Macrophage migration inhibitory factor mediates skin aging via CD74: Insights from single-cell and bulk RNA sequencing data.

Cell-cell communication is crucial for regulating signaling and cellular function. However, the precise cellular and molecular changes remain poorly understood in skin aging. Based on single-cell and bulk RNA data, we explored the role of cell-cell ligand-receptor interaction in skin aging. We found that the macrophage migration inhibitory factor (MIF)/CD74 ligand-receptor complex was significantly upregulatedin aged skin, showing the predominant paracrine effect of keratinocytes on fibroblasts. Enrichment analysis and in vitro experiment revealed a close association of the activation of the MIF/CD74 with inflammatory pathways and immune response. Mechanistically, MIF/CD74 could significantly inhibit PPARγ protein, which thus significantly increased the degree of fibroblast senescence, and significantly up-regulated the expression of senescence-associated secretory phenotype (SASP) factors and FOS gene. Therefore, our study reveals that MIF/CD74 inhibits the activation of the PPAR signaling pathway, subsequently inducing the production of SASP factors and the upregulation of FOS expression, ultimately accelerating fibroblast senescence.

Identification of dietary factors that impact the gut microbiota associated with vitiligo: A Mendelian randomization study and meta-analysis.

Previous observational studies have suggested that gut microbiota might be associated with vitiligo. However, owing to the limitations in observational studies of reverse causality and confounders, it remains unclear that whether and how the causal relationships exist. The results suggested that pylum.Bacteroidetes, family.BacteroidalesS24.7, genus.LachnospiraceaeND3007, genus.Marvinbryantia are protective factors for vitiligo. Conversely, family.Lachnospiraceae, order.Burkholderiales, genus.Adlercreutzia, genus.Catenibacterium and genus.Lachnospira are risk factors for vitiligo. In addition, the causative connection between dietary factors and the gut microbiota associated with vitiligo was also investigated. The results revealed that 'alcohol intake versus 10 years pervious' results in a reduction in the abundance of genus.Lachnospiraceae ND3007 and family.BacteroidalesS24.7, bread intake leads to a reduction of genus.Marvinbryantia, 'average weekly red wine intake' is linked to a decrease in the abundance of order.Burkholderiales, tea intake is associated with an augmentation in the abundance of genus.Catenibacterium, salad/raw vegetable intake elevates the abundance of order.Burkholderiales. In summary, this Mendelian randomization study substantiates potential causal effects of gut microbiota on vitiligo. Modulating the gut microbiota through regulating dietary composition may be a novel strategy for preventing vitiligo.

The amino acid transporter SLC16A10 promotes melanogenesis by facilitating the transportation of phenylalanine.

Phenylalanine is a crucial amino acid in the process of melanogenesis. However, the exact mechanism by which it is transported into melanocytes has not been disclosed. The aim of this study was to identify and examine the key transporters that are responsible for phenylalanine transportation and evaluate their significance in melanogenesis. The amino acid transporter SLC16A10 was found to be up-regulated in both melasma (GSE72140) and sun-exposed skin (GSE67098). The protein levels of SLC16A10 were proportional to the melanin content in melanocytic nevi, indicating that SLC16A10 was related to melanogenesis. After SLC16A10 overexpression, melanin increased significantly in MNT1 cells. Meanwhile, the expression of melanogenesis-related proteins such as TYR and TYRP1 increased, while their RNA levels did not change. Transcriptomics data indicated that SLC16A10 can enhance the function of ribosome. Furthermore, targeted metabolomics data and ELISA results demonstrated SLC16A10 mainly affected the transport of phenylalanine into the cells. Then, phenylalanine was added to the cell culture medium after SLC16A10 overexpression, melanin synthesis in cells furtherly increased, which verified that SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine. Finally, we found that SLC16A10 expression increased after UVB irradiation. Knockdown SLC16A10 reduced UVB-induced melanin production and phenylalanine uptake by cells. In summary, SLC16A10 enhances melanogenesis by promoting the uptake of phenylalanine, and upregulation SLC16A10 is likely responsible for the UVB-induced hyperpigmentation as well.

Polycyclic aromatic hydrocarbons exposure associated with increased risk of psoriasis.

Psoriasis is considered to be multifactorial, with both genetic and environmental factors contributing to its development. Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment, originating from sources such as cigarette smoke, exhaust emissions, grilled foods, smoked foods and urban air. Researchs have established a link between PAHs exposure and autoimmune disorders; however, specific effects of PAHs on psoriasis remain underexplored. This study aims to evaluate the correlation between PAHs exposure and susceptibility to psoriasis. We analysed eight monohydroxy PAHs (1-Hydroxynaphthalene (1-NAP), 2-Hydroxynaphthalene (2-NAP), 3-Hydroxyfluorene (3-FLU), 2-Hydroxyfluorene (2-FLU), 1-Hydroxyphenanthrene (1-PHE), 1-Hydroxypyrene (1-PYR), 2-Hydroxyphenanthrene (2-PHE) and 3-Hydroxyphenanthrene (3-PHE)) in 5996 participants from the National Health and Nutrition Examination Survey (NHANES). We employed multivariate logistic regression, trend analysis, weighted quantile sum (WQS) regression and restricted cubic spline (RCS) analysis to investigate the relationship between PAHs exposure and psoriasis risk. Multivariate logistic regression and trend analysis revealed that monohydroxy PAHs, including 2-NAP, 3-FLU, 2-FLU and the mixture of 2-PHE and 3-PHE, are associated with an increased risk of psoriasis. Additionally, WQS regression showed a significant positive correlation between combined exposure to monohydroxy PAHs and psoriasis risk, with the mixture of 2-PHE and 3-PHE (47.3%) being the most influential factor. RCS regression further corroborated these findings. Specifically, 2-FLU can increase the expression of psoriasis-related inflammatory factors in HaCaT cells. In conclusion, PAHs exposure increases the risk of developing psoriasis. Efforts to reduce PAHs levels in the environment and minimise exposure are crucial for public health strategies aimed at preventing psoriasis.

Efficacy of Photodynamic Therapy in the Treatment of Actinic Keratosis: A Network Meta-Analysis.

BACKGROUND: Photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) and uses different light sources as well as photosensitizers. In addition, PDT is often combined with other physical therapies or drugs. OBJECTIVES: This study was aimed to compare the efficacy of different PDTs against AK lesions based on Complete Response (CR) by conducting a network meta-analysis (NMA). METHODS: Randomized controlled trials (RCTs) using PDT for AK were screened and a Bayesian model was developed to perform an NMA of CR at 3 months after the first treatment. RESULTS: Twenty-six trials involving 2285 patients and 14 treatments were included. The treatments were broadly divided into mono-PDT and combination therapy. The photodynamic monotherapies included methyl 5-aminolevulinic acid (MAL)-daylight (DL)-PDT, MAL-light-emitting diode (LED)-PDT, 5-aminolevulinic acid (ALA)-LED-PDT, etc. Combination therapies included ablative fractional laser (AFL)-assisted MAL-LED-PDT, calcipotriol (CAL)-assisted MAL-LED-PDT, and 5-fluorouracil (5-Fu)-assisted MAL-DL-PDT. The results of the NMA showed that there is a high probability that AFL-MAL-LED-PDT is the most effective treatment option, followed by CAL-MAL-LED-PDT and ALA-LED-PDT. The subgroup analysis showed that MAL-based PDT had better efficacy when using LED versus other light sources, while LED-based PDT was likely to have better efficacy when using ALA versus other photosensitizers. CONCLUSIONS: The results of this NMA suggest that AFL-MAL-LED-PDT may be the superior choice for achieving complete clearance of AK lesions. PDT using LED as the light source and ALA as the photosensitizer may be more effective for the treatment of AK. However, more RCTs are needed to verify the results of this analysis.

UVB promotes melanogenesis by regulating METTL3.

Ultraviolet (UV) radiation is the primary exogenous inducer of skin pigmentation, although the mechanism has not been fully elucidated. N6-methyladenosine (m6 A) modification is one of the key epigenetic form of gene regulation that affects multiple biological processes. The aim of this study was to explore the role and underlying mechanisms of m6 A modification in UVB-induced melanogenesis. Low-dose UVB increased global m6 A modification in melanocytes (MCs) and MNT1 melanoma cell line. The GEPIA database predicted that methyltransferase METTL3 is positively correlated with the melanogenic transcription factor MITF in the sun-exposed skin tissues. After METTL3 respectively overexpressed and knocked down in the MNT1, the melanin content and melanogenesis-related genes were significantly upregulated after overexpression of METTL3, especially with UVB irradiation, and downregulated after METTL3 knockdown. METTL3 levels were also higher in melanocytic nevi with high melanin content. METTL3 overexpression and knockdown also altered the protein level of YAP1. SRAMP analysis predicted four high-potential m6 A modification sites on YAP1 mRNA, of which three were confirmed by methylated RNA immunoprecipitation. Inhibition of YAP1 expression can partially reverse melanogenesis induced by overexpression of METTL3. In conclusion, UVB irradiation promotes global m6 A modification in MCs and upregulates METTL3, which increases the expression level of YAP1 through m6 A modification, thereby activating the co-transcription factor TEAD1 and promoting melanogenesis.

Characteristics and pathogenesis of Koebner phenomenon.

The Koebner phenomenon, also known as isomorphic reaction, refers to the development of secondary lesions with the same clinical manifestations and histopathological characteristics as the primary lesions in normal skin after trauma or other stimuli. The triggering factors of Koebner phenomenon include physical trauma, chemical stimulation, mechanical stress, iatrogenic stimulation and pathogenic infection. Vitiligo, psoriasis and lichen planus are considered true Koebner phenomenon. Recent studies have shown that immunological disorders, oxidative stress, defective melanocyte adhesion and growth factor deficiency are the main pathological mechanisms of vitiligo Koebner phenomenon. In psoriasis, triggers may drive skin inflammation to induce a psoriatic phenotype through multiple signalling pathways and thereby cause Koebner phenomenon in susceptible individuals. Significantly, keratinocytes mediate the occurrence of Koebner phenomenon in psoriasis through mechano-induced signalling pathways after sensing mechanical signals and explains the high frequency of psoriasis lesions on the extensor side of the elbow and knee joints. On the contrary, TRPA1-driven mechano-transduction, autoimmunity and actinic damage are the underlying mechanisms of Koebner phenomenon in lichen planus. In this review, we have summarized the current understanding of the characteristics and pathogenesis of Koebner phenomenon.

Melatonin reduces melanogenesis by inhibiting the paracrine effects of keratinocytes.

Keratinocytes regulate melanogenesis in a paracrine manner. Previous studies have shown that melatonin can directly inhibit melanin production in the melanocytes. However, it is unclear whether melatonin can also indirectly regulate melanogenesis through the keratinocytes. In this study, we explored the role of melatonin in regulating keratinocyte-mediated melanogenesis using reconstructed human epidermis (RHE). Melatonin showed an inhibitory effect on melanin synthesis in this model. Furthermore, the conditioned media from melatonin-treated HaCaT cells downregulated melanogenesis-related genes, including MITF, TYR, TYRP1, DCT and RAB27A in the pigment MNT1 cells, and decreased levels of phosphorylated ERK, JNK and p38. RNA sequencing further showed that mitochondrial functions and oxidative stress pathway in the MNT1 cells were inhibited by the conditioned medium from melatonin-treated HaCaT cells. Furthermore, melatonin reduced the secretion of ET-1 and PTGS2 from HaCaT cells by inhibiting the JAK2/STAT3 signalling pathway. In conclusion, melatonin downregulates the paracrine factors ET-1 and PTGS2 in the keratinocytes by inhibiting the JAK2/STAT3 pathway, which reduces melanin production in pigment cells. Thus, melatonin has a potential therapeutic effect on skin pigmentation disorders.

Disease Awareness and Treatment Preferences in Vitiligo: A Cross-sectional Study in China.

In China, there is a lack of data regarding the awareness and treatment preferences among patients with vitiligo and their families. To address this gap, a cross-sectional questionnaire-based study was conducted to investigate disease awareness and treatment preferences in Chinese patients with vitiligo. The study also evaluated willingness to pay, using 2 standardized items, and assessed quality of life, using the Dermatology Life Quality Index (DLQI) score. Data from 307 patients with vitiligo (59.3% women, mean age 28.98 years, range 2-73 years) were analysed. Of these patients, 44.7% had insufficient knowledge of vitiligo, particularly those from rural areas or with low levels of education. Mean DLQI total score was 4.86 (5.24 for women and 4.30 for men). Among the most accepted treatments were topical drugs, phototherapy, and systemic therapy. Patients were relatively conservative about the duration and cost of treatment, with only 27.7% willing to pay more than 10,000 Chinese yuan renminbi (CNY) for complete disease remission. High level of education, high income, skin lesions in specific areas, and skin transplantation therapy predicted higher willingness to pay. Insufficient knowledge was associated with a higher burden of disease. In order to reduce the disease burden and improve treatment adherence it is crucial to enhance disease awareness and take into account patient preferences.

Selaginellin Inhibits Melanogenesis via the MAPK Signaling Pathway.

Hyperpigmented skin diseases such as melasma, freckles, and melanosis usually mar the appearance of patients. Traditional herbal medicines are highly accepted in inhibiting skin pigmentation, with advantages of high efficiency, low cost, and low side effects. Selaginellin (SEL), one of the active compounds of selaginella, has been proved to be exhibit antineoplastic, antioxidant, antisenescence, and antiapoptosis activities. In this study, we found that SEL can inhibit melanogenesis in vitro and in vivo. A mechanism study found that SEL inhibits melanogenesis through inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway, then down-regulating the expression of microphthalmia-associated transcription factor (MITF) and downstream genes tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2). UVB-activated paracrine function of fibroblasts and keratinocytes promotes melanogenesis of melanocytes. Interestingly, SEL antagonizes UVB-activated paracrine function of fibroblasts and keratinocytes. These findings indicate that SEL can be a potential whitening compound to inhibit melanogenesis.

Taurine up-regulated gene 1 and disease development. / ç‰›ç£ºé ¸ä¸Šè°ƒåŸºå› 1ä¸Žç–¾ç— çš„å ³ç³».

Long non-coding RNA (lncRNA) have been attracted attention due to its role in many diseases. Taurine up-regulated gene 1(TUG1)is a non-coding RNA of 7.1 kb in length, which locates on chromosome 22q12. More and more studies have found that TUG1 not only participates in the occurrence and development of tumors, but also plays an important role in the progression of diseases in cardiovascular system, endocrine system, nervous system and so on. It is expected to become the therapeutic targets and indicators for evaluating prognosis of a variety of diseases such as diabetes, myocardial ischemia, osteoarthritis, atherosclerosis and so on.

Downregulation of TUG1 promotes melanogenesis and UVB-induced melanogenesis.

Studies have revealed that taurine upregulated gene 1 (TUG1), an important member of the long non-coding RNA family, is involved in the regulation of cell growth, tumorigenesis and invasion, insulin secretion and so on. However, its role in melanogenesis has not been explored. This study attempts to explore the effects of TUG1 on melanogenesis and its regulatory mechanisms. We evaluated the expression changes in melanogenesis-related genes and detected phosphorylation levels of ERK, JNK and P38 in TUG1 downregulated melanocytes. After exposure of melanocytes to UVB irradiation, the expression of TUG1 and melanogenesis-related genes was detected. We found that the expression of tyrosinase (TYR), tyrosine-related protein 1 (TYRP1) and tyrosine-related protein 2 (TYRP2) was upregulated and that the phosphorylation level of ERK was downregulated by downregulating TUG1. Inhibition of TUG1 could further upregulate the expression of UVB-induced melanogenesis-related genes. In conclusion, TUG1 negatively regulates melanocyte melanogenesis via the ERK pathway and plays a negative role in UVB-induced melanogenesis.

UVB-inhibited H19 activates melanogenesis by paracrine effects.

The long noncoding RNA H19 was reported to associate with melanogenesis. However, it remains unknown whether H19 expression will be changed by UVB irradiation and whether H19 will regulate melanocytes melanogenesis by paracrine effects. Here, we analysed the expression changes of H19 irradiated by UVB in keratinocytes and explored the mechanism of melanogenesis stimulated by H19 through paracrine effects. First, after keratinocytes were exposed to UVB irradiation, expression of H19 and pro-opiomelanocortin (POMC) was measured by qRT-PCR. Also, α-melanocyte-stimulating hormone (α-MSH) contents in cells supernatant were measured by ELISA. Then, H19 siRNAs were designed and transfected into keratinocytes by liposome. The expression changes of H19, POMC and α-MSH were detected. Besides, expression of p53 was detected by Western blot. After that, supernatant of keratinocytes with H19 siRNAs or negative control siRNA was cocultured with immortalized melanocyte line PIG1. Expression levels of MiTF, TYR, Rab27A, TYRP2, FSCN1 and MYO5A in PIG1 cells were detected by Western blot and qRT-PCR. We found that H19 expression of keratinocytes cells decreased after UVB irradiation. However, the levels of POMC, α-MSH and p53 were upregulated in UVB-irradiated cells. Compared with the negative control, H19 siRNAs could significantly increase the expression of POMC, α-MSH and p53. After supernatant of keratinocytes transfected with H19 siRNAs was cocultured with PIG1 cells, the levels of MiTF, TYR and Rab27A were upregulated in PIG1 cells. In conclusion, UVB-inhibited H19 may promote α-MSH secretion by p53 in keratinocytes and then regulate melanocytes melanogenesis through paracrine effects.

Anti-Obesity Effect of Chitosan Oligosaccharide Capsules (COSCs) in Obese Rats by Ameliorating Leptin Resistance and Adipogenesis.

Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a high-fat diet (HFD). After the eight-week administration of COSCs on obese rats, the body weight gain, fat/body ratio, and related biochemical indices were measured. The hepatic expressions of the leptin signal pathway (JAK2-STAT3) and gene expressions of adipogenesis-related targets were also determined. Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment.

Determination of the Deacetylation Degree of Chitooligosaccharides.

The methods for determination of chitosan content recommended in the Chinese Pharmacopoeia and the European Pharmacopoeia are not applicable for evaluation of the extent of deacetylation (deacetylation degree, DD) in chitooligosaccharides (COS). This study explores two different methods for assessment of DD in COS having relatively high and low molecular weights: an acid-base titration with bromocresol green indicator and a first order derivative UV spectrophotometric method for assessment of DD in COS. The accuracy of both methods as a function of molecular weight was also investigated and compared to results obtained using ¹H NMR spectroscopy. Our study demonstrates two simple, fast, widely adaptable, highly precise, accurate, and inexpensive methods for the effective determination of DD in COS, which have the potential for widespread commercial applications in developing country.

Reflectance confocal microscopy for the early diagnosis of herpes zoster.

For herpes zoster (HZ) infection, early diagnosis and treatment are important in order to shorten the course of the disease and reduce sequelae, however, there is a lack of non-invasive diagnostic methods. Reflectance confocal microscopy (RCM) is a non-invasive technique often used to diagnose dyspigmented dermatosis, skin tumours, human papillomavirus infectious dermatosis, etc. To evaluate the clinical value of RCM for the early diagnosis of HZ. We collected RCM images from 30 HZ patients with typical vesicles in order to analyse their features. We then utilized RCM to analyse early lesions of another 12 HZ patients, who presented with localized erythema or papules, but not typical vesicles. In addition, we recruited one patient with HZ and observed the lesions over 14 days also using RCM. RCM images showed that the typical lesions of HZ mainly involved oedema of the spinous layer, intraepidermal blister formation, ballooning multinucleated giant (BMG) cells, and dermal papillary oedema. Among them, BMG cells were of specific diagnostic value. Early lesions of HZ patients without typical vesicles showed BMG cells under RCM. A few BMG cells were observed during the early stage of HZ. However, the number of BMG cells increased significantly as typical clustered blisters gradually appeared in the lesions. With the regression of the lesions, the number of BMG cells decreased gradually. RCM, with the advantages of being non-invasive, rapid, and convenient, has an important role in monitoring the evolution of HZ.

UVB-induced TRPS1 regulates MITF transcription activity to promote skin pigmentation.

Hyperpigmented dermatoses are characterized by increased skin pigmentation caused by genetic, environmental factors and inflammation, which lasts a long time and is difficult to treat. Ultraviolet (UV), especially ultraviolet B (UVB), is the primary external factor inducing skin pigmentation. However, the specific regulatory mechanisms are not fully understood. Through analysis of GEO datasets from four UV-exposed skin cell/tissue samples, we found that TRPS1 is the only gene differentially expressed in multiple datasets (GSE22083, GSE67098 and GSE70280) and highly positively correlated with the expression of key melanogenesis genes. Consistently, we observed that TRPS1 is highly expressed in sun-exposed skin tissues compared to non-exposed skin. Additionally, the expression of TRPS1 was also significantly upregulated after UVB irradiation in isolated skin tissues and melanocytes, while knockdown of TRPS1 expression inhibited the UVB-induced melanogenesis. Further research revealed that overexpression of TRPS1 increased melanin content and tyrosinase activity in MNT1 cells, as well as upregulated the expression levels of key melanogenesis genes (MITF, TYR, TYRP1, DCT). In contrast, inhibition of TRPS1 expression showed the opposite effect. Moreover, we found that TRPS1 can bind to the promoter region of MITF, inhibiting the expression of MITF can antagonize the melanogenesis induced by TRPS1. In conclusion, UVB-induced TRPS1 promotes melanogenesis by activating the transcriptional activity of MITF.

Dynamic panoramic presentation of skin function after fractional CO2 laser treatment.

Fractional CO2 laser, as a typical ablative laser, has been used to assist in the treatment of many skin diseases, such as photoaging, atrophic scar, hypertrophic scar, superficial pigmentation, vitiligo, and so on. However, the dynamic changes in skin function after fractional CO2 laser treatment are still unclear. This study explored the changes in local skin function and possible regulatory mechanisms after fractional CO2 laser treatment for 1, 3, 5, and 7 days through transcriptome high-throughput sequencing. The results showed that fractional CO2 laser tended to transform the "lesions" into "normal skin", regulate the skin barrier, coordinate the rearrangement of collagen, enhance the local microvascular circulation, activate the immune system to secrete a large number of cytokines, and act as an auxiliary tool to assist drug transport. In conclusion, according to the basic principle of destruction before reconstruction, fractional CO2 laser plays a key role of balancer in skin reconstruction.

Decreased oxidative stress response and oxidant detoxification of skin during aging.

Oxidative stress plays an important role in the skin aging process; however, the mechanisms are not fully elucidated. Especially the changes in various types of skin cells with aging and the key oxidative stress-related genes that play a regulatory role are not clear. In this study, single-cell RNA sequencing data and microarray transcriptome data were used to explore the changes in oxidative stress response and oxidant detoxification capacity of skin cells during aging and oxidative stress-related genes potentially involved in regulating skin aging were searched. The oxidative stress response and oxidant detoxification ability were weakened in the elderly compared with those of the young. Among the different types of skin cells, keratinocytes, melanocytes, vascular endothelial cells, fibroblasts, and lymphatic endothelial cells exhibited a stronger oxidative stress response and oxidant detoxification ability, while immune cells exhibited a weaker oxidative stress response and detoxification capacity. During aging, the oxidative stress response and oxidant detoxification capacity of keratinocytes, fibroblasts, macrophages, and vascular endothelial cells were significantly weakened. Annexin A1 (ANXA1) and Apolipoprotein E (APOE) may be key oxidative stress-related genes affecting skin aging.