International Journal of Molecular Sciences

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13 pages, 1538 KiB

Open AccessArticle

The Influence of the Amphiphilic Properties of Peptides on the Phosphatidylinositol Monolayer in the Presence of Ascorbic Acid

by Iwona Golonka, Izabela W. Łukasiewicz, Aleksandra Sebastiańczyk, Katarzyna E. Greber, Wiesław Sawicki and Witold Musiał

Int. J. Mol. Sci. 2024, 25(23), 12484; https://doi.org/10.3390/ijms252312484 - 21 Nov 2024

Cited by 2 | Viewed by 1032

Abstract

Acne vulgaris is one of the most common dermatological diseases and is strongly connected with the pathological growth of the Cutibacterium acnes. More than half of the cultures of this bacterium are resistant to antibiotics, resulting in the proposal of the use [...] Read more.

Acne vulgaris is one of the most common dermatological diseases and is strongly connected with the pathological growth of the Cutibacterium acnes. More than half of the cultures of this bacterium are resistant to antibiotics, resulting in the proposal of the use of antibacterial peptides as an alternative to traditional antibiotics. Ascorbic acid (AA) and its antioxidant properties may ally in acne therapy. The aim of this study was to determine the influence of the selected antibacterial peptides in the presence of ascorbic acid and 3-O-ethyl-ascorbic acid (EAA) on the properties of the monolayer formed by phosphatidylinositol. Studies of the properties of the phosphatidylinositol monolayer were carried out using the Langmuir–Wilhelmy balance. The recorded compression isotherms, hysteresis loops, and surface pressure values recorded at specific time intervals were evaluated to assess the influence of ascorbic acid and its derivatives in the presence of antimicrobial peptides on the stability and organization of phosphatidylinositol monolayers. The addition of AA to the subphase caused a faster phase transition at over 60 Å²/molecule and significantly reduced the plateau surface pressure by about 20% in most of the systems tested. The studied monolayers were found to be in the expanded liquid state (40.23–49.95 [mN/m]) or in the transition between the expanded and condensed liquid phase (51.47–60.98 [mN/m]). Compression and decompression isotherms indicated the highest flexibility of the systems at 20 °C and 25 °C. The surface pressure versus time dependence indicated the stability of the phosphatidylinositol monolayer with 3-O-ethyl–ascorbic acid and antimicrobial peptides up to 35 °C. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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11 pages, 2313 KiB

Open AccessArticle

Exposure to Radiofrequency Electromagnetic Fields Enhances Melanin Synthesis by Activating the P53 Signaling Pathway in Mel-Ab Melanocytes

by Ju Hwan Kim, Dong-Jun Kang, Jun Young Seok, Mi-Hye Kim, Dong-Seok Kim, Sang-Bong Jeon, Hyung-Do Choi, Jung Ick Moon, Nam Kim and Hak Rim Kim

Int. J. Mol. Sci. 2024, 25(22), 12457; https://doi.org/10.3390/ijms252212457 - 20 Nov 2024

Viewed by 1996

Abstract

The skin is the largest body organ that can be physiologically affected by exposure to radiofrequency electromagnetic fields (RF-EMFs). We investigated the effect of RF-EMFs on melanogenesis; Mel-Ab melanocytes were exposed to 1760 MHz radiation with a specific absorption rate of 4.0 W/kg [...] Read more.

The skin is the largest body organ that can be physiologically affected by exposure to radiofrequency electromagnetic fields (RF-EMFs). We investigated the effect of RF-EMFs on melanogenesis; Mel-Ab melanocytes were exposed to 1760 MHz radiation with a specific absorption rate of 4.0 W/kg for 4 h/day over 4 days. Exposure to the RF-EMF led to skin pigmentation, with a significant increase in melanin production in Mel-Ab melanocytes. The phosphorylation level of cAMP response element binding protein (CREB) and the expression of microphthalmia-associated transcription factor (MITF), which regulate the expression of tyrosinase, were significantly increased in Mel-Ab after RF-EMF exposure. Interestingly, the expression of tyrosinase was significantly increased, but tyrosinase activity was unchanged in the RF-EMF-exposed Mel-Ab cells. Additionally, the expression of p53 and melanocortin 1 receptor (MC1R), which regulate MITF expression, was significantly increased. These results suggest that the RF-EMF induces melanogenesis by increasing phospho-CREB and MITF activity. Importantly, when Mel-Ab cells were incubated at 38 °C, the melanin production and the levels of tyrosinase significantly decreased, indicating that the increase in melanin synthesis by RF-EMF exposure is not due to a thermal effect. In conclusion, RF-EMF exposure induces melanogenesis in Mel-Ab cells through the increased expression of tyrosinase via the activation of MITF or the phosphorylation of CREB, which are initiated by the activation of p53 and MC1R. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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17 pages, 36014 KiB

Open AccessArticle

Hair Growth Promoting Effects of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor in Human Follicle Dermal Papilla Cells

by Hye Won Lim, Hak Joong Kim, Chae Young Jeon, Yurim Lee, Mujun Kim, Jinsick Kim, Soon Re Kim, Sanghwa Lee, Dong Chul Lim, Hee Dong Park, Byung Cheol Park and Dong Wook Shin

Int. J. Mol. Sci. 2024, 25(13), 7485; https://doi.org/10.3390/ijms25137485 - 8 Jul 2024

Cited by 3 | Viewed by 3241

Abstract

Prostaglandin E₂ (PGE₂) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF_2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, [...] Read more.

Prostaglandin E₂ (PGE₂) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF_2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE₂ levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema^®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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12 pages, 3150 KiB

Open AccessArticle

Investigating Distinct Skin Microbial Communities and Skin Metabolome Profiles in Atopic Dermatitis

by Suyeon Kim, Minah Cho, Eun Sung Jung, Inseon Sim and Yu Ri Woo

Int. J. Mol. Sci. 2024, 25(10), 5211; https://doi.org/10.3390/ijms25105211 - 10 May 2024

Cited by 2 | Viewed by 2191

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by genetic predisposition, environmental factors, immune dysregulation, and skin barrier dysfunction. The skin microbiome and metabolome play crucial roles in modulating the skin’s immune environment and integrity. However, their specific contributions to AD [...] Read more.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by genetic predisposition, environmental factors, immune dysregulation, and skin barrier dysfunction. The skin microbiome and metabolome play crucial roles in modulating the skin’s immune environment and integrity. However, their specific contributions to AD remain unclear. We aimed to investigate the distinct skin microbial communities and skin metabolic compounds in AD patients compared to healthy controls (HCs). Seven patients with AD patients and seven HCs were enrolled, from whom skin samples were obtained for examination. The study involved 16S rRNA metagenomic sequencing and bioinformatics analysis as well as the use of gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to detect metabolites associated with AD in the skin. We observed significant differences in microbial diversity between lesional and non-lesional skin of AD patients and HCs. Staphylococcus overgrowth was prominent in AD lesions, while Cutibacterium levels were decreased. Metabolomic analysis revealed elevated levels of several metabolites, including hypoxanthine and glycerol-3-phosphate in AD lesions, indicating perturbations in purine metabolism and energy production pathways. Moreover, we found a positive correlation between hypoxanthine and glycerol-3-phosphate and clinical severity of AD and Staphylococcus overgrowth. These findings suggest potential biomarkers for monitoring AD severity. Further research is needed to elucidate the causal relationships between microbial dysbiosis, metabolic alterations, and AD progression, paving the way for targeted therapeutic interventions. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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10 pages, 1804 KiB

Open AccessCommunication

Exploring the Role of Gut Microbiota in Patients with Alopecia Areata

by Ji Hae Lee, Ji Hae Shin, Ji Yoon Kim, Hyun Jeong Ju and Gyong Moon Kim

Int. J. Mol. Sci. 2024, 25(8), 4256; https://doi.org/10.3390/ijms25084256 - 11 Apr 2024

Cited by 5 | Viewed by 3368

Abstract

Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome [...] Read more.

Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome in patients affected by AA and those in a healthy control (HC) group, and to investigate possible bacterial biomarkers for the disease. Fecal samples were collected from 19 AA patients and 20 HCs to analyze the relationship with fecal bacteria. The three major genera constituting the gut microbiome of AA patients were Bacteroides, Blautia, and Faecalibacterium. The alpha diversity of the AA group was not statistically significant different from that of the HC group. However, bacterial community composition in the AA group was significantly different from that of HC group according to Jensen–Shannon dissimilarities. In patients with AA, we found an enriched presence of the genera Blautia and Eubacterium_g5 compared to the HC group (p < 0.05), whereas Bacteroides were less prevalent (p < 0.05). The gut microbiota of AA patients was distinct from those of the HC group. Our findings suggest a possible involvement of gut microbiota in in the as-yet-undefined pathogenesis of AA. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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15 pages, 3978 KiB

Open AccessArticle

Multi-System-Level Analysis Reveals Differential Expression of Stress Response-Associated Genes in Inflammatory Solar Lentigo

by Jisu Jeong, Wonmin Lee, Ye-Ah Kim, Yun-Ji Lee, Sohyun Kim, Jaeyeon Shin, Yueun Choi, Jihan Kim, Yoonsung Lee, Man S. Kim and Soon-Hyo Kwon

Int. J. Mol. Sci. 2024, 25(7), 3973; https://doi.org/10.3390/ijms25073973 - 3 Apr 2024

Cited by 1 | Viewed by 1819

Abstract

Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. [...] Read more.

Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein–protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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16 pages, 2926 KiB

Open AccessArticle

Tocotrienol-Rich Fraction Attenuates Blue Light-Induced Oxidative Stress and Melanogenesis in B16-F1 Melanocytes via Anti-Oxidative and Anti-Tyrosinase Properties

by Juvenia Rui En Neo, Cheryl Wei Ling Teo, Yee Wei Ung and Wei Ney Yap

Int. J. Mol. Sci. 2023, 24(20), 15373; https://doi.org/10.3390/ijms242015373 - 19 Oct 2023

Cited by 1 | Viewed by 2154

Abstract

Our skin is constantly exposed to blue light (BL), which is abundant in sunlight and emitted by digital devices. Prolonged exposure to BL can lead to oxidative stress-induced damages and skin hyperpigmentation. For this study, we used a cell line-based model to examine [...] Read more.

Our skin is constantly exposed to blue light (BL), which is abundant in sunlight and emitted by digital devices. Prolonged exposure to BL can lead to oxidative stress-induced damages and skin hyperpigmentation. For this study, we used a cell line-based model to examine the protective effects of tocotrienol-rich fraction (TRF) on BL-induced oxidative stress and hyperpigmentation in B16-F1 melanocytes. Alpha-tocopherol (αTP) was used as a comparator. Molecular assays such as cell viability assay, flow cytometry, western blotting, fluorescence imaging, melanin and tyrosinase analysis were performed. Our results showed that TRF effectively suppressed the formation of reactive oxygen species and preserved the mitochondrial membrane potential. Additionally, TRF exhibited anti-apoptotic properties by reducing the activation of the p38 mitogen-activated protein kinase molecule and downregulating the expression of cleaved caspase-3. Moreover, TRF modulated tyrosinase activity, resulting in a lowered rate of melanogenesis and reduced melanin production. In contrast, αTP did not exhibit significant protective effects against skin damages and pigmentation in BL-induced B16-F1 cells. Therefore, this study indicates that TRF may offer superior protective effects over αTP against the effects of BL on melanocytes. These findings demonstrate the potential of TRF as a protective natural ingredient that acts against BL-induced skin damages and hyperpigmentation via its anti-oxidative and anti-melanogenic properties. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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Review

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20 pages, 996 KiB

Open AccessReview

The Role of the Skin Microbiome in Acne: Challenges and Future Therapeutic Opportunities

by Alicja Niedźwiedzka, Maria Pia Micallef, Manuele Biazzo and Christine Podrini

Int. J. Mol. Sci. 2024, 25(21), 11422; https://doi.org/10.3390/ijms252111422 - 24 Oct 2024

Cited by 5 | Viewed by 5824

Abstract

Acne vulgaris is a widespread dermatological condition that significantly affects the quality of life of adolescents and adults. Traditionally, acne pathogenesis has been linked to factors such as excess sebum production, follicular hyperkeratinization, and the presence of Cutibacterium acnes (C. acnes). [...] Read more.

Acne vulgaris is a widespread dermatological condition that significantly affects the quality of life of adolescents and adults. Traditionally, acne pathogenesis has been linked to factors such as excess sebum production, follicular hyperkeratinization, and the presence of Cutibacterium acnes (C. acnes). However, recent studies have highlighted the role of the skin microbiome, shifting focus from individual pathogens to microbial community dynamics. This review critically evaluates existing research on the skin microbiome and its relationship to acne, focusing on microbial diversity, C. acnes strain variability, and emerging therapies targeting the microbiome. While certain studies associate C. acnes with acne severity, others show this bacterium’s presence in healthy skin, suggesting that strain-specific differences and overall microbial balance play crucial roles. Emerging therapeutic approaches, such as probiotics and bacteriophage therapy, aim to restore microbial equilibrium or selectively target pathogenic strains without disturbing the broader microbiome. However, the lack of standardized methodologies, limited longitudinal studies, and the narrow focus on bacterial communities are major limitations in current research. Future research should explore the broader skin microbiome, including fungi and viruses, use consistent methodologies, and focus on longitudinal studies to better understand microbial fluctuations over time. Addressing these gaps will enable the development of more effective microbiome-based treatments for acne. In conclusion, while microbiome-targeted therapies hold promise, further investigation is needed to validate their efficacy and safety, paving the way for innovative, personalized acne management strategies. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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26 pages, 1952 KiB

Open AccessReview

Prurigo Nodularis: Pathogenesis and the Horizon of Potential Therapeutics

by Hwa Jung Yook and Ji Hyun Lee

Int. J. Mol. Sci. 2024, 25(10), 5164; https://doi.org/10.3390/ijms25105164 - 9 May 2024

Cited by 4 | Viewed by 10172

Abstract

Chronic pruritus that lasts for over 6 weeks can present in various forms, like papules, nodules, and plaque types, with prurigo nodularis (PN) being the most prevalent. The pathogenesis of PN involves the dysregulation of immune cell–neural circuits and is associated with peripheral [...] Read more.

Chronic pruritus that lasts for over 6 weeks can present in various forms, like papules, nodules, and plaque types, with prurigo nodularis (PN) being the most prevalent. The pathogenesis of PN involves the dysregulation of immune cell–neural circuits and is associated with peripheral neuropathies, possibly due to chronic scratching. PN is a persistent and challenging condition, involving complex interactions among the skin, immune system, and nervous system. Lesional skin in PN exhibits the infiltration of diverse immune cells like T cells, eosinophils, macrophages, and mast cells, leading to the release of inflammatory cytokines and itch-inducing substances. Activated sensory nerve fibers aggravate pruritus by releasing neurotransmitters, perpetuating a vicious cycle of itching and scratching. Traditional treatments often fail, but recent advancements in understanding the inflammatory and itch transmission mechanisms of PN have paved the way for innovative therapeutic approaches, which are explored in this review. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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22 pages, 1201 KiB

Open AccessReview

Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances

by Hyun Jee Kim and Yeong Ho Kim

Int. J. Mol. Sci. 2024, 25(5), 2984; https://doi.org/10.3390/ijms25052984 - 4 Mar 2024

Cited by 21 | Viewed by 7756

Abstract

Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic and epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing on molecular mechanisms [...] Read more.

Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic and epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing on molecular mechanisms in melanoma genesis. It highlights how mutations, particularly in the BRAF, NRAS, c-KIT, and GNAQ/GNA11 genes, affect critical signaling pathways. The evolution of diagnostic techniques, such as genomics, transcriptomics, liquid biopsies, and molecular biomarkers for early detection and prognosis, is also discussed. The therapeutic landscape has transformed with targeted therapies and immunotherapies, improving patient outcomes. This paper examines the efficacy, challenges, and prospects of these treatments, including recent clinical trials and emerging strategies. The potential of novel treatment strategies, including neoantigen vaccines, adoptive cell transfer, microbiome interactions, and nanoparticle-based combination therapy, is explored. These advances emphasize the challenges of therapy resistance and the importance of personalized medicine. This review underlines the necessity for evidence-based therapy selection in managing the increasing global incidence of melanoma. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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20 pages, 1690 KiB

Open AccessReview

The Biology and Genomics of Human Hair Follicles: A Focus on Androgenetic Alopecia

by Raquel Cuevas-Diaz Duran, Emmanuel Martinez-Ledesma, Melissa Garcia-Garcia, Denisse Bajo Gauzin, Andrea Sarro-Ramírez, Carolina Gonzalez-Carrillo, Denise Rodríguez-Sardin, Alejandro Fuentes and Alejandro Cardenas-Lopez

Int. J. Mol. Sci. 2024, 25(5), 2542; https://doi.org/10.3390/ijms25052542 - 22 Feb 2024

Cited by 10 | Viewed by 10755

Abstract

Androgenetic alopecia is a highly prevalent condition mainly affecting men. This complex trait is related to aging and genetics; however, multiple other factors, for example, lifestyle, are also involved. Despite its prevalence, the underlying biology of androgenetic alopecia remains elusive, and thus advances [...] Read more.

Androgenetic alopecia is a highly prevalent condition mainly affecting men. This complex trait is related to aging and genetics; however, multiple other factors, for example, lifestyle, are also involved. Despite its prevalence, the underlying biology of androgenetic alopecia remains elusive, and thus advances in its treatment have been hindered. Herein, we review the functional anatomy of hair follicles and the cell signaling events that play a role in follicle cycling. We also discuss the pathology of androgenetic alopecia and the known molecular mechanisms underlying this condition. Additionally, we describe studies comparing the transcriptional differences in hair follicles between balding and non-balding scalp regions. Given the genetic contribution, we also discuss the most significant risk variants found to be associated with androgenetic alopecia. A more comprehensive understanding of this pathology may be generated through using multi-omics approaches. Full article

(This article belongs to the Special Issue Molecular Research Progress of Skin and Skin Diseases)

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