Vitamin D and Cutaneous Melanoma Risk: An Umbrella Review of Systematic Reviews and Meta-Analyses.

Background: Vitamin D (VitD) properties can impact cancer cells. Despite the documented link between VitD levels and prevalence of several cancer types, conflicting findings have been reported for cutaneous melanoma (CM). Objective: This overview aims to compile the evidence from existing systematic reviews and meta-analyses, emphasizing the relationships between VitD serum levels, intake, receptor (VDR) gene polymorphisms, and CM risk. Methods: A literature search in electronic databases was conducted, based on certain inclusion criteria. Results: Twenty-one studies were included. Conflicting evidence between high VitD serum levels, dietary/supplementary intake, and CM risk is highlighted. VDR polymorphisms may play a role in the intricate CM pathogenesis. Also, high serum levels of VitD are associated with improved CM prognosis. Conclusions: This overview showed that the impact of VitD on CM is not clear, and thus further research is suggested to explore its true effect size on CM risk.

A novel multifunctional microneedle patch for synergistic photothermal- gas therapy against maxillofacial malignant melanoma and associated skin defects.

Considering the high recrudescence and the long-lasting unhealed large-sized wound that affect the aesthetics and cause dysfunction after resection of maxillofacial malignant skin tumors, a groundbreaking strategy is urgently needed. Photothermal therapy (PTT), which has become a complementary treatment of tumors, however, is powerless in tissue defect regeneration. Therefore, a novel multifunctional sodium nitroprusside and Fe2+ ions loaded microneedles (SNP-Fe@MNs) platform was fabricated by accomplishing desirable NIR-responsive photothermal effect while burst releasing nitric oxide (NO) after the ultraviolet radiation for the ablation of melanoma. Moreover, the steady releasing of NO in the long term by the platform can exert its angiogenic effects via upregulating multiple related pathways to promote tissue regeneration. Thus, the therapeutic dilemma caused by postoperative maxillofacial skin malignancies could be conquered through promoting tumor cell apoptosis via synergistic PTT-gas therapy and subsequent regeneration process in one step. The bio-application of SNP-Fe@MNs could be further popularized based on its ideal bioactivity and appealing features as a strategy for synergistic therapy of other tumors occurred in skin.

Huang Lian Jie Du Decoction enhances the anti-tumor efficacy of immune checkpoint inhibitors by activating TLR7/8 signalling in melanoma.

BACKGROUND: The clinical application of immune checkpoint inhibitors (ICIs) is limited by their drug resistance, necessitating the development of ICI sensitizers to improve cancer immunotherapy outcomes. Huang Lian Jie Du Decoction (HLJD, Oren-gedoku-to in Japanese, Hwangryunhaedok-tang in Korean), a famous traditional Chinese medicinal prescription, has exhibited potential in the field of cancer treatment. This study aims to investigate the impact of HLJD on the efficacy of ICIs in melanoma and elucidate the underlying mechanisms. METHODS: The potential synergistic effects of HLJD and ICIs were investigated on the tumor-bearing mice model of B16F10 melanoma, and the tumor infiltration of immune cells was tested by flow cytometry. The differential gene expression in tumors between HLJD and ICIs group and ICIs alone group were analyzed by RNA-seq. The effects of HLJD on oxidative stress, TLR7/8, and type I interferons (IFN-Is) signaling were further validated by immunofluorescence, PCR array, and immunochemistry in tumor tissue. RESULTS: HLJD enhanced the anti-tumor effect of ICIs, significantly inhibited tumor growth, and prolonged the survival duration in melanoma. HLJD increased the tumor infiltration of anti-tumor immune cells, especially DCs, CD4+ T cells and CD8+T cells. Mechanically, HLJD activated the oxidative stress and TLR7/8 signaling pathway and IFN-Is-related genes in tumors. CONCLUSIONS: HLJD enhanced the therapeutic benefits of ICIs in melanoma, through increasing reactive oxygen species (ROS), promoting the TLR7/8 pathway, and activating IFN-Is signaling, which in turn activated DCs and T cells.

KLF4 suppresses anticancer effects of brusatol via transcriptional upregulating NCK2 expression in melanoma.

Brusatol (Bru), a main extract from traditional Chinese medicine Brucea javanica, has been reported to exist antitumor effect in many tumors including melanoma. However, the underlying mechanism in its anti-melanoma effect still need further exploration. Here, we reported that the protein expression of KLF4 in melanoma cells were significantly downregulated in response to brusatol treatment. Overexpression of KLF4 suppressed brusatol-induced melanoma cell apoptosis; while knockdown of KLF4 enhanced antitumor effects of brusatol on melanoma cells not only in vitro but also in vivo. Further studies on the mechanism revealed that KLF4 bound to the promoter of NCK2 directly and facilitated NCK2 transcription, which suppressed the antitumor effect of brusatol on melanoma. Furthermore, our findings showed that miR-150-3p was dramatically upregulated under brusatol treatment which resulted in the downregulation of KLF4. Our results suggested that the miR-150-3p/KLF4/NCK2 axis might play an important role in the antitumour effects of brusatol in melanoma.

The fusion of light and immunity: Advancements in photoimmunotherapy for melanoma.

Metastatic melanoma is an aggressive skin cancer with high mortality and recurrence rates. Despite the clinical success of recent immunotherapy approaches, prevailing resistance rates necessitate the continued development of novel therapeutic options. Photoimmunotherapy (PIT) is emerging as a promising immunotherapy strategy that uses photodynamic therapy (PDT) to unleash systemic immune responses against tumor sites while maintaining the superior tumor-specificity and minimally invasive nature of traditional PDT. In this review, we discuss recent advances in PIT and strategies for the management of melanoma using PIT. PIT can strongly induce immunogenic cell death, inviting the concomitant application of immune checkpoint blockade or adoptive cell therapies. PIT can also be leveraged to selectively remove the suppressive immune populations associated with immunotherapy resistance. The modular nature of PIT therapy design combined with the potential for patient-specific antigen selection or drug co-delivery makes PIT an alluring option for future personalized melanoma care.

Qinzhuliangxue mixture ameliorates psoriasis by restraining apoptosis in psoriasis via downregulating the MDA-5 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is characterized by hyperkeratosis that produces the classic silvery scales, and the pathogenesis of psoriasis involves abnormal proliferation of keratinocytes. Emerging evidence supports that apoptosis regulates keratinocyte proliferation and formation of stratum corneum, which maintains the homeostasis of the skin. Qinzhuliangxue mixture (QZLX) is a representative formula for the treatment of psoriasis, which was earliest recorded in the classic Chinese medicine book Xia's Surgery. In our previous clinical studies, QZLX demonstrated 83.33% efficacy with few side effects in the treatment of psoriasis. Furthermore, our published basic research has also proved that the QZLX mixture effectively inhibits the hyperproliferation of keratinocytes, thus exerting therapeutic effects on psoriasis. However, whether QZLX mixture can regulate keratinocytes apoptosis requires further clarification. OBJECTIVE OF THE STUDY: To investigate the mechanism of QZLX in the treatment of psoriasis from the perspective of keratinocyte apoptosis. MATERIALS AND METHODS: First, psoriasis-like mice with imiquimod (IMQ)-induced were given QZLX intragastric administration and Psoriasis Area Severity Index (PASI) scores were recored for 11 consecutive days to appraise the efficacy. Then, tissue samples were collected for transcriptome analysis. The DEseq2 method detected significantly differentially expressed genes (DEGs), Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway databases were used to analyze the functions and pathway enrichment of DEGs. After that, the therapeutic mechanisms of QZLX in intervening with psoriasis were explored using TUNEL, immunohistochemical staining, and western blotting. RESULTS: QZLX ameliorated the symptoms and pathological characteristics of IMQ-induced psoriasis in mice. The epidermal cell hyperplasia in the skin was inhibited, in accordance with the suppressed expression of PCNA and Ki67 after treatment. Transcriptome sequencing showed that melanoma differentiation associated gene-5 (MDA-5) was downregulated. GO and KEGG enrichment analysis of the signaling pathways indicated that the differentially expressed genes were significantly enriched in apoptosis pathways. Besides, QZLX treatment decreased the apoptosis of keratinocyte as shown by reduced TUNEL-positive cells. As MDA-5 protein levels decreased, so did the expression of the downstream protein Caspase-8, which indicates that the apoptotic pathway was triggered. Furthermore, QZLX therapy might also help to balance the apoptotic Bcl-2 family expression. CONCLUSION: QZLX restrains the apoptosis of keratinocyte in psoriasis-like mice by downregulating the MDA-5 pathway. The restoration of the balance between cell apoptosis and proliferation in the skin may lead to considerable psoriasis relief. Our study reveals the possible molecular processes behind the effects of QZLX therapy on the skin lesions of psoriasis, and lends support to its clinical efficacy.

Combination of Molecule-Targeted Therapy and Photodynamic Therapy Using Nanoformulated Verteporfin for Effective Uveal Melanoma Treatment.

Uveal melanoma (UM) is the most common primary ocular malignancy in adults and has high mortality. Recurrence, metastasis, and therapeutic resistance are frequently observed in UM, but no beneficial systemic therapy is available, presenting an urgent need for developing effective therapeutic drugs. Verteporfin (VP) is a photosensitizer and a Yes-Associated Protein (YAP) inhibitor that has been used in clinical practice. However, VP's lack of tumor targetability, poor biocompatibility, and relatively low treatment efficacy hamper its application in UM management. Herein, we developed a biocompatible CD44-targeting hyaluronic acid nanoparticle (HANP) carrying VP (HANP/VP) to improve UM treatment efficacy. We found that HANP/VP showed a stronger inhibitory effect on cell proliferation than that of free VP in UM cells. Systemic delivery of HANP/VP led to targeted accumulation in the UM-tumor-bearing mouse model. Notably, HANP/VP mediated photodynamic therapy (PDT) significantly inhibited UM tumor growth after laser irradiation compared with no treatment or free VP treatment. Consistently, in HANP/VP treated tumors after laser irradiation, the tumor proliferation and YAP expression level were decreased, while the apoptotic tumor cell and CD8+ immune cell levels were elevated, contributing to effective tumor growth inhibition. Overall, the results of this preclinical study showed that HANP/VP is an effective nanomedicine for tumor treatment through PDT and inhibition of YAP in the UM tumor mouse model. Combining phototherapy and molecular-targeted therapy offers a promising approach for aggressive UM management.

Melanin Inhibitory Effect of Tuber himalayense Isolated in Incheon, Korea.

There has been a growing interest in skin beauty and antimelanogenic products. Melanogenesis is the process of melanin synthesis whereby melanocytes are activated by UV light or hormone stimulation to produce melanin. Melanogenesis is mediated by several enzymes, such as tyrosinase (TYR), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1), and TRP-2. In this study, we investigated the effect of Tuber himalayense extract on melanin synthesis in α-melanocyte-stimulating hormone (α-MSH)-treated B16F10 melanoma cells. We confirmed that T. himalayense extract was not toxic to α-MSH-treated B16F10 melanoma cells and exhibited a significant inhibitory effect on melanin synthesis at concentrations of 25, 50, and 100 µg/ml. Additionally, the T. himalayense extract inhibited melanin, TRP-1, TRP-2, tyrosinase, and MITF, which are enzymes involved in melanin synthesis, in a concentration-dependent manner. Furthermore, T. himalayense extract inhibited the mitogen-activated protein kinase (MAPK) pathways, such as extracellular signal-regulated kinase-1/2 (ERK), c-Jun N-terminal kinase (JNK), and p38. Therefore, we hypothesized that various components of T. himalayense extract affect multiple factors involved in melanogenesis in B16F10 cells. Our results indicate that T. himalayense extract could potentially be used as a new material for preparing whitening cosmetics.

Discovery of novel peptide-dehydroepiandrosterone hybrids inducing endoplasmic reticulum stress with effective in vitro and in vivo anti-melanoma activities.

Steroid hybrids have emerged as a type of advantageous compound as they could offer improved pharmacological and pharmaceutical properties. Here, we report a series of novel peptide-dehydroepiandrosterone hybrids, which would effectively induce endoplasmic reticulum stress (ERS) and lead to apoptosis with outstanding in vitro and in vivo anti-melanoma effects. The lead compound IId among various steroids conjugated with peptides and pyridines showed effective in vivo activity in B16 xenograft mice: in medium- and high-dose treatment groups (60 and 80 mg/kg), compound IId would significantly inhibit the growth of tumours by 98%-99% compared to the control group, with the highest survival rate as well. Further mechanism studies showed that compound IId would damage the endoplasmic reticulum and upregulate the ERS markers C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), which could further regulate caspase and Bcl-2 family proteins and lead to cell apoptosis. The compound IId was also proven to be effective in inhibiting B16 cell migration and invasion.

Primary Cutaneous Melanoma-Management in 2024.

Background: Maximizing survival for patients with primary cutaneous melanomas (melanomas) depends on an early diagnosis and appropriate management. Several new drugs have been shown to improve survival in high-risk melanoma patients. Despite well-documented guidelines, many patients do not receive optimal management, particularly when considering patient age. Objective: to provide an update on melanoma management from the time of the decision to biopsy a suspicious skin lesion. Methods: We reviewed melanoma-management research published between 2018 and 2023 and identified where such findings impact and update the management of confirmed melanomas. Pubmed, Google Scholar, Ovid and Cochrane Library were used as search tools. Results: We identified 81 publications since 2017 that have changed melanoma management; 11 in 2018, 12 in 2019, 10 in 2020, 12 in 2021, 17 in 2022 and 18 in 2023. Discussion: Delayed or inaccurate diagnosis is more likely to occur when a partial shave or punch biopsy is used to obtain the histopathology. Wherever feasible, a local excision with a narrow margin should be the biopsy method of choice for a suspected melanoma. The Breslow thickness of the melanoma remains the single most important predictor of outcome, followed by patient age and then ulceration. The BAUSSS biomarker, (Breslow thickness, Age, Ulceration, Subtype, Sex and Site) provides a more accurate method of determining mortality risk than older currently employed approaches, including sentinel lymph node biopsy. Patients with metastatic melanomas and/or nodal disease should be considered for adjuvant drug therapy (ADT). Further, high-risk melanoma patients are increasingly considered for ADT, even without disease spread. Invasive melanomas less than 1 mm thick are usually managed with a radial excision margin of 10 mms of normal skin. If the thickness is 1 to 2 mm, select a radial margin of 10 to 20 mm. When the Breslow thickness is over 2 mm, a 20 mm clinical margin is usually undertaken. In situ melanomas are usually managed with a 5 to 10 mm margin or Mohs margin control surgery. Such wide excisions around a given melanoma is the only surgery that can be regarded as therapeutic and required. Patients who have had one melanoma are at increased risk of another melanoma. Ideal ongoing management includes regular lifelong skin checks. Total body photography should be considered if the patient has many naevi, especially when atypical/dysplastic naevi are identified. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet light are important. Management also needs to include the consideration of vitamin D supplementary therapy.

YY1-induced lncRNA00511 promotes melanoma progression via the miR-150-5p/ADAM19 axis.

Increasing evidence indicates that long noncoding RNAs (lncRNAs) are therapeutic targets and key regulators of tumors development and progression, including melanoma. Long intergenic non-protein-coding RNA 511 (LINC00511) has been demonstrated as an oncogenic molecule in breast, stomach, colorectal, and lung cancers. However, the precise role and functional mechanisms of LINC00511 in melanoma remain unknown. This study confirmed that LINC00511 was highly expressed in melanoma cells (A375 and SK-Mel-28 cells) and tissues, knockdown of LINC00511 could inhibit melanoma cell migration and invasion, as well as the growth of subcutaneous tumor xenografts in vivo. By using Chromatin immunoprecipitation (ChIP) assay, it was demonstrated that the transcription factor Yin Yang 1 (YY1) is capable of binding to the LINC00511 promoter and enhancing its expression in cis. Further mechanistic investigation showed that LINC00511 was mainly enriched in the cytoplasm of melanoma cells and interacted directly with microRNA-150-5p (miR-150-5p). Consistently, the knockdown of miR-150-5p could recover the effects of LINC00511 knockdown on melanoma cells. Furthermore, ADAM metallopeptidase domain expression 19 (ADAM19) was identified as a downstream target of miR-150-5p, and overexpression of ADAM19 could promote melanoma cell proliferation. Rescue assays indicated that LINC00511 acted as a competing endogenous RNA (ceRNA) to sponge miR-150-5p and increase the expression of ADAM19, thereby activating the PI3K/AKT pathway. In summary, we identified LINC00511 as an oncogenic lncRNA in melanoma and defined the LINC00511/miR-150-5p/ADAM19 axis, which might be considered a potential therapeutic target and novel molecular mechanism the treatment of patients with melanoma.

Quercetin Limits Tumor Immune Escape through PDK1/CD47 Axis in Melanoma.

Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.

Isoalantolactone exerts anti-melanoma effects via inhibiting PI3K/AKT/mTOR and STAT3 signaling in cell and mouse models.

BACKGROUND AND AIM: Although the anti-cancer activity of isoalantolactone (IATL) has been extensively studied, the anti-melanoma effects of IATL are still unknown. Here, we have investigated the anti-melanoma effects and mechanism of action of IATL. MTT and crystal violet staining assays were performed to detect the inhibitory effect of IATL on melanoma cell viability. Apoptosis and cell cycle arrest induced by IATL were examined using flow cytometry. The molecular mechanism of IATL was explored by Western blotting, confocal microscope analysis, molecular docking, and cellular thermal shift assay (CETSA). A B16F10 allograft mouse model was constructed to determine the anti-melanoma effects of IATL in vivo. The results showed that IATL exerted anti-melanoma effects in vitro and in vivo. IATL induced cytoprotective autophagy in melanoma cells by inhibiting the PI3K/AKT/mTOR signaling. Moreover, IATL inhibited STAT3 activation both in melanoma cells and allograft tumors not only by binding to the SH2 domain of STAT3 but also by suppressing the activity of its upstream kinase Src. These findings demonstrate that IATL exerts anti-melanoma effects via inhibiting the STAT3 and PI3K/AKT/mTOR signaling pathways, and provides a pharmacological basis for developing IATL as a novel phytotherapeutic agent for treating melanoma clinically.

Evaluating the Mechanism of Cell Death in Melanoma Induced by the Cannabis Extract PHEC-66.

Research suggests the potential of using cannabinoid-derived compounds to function as anticancer agents against melanoma cells. Our recent study highlighted the remarkable in vitro anticancer effects of PHEC-66, an extract from Cannabis sativa, on the MM418-C1, MM329, and MM96L melanoma cell lines. However, the complete molecular mechanism behind this action remains to be elucidated. This study aims to unravel how PHEC-66 brings about its antiproliferative impact on these cell lines, utilising diverse techniques such as real-time polymerase chain reaction (qPCR), assays to assess the inhibition of CB1 and CB2 receptors, measurement of reactive oxygen species (ROS), apoptosis assays, and fluorescence-activated cell sorting (FACS) for apoptosis and cell cycle analysis. The outcomes obtained from this study suggest that PHEC-66 triggers apoptosis in these melanoma cell lines by increasing the expression of pro-apoptotic markers (BAX mRNA) while concurrently reducing the expression of anti-apoptotic markers (Bcl-2 mRNA). Additionally, PHEC-66 induces DNA fragmentation, halting cell progression at the G1 cell cycle checkpoint and substantially elevating intracellular ROS levels. These findings imply that PHEC-66 might have potential as an adjuvant therapy in the treatment of malignant melanoma. However, it is essential to conduct further preclinical investigations to delve deeper into its potential and efficacy.

The secretome from human-derived mesenchymal stem cells augments the activity of antitumor plant extracts in vitro.

Cancer is understood as a multifactorial disease that involve multiple cell types and phenotypes in the tumor microenvironment (TME). The components of the TME can interact directly or via soluble factors (cytokines, chemokines, growth factors, extracellular vesicles, etc.). Among the cells composing the TME, mesenchymal stem cells (MSCs) appear as a population with debated properties since it has been seen that they can both promote or attenuate tumor progression. For various authors, the main mechanism of interaction of MSCs is through their secretome, the set of molecules secreted into the extracellular milieu, recruiting, and influencing the behavior of other cells in inflammatory environments where they normally reside, such as wounds and tumors. Natural products have been studied as possible cancer treatments, appealing to synergisms between the molecules in their composition; thus, extracts obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been produced and studied previously on different models, showing promising results. The effect of plant extracts on the MSC secretome has been poorly studied, especially in the context of the TME. Here, we studied the effect of Anamu-SC and P2Et extracts in the human adipose-derived MSC (hAMSC)-tumor cell interaction as a TME model. We also investigated the influence of the hAMSC secretome, in combination with these natural products, on tumor cell hallmarks such as viability, clonogenicity, and migration. In addition, hAMSC gene expression and protein synthesis were evaluated for some key factors in tumor progression in the presence of the extracts by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Multiplex, respectively. It was found that the presence of the hAMSC secretome did not affect the cytotoxic or clonogenicity-reducing activities of the natural extracts on cancer cells, and even this secretome can inhibit the migration of these tumor cells, in addition to the fact that the profile of molecules can be modified by natural products. Overall, our findings demonstrate that hAMSC secretome participation in TME interactions can favor the antitumor activities of natural products.

Biosynthesis and biocompatibility evaluation of zinc oxide nanoparticles prepared using Priestia megaterium bacteria.

The current study aimed to find an effective, simple, ecological, and nontoxic method for bacterial green synthesis of zinc oxide nanoparticles (ZnONPs) using the bacterial strain Priestia megaterium BASMA 2022 (OP572246). The biosynthesis was confirmed by the change in color of the cell-free supernatant added to the zinc nitrate from yellow to pale brown. The Priestia megaterium zinc oxide nanoparticles (Pm/ZnONPs) were characterized using UV-Vis spectroscopy, high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), and zeta potential. The Pm/ZnONPs characterization showed that they have a size ranging between 5.77 and 13.9 nm with a semi-sphere shape that is coated with a protein-carbohydrate complex. An EDX analysis of the Pm/ZnONPs revealed the presence of the shield matrix, which was composed of carbon, nitrogen, oxygen, chlorine, potassium, sodium, aluminum, sulfur, and zinc. The results of the FTIR analysis showed that the reduction and stabilization of the zinc salt solution were caused by the presence of O-H alcohols and phenols, O=C=O stretching of carbon dioxide, N=C=S stretching of isothiocyanate, and N-H bending of amine functional groups. The produced ZnONPs had good stability with a charge of - 16.2 mV, as evidenced by zeta potential analysis. The MTT assay revealed IC50 values of 8.42% and 200%, respectively, for the human A375 skin melanoma and human bone marrow 2M-302 cell lines. These findings revealed that the obtained Pm/ZnONPs have the biocompatibility to be applied in the pharmaceutical and biomedical sectors.

A Digital Intervention to Improve Skin Self-Examination Among Survivors of Melanoma: Protocol for a Type-1 Hybrid Effectiveness-Implementation Randomized Trial.

BACKGROUND: Although melanoma survival rates have improved in recent years, survivors remain at risk of recurrence, second primary cancers, and keratinocyte carcinomas. The National Comprehensive Cancer Network recommends skin examinations by a physician every 3 to 12 months. Regular thorough skin self-examinations (SSEs) are recommended for survivors of melanoma to promote the detection of earlier-stage, thinner melanomas, which are associated with improved survival and lower treatment costs. Despite their importance, less than a quarter of survivors of melanoma engage in SSEs. OBJECTIVE: Previously, our team developed and evaluated a web-based, fully automated intervention called mySmartSkin (MSS) that successfully improved SSE among survivors of melanoma. Enhancements were proposed to improve engagement with and outcomes of MSS. The purpose of this paper is to describe the rationale and methodology for a type-1 hybrid effectiveness-implementation randomized trial evaluating the enhanced MSS versus control and exploring implementation outcomes and contextual factors. METHODS: This study will recruit from state cancer registries and social media 300 individuals diagnosed with cutaneous malignant melanoma between 3 months and 5 years after surgery who are currently cancer free. Participants will be randomly assigned to either enhanced MSS or a noninteractive educational web page. Surveys will be collected from both arms at baseline and at 3, 6, 12, and 18 months to assess measures of intervention engagement, barriers, self-efficacy, habit, and SSE. The primary outcome is thorough SSE. The secondary outcomes are the diagnosis of new or recurrent melanomas and sun protection practices. RESULTS: Multilevel modeling will be used to examine whether there are significant differences in survivor outcomes between MSS and the noninteractive web page over time. Mixed methods will evaluate reach, adoption, implementation (including costs), and potential for maintenance of MSS, as well as contextual factors relevant to those outcomes and future scale-up. CONCLUSIONS: This trial has the potential to improve outcomes in survivors of melanoma. If MSS is effective, the results could guide its implementation in oncology care and nonprofit organizations focused on skin cancers. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/52689.

Sesquiterpene Lactones and Flavonoid from the Leaves of Basin Big Sagebrush (Artemisia tridentata subsp. tridentata): Isolation, Characterization and Biological Activities.

This research is an exploratory study on the sesquiterpenes and flavonoid present in the leaves of Artemisia tridentata subsp. tridentata. The leaf foliage was extracted with 100% chloroform. Thin-layer chromatography (TLC) analysis of the crude extract showed four bands. Each band was purified by column chromatography followed by recrystallization. Three sesquiterpene lactones (SLs) were isolated-leucodin, matricarin and desacetylmatricarin. Of these, desacetylmatricarin was the major component. In addition, a highly bio-active flavonoid, quercetagetin 3,6,4'-trimethyl ether (QTE), was also isolated. This is the first report on the isolation of this component from the leaves of Artemisia tridentata subsp. tridentata. All the components were identified and isolated by TLC, high-performance liquid chromatography (HPLC) and mass spectrometry (MS) techniques. Likewise, the structure and stereochemistry of the purified components were characterized by extensive spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) studies. The antioxidant activities of crude extract were analyzed, and their radical-scavenging ability was determined by Ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The crude extract showed antioxidant activity of 18.99 ± 0.51 and 11.59 ± 0.38 µmol TEg-1 FW for FRAP and DPPH assay, respectively, whereas the activities of matricarin, leucodin, desacetylmatricarin and QTE were 13.22, 13.03, 14.90 and 15.02 µmol TEg-1 FW, respectively, for the FRAP assay. The antitumor properties were probed by submitting the four isolated compounds to the National Cancer Institute (NCI) for NCI-60 cancer cell line screening. Overall, the results of the one-dose assay for each SL were unremarkable. However, the flavonoid's one-dose mean graph demonstrated significant growth inhibition and lethality, which prompted an evaluation of this compound against the 60-cell panel at a five-dose assay. Tests from two separate dates indicate a lethality of approximately 75% and 98% at the log-4 concentration when tested against the melanoma cancer line SK-Mel 5. This warrants further testing and derivatization of the bioactive components from sagebrush as a potential source for anticancer properties.

Salvianolic Acid B Significantly Suppresses the Migration of Melanoma Cells via Direct Interaction with ß-Actin.

Melanoma is the most aggressive and difficult to treat of all skin cancers. Despite advances in the treatment of melanoma, the prognosis for melanoma patients remains poor, and the recurrence rate remains high. There is substantial evidence that Chinese herbals effectively prevent and treat melanoma. The bioactive ingredient Salvianolic acid B (SAB) found in Salvia miltiorrhiza, a well-known Chinese herbal with various biological functions, exhibits inhibitory activity against various cancers. A375 and mouse B16 cell lines were used to evaluate the main targets and mechanisms of SAB in inhibiting melanoma migration. Online bioinformatics analysis, Western blotting, immunofluorescence, molecular fishing, dot blot, and molecular docking assays were carried out to clarify the potential molecular mechanism. We found that SAB prevents the migration and invasion of melanoma cells by inhibiting the epithelial-mesenchymal transition (EMT) process of melanoma cells. As well as interacting directly with the N-terminal domain of ß-actin, SAB enhanced its compactness and stability, thereby inhibiting the migration of cells. Taken together, SAB could significantly suppress the migration of melanoma cells via direct binding with ß-actin, suggesting that SAB could be a helpful supplement that may enhance chemotherapeutic outcomes and benefit melanoma patients.

Evodiamine inhibits growth of vemurafenib drug-resistant melanoma via suppressing IRS4/PI3K/AKT signaling pathway.

Evodiamine, a novel alkaloid, was isolated from the fruit of tetradium. It exerts a diversity of pharmacological effects and has been used to treat gastropathy, hypertension, and eczema. Several studies reported that evodiamine has various biological effects, including anti-nociceptive, anti-bacterial, anti-obesity, and anti-cancer activities. However, there is no research regarding its effects on drug-resistant cancer. This study aimed to investigate the effect of evodiamine on human vemurafenib-resistant melanoma cells (A375/R cells) proliferation ability and its mechanism. Cell activity was assessed using the cell counting kit-8 (CCK-8) method. Flow cytometry assay was used to assess cell apoptosis and cell cycle. A xenograft model was used to analyze the inhibitory effects of evodiamine on tumor growth. Bioinformatics analyses, network pharmacology, and molecular docking were used to explore the potential mechanism of evodiamine in vemurafenib-resistant melanoma. RT-qPCR and Western blotting were performed to reveal the molecular mechanism. The alkaloid extract of the fruit of tetradium, evodiamine showed the strongest tumor inhibitory effect on vemurafenib-resistant melanoma cells compared to treatment with vemurafenib alone. Evodiamine inhibited vemurafenib-resistant melanoma cell growth, proliferation, and induced apoptosis, conforming to a dose-effect relationship and time-effect relationship. Results from network pharmacology and molecular docking suggested that evodiamine might interact with IRS4 to suppress growth of human vemurafenib-resistant melanoma cells. Interestingly, evodiamine suppressed IRS4 expression and then inhibited PI3K/AKT signaling pathway, and thus had the therapeutic action on vemurafenib-resistant melanoma.