Proliferation Of HaCaT Cells Research Articles

Wound healing mechanism of antimicrobial peptide cathelicidin-DM.

Background and Purpose: Chronic wound infections and the development of antibiotic resistance are serious clinical problems that affect millions of people worldwide. Cathelicidin-DM, an antimicrobial peptide from Duttaphrynus melanostictus, has powerful antimicrobial activity and wound healing efficacy. So, it could be a potential candidate to address this problem. In this paper, we investigate the wound healing mechanism of cathelicidin-DM to establish a basis for preclinical studies of the drug. Experimental Approach: The effects of cathelicidin-DM on cell proliferation and migration, cytokines, and mitogen-activated protein kinase (MAPK) signaling pathways were examined. Then mice whole skin wound model was constructed to evaluate the wound healing activity of cathelicidin-DM, and further histological changes in the wounds were assessed by hematoxylin-eosin staining (H&E) and immunohistochemical assays. Key Results: Cathelicidin-DM promotes the proliferation of HaCaT, HSF, and HUVEC cells in a concentration-dependent manner and the migration of HSF, HUVEC, and RAW.264.7 cells. Moreover,cathelicidin-DM can involve in wound healing through activation of the MAPK signaling pathway by upregulating phosphorylation of ERK, JNK, and P38. However, cathelicidin-DM didn't affect the secretion of IL-6 and TNF-α. At the animal level, cathelicidin-DM accelerated skin wound healing and early debridement in mice as well as promoted re-epithelialization and granulation tissue formation, α-SMA expression, and collagen I deposition in mice. Conclusion and Implications: Our data suggest that cathelicidin-DM can be engaged in the healing of infected and non-infected wounds through multiple pathways, providing a new strategy for the treatment of infected chronic wounds.

Expression of concern: MicroRNA138 regulates keratin 17 protein expression to affect HaCaT cell proliferation and apoptosis by targeting hTERT in psoriasis vulgaris [Biomedicine & Pharmacotherapy 85 (2017) 169–176

Expression of concern: MicroRNA138 regulates keratin 17 protein expression to affect HaCaT cell proliferation and apoptosis by targeting hTERT in psoriasis vulgaris [Biomedicine & Pharmacotherapy 85 (2017) 169–176

Heat-clearing and blood-cooling decoction alleviates psoriasis by suppressing proliferation and inflammatory response of keratinocytes via EZH2/NF-κB

Psoriasis is a chronic recurrent dermatological disease that patients always suffer from different comorbidities. Chinese herbal medicine has been commonly used in the treatment of psoriasis for a long history. However, the mechanism operating between Qing-Ying Dizhuo Decoction (QYDD) (a heat-clearing and blood-cooling decoction) and psoriasis remains unclear. This paper aimed to study the role of QYDD in psoriasis and its underlying mechanism. HaCaT cells were induced by a mixture of IL-22, IL-17A, oncostatin M, TNF-α and IL-1α (M5) to construct the in vitro model of psoriasis. CCK-8 assay was utilized to assess the cell proliferation ability. The expressions of KRT1, KRT6, TNF-α, IL-1β, IL-6, IL-23, EZH2, IκBα, p65 and IKK were determined by qRT-PCR, western blot and ELISA. M5 induction increased levels of KRT6, IL-1β, IL-6, TNF-α and IL-23, enhanced the proliferation ability of HaCaT cells and decreased KRT1 expression, while QYDD treatment reversed these trends. Overexpression of EZH2 reversed the inhibitory effects of QYDD on cell inflammatory response and proliferation of M5-induced HaCaT cells. QYDD suppressed M5-activated NF-κB signaling pathway as evidenced by decreased levels of phosphorylated IKK and p65 and increased level of phosphorylated IκBα, while overexpression of EZH2 offset, in part, the regulation of the NF-κB pathway by QYDD. An NF-κB activator (betulinic acid) weakened the inhibitory effect of QYDD on the inflammatory response of HaCaT keratinocytes. QYDD appears to inactivate the NF-κB signaling pathway by inhibiting EZH2, thereby repressing the proliferation and suppressing inflammatory response of HaCaT cells and attenuating psoriasis.

Evaluation of Poly-3-Hydroxybutyrate (P3HB) Scaffolds Used for Epidermal Cells Growth as Potential Biomatrix.

Advances in tissue engineering have made possible the construction of organs and tissues with the use of biomaterials and cells. Three important elements are considered: a specific cell culture, an adequate environment, and a scaffold. The present study aimed to develop P3HB scaffolds by 3D printing and evaluate their biocompatibility with HaCaT epidermal cells, as a potential model that allows the formation of functional tissue. By using a method of extraction and purification with ethanol and acetone, a biopolymer having suitable properties for use as a tissue support was obtained. This polymer exhibited a higher molecular weight (1500 kDa) and lower contact angle (less than 90°) compared to the material obtained using the conventional method. The biocompatibility analysis reveals that the scaffold obtained using the ethanol–acetone method and produced by 3D printing without pores was not cytotoxic, did not self-degrade, and allowed high homogenous cell proliferation of HaCaT cells. In summary, it is possible to conclude that the P3HB scaffold obtained by 3D printing and a simplified extraction method is a suitable support for the homogeneous development of HaCaT keratinocyte cell lineage, which would allow the evaluation of this material to be used as a biomatrix for tissue engineering.

Phellopterin cream exerts an anti-inflammatory effect that facilitates diabetes-associated cutaneous wound healing via SIRT1

BackgroundDiabetic ulcers, which are characterized by chronic nonhealing wounds with a long-lasting inflammatory state, are a typical symptom in individuals with diabetes, and there is still no effective treatment for these lesions. Angelica dahurica plays a critical role in inflammatory diseases. Among numerous monomeric compounds, phellopterin has been shown to have anti-inflammatory properties. PurposeTo research the bioactive constituents in Angelica dahurica and their mechanism of action in treating diabetic ulcers. Study designChemical research of Angelica dahurica led to the identification of a new coumarin, dahuricoumarin A (1), along with seven known compounds (2 − 8). All compounds were tested for anti-inflammatory activity, and phellopterin, compound (3), significantly decreased the expression of intercellular cell adhesion molecule-1 (ICAM-1), a representative indicator of inflammation. Phellopterin can also increase SIRT1 protein, a key target for inflammation. In our research, we confirmed the anti-inflammatory effects of phellopterin on diabetic ulcers and explored the underlying mechanism of action. MethodsThe expression of IFN-γ, SIRT1, and ICAM-1 in human diabetic ulcer tissues was studied using immunohistochemistry. Streptozotocin was used to induce a diabetic model in C57BL/6J mice, and ulcers were surgically introduced. After phellopterin treatment, the skin lesions of diabetic mice were observed over a period of time. The protein and mRNA expression levels of SIRT1 and ICAM-1 were measured using H&E, qRT–PCR and immunohistochemical staining. A HaCaT cell inflammatory model was induced by IFN-γ. Using a lentiviral packaging technique, MTT assay, and Western blotting, the effect of phellopterin on the proliferation of HaCaT cells and the expression of ICAM-1 was evaluated under normal and SIRT1 knockdown conditions. ResultsHigh levels of ICAM-1 and IFN-γ were identified, but low levels of SIRT1 were found in human diabetic ulcer tissues, and phellopterin showed therapeutic benefits in the healing process by attenuating chronic inflammation and promoting re-epithelialization, along with SIRT1 upregulation and ICAM-1 downregulation. However, inhibiting SIRT1 reversed its proliferative and anti-inflammatory effects. ConclusionIn vitro and in vivo, phellopterin exerts anti-inflammatory and proliferative effects that promote diabetic wound healing, and the potential mechanism depends on SIRT1.

Inhibition of JAK1/STAT3 pathway by 2-methoxyestradiol ameliorates psoriatic features in vitro and in an imiquimod-induced psoriasis-like mouse model

Psoriasis is characterized by hyperproliferative keratinocytes, dilated capillaries and leukocyte infiltration. 2-Methoxyestradiol (2-ME) has shown significant inhibition on proliferation, angiogenesis and inflammation. To evaluate the anti-psoriatic potential of 2-ME, psoriasis-like dermatitis was induced by topical application of imiquimod (IMQ) on the dorsal skin of C57BL/6 mice for seven consecutive days, followed by treatment of vehicle or 2-ME ointment from Day 4 on. The psoriasis area and severity index (PASI) was assessed daily. On Day 8, skin histology and spleen index were assessed. The effects of 2-ME on the proliferation, apoptosis, cell cycle, vascular endothelial growth factor A (VEGFA), and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways of HaCaT cells stimulated by interleukin-17 (IL-17A) were detected, together with its effect on the proliferation, tube formation and VEGF receptor expression of human umbilical vein endothelial cells (HUVECs). We found that topical 2-ME treatment significantly improved IMQ-induced psoriasis-like dermatitis and decreased the PASI scores, the activation of STAT3 in the skin (P < 0.05), and the spleen index in mice (P < 0.01). In vitro, 2-ME inhibited the proliferation of HaCaT cells by inducing apoptosis and G2/M phase arrest (P < 0.01). Moreover, 2-ME suppressed IL-17A-induced VEGFA (2.5 μM: P < 0.05; 5 μM: P < 0.01) and phosphorylation of STAT3 by blocking p-JAK1 in HaCaT cells and prevented tube formation (P < 0.01) and proliferation by targeting VEGF receptors 1 (VEGFR1) and 2 (VEGFR2) in HUVECs. We conclude that 2-ME alleviated psoriasis in vivo and in vitro by inhibiting JAK1/STAT3 pathway and was a promising therapeutic agent for psoriasis.

Arbutin Inhibited Heat Stress-Induced Apoptosis and Promoted Proliferation and Migration of Heat-Injured Dermal Fibroblasts and Keratinocytes by Activating PI3K/AKT Signaling Pathway.

Objective Studies have shown that arbutin has antioxidant and anti-inflammatory activities, which makes it suitable for treating skin wounds. We designed this study to investigate the effect of arbutin on heat-induced apoptosis, proliferation, and migration of dermal fibroblasts and keratinocytes and to explore the molecular mechanism. Methods In vitro, HaCAT and dermal fibroblast (DFL) cells were cultured and used to establish a heat stress-injured skin cell model. We investigated the effects of arbutin on apoptosis, proliferation, and migration of HaCAT and DFL cells after heat stress injury. We then used immunoblotting to detect the expression of p-PI3K, PI3K, p-AKT, and AKT proteins for studying the underlying mechanisms and used a PI3K/AKT inhibitor (LY294002) to verify the efficacy of arbutin in HaCAT and DFL cells with heat stress injury. Results Arbutin strongly inhibited heat stress-induced apoptosis, proliferation inhibition, and migration inhibition of HaCAT and DFL cells in vitro. Our results also showed that arbutin strongly decreased the ratio of Bax/Bcl2 protein expression and PCNA protein expression in HaCAT and DFL cells after treatment with heat stress. Furthermore, we also found that arbutin significantly increased the ratio of p-PI3K/PI3K and p-AKT/AKT protein expression, and LY294002 markedly reversed the effect of arbutin on heat stress-induced apoptosis, proliferation inhibition, and migration inhibition of HaCAT and DFL cells. Conclusion Our finding indicated that arbutin inhibited heat stress-induced apoptosis and promoted proliferation and migration of heat-injured dermal fibroblasts and epidermal cells by activating the PI3K/AKT signaling pathway, suggesting that arbutin may provide an alternative therapeutic approach for the treatment of skin injury.

Food-derived Crassostrea gigas peptides self-assembled supramolecules for scarless healing

Peptides self-assembled materials are considered as excellent candidates for tissue engineering due to their excellent efficacy. However, their development and application are severely restricted on account of their single function, low yield and limited source, so it is urgent to explore new research strategy of self-assembly materials of multifunctional active peptides. In this study, we prepared multifunctional supramolecular materials (CNPs) with randomized peptides self-assemblies from Crassostrea gigas meats utilizing Controllable-hydrolysis (Neutral protease) process to explore their mechanism on dermal wound healing in in vitro and in vivo experiments through two (topical application & oral) administration pathways. Physical and chemical analysis results demonstrated that CNPs were novel supramolecules consisting of peptides with molecular weights of 605–2067 Da and lengths of 5–15 amino acids that randomly self-assemble into nano-structures. Results of in vitro tests suggested that CNPs possessed procoagulant, antioxidant effect and promote the proliferation of HaCaT cells. Results of in vivo studies revealed that two administration pathways of naturally safe CNPs could inhibit inflammation, promote fibroblast proliferation and revascularization, and accelerate the epithelialization process. Thus favoring a balanced repair tissue collagen I/III ratio and the promotion of hair follicle regeneration, with no effect on the intestinal flora structure and having a certain positive effect to achieve scarless healing. Overall, this study presents a simple preparation method of a safe and multifunctional novel self-assembling peptides material and its great potential in soft tissue repair.

Anti-Fibrotic Potential of Tomentosenol A, a Constituent of Cerumen from the Australian Native Stingless Bee, Tetragonula carbonaria.

Bioactivity-guided fractionation was used to isolate two compounds, tomentosenol A (1) and torellianone A (2), from a cerumen extract from Tetragonula carbonaria. The anti-fibrotic activity of these compounds was examined using human cultured neonatal foreskin fibroblasts (NFF) and immortalised keratinocytes (HaCaTs). Tomentosenol A (1), inhibited NFF and HaCaT cell proliferation and prevented NFF and HaCaT scratch wound repopulation at 12.5–25 µM concentrations. These inhibitory effects were associated with reduced cell viability, determined by tetrazolium dye (MTT) and sulforhodamine B (SRB) assays. Compound 1 further inhibited transforming growth factor-β1 (TGF-β1)-stimulated, NFF-myofibroblast differentiation and soluble collagen production; and was an effective scavenger of the model oxidant, 2,2-diphenyl-1-picrylhydrazyl (DPPH·), with an EC50 value of 44.7 ± 3.1 µM. These findings reveal significant anti-fibrotic potential for cerumen-derived tomentosenol A (1).

Sinomenine Suppressed Keratinocyte Proliferation and Imiquimod-Induced Psoriasis-Like Dermatitis by Regulating lncRNA XIST

Background: Psoriasis is a chronic inflammatory skin disease. Sinomenine (SIN) has anti-inflammatory and antioxidant effects. Objective: The objective of this study was to confirm the anti-inflammatory effects and mechanism of SIN in imiquimod (IMQ)-induced psoriasis-like mouse model and IMQ-induced differentiated human keratinocytes (HaCaT) cells. Methods: BALB/c mice were treated with IMQ to construct a psoriasis-like mice model. PASI score and HE staining were used to observe pathology injury of skin tissue. The secretion of inflammatory factors and the oxidative stress level were detected by ELISA. HaCaT cells after induction of differentiation were treated with IMQ (100 μM) and SIN (10 μg/mL or 50 μg/mL), cell viability, the secretion of inflammatory factors, and the oxidative stress level were detected by MTT assay, ELISA, respectively. The expression of lncRNA XIST was detected by RT-qPCR. The relationship between XIST and EIF4G2 protein was detected by RNA immunoprecipitation (RIP) assay and ubiquitination experiment. Results: SIN significantly reduced PASI score, epidermal thickness, inflammatory response, and oxidative stress levels that increased by IMQ in vivo. SIN inhibited IMQ-induced HaCaT cell proliferation, inflammatory response, and oxidative stress levels and decreased the expression of XIST. Overexpression of XIST negated the protective effect of SIN on HaCaT cells. XIST interacted directly with EIF4G2 and regulated EIF4G2 expression via K48 ubiquitin. Knockdown of XIST reduced the half-life of EIF4G2 and decreased EIF4G2 protein stability. In addition, the E3 ubiquitin protein ligase MDM2 interacted with EIF4G2 and downregulated EIF4G2 expression. XIST reduced the interaction between MDM2 and EIF4G2, which mediated EIF4G2 K48 ubiquitination. Overexpression of XIST negated the protective effect of SIN on the inflammation of HaCaT cells through activating the NF-κB signaling pathway, while NF-κB pathway inhibitor PDTC reversed this result. Conclusion: SIN had a protective effect on psoriasis and could inhibit HaCaT cell proliferation and inflammatory response via XIST/MDM2/EIF4G2/NF-κB axis.

Free-cell therapeutics and mechanism of exosomes from adipose-derived stem cells in promoting wound healing: current understanding and future applications.

Free-cell therapeutics and mechanism of exosomes from adipose-derived stem cells in promoting wound healing: current understanding and future applications.

Bone marrow mesenchymal stem cells facilitate diabetic wound healing through the restoration of epidermal cell autophagy via the HIF-1α/TGF-β1/SMAD pathway

BackgroundThe biological activity and regenerative medicine of bone marrow mesenchymal stem cells (BMSCs) have been focal topics in the broad fields of diabetic wound repair. However, the molecular mechanisms are still largely elusive for other cellular processes that are regulated during BMSC treatment. Our previous studies have shown that hypoxia is not only a typical pathological phenomenon of wounds but also exerts a vital regulatory effect on cellular bioactivity. In this study, the beneficial effects of hypoxic BMSCs on the cellular behaviors of epidermal cells and diabetic wound healing were investigated.MethodThe viability and secretion ability of hypoxic BMSCs were detected. The autophagy, proliferation and migration of HaCaT cells cultured with hypoxic BMSCs-derived conditioned medium were assessed by estimating the expression of autophagy-related proteins, MTS, EdU proliferation and scratch assays. And the role of the SMAD signaling pathway during hypoxic BMSC-evoked HaCaT cell autophagy was explored through a series of in vitro gain- and loss-of-function experiments. Finally, the therapeutic effects of hypoxic BMSCs were evaluated using full-thickness cutaneous diabetic wound model.ResultsFirst, we demonstrated that hypoxic conditions intensify HIF-1α-mediated TGF-β1 secretion by BMSCs. Then, the further data revealed that BMSC-derived TGF-β1 was responsible for the activation of epidermal cell autophagy, which contributed to the induction of epidermal cell proliferation and migration. Here, the SMAD signaling pathway was identified as downstream of BMSC-derived TGF-β1 to regulate HaCaT cell autophagy. Moreover, the administration of BMSCs to diabetic wounds increased epidermal autophagy and the rate of re-epithelialization, leading to accelerated healing, and these effects were significantly attenuated, accompanied by the downregulation of Smad2 phosphorylation levels due to TGF-β1 interference in BMSCs.ConclusionIn this report, we present evidence that uncovers a previously unidentified role of hypoxic BMSCs in regulating epidermal cell autophagy. The findings demonstrate that BMSC-based treatment by restoring epidermal cell autophagy could be an attractive therapeutic strategy for diabetic wounds and that the process is mediated by the HIF-1α/TGF-β1/SMAD pathway.

The role of human antigen R (HuR) in modulating proliferation, senescence and radiosensitivity of skin cells.

The skin is the largest outermost organ of the human body. It is vulnerable to various damages, such as ionizing radiation. Exploration of proliferation, senescence and radiosensitivity of skin cells contributes to the development of medical and cosmetic countermeasures against skin aging and toward injury protection. Human antigen R (HuR) is one of the most widely studied RNA-binding proteins and serves an important role in stabilization of mRNA and regulation of the expression of the target genes. To investigate the role of HuR in modulating proliferation, senescence and radiosensitivity of skin cells, the present study performed an in vitro study using lentivirus-mediated overexpression or silencing of HuR in human keratinocyte HaCaT cells and human skin fibroblast WS1 cells. The results indicated that overexpression of HuR promoted proliferation, whereas downregulation of HuR inhibited proliferation of HaCaT and WS1 cells. Overexpression of HuR reduced apoptosis and senescence in skin cells. RNA-Seq of skin cells with HuR overexpression or knockdown identified 77 mRNAs positively or negatively correlated with HuR expression levels. In addition, silencing of HuR induced a significant increase in radiogenic reactive oxygen species after irradiation. Overexpression of HuR increased radiotolerance of HaCaT and WS1 cells. RNA immunoprecipitation coupled with RNA-Seq identified 14 mRNAs interacting with HuR upon radiation exposure. Overall, the findings of the present study illustrated the key role of HuR in modulating proliferation, senescence and radiosensitivity of skin cells providing a new therapeutic strategy for cosmetic treatments and to combat skin injury.

Metformin Inhibits HaCaT Cell Proliferation Under Hyperlipidemia Through Reducing Reactive Oxygen Species via FOXO3 Activation.

PurposeMetformin (MET) has been proved to be effective for the treatment of psoriasis. The mechanisms of its action under the hyperlipidemia have yet to be fully elucidated. Here, we investigated the effect of metformin on the cell proliferation induced by hyperlipidemia and the underlying mechanism in immortalized human keratinocyte cell line (HaCat).MethodsWild-type or FOXO3 knockdown HaCat cells were treated with free fatty acids (FFA) for 10 days and then co-treated with metformin for another 4 days. Triglyceride (TG) level, cell viability, proliferation, apoptosis, antioxidant enzymes, reactive oxygen species (ROS) levels, as well as the transcription activity of FOXO3 were analyzed.ResultsMetformin decreased HaCaT cell proliferation and induced cell apoptosis after FFA treatment. Metformin was found to significantly increase the expressions and the activities of superoxide dismutase (SOD) as well as catalase (CAT), and reduced the reactive oxygen species (ROS) level. Metformin significantly promoted the autophagy and increase FOXO3 protein level in the nucleus under hyperlipidemia. However, all of the effects from metformin were partially blocked by FOXO3 knockdown.ConclusionThis study demonstrated that under the hyperlipidemia, metformin has significant antiproliferation and proapoptosis effects by reducing ROS level as well as increasing autophagy. All of these effects from metformin were through FOXO3-dependent pathway.

Study of the in vitro degradation and characterization of the HaCat keratinocytes adherence on electrospun scaffolds based polyvinyl alcohol/sodium alginate

AbstractBiomaterial scaffolds house and direct cells to grow, exposing them to appropriate growth factors. Most of them are designed to degrade at a controlled rate as the new host tissue replaces them. Here, we show that scaffolds obtained through electrospinning of PVA with 3.5, 4.0, and 5.0 wt% of SA showed a gradual degradation rate under physiological conditions during 100 days of incubation. This behavior is proportional to the SA concentration used, with a mass loss of (41%, 47%, and 49% for each system) after 60 days. Moreover, the dielectric properties (EIS) of the scaffolds correlate with their degradation rate throughout the exposition period (100 days), as indicated by the observed decrease in resistance over time. The 4.0 wt% system showed the lowest capacitance value (1.5 10–5 F) and the highest resistance (4.6106 ohm‐cm2) behavior among all concentrations. Additionally, the morphological analysis through SEM and AFM showed a shrank in the surface morphology after the degradation process and determined the degree of roughness (Ra). Higher roughness prior to the cytocompatibility test promoted increased proliferation and adhesion of HaCat cells, as observed in the 4.0 wt% PVA/SA system (1422 nm Ra). These biomaterials have great potential in wound dressing applications.

Long-Acting β2 Adrenergic Receptor Agonist Ameliorates Imiquimod-Induced Psoriasis-Like Skin Lesion by Regulating Keratinocyte Proliferation and Apoptosis.

Psoriasis is a chronic inflammatory disease that affects approximately 1%–5% of the population worldwide. Considering frequent relapse, adverse drug reactions, and large costs of treatment, it is urgent to identify new medications for psoriasis. Keratinocytes play an essential role during psoriasis development, and they express high levels of β2-Adrenergic receptor (β2-AR), which increases intracellular cAMP levels when activated. Increased level of cAMP is associated with the inhibition of epidermal cell proliferation. In the present study, we observed the effect of salmeterol, a long-acting β2-AR agonist, on the proliferation and apoptosis of keratinocytes as well as imiquimod-induced psoriasis-like skin lesions in mice. As phosphodiesterase 4 (PDE4) inhibitors increases intracellular cAMP concentration by inhibiting its inactivation, we further explored the synergetic effect of a PDE4 inhibitor and salmeterol on psoriasis-like skin lesions in mice. Our results indicated that salmeterol effectively inhibited the proliferation of HaCaT cells induced by TNF-α and serum, and this effect was accompanied by significantly increased apoptosis and CREB phosphorylation, which were reversed by the PKA inhibitor, H89. Salmeterol ameliorated imiquimod-induced psoriasis-like skin lesions in mice, but salmeterol combined with a PDE4 inhibitor had no synergetic effect in improving skin lesions in mice. Of note, the synergistic effects of anti-proliferation and induction of apoptosis in HaCaT cells appeared by inhibiting ERK signaling. In summary, salmeterol, a long-acting β2-AR agonist, alleviates the severity of psoriasis via inhibiting the proliferation and promoting apoptosis of keratinocytes, partially by activating the cAMP/PKA signaling pathway.

A Modified Hyaluronic Acid-Based Dissolving Microneedle Loaded With Daphnetin Improved the Treatment of Psoriasis.

Psoriasis is a common chronic immune-inflammatory disease. Challenges exist in the present treatment of psoriasis, such as difficulties in transdermal drug administration and severe side effects. We hope to achieve a better therapeutic outcome for psoriasis treatment. By using modified soluble microneedles (MNs) loaded with daphnetin, the psoriasis symptoms of mice, the abnormal proliferation of keratinocytes, and the secretion of inflammatory factors were significantly reduced. In vitro, daphnetin is proven to inhibit the NF-κB signaling pathway and to inhibit the proliferation of HaCaT cells and the release of inflammatory factors, especially CCL20. This research showed that the modified microneedle loaded with daphnetin optimized transdermal drug delivery and relieved the symptoms of psoriasis more effectively. The novel route of Daph administration provides a future research direction for the treatment of psoriasis.

Fabrication of Biocompatible Electrospun Poly(ε-caprolactone)/Gelatin Nanofibers Loaded with Pinus radiata Bark Extracts for Wound Healing Applications.

In this study, poly(ε-caprolactone) (PCL)/gelatin (GEL) electrospun nanofibers loaded with two different concentrations of Pinus radiata bark extracts (PEs) were fabricated via electrospinning for wound healing applications. The effects of incorporating PE into PCL/GEL electrospun nanofibers were investigated regarding their physicochemical properties and in vitro biocompatibility. All electrospun nanofibers showed smooth, uniform, and bead-free surfaces. Their functional groups were detected by ATR-FTIR spectroscopy, and their total phenol content was measured by a Folin–Ciocalteu assay. With PE addition, the electrospun nanofibers exhibited an increase in their wettability and degradation rates over time and a decrease in their tensile stress values from 20 ± 4 to 8 ± 2 MPa for PCL/GEL and PCL/GEL/0.36%PE samples, respectively. PE was also released from the fibrous mats in a rather controlled fashion. The PCL/GEL/0.18%PE and PCL/GEL/0.36%PE electrospun nanofibers inhibited bacterial activity at around 6 ± 0.1% and 23 ± 0.3% against E. coli and 14 ± 0.1% and 18 ± 0.2% against S. aureus after 24 h incubation, respectively. In vitro cell studies showed that PE-loaded electrospun nanofibers enhanced HaCaT cell growth, attachment, and proliferation, favoring cell migration towards the scratch area in the wound healing assay and allowing a complete wound closure after 72 h treatment. These findings suggested that PE-loaded electrospun nanofibers are promising materials for antibiotic-free dressings for wound healing applications.

D-tryptophan triggered epithelial-mesenchymal transition by activating TGF-β signaling pathway

D-tryptophan is a special kind of nonprotein amino acid showing multiple physiological functions, but the detailed mechanisms are not fully revealed, impairing its further development and applications. This work was to investigate D-tryptophan physiological function and demonstrate the underlying mechanisms. D-tryptophan suppressed HaCaT cell proliferation but increased cell migration. Specifically, D-tryptophan decreased E-cadherin and increased Snail, Twist, and Slug expression, resulting in the development of an epithelial-mesenchymal transitions (EMT) phenomenon. Moreover, D-tryptophan promoted the expression of transforming growth factor-β (TGF-β) 1, and Smad4 knockout damages D-tryptophan's ability. These results indicated that D-tryptophan stimulated HaCaT cells to produce TGF-β1 and thus activated the TGF-β/Samd pathway, resulting in the triggering of EMT. This study revealed the molecular mechanisms of D-tryptophan activity, provided D-tryptophan as a potential approach for cancer treatment, wound healing, organ development and other relevant applications.

Protective Effects of Grapefruit Essential Oil against Staphylococcus Aureus-Induced Inflammation and Cell Damage in Human Epidermal Keratinocytes.

Staphylococcus aureus (S. aureus) is a common skin pathogenic bacterium, over-colonization can induce skin infections, while its metabolites can also produce irritation to the skin, often accompanied by eczema dermatitis, specific dermatitis and other skin diseases. Grapefruit essential oil is extracted from the fruit of grapefruit (Citrus maxima (Burm) Merr.), a citrus plant that is rich in flavonoids, phenolic acids and high flavanones. Due to its good odor and biological activity such as anti-inflammatory, antibacterial, etc., grapefruit essential oil has been widely used as an additive in food. To evaluate the potential application of grapefruit essential oil as raw materials in cosmetics products and health foods, we developed a cell damage model of skin inflammation stimulated by S. aureus metabolites. Compared to that of lime essential oil, an internal control, we found that grapefruit essential oil could significantly promote HaCaT cells proliferation, reduce reactive oxygen species (ROS) production induced by S. aureus metabolites, inhibit the upregulated expression of IL-1 and COX-2. In the 3D epidermal model, grapefruit essential oil could recover the decreased LOR and FLG contents caused by S. aureus metabolites. These results demonstrated pharmacological evidence for the anti-inflammatory effect of grapefruit essential oil, suggesting a potential application of grapefruit essential oil as cosmetic raw materials for repair and alleviating of skin inflammation caused by S. aureus.