Clinical Efficacy and Safety of Low-Energy Extracorporeal Shock Wave Therapy for Various Conditions of Deep Dermal and Subdermal Fibrosis.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) enhances extracellular matrix remodeling and tissue regeneration by promoting growth factor release, regulating blood and lymphatic flows, and reducing fat and fibrotic tissues. Focused shock wave therapy (F-SWT), radial shock wave therapy (R-SWT), and combined F-SWT and R-SWT have been used to deliver different patterns of shock energy depending on the characteristics of the target lesions. METHODS: We investigated the efficacy and safety of ESWT in patients with dermal and subdermal fibrosis. Fifty-two patients treated with F-SWT and/or R-SWT for dermal and subdermal fibrosis caused due to various reasons were retrospectively analyzed by reviewing their medical records, clinical images, and ultrasound study images. RESULTS: The mean number of pulses administered for F-SWT on the cheek, temple, and chin were 2600.0 ± 1040.8 shocks/session and for R-SWT were 5080.0 ± 2234.6 pulses/session, and the number of treatment sessions were 8.0 ± 4.4. In patients who were treated with ESWT on the abdomen, the mean number of pulses for F-SWT were 2600.0 ± 2408.3 shocks/session and for R-SWT were 8400.0 ± 894.4 pulses/session, and the number of treatment sessions were 3.2 ± 1.6. Most patients were satisfied with the results. Pain during ESWT was well tolerated and post-ESWT edema was more common in R-SWT than in F-SWT. CONCLUSION: Our data demonstrated that ESWT effectively and safely improved the clinical appearance and functional movement of patients with dermal and subdermal fibrosis caused due to various reasons.

Visible light accelerates skin wound healing and alleviates scar formation in mice by adjusting STAT3 signaling.

During the wound healing process, the activation of signal transducer and activator of transcription 3 (STAT3) is considered crucial for the migration and proliferation of epithelial cells, as well as for establishing the inflammatory environment. However, an excessive STAT3 activation aggravates scar formation. Here we show that 450 nm blue light and 630 nm red light can differentially regulate the phosphorylation of STAT3 (p-STAT3) and its downstream cytokines in keratinocytes. Further mechanistic studies reveal that red light promotes wound healing by activating the PI3 kinase p110 beta (PI3Kß)/STAT3 signaling axis, while blue light inhibits p-STAT3 at the wound site by modulating cytochrome c-P450 (CYT-P450) activity and reactive oxygen species (ROS) generation. In a mouse scar model, skin wound healing can be significantly accelerated with red light followed by blue light to reduce scar formation. In summary, our study presents a potential strategy for regulating epithelial cell p-STAT3 through visible light to address skin scarring issues and elucidates the underlying mechanisms.

Monolithically integrated neuromorphic electronic skin for biomimetic radiation shielding.

Melanogenesis, a natural responsive mechanism of human skin to harmful radiation, is a self-triggered defensive neural activity safeguarding the body from radiation exposure in advance. With the increasing significance of radiation shielding in diverse medical health care and wearable applications, a biomimetic neuromorphic optoelectronic system with adaptive radiation shielding capability is often needed. Here, we demonstrate a transparent and flexible metal oxide-based photovoltaic neuromorphic defensive system. By using a monolithically integrated ultraflexible optoelectronic circuitry and electrochromic device, seamless neural processing for ultraviolet (UV) radiation shielding including history-based sensing, memorizing, risk recognition, and blocking can be realized with piling the entire signal chain into the flexible devices. The UV shielding capability of the system can be evaluated as autonomous blocking up to 97% of UV radiation from 5 to 90 watts per square meter in less than 16.9 seconds, demonstrating autonomously modulated sensitivity and response time corresponding to UV environmental conditions and supplied bias.

Anti-Photoaging Effects of Antioxidant Peptide from Seahorse (Hippocampus abdominalis) in In Vivo and In Vitro Models.

Overexposure to ultraviolet (UV) radiation can lead to photoaging, which contributes to skin damage. The objective of this study was to evaluate the effects of an antioxidant peptide (SHP2) purified from seahorse (Hippocampus abdominalis) alcalase hydrolysate on UVB-irradiated skin damage in human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells and a zebrafish model. The data revealed that SHP2 significantly enhanced cell viability by attenuating apoptosis through the reduction of intracellular reactive oxygen species (ROS) levels in UVB-stimulated HaCaT cells. Moreover, SHP2 effectively inhibited ROS, improved collagen synthesis, and suppressed the secretion of matrix metalloproteinases (MMPs) in UVB-irradiated HDF cells. SHP2 restored the protein levels of HO-1, Nrf2, and SOD, while decreasing Keap1 expression in UVB-treated HDF, indicating stimulation of the Keap1/Nrf2/HO-1 signaling pathway. Furthermore, an in vivo study conducted in zebrafish confirmed that SHP2 inhibited photoaging by reducing cell death through the suppression of ROS generation and lipid peroxidation. Particularly, 200 µg/mL of SHP2 exerted a remarkable anti-photoaging effect on both in vitro and in vivo models. These results demonstrate that SHP2 possesses antioxidant properties and regulates skin photoaging activities, suggesting that SHP2 may have the potential for use in the development of cosmetic products.

Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis.

Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis exists. The lack of well-characterized, clinically relevant animal models of human radiation dermatitis contributes to the absence of strategies to mitigate radiation dermatitis. Here, we establish and characterize a hairless SKH-1 mouse model of human radiation dermatitis by correlating temporal stages of clinical and pathological skin injury. We demonstrate that a single ionizing radiation treatment of 30 Gy using 6 MeV electrons induces severe clinical grade 3 peak toxicity at 12 days, defined by marked erythema, desquamation and partial ulceration, with resolution occurring by 25 days. Histopathology reveals that radiation-induced skin injury features temporally unique inflammatory changes. Upregulation of epidermal and dermal TGF-ß1 and COX-2 protein expression occurs at peak dermatitis, with sustained epidermal TGF-ß1 expression beyond resolution. Specific histopathological variables that remain substantially high at peak toxicity and early clinical resolution, including epidermal thickening, hyperkeratosis and dermal fibroplasia/fibrosis, serve as specific measurable parameters for in vivo interventional preclinical studies that seek to mitigate radiation-induced skin injury.

Succinylated Type I Collagen Regulates Ferroptosis to Attenuate Skin Photoaging.

During the process of photoaging in the skin, Succinylated type I collagen has a significant effect on reversing the damage caused by UVB radiation, with the regulation of cellular ferroptosis being one of its important pathophysiological mechanisms. Specifically, Succinylated type I collagen reduces the expression of key cell cycle regulators P16, P21, and P53, as well as the ferroptosis-related factor Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4), induced by UVB radiation in cells and tissues. Meanwhile, it increases the expression of key factors Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11), which inhibit ferroptosis. Additionally, our study also reveals the impact of Succinylated type I collagen on the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) in cells and tissues, directly affecting the cells' ability to cope with oxidative stress. This further suggests that Succinylated type I collagen may improve skin photoaging through various pathways, including regulating ferroptosis, antioxidation, promoting collagen synthesis, protecting the skin barrier, reducing pigmentation, and inhibiting inflammatory responses, contributing to maintaining healthy and youthful skin.

Enhanced SIRT1 Activity by Galangin Mitigates UVB-Induced Senescence in Dermal Fibroblasts via p53 Acetylation Regulation and Activation.

Human skin aging, a complex process influenced by intrinsic aging and extrinsic photoaging, is marked by the accumulation of reactive oxygen species (ROS) that cause DNA damage, impaired dermal fibroblast function, and wrinkle formation. External stressors, such as ultraviolet (UV) radiation, can trigger cellular senescence. Sirtuin-1 (SIRT1), an NAD+-dependent enzyme in the sirtuin family, plays a crucial role in deacetylating p53, thereby inhibiting its nuclear translocation and reducing skin senescence. Galangin, a flavonoid found in honey and Alpinia officinarum root, has antioxidant and anti-inflammatory properties. This study investigates the protective mechanism of galangin against UVB-induced senescence in human dermal fibroblasts (HDFs) by examining its effects on SIRT1 and its target, acetylated-p53. An in vitro model of UVB-induced senescence using HDFs and an in vivo model using nude mice were employed to assess the dermal protective effects of galangin. The results demonstrate that while UVB exposure does not decrease SIRT1 protein levels, it impairs its enzymatic function. However, galangin treatment counteracts these adverse effects. Additionally, UVB exposure significantly reduces cell viability and upregulates senescence markers like p16, p21, and p53 nuclear transactivation. An increase in senescence-associated ß-galactosidase (SA-ß-gal) positive cells was observed in UVB-exposed dermal fibroblasts. Galangin treatment mitigates UVB-induced cellular senescence by enhancing SIRT1-mediated p53 deacetylation, thereby inhibiting nuclear translocation and reducing dermal senescence. These findings suggest that galangin is a promising agent for alleviating UVB-induced skin aging and could be a potential component in antiaging cosmetic formulations.

The Influence of Circadian Rhythms on DNA Damage Repair in Skin Photoaging.

Circadian rhythms, the internal timekeeping systems governing physiological processes, significantly influence skin health, particularly in response to ultraviolet radiation (UVR). Disruptions in circadian rhythms can exacerbate UVR-induced skin damage and increase the risk of skin aging and cancer. This review explores how circadian rhythms affect various aspects of skin physiology and pathology, with a special focus on DNA repair. Circadian regulation ensures optimal DNA repair following UVR-induced damage, reducing mutation accumulation, and enhancing genomic stability. The circadian control over cell proliferation and apoptosis further contributes to skin regeneration and response to UVR. Oxidative stress management is another critical area where circadian rhythms exert influence. Key circadian genes like brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) modulate the activity of antioxidant enzymes and signaling pathways to protect cells from oxidative stress. Circadian rhythms also affect inflammatory and immune responses by modulating the inflammatory response and the activity of Langerhans cells and other immune cells in the skin. In summary, circadian rhythms form a complex defense network that manages UVR-induced damage through the precise regulation of DNA damage repair, cell proliferation, apoptosis, inflammatory response, oxidative stress, and hormonal signaling. Understanding these mechanisms provides insights into developing targeted skin protection and improving skin cancer prevention.

Acoustic radiation characteristics of shark skin inspired surface modified plates.

This paper aims to evaluate the acoustic radiation characteristics of thin plates featuring a layer of small-scale biomimetic shark skin type additive surface treatment. The shark skin dermal denticles are modelled as point masses arranged in a bi-directional pattern on both the upper and lower surfaces of the plate. The governing equations are obtained through a variational approach, incorporating the Dirac Delta function in the derivation of the proposed semi-analytical model for the shark skin layer. A semi-analytical method based on the Rayleigh-Ritz formulation is utilized to analyze the vibrations of these plates with surface modification. The sound radiation characteristics are then derived from the solution of the Rayleigh integral. A comprehensive investigation is performed on the influence of surface modification on different vibro-acoustic characteristics, using a continuous structural mode and power transfer matrix-based approach. Notable observations include a reduction in peak vibro-acoustic responses with dense denticle arrangements, especially at resonance, demonstrating a direct relationship with mass ratios, i.e., the ratio of denticle mass to plate mass. The study further reveals a shift of vibro-acoustic responses towards low frequencies with an increase in mass ratios. A thorough comparative study indicates that while additive surface modifications inspired by shark skin may weaken sound radiation characteristics at resonance frequencies, a reverse effect can be observed at intermittent operational frequencies.

Characterization of macrophages associated with human skin models exposed to UV radiation.

Skin macrophages play important roles in the response to external stimuli. Human skin equivalents (HSEs) incorporating the human monocytic cell line THP-1 were fabricated to generate immunocompetent human skin models. These HSEs were used to investigate the influence of the skin microenvironment and ultraviolet A (UVA) on macrophages. Transcriptomic analysis revealed that THP-1 cells in HSEs were enriched in extracellular matrix interaction hallmark but downregulated in DNA replication hallmark. Upon UVA exposure, immunocompetent HSEs presented epidermal distortion and increased DNA double-strand breaks (DSBs). The genes associated with oxidative stress and the inflammatory response were significantly upregulated in THP-1 cells. When the photoprotective agent mycosporine-2-glycine from cyanobacteria was applied to HSEs, the incidence of UVA-induced DSBs was significantly lower, and inflammatory and UV response hallmarks were downregulated in THP-1 cells. Taken together, these results suggest that immunocompetent HSEs can be used to investigate the responses of skin-resident macrophages to external stimuli.

Ultrasound Findings After Breast Cancer Radiation Therapy: Cutaneous, Pleural, Pulmonary, and Cardiac Changes.

External beam radiation therapy (RT) can induce toxicity in patients surgically treated for breast cancer. Modern irradiation techniques have lowered the incidence and severity of radiation-induced injuries; however, their side effects on normal tissues remain challenging. This review illustrates early and late changes observed using ultrasound (US) imaging, including echocardiography, at the skin, muscle, pleura, lungs, and heart levels. The US findings and the potential role of this technique in detecting and grading early and late complications of RT are highlighted in this article. US has proven useful in the differential diagnosis of post-RT complications, including but not limited to cancer recurrence and toxicity from other sources, such as anticancer drugs. Additionally, considering the progressive nature of RT-induced injury, early detection of toxicity may be helpful in the individual stratification of damage risk and serve as a tool for patient screening and management. In these cases, US can be used as a radiation-free biomarker of RT side effects at the subclinical stage.

Upregulation of PRRX2 by silencing Marveld3 as a protective mechanism against radiation-induced ferroptosis in skin cells.

BACKGROUND: Radiation-induced skin injury (RISI) represents a significant complication in patients receiving radiotherapy and individuals exposed to nuclear accidents, characterized by a protracted wound-healing process relative to injuries from other etiologies. Current preventive and management approaches remain inadequate. Consequently, investigating efficacious intervention strategies that target the disease's progression characteristics holds significant practical importance. METHODS: Small interfering RNA (siRNA) and overexpression plasmid were used to modulate the expression of Marvel domain containing 3 (Marveld3) and paired related homeobox 2 (PRRX2). Protein and mRNA levels were estimated by Western Blot and real-time PCR, respectively. Intracellular levels of Malondialdehyde (MDA), a terminal product of lipid peroxidation, were measured following the manufacturer's protocol for MDA assay kit. Similarly, intracellular levels of ferrous iron (Fe2+) and reactive oxygen species (ROS) were determined using their respective assay kits. Lipid peroxidation status within the cells was evaluated via BODIPY staining. Immunohistochemistry was conducted to ascertain the expression of PRRX2 in skin tissues collected at various time points following irradiation of rats. The H-score method was used to evaluate the percentage of positively stained cells and staining intensity. RNA sequencing, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted by OE Biotech Company. RESULTS: In this study, our findings indicated that Marveld3 suppression could effectively inhibit lipid peroxidation levels in irradiated skin cells, concomitantly reducing intracellular Fe2+ content. Additionally, the silencing of Marveld3 effectively abrogated the impact of a ferroptosis agonist on cellular viability, resulting in the upregulation of 66 and 178 genes, as well as the downregulation of 188 and 31 genes in irradiated HaCaT and WS1 cells, respectively. Among the differentially expressed genes, the PRRX2 which was found to be involved in the process of ferroptosis, exhibited statistically significant upregulation. And the upregulation of PRRX2 expression may attenuate radiation-induced lipid peroxidation in skin cells, thereby functioning as a potential stress-responsive mechanism to counteract radiation effects. CONCLUSIONS: This study elucidates the role of Marveld3 in radiation-induced ferroptosis in skin cells. Inhibition of Marveld3 led to the upregulation of PRRX2, which subsequently resulted in a reduction of Fe2+ and ROS levels, as well as the suppression of lipid peroxidation. These effects collectively mitigated the occurrence of ferroptosis.

Epigenetic memory of radiotherapy in dermal fibroblasts impairs wound repair capacity in cancer survivors.

Radiotherapy (RT), a common cancer treatment, unintentionally harms surrounding tissues, including the skin, and hinders wound healing years after treatment. This study aims to understand the mechanisms behind these late-onset adverse effects. We compare skin biopsies from previously irradiated (RT+) and non-irradiated (RT-) sites in breast cancer survivors who underwent RT years ago. Here we show that the RT+ skin has compromised healing capacity and fibroblast functions. Using ATAC-seq, we discover altered chromatin landscapes in RT+ fibroblasts, with THBS1 identified as a crucial epigenetically primed wound repair-related gene. This is further confirmed by single-cell RNA-sequencing and spatial transcriptomic analysis of human wounds. Notably, fibroblasts in both murine and human post-radiation wound models show heightened and sustained THBS1 expression, impairing fibroblast motility and contractility. Treatment with anti-THBS1 antibodies promotes ex vivo wound closure in RT+ skin from breast cancer survivors. Our findings suggest that fibroblasts retain a long-term radiation memory in the form of epigenetic changes. Targeting this maladaptive epigenetic memory could mitigate RT's late-onset adverse effects, improving the quality of life for cancer survivors.

Revisiting Unaddressed Safety Concerns Regarding Intense Pulsed Light Treatment: Past and Present Perspectives.

BACKGROUND: The light spectrum of intense pulsed light (IPL) comprises visible to near-infrared light. It has been widely employed in the field of aesthetics for approximately 30 years. However, several studies have demonstrated the appearance of various undesirable biomarkers on the skin after IPL irradiation, which remain elucidated. METHODS: We reviewed the evolving concepts and explored the potentially harmful effects of IPL that may have been neglected in the past. RESULTS: Increased levels of reactive oxidative stress, p53, p16, proliferating cell nuclear antigen, interleukin-6, C-reactive protein, and cleaved caspase 3 and decreased albumin levels in human or mouse skin have been observed after IPL treatment. Visible and infrared light can exert harmful and beneficial effects on human skin. CONCLUSION: If perform improperly, IPL treatment may lead to cellular senescence, photoaging, photocarcinogenesis, thermal aging, and inflammaging. Further studies are required to verify the significance of the changes in the relevant biomarkers. The selection of treatment candidates, optimal parameters, and standardized protocols for IPL therapy are necessary.

Synergistic Toxicity of Pollutant and Ultraviolet Exposure from a Mitochondrial Perspective.

Ultraviolet (UV) exposure and atmospheric pollution are both independently implicated in skin diseases such as cancer and premature aging. UVA wavelengths, which penetrate in the deep layers of the skin dermis, exert their toxicity mainly through chromophore photosensitization reactions. Benzo[a]pyrene (BaP), the most abundant polycyclic aromatic hydrocarbon originating from the incomplete combustion of organic matter, could act as a chromophore and absorb UVA. We and other groups have previously shown that BaP and UVA synergize their toxicity in skin cells, which leads to important oxidation. Even if mitochondria alterations have been related to premature skin aging and other skin disorders, no studies have focused on the synergy between UV exposure and pollution on mitochondria. Our study aims to investigate the combined effect of UVA and BaP specifically on mitochondria in order to assess the effect on mitochondrial membranes and the consequences on mitochondrial activity. We show that BaP has a strong affinity for mitochondria and that this affinity leads to an important induction of lipid peroxidation and membrane disruption when exposed to UVA. Co-exposure to UVA and BaP synergizes their toxicity to negatively impact mitochondrial membrane potential, mitochondrial metabolism and the mitochondrial network. Altogether, our results highlight the implication of mitochondria in the synergistic toxicity of pollution and UV exposure and the potential of this toxicity on skin integrity.

Pilose Antler Protein Relieves UVB-Induced HaCaT Cells and Skin Damage.

Extended exposure to UVB (280-315 nm) radiation results in oxidative damage and inflammation of the skin. Previous research has demonstrated that pilose antler extracts have strong anti-inflammatory properties and possess antioxidant effects. This study aimed to elucidate the mechanism of pilose antler protein in repairing photodamage caused by UVB radiation in HaCaT cells and ICR mice. Pilose antler protein (PAP) was found to increase the expression of type I collagen and hyaluronic acid in HaCaT cells under UVB irradiation while also inhibiting reactive oxygen species (ROS) production and oxidative stress in vitro. In vivo, the topical application of pilose antler protein effectively attenuated UVB-induced skin damage in ICR mice by reducing interleukin-1ß (IL-ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and inhibiting skin inflammation while alleviating UVB-induced oxidative stress. It was shown that pilose antler protein repaired UVB-induced photodamage through the MAPK and TGF-ß/Smad pathways.

Co-Assembled Binary Polyphenol Natural Products for the Prevention and Treatment of Radiation-Induced Skin Injury.

Radiation therapy, a fundamental treatment for tumors, is often accompanied by radiation-induced skin injury (RISI). Excessive production of reactive oxygen species (ROS) and subsequent inflammation are two key factors in RISI development that will cause skin injury and affect radiotherapy. Herein, the co-assembled binary polyphenol natural products inspired the development of a dual-functional cascade microneedle system for prevention and treatment of RISI. Specifically, epigallocatechin gallate (EGCG) and curcumin (CUR) were co-assembled into nanoparticles (CEPG) by intermolecular interactions and then incorporated with catalase (CAT) to achieve a cascade system in the microneedles (this microneedle system was conducive to penetrate into the epidermal keratinocytes where RISI had the greatest impact). When using microneedles, the tip dissolved rapidly and delivered CEPG and CAT into the dermis, where CEPG NPs were able to respond to ROS and decompose into EGCG and CUR. More importantly, EGCG and CAT formed a cascade that converts superoxide anions into water step-by-step, which can reduce cell damage caused by free radicals in the early stages of radiation for prevention; meanwhile, CUR inhibited inflammatory pathways, achieving the treatment of skin inflammation in the post-radiotherapy period. These explorations broaden the strategy for the application of natural products in RISI.

A Customized 3D-Printed Bolus for High-Risk Breast Cancer with Skin Infiltration: A Pilot Study.

BACKGROUND: In high-risk breast cancer patients with skin infiltration, the administration of a uniform dose to superficial tissues is fundamental in order to reduce local skin relapse. A personalized bolus may prevent the potential inadequate dose distribution of a standard bolus due to air gaps between the bolus and the skin. In this pilot study, we introduced into clinical practice the use of a personalized 3D-printed bolus filled with ultrasound transmission gel. METHODS: Seven patients undergoing radiotherapy after mastectomy were selected. A 3D-printed bolus dosimetric assessment was performed with MOSFET dosimeters on an anthropomorphic phantom and, subsequently, on three selected cases with increasing bolus shape irregularity. Acute/late toxicity and local control were assessed. RESULTS: Overall, for the clinical cases, the percentage median difference between the measured and calculated doses was -2.7% (-7.0-4.9%). The median follow-up was 21 months. After two years, one patient showed G2 pain, one patient manifested G1 telangiectasia, one patient showed G1 hyperpigmentation, and two patients had no relevant toxicity. CONCLUSIONS: A personalized 3D-printed bolus filled with ultrasound gel may easily reproduce the standard bolus' consistency and provide accurate coverage of the target area with tolerable acute/late toxicity grades. This is a pilot study, and further investigations are needed.

Fermented Fish Collagen Attenuates Melanogenesis via Decreasing UV-Induced Oxidative Stress.

Excessive melanogenesis leads to hyperpigmentation-related cosmetic problems. UV exposure increases oxidative stress, which promotes melanogenesis-related signal pathways such as the PKA, microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2) pathways. Glycine is a source of endogenous antioxidants, including glutathione. Fermented fish collagen (FC) contains glycine; thus, we evaluated the effect of FC on decreasing melanogenesis via decreasing oxidative stress. The glycine receptor (GlyR) and glycine transporter-1 (GlyT1) levels were decreased in UV-irradiated keratinocytes; however, the expression levels of these proteins increased upon treatment with FC. The FC decreased oxidative stress, as indicated by the decreasing expression of NOX1/2/4, increased expression of GSH/GSSG, increased SOD activity, and decreased 8-OHdG expression in UV-irradiated keratinocytes. Administration of conditioned media from FC-treated keratinocytes to melanocytes led to decreased p38, PKC, MITF, TRP1, and TRP2 expression. These changes induced by the FC were also observed in UV-irradiated animal skin. FC treatment increased the expression of GlyR and GlyT, which was accompanied by decreased oxidative stress in the UV-irradiated skin. Moreover, the FC negatively regulated the melanogenesis signaling pathways, leading to decreased melanin content in the UV-irradiated skin. In conclusion, FC decreased UV-induced oxidative stress and melanogenesis in melanocytes and animal skin. FC could be used in the treatment of UV-induced hyperpigmentation problems.

Ameliorative effect of transfersome gel of kepok banana peel extract (Musa balbisiana) against photoaging in Wistar rat skin.

Background: Repeated acute exposure to ultraviolet B (UVB) rays can cause photoaging. Musa balbisiana peel contains flavonoid compounds which act as antioxidants. However, the physicochemicals of flavonoids are unstable, have high molecular weight, and are easily oxidized, causing their use is still limited and transdermal delivery to be inefficient. Aim: To investigate the ameliorative effect of transfersome gel of M. balbisiana peels against photoaging in Wistar rat skin. Methods: Transfersome gel was characterized by transmission electron microscopy (TEM). In vivo research was used to determine the ameliorative effects of M. balbisiana peel. The composition of transfersome consists of ethanol extracts of M. balbisiana peel, soybean phosphatidylcholine, and tween 80. The gel was applied three times a week for 4 weeks with a total UVB radiation dose of 840 mJ/cm2. To evaluate the repair mechanism by measuring the degree of wrinkles, epidermal thickening, dermal thinning, collagen fiber irregularity, matrix metalloproteinase 1 (MMP-1), and transforming growth factor-ß (TGF-ß) expression, malondialdehyde (MDA) and tumor necrosis factor-α (TNFα) levels. Results: TEM results show that gel transfersome M. balbisiana peel has a round morphology with a diameter of ±50 nm and no aggregation, which are defined as nanoparticles. Transfersome gel ameliorated the degree of wrinkle, epidermal thickening, dermal thinning, and irregularity of collagen fibers caused by UVB exposure, suppresses lipid peroxidation by decreasing MDA and TNFα level, also collagen imbalance by inhibiting MMP-1 expression and activating TGF-ß expression, which was found statistically significantly different from non-transfersome gel group. Conclusion: Transfersome gel of M. balbisiana peel can act as an alternative medicine to ameliorate clinical photoaging due to exposure to UVB.