 days for reaction completion). Furthermore, NC allowed for a narrower size distribution of AgNPs. NC-supported and non-supported AgNPs had sizes of 5.1 ± 1.6 nm and 16.7 ± 4.62 nm, respectively. Immortalized human keratinocytes (HaCat) cells were then employed as model to evaluate the cytotoxicity of the AgNPs-NC compound. The latter was found not to impact cell proliferation at any formulation, while decreasing the viability by only 6.8% after 72 h. This study contributes to the development of more environmentally benign routes to produce nanomaterials and to the understanding of their impact on cells.

Cannabidiol (CBD), which is derived from hemp, is gaining recognition because of its anti-inflammatory and lipid-modulating properties that could be utilized to treat acne. We conducted experiments to quantitatively assess the effects of CBD on acne-related cellular pathways. SEB-1 sebocytes and HaCaT keratinocytes were exposed to various CBD concentrations. CBD exhibited a concentration-dependent impact on cell viability and notably reduced SEB-1 viability; furthermore, it induced apoptosis and a significant increase in the apoptotic area at higher concentrations. Additionally, CBD remarkably reduced pro-inflammatory cytokines, including CXCL8, IL-1α, and IL-1β. Additionally, it inhibited lipid synthesis by modulating the AMPK-SREBP-1 pathway and effectively reduced hyperkeratinization-related protein keratin 16. Simultaneously, CBD stimulated the synthesis of elastin, collagen 1, and collagen 3. These findings emphasize the potential of CBD for the management of acne because of its anti-inflammatory, apoptotic, and lipid-inhibitory effects. Notably, the modulation of the Akt/AMPK-SREBP-1 pathway revealed a novel and promising mechanism that could address the pathogenesis of acne.

Podophyllotoxin (PPT) is an active pharmaceutical ingredient (API) with established antitumor potential. However, due to its systemic toxicity, its use is restricted to topical treatment of anogenital warts. Less toxic PPT derivatives (e.g., etoposide and teniposide) are used intravenously as anticancer agents. PPT has been exploited as a scaffold of new potential therapeutic agents; however, fewer studies have been conducted on the parent molecule than on its derivatives. We have undertaken a study of ultrastructural changes induced by PPT on HaCaT keratinocytes. We have also tracked the intracellular localization of PPT using its fluorescent derivative (PPT-FL). Moreover, we performed molecular docking of both PPT and PPT-FL to compare their affinity to various binding sites of tubulin. Using the Presto blue viability assay, we established working concentrations of PPT in HaCaT cells. Subsequently, we have used selected concentrations to determine PPT effects at the ultrastructural level. Dynamics of PPT distribution by confocal microscopy was performed using PPT-FL. Molecular docking calculations were conducted using Glide. PPT induces a time-dependent cytotoxic effect on HaCaT cells. Within 24 h, we observed the elongation of cytoplasmic processes, formation of cytoplasmic vacuoles, progressive ER stress, and shortening of the mitochondrial long axis. After 48 h, we noticed disintegration of the cell membrane, progressive vacuolization, apoptotic/necrotic vesicles, and a change in the cell nucleus\'s appearance. PPT-FL was detected within HaCaT cells after ~10 min of incubation and remained within cells in the following measurements. Molecular docking confirmed the formation of a stable complex between tubulin and both PPT and PPT-FL. However, it was formed at different binding sites. PPT is highly toxic to normal human keratinocytes, even at low concentrations. It promptly enters the cells, probably via endocytosis. At lower concentrations, PPT causes disruptions in both ER and mitochondria, while at higher concentrations, it leads to massive vacuolization with subsequent cell death. The novel derivative of PPT, PPT-FL, forms a stable complex with tubulin, and therefore, it is a useful tracker of intracellular PPT binding and trafficking.

Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a \"burst release\". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.

Oil-core nanocapsules (NCs, also known as nanoemulsions) are of great interest due to their application as efficient carriers of various lipophilic bioactives, such as drugs. Here, we reported for the first time the preparation and characterization of NCs consisting of chondroitin sulfate (CS)-based shells and liquid oil cores. For this purpose, two amphiphilic CS derivatives (AmCSs) were obtained by grafting the polysaccharide chain with octadecyl or oleyl groups. AmCS-based NCs were prepared by an ultrasound-assisted emulsification of an oil phase consisting of a mixture of triglyceride oil and vitamin E in a dispersion of AmCSs. Dynamic light scattering and cryo-transmission electron microscopy showed that the as-prepared core-shell NCs have typical diameters in the range of 30-250 nm and spherical morphology. Since CS is a strong polyanion, these particles have a very low surface potential, which promotes their stabilization. The cytotoxicity of the CS derivatives and CS-based NCs and their impact on cell proliferation were analyzed using human keratinocytes (HaCaTs) and primary human skin fibroblasts (HSFs). In vitro studies showed that AmCSs dispersed in an aqueous medium, exhibiting mild cytotoxicity against HaCaTs, while for HSFs, the harmful effect was observed only for the CS derivative with octadecyl side groups. However, the nanocapsules coated with AmCSs, especially those filled with vitamin E, show high biocompatibility with human skin cells. Due to their stability under physiological conditions, the high encapsulation efficiency of their hydrophobic compounds, and biocompatibility, AmCS-based NCs are promising carriers for the topical delivery of lipophilic bioactive compounds.

Atopic dermatitis (AD) is a chronic cutaneous disease with a complex underlying mechanism, and it cannot be completely cured. Thus, most treatment strategies for AD aim at relieving the symptoms. Although corticosteroids are topically applied to alleviate AD, adverse side effects frequently lead to the withdrawal of AD therapy. Tacrolimus (TAC), a calcineurin inhibitor, has been used to treat AD, but its high molecular weight and insolubility in water hinder its skin permeability. Herein, we developed and optimized TAC-loaded chitosan-based nanoparticles (TAC@CNPs) to improve the skin permeability of TAC by breaking the tight junctions in the skin. The prepared nanoparticles were highly loadable and efficient and exhibited appropriate characteristics for percutaneous drug delivery. TAC@CNP was stable for 4 weeks under physiological conditions. CNP released TAC in a controlled manner, with enhanced skin penetration observed. In vitro experiments showed that CNP was non-toxic to keratinocyte (HaCaT) cells, and TAC@CNP dispersed in an aqueous solution was as anti-proliferative as TAC solubilized in a good organic solvent. Importantly, an in vivo AD mouse model revealed that topical TAC@CNP containing ~1/10 of the dose of TAC found in commercially used Protopic® Ointment exhibited similar anti-inflammatory activity to that of the commercial product. TAC@CNP represents a potential therapeutic strategy for the management of AD.

BACKGROUND: The non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs.
RESULTS: The DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice.
CONCLUSIONS: Results obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.

Psoriasis is a complex and recurrent chronic inflammatory skin disease, and the abnormal proliferation of keratinocytes plays a crucial role in the pathogenesis of psoriasis. Long non-coding RNAs (lncRNAs) play an indispensable role in regulating cellular functions. This research aims to explore the potential impact of lncRNA MIR181A2HG on the regulation of keratinocyte proliferation.
The expression level of MIR181A2HG and the mRNA level of KRT6, KRT16, and SOX6 were assessed using qRT-PCR. The viability and proliferation of keratinocytes were evaluated using CCK-8 and EdU assays. Cell cycle analysis was performed using flow cytometry. Dual-luciferase reporter assays were applied to test the interaction among MIR181A2HG/miR-223-3p/SOX6. Protein level was detected by Western blotting analysis.
The findings indicated that psoriasis lesions tissue exhibited lower levels of MIR181A2HG expression compared to normal tissue. The overexpression of MIR181A2HG resulted in the inhibition of HaCaT keratinocytes proliferation. The knockdown of MIR181A2HG promoted cell proliferation. The dual-luciferase reporter assay and rescue experiments provided evidence of the interaction among MIR181A2HG, SOX6, and miR-223-3p.
The lncRNA MIR181A2HG functions as a miR-223-3p sponge targeting SOX6 to regulate the proliferation of keratinocytes, which suggested that MIR181A2HG/miR-223-3p/SOX6 might be potential diagnostic and therapeutic targets for psoriasis.

Skin photoaging is a skin degenerative disease that causes patients to develop malignant tumors. The existing clinical treatment of photoaging has limitations. This greatly reduces the recovery rate of photoaging patients. Studies have confirmed that Ligusticum wallichii Franch (LWF) monomer tetramethylpyrazine (TMP) alleviates various skin diseases. The combination of traditional Chinese medicine and Western medicine helps with this process. Our research aimed to explore the specific treatment mode and molecular mechanism of TMP in treating skin photoaging. CCK-8 assays were used to evaluate the activity and toxicity of HaCaT cells. β-galactosidase aging, Carbonyl compound and nitrosylated tyrosine assays were used to analyze the aging of HaCaT cells. ROS assays and ELISA were used to analyze the enrichment of ROS. The molecular docking experiment analyzed the binding of TMP and HIF-1α. qRT-PCR and Western blot were used to detect the activation of skin aging-related pathways. HE staining was used to analyze the thickness of the stratum corneum skin on the back skin of mice. 200μg/L LWF alleviates cellular photoaging and mouse skin photoaging by reducing ROS enrichment. Its monomer TMP plays an important role in this process. The combination of TMP and HIF-1α accelerates the degradation of ROS by activating the Nrf2/ARE signaling pathway. This process reduces the apoptosis of cells damaged by light. In addition, we also found that the combination of TMP and retinoic acid (RA) is more beneficial for the treatment of skin damage caused by light in mice. The combination therapy of TMP and RA alleviates skin oxidative stress response through overexpression of HIF-1α. This plan is beneficial for the treatment of skin photoaging.