Melanin Production Research Articles

Abstract 1704: Interplay of MITF and NCOA3 in orchestrating oncogenic transcriptional network in uveal melanoma

Abstract Uveal melanoma (UM) originates from melanocytes residing in the uveal tract of an eye. Despite effective local control, 50% of patients develop metastatic disease responding poorly to chemotherapy, targeted therapy, and immunotherapy. The molecular basis of events leading to initiation of UM is related to mutations in G alpha proteins GNAQ or GNA11, rendering them constitutively active and activating downstream PKC, ERK and AKT pathways sustaining cell proliferation. In our previous work, we showed that NCOA3 regulates proliferation of UM cells in vitro and the growth of UM xenografts in vivo downstream of GNAQ or GNA11. The critical role of NCOA3 in UM is manifested by transcriptional regulation of proliferation-related genes that are massively suppressed by NCOA3 knockout or knockdown. Here, we interrogated transcription factors that NCOA3 interacts with in UM to execute oncogenic programs and identified Melanocyte inducing transcription factor (MITF) as its critical partner. Chromatin immunoprecipitation (ChIP) using an NCOA3 recognizing antibody followed by sequencing was performed to determine NCOA3 binding sites in the human genome. The known transcription binding motifs within NCOA3 peaks were discovered using HOMER algorithm. Co-immunoprecipitation was performed to examine direct NCOA3 and MITF interaction. ChIP sequencing for MITF was performed to determine co-localization of NCOA3 and MITF at chromatin. Proliferation of UM cells after inhibition of MITF by either siRNA mediated knockdown or MITF inhibitor ML329 was evaluated using MTT assay. Functional enrichment analysis of transcriptome was used to identify classes of genes regulated by MITF, with specific attention to the subset regulated by MITF partnered with NCOA3. NCOA3 chromatin peaks are highly enriched in MITF binding motifs, and 77% of the NCOA3 peaks co-localizes with the MITF peaks. NCOA3 co-immunoprecipitates with MITF. Among transcriptional programs regulated by MITF in UM are those related to melanocyte biology, differentiation, and melanin production, but also those related to melanoma growth, especially cell division, DNA replication, myc response, purine and pyrimidine metabolism, and mTOR signaling. Strong suppression of these transcriptional signatures by inhibition of MITF using siRNA-mediated knockdown or pharmacological inhibition correlates with dramatic loss of cell viability. Clinical data indicate that higher expression of MITF-positively regulated genes correlates with lower survival rates of UM patients. Importantly, the transcriptional programs regulated by MITF cooperating with NCOA3 were related to TGF beta signaling, cell adhesion, ECM interaction and actin cytoskeleton. Importance of MITF as an oncogene is manifested in uveal melanoma cell lines and clinical data. Oncogenic function of MITF is partially dependent on its interaction with a transcription co-activator NCOA3. Citation Format: Aleksandra Rusin, Maria E. Echartea, Sai P. Manikonda, Darlene G. Skapura, Christel M. Davis, Erik A. Ehli, Sandra L. Grimm, Cristian Coarfa, Salma Kaochar. Interplay of MITF and NCOA3 in orchestrating oncogenic transcriptional network in uveal melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1704.

Utilization of Inedible Parts of Aralia cordata with High-Content Chlorogenic Acid Cultivated in Tokyo

Aralia cordata is called “Udo” and is one of the famous herbaceous perennial plants found in Korea, China, and Japan. In Japan, aerial parts of A. cordata have been consumed. Furthermore, its rhizome and root are utilized as crude drugs known as “dokukatsu” and “wakyoukatsu”, respectively. A. cordata is cultivated as a vegetable in many places in Japan, and one of the production areas is Tokyo. A. cordata made in Tokyo is known as a high-quality “Udo” product (aerial part) using a unique cultivation method, known as “Udo muro”. “Udo muro” blocks light and maintains optimal temperature and humidity throughout the year, facilitating the soft cultivation of udo. However, the roots of A. cordata cultivated in Tokyo are all discarded. Thus, the utilization of the A. cordata root cultivated in Tokyo might lead to sustainability and income improvement for farmers. In this study, we investigated the effect of “Udo muro” with or without cultivation and drying temperature on chlorogenic acid (CA) contents in A. cordata root and compared it with A. cordata produced in other areas (“wakyoukatsu”) by a quantitative analysis of the CA content using high-performance liquid chromatography. The results indicate that the CA content of the roots of A. cordata grown in Tokyo was higher than those grown in other areas. Furthermore, the usefulness of A. cordata root was evaluated using inhibitory activity tests such as nitric oxide production and melanin production using Raw264.7 and B16F10 cell lines, respectively.

설견초와 병풀 추출물의 미백활성

This study attempted to assess the whitening activities of Salvia plebeia R. Br. and Centella asiatica extracts which were provided by MEIDEME CO., LTD., their safety was confirmed through cell viability testing. The whitening activities were evaluated by inhibition of melanin synthesis and reduction of whitening-related transcription factors and protein production. The results found that no statistically significant cytotoxicity was observed at 10㎍/㎖, 20㎍/㎖and 40㎍/㎖. In addition, melanin production decreased by 28.4% at Salvia plebeia R. BR and Centella asiatica extract(SCE) 40㎍/㎖. In transcription factors, tyrosinase, tyrosianse related protein(TRP-1) and dopachrome tautomerase(TRP-2) decreased by 17%, 21% and 22% respectively at SCE 40㎍/㎖, confirming statistical significance. Protein production also showed statistically significant results with decrease in tyrosinase, TRP-1 and TRP-2 by 87%, 40% and 27% each at SCE 40㎍/㎖. The above results confirm that SCE is effective in promoting whitening and would be available as a cosmetic ingredient for whitening cosmetics.

An ELISA-based method for Galleria mellonella apolipophorin-III quantification.

Mammalian models, such as murine, are used widely in pathophysiological studies because they have a high degree of similarity in body temperature, metabolism, and immune response with humans. However, non-vertebrate animal models have emerged as alternative models to study the host-pathogen interaction with minimal ethical concerns. Galleria mellonella is an alternative model that has proved useful in studying the interaction of the host with either bacteria or fungi, performing drug testing, and assessing the immunological response to different microorganisms. The G. mellonella immune response includes cellular and humoral components with structural and functional similarities to the immune effectors found in higher vertebrates, such as humans. An important humoral effector stimulated during infections is apolipophorin III (apoLp-III), an opsonin characterized by its lipid and carbohydrate-binding properties that participate in lipid transport, as well as immunomodulatory activity. Despite some parameters, such as the measurement of phenoloxidase activity, melanin production, hemocytes counting, and expression of antimicrobial peptides genes are already used to assess the G. mellonella immune response to pathogens with different virulence degrees, the apoLp-III quantification remains to be a parameter to assess the immune response in this invertebrate. Here, we propose an immunological tool based on an enzyme-linked immunosorbent assay that allows apoLp-III quantification in the hemolymph of larvae challenged with pathogenic agents. We tested the system with hemolymph coming from larvae infected with Escherichia coli, Candida albicans, Sporothrix schenckii, Sporothrix globosa, and Sporothrix brasiliensis. The results revealed significantly higher concentrations of apoLp-III when each microbial species was inoculated, in comparison with untouched larvae, or inoculated with phosphate-buffered saline. We also demonstrated that the apoLp-III levels correlated with the strains' virulence, which was already reported. To our knowledge, this is one of the first attempts to quantify apoLp-III, using a quick and easy-to-use serological technique.

New Aspects of the Medicinal Value of Cornsilk: A Review

Abstract: Cornsilk has been a natural remedy for centuries to treat various medical conditions. Recent research shows the anti-inflammatory activities of cornsilk extract, which can help relieve pain. Certain biopeptides are involved in the induction of anti-inflammatory action in the administration of cornsilk extract. The analgesic activity of cornsilk is due to the presence of tannins and polyphenolic constituents in Zea mays. Besides maysin, many other factors, such as steroids, flavonoids, volatile oils, and various phenolic compounds, make cornsilk extract a modern anti-inflammatory and analgesic drug with minor side effects. In diverse cultures and folk medicines, cornsilk is used for its diuretic properties, reduction in melanin production properties, and antioxidant, anti-inflammatory, and analgesic properties. Silver nanoparticles using a combined extract of cornsilk, parsley, and Arabic gum extract have been reported to reduce inflammation. These effects have been observed in vivo. This formulation has anti-microbial as well as antioxidant properties. This review article focuses on the newer aspects of the medicinal value of cornsilk.

Inhibitory Effect of 2-Aza-8-oxohypoxanthine on Tyrosinase Activity and Melanin Production

A fairy chemical, 2-aza-8-oxohypoxanthine, has exhibited broad effects on skin barrier function, leading to its launch as a cosmetic ingredient. A clinical trial on a lotion containing 0.1% 2-aza-8-oxohypoxanthine demonstrated the ability of this chemical to increase skin lightness based on the analysis of L* values. In the present study, to elucidate the mechanism underlying the increase in skin lightness, we aimed to investigate the effect of 2-aza-8-oxohypoxanthine on murine melanoma cell lines, focusing on its influence on tyrosinase activity and melanin production. Our findings revealed that the addition of 2-aza-8-oxohypoxanthine inhibited tyrosinase activity by 13% compared with the untreated control. Similarly, melanin production was suppressed by 36% compared with the control. These results strongly suggest that the inhibition of tyrosinase effectively suppressed melanin production. Thus, 2-aza-8-oxohypoxanthine acts by inhibiting tyrosinase and melanin production to promote skin lightening. This study provides novel insights into the skin-lightening mechanism of 2-aza-8-oxohypoxanthine, demonstrating its ability to inhibit melanin production through the suppression of pro-inflammatory factors, thereby highlighting its potential as an effective cosmetic ingredient for lightening skin tone.

Tyrosinase regulates the motility of human melanoma cell line A375 through its hydroxylase enzymatic activity

Melanoma, originating from melanocytes, is a highly aggressive tumor. Tyrosinase is involved in melanin production in melanocytes, and its overexpression is noted in malignant melanomas. However, the role of tyrosinase in melanomas remains unclear. Therefore, this study aimed to evaluate the potential functions of tyrosinase in the human melanoma cell line A375. The expression level of tyrosinase in A375 cells was undetectable. However, markedly increased expression level was observed in the mouse melanoma cell line B16F10 and the human melanoma cell line WM266-4. Subsequently, we investigated the effect of ectopic tyrosinase expression on A375 cell motility using wound-healing assay. The overexpression of tyrosinase resulted in enhanced cell migration in both stable and transient tyrosinase expression cells. The levels of filamentous actin were decreased in tyrosinase-expressing A375 cells, suggesting that tyrosinase regulates cell motility by modulating actin polymerization. Histidine residues in tyrosinase are important for its enzymatic activity for synthesizing melanin. Substitution of these histidine residues to alanine residues mitigated the promotion of tyrosinase-induced A375 cell metastasis. Furthermore, melanin treatment enhanced A375 cell metastasis and phosphorylation of Cofilin. Thus, our findings suggest that tyrosinase increases the migration of A375 cells by regulating actin polymerization through its enzymatic activity.

Anti-melanogenic effect of <i>Amaranthus tricolorextract</i> on UV radiation-exposed melanoma cells

Purpose: To determine the inhibitory effect of A. tricolor extract (ATE) on melanogenesis in UV radiation-exposed B16F10 cells. 
 Methods: Total phenolic and anthocyanin contents of ATE were examined by Folin-Ciocalteu and pH differential methods, respectively. The tyrosinase inhibitory effect of ATE was investigated using L-DOPA as a substrate and the suppressive effect of ATE on melanin production was determined in melanoma cells. Furthermore, the antioxidant activity was assessed by DPPH method and reactive oxygen species formation while protein expression levels were evaluated by western blot method. 
 Results: The total phenolic and anthocyanin contents were identified up to 35 mg/g extract and 0.85 mg/g extract, respectively. ATE was found to inhibit both mushroom and cellular tyrosinase at IC50 values of 242.2 ± 9.5 μg/mL and 202.9 ± 11.6 μg/mL, respectively. Moreover, ATE treatment reduced melanin production up to (30 ± 5) % and suppressed p38 MAPK phosphorylation at the concentration of 400 μg/mL. In addition, ATE significantly scavenged DPPH radical with EC50 value of 189.2 ± 8.9 μg/mL and abolished ROS formation in the cells. 
 Conclusion: These results indicate that A. tricolor extract has a potential protective effect against melanin production, suggesting its potential value in skin-lightening formulations.

Comparative Study of the Effects of Curcuminoids and Tetrahydrocurcuminoids on Melanogenesis: Role of the Methoxy Groups

Curcuminoids are naturally occurring yellow-colored compounds that, when hydrogenated to remove their conjugated double bond, become colorless and are referred to as tetrahydrocurcuminoids. Curcuminoids consist of pure curcumin (PC) in major amounts and demethoxycurcumin (DC) and bisdemethoxycurcumin (BDC) in minor amounts. Tetrahydrocurcuminoids similarly consist mainly of tetrahydrocurcumin (THC), along with minor amounts of tetrahydrodemethoxycurcumin (THDC) and tetrahydrobisdemethoxycurcumin (THBDC). Previous studies have shown the inhibitory effects of PC, DC, and BDC on melanin production, but there are contradictory findings about THC. In addition, there are currently no reports on the effects of THDC and THBDC on melanogenesis. Our previous report described that, in contrast to PC, which suppressed melanin production, THC stimulated melanin production in B16F10 and MNT-1 cells; this effect was ascribed to the loss of the conjugated heptadiene moiety of PC. However, whether this finding can be generalized to the two curcumin derivatives (DC and BDC), such that THDC and THBDC might also stimulate melanogenesis, has not been addressed. Herein, a comparative study of six curcumin derivatives (PC, DC, BDC, THC, THDC, and THBDC) was undertaken to identify their effects on melanogenesis with the goal of elucidating the structure–activity relationships (SARs) focused on assessing the two regions of the parent curcumins’ structure: (i) the hydrogenation of the two double bonds bridging the phenyl rings to the β-diketone moiety, and (ii) the effect of the ortho-methoxy substituent (-OCH3) on the two phenyl rings. To determine the direct effects of the six compounds, antioxidant activity and tyrosinase activity were assessed in cell-free systems before cellular experiments utilizing the B16F10 mouse melanoma cells, MNT-1 human melanoma cells, and primary cells. Evaluations were made on cytotoxicity, melanin concentration, and cellular tyrosinase activity. The results showed that BDC inhibited melanogenesis in B16F10 and MNT-1 cells. However, it was ineffective in primary human melanocytes, while THBDC continued to exhibit anti-melanogenic capacity in normal human melanocytes. Moreover, these findings provide a novel perspective into the role of the methoxy groups of PC on the biological effects of melanogenesis and also confirm that the removal of the conjugated double bonds abolishes the anti-melanogenic capacity of PC and DC only, but not BDC, as THBDC maintained anti-melanogenic activity that was greater than BDC. However, the outcome is contingent upon the specific kind of cell involved. To the best of our knowledge, this work presents novel findings indicating that the anti-melanogenic capacity of the colored BDC is not only intact but enhanced after its hydrogenation as observed in THBDC. The findings show potential for using colorless THBDC as a pharmacological candidate to diminish the increased pigmentation characteristic of skin hyperpigmentation disorders. Future pharmacological therapeutics that incorporate pure THBDC or THBDC-enriched extracts, which retain both a colorless appearance and potent anti-melanogenic activity, can be applied to compounds for anti-melanoma therapeutics where the demand for nontoxic novel molecules is desired for established efficacies.

Bioproduction and characterization of melanin pigment produced by the fungal strain Gliocephalotrichum sp. DSGB2

Introduction and Aim: The biosynthetic method of naturally occurring pigment melanin production has become a predominant technique in recent years owing to its cost-effectiveness, low chemical usage, and reduced purification procedure. This study aimed to investigate the significant production, characterization, and biological applications of fungal melanin pigment. Materials and Methods: Melanin production in Gliocephalotrichum sp. DSGB2 strain was carried out by submerged fermentation in tyrosine broth and further purified by acidification and precipitation methods. The purified melanin was characterized by analytical methods such as ultraviolet-visible absorbance, TLC, FTIR spectroscopy, and LC-MS. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging analysis was performed to evaluate antioxidant properties of melanin. Results: Pigment was confirmed as melanin based on tyrosinase enzyme assay, UV-visible spectroscopy absorbance, TLC, FTIR, and LC-MS analysis. The biosynthesis of melanin was optimized by varying the culture conditions, and the highest yield was obtained under pH 6 at 30ºC. The strain produced about 3.82 gL-1 of melanin in 5 days under optimum conditions and exhibited antioxidant activity. Conclusion: The study provides new ideas into the biosynthesis of water-soluble melanin by the fungal strain Gliocephalotrichum sp. DSGB2 has broad potential applications as an efficient biomaterial in the biopolymer, pharmaceutical sectors, cosmetic, and environmental.

Weakened tanning ability is an important mechanism for evolutionary skin lightening in East Asians

The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments. East Asians are ideal populations for studying skin color evolution because of the complex environment of East Asia. Here, we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase (PAH) in light-skinned Han Chinese individuals. The intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males (P < 0.05). In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for PAH. However, the derived T allele (the major allele in East Asians) of rs10778203 decreases the binding activity of transcription factors and enhancer activity. Meanwhile, the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish embryos. Furthermore, rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B (UVB) treatment. Collectively, PAH is a potential pigmentation gene that regulates skin tanning ability. Natural selection has enriched the adaptive allele, resulting in weakened tanning ability in East Asians, suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.

Post-inflammatory hyperpigmentation post-acne: possibilities of topical therapy

Post-inflammatory hyperpigmentation (PIH) is one of the most significant problems in patients with acne. The prevalence of PIH among patients with acne varies from 45 to 87%. Post-acne, including PIH, has an extremely negative impact on the quality of life and psychological well-being of patients, as it is often resistant to therapy and can persist for even several years. Successful acne treatment does not guarantee complete elimination of PIH and other post-acne symptoms. In the development of PIH, a key role is played by the mechanism associated with the production and distribution of melanin, which is activated by inflammation and the release of cytokines that promote an increase in the level of immunoreactive tyrosinase, which stimulates melanocytes, activation of melanogenesis and further transfer of melanosomes to surrounding keratinocytes. It is important for clinicians to recognize the psychosocial impact of PIH and manage inflammation, as well as proactively address residual PIH with appropriate treatment. Thus, prevention and correction of PIH should be one of the goals of acne treatment. Topical therapy for PIH in acne is considered the most acceptable and can be prescribed both as monotherapy and as part of combined methods. Tyrosinase is a target for topical anti-pigmentation agents, including hydroquinone, kojic acid, and resorcinyl thiazole derivatives. The latter includes isobutylamidothiazolyl resorcinol – thiamidol. The article provides a brief overview of data on the epidemiology of PIH, its pathogenesis, impact on the quality of life of patients and the perception of their image by people around them. Clinical experience with the use of anti-hyperpigmentation serum with thiamidol, licochalcone A and sodium hyaluronate is presented, which confirms the effectiveness, safety and feasibility of prescribing products with thiamidol for the treatment of PIH caused by acne.

Whole-genome resequencing identifies candidate genes and SNPs in genomic regions associated with shell color selection in the Pacific oyster, Crassostrea gigas

The various shell colors of bivalves not only result in a better visual perception but also show great commercial value as a highly potential breeding trait. Four shell color strains of Pacific oyster (Crassostrea gigas) characterized by black (SB), white (SW), gold (SG), and orange (SO) were bred purposefully for more than ten generations. In this study, whole-genome resequencing was performed on 20 oysters from each of the four strains, and a total of 14.67 million single nucleotide polymorphisms (SNPs) were obtained after stringent filtering, with an average sequencing depth of >10×. The population structure analysis provided support for the subdivision of all samples into four major genetic clusters corresponding to shell color phenotypes, indicating a high level of genomic differentiation driven by artificial selection. Then, a composite measure of fixation index (FST) and cross-population composite likelihood ratio (XP-CLR) allowed us to identify 336 to 414 candidate divergent regions (CDRs) in pairwise comparisons of different shell colors, with a total of 480 to 614 corresponding genes distributed. Of particular interest were tyrosinase (TYR) and perilipin2 (PLIN2) occurring with extremely high frequency, which participates in shell color determination by regulating melanin production and carotenoid metabolism, respectively. In addition, two genes, namely porphobilinogen deaminase (PBGD) and hephaestin (HEPH), may have a potential function in the accumulation of specific porphyrin in orange shells, while the kynurenine 3-monooxygenase (KMO) gene, known to be involved in ommochrome biosynthesis, may contribute to the darker coloration in black shells. Further, a total of 304 SNPs were extracted from the exons of candidate genes mentioned above, of which 25 loci had highly significant differences among populations (p-value ≤0.01). After Sanger sequencing in another population, 14 SNPs were successfully validated as specific loci closely linked to different shell colors of black, white, gold, and orange, respectively. All in all, the results of this study shed light on the molecular basis of pigmentation and facilitate the selective breeding of C. gigas with desired phenotypic color.

Effect of Sargassum polycystum on Expression of Tyrosinase and Production of Melanin

Introduction: Melanogenesis, the process responsible for producing melanin pigment, hinges on the activation of the amino acid L-tyrosine by the pivotal enzyme tyrosinase. In cases of hyperpigmentation induced by ultraviolet radiation, there's a surge in both tyrosinase enzyme levels and melanin production. Sargassum polycystum is currently under active investigation for its potential in this regard. This review aims to delve deeper into the properties of Sargassum polycystum and its impact on tyrosinase expression and melanin production. Literature Review: Sargassum polycystum, a brown seaweed commonly found in coastal regions with abundant coral reefs, harbors active compounds like flavonoids, fucoidan, fucoxanthin, and phloroglucinol. Fucoidan, an extract from brown seaweed, exhibits promising anti-inflammatory and antioxidant properties. Recent studies have revealed its ability to impede the melanogenesis process. Specifically, it was observed that fucoidan from brown seaweed extract could dampen α-MSH stimulation while enhancing the activation of the ERK-MAPK pathway, thereby acting as a negative regulator for melanogenesis. Fucoxanthin, another component, showcases antioxidant capabilities. Furthermore, phloroglucinol, found in Sargassum polycystum, exerts tyrosinase inhibitory effects by chelating copper within the enzyme. Flavonoids like catechin, hesperidin, kaempferol, and baicalein in Sargassum polycystum demonstrate inhibitory effects on melanogenesis activation pathways, including suppression of the Erk1/2 pathway, MiTF, and direct inhibition of tyrosinase. Consequently, this leads to reduced tyrosinase expression and melanin production, ultimately attenuating the melanogenesis process. Conclusion: Sargassum polycystum emerges as a promising candidate for combating hyperpigmentation induced by exposure to ultraviolet B radiation.

Streptomycetes as Microbial Cell Factories for the Biotechnological Production of Melanin.

Melanins are complex, polymeric pigments with interesting properties like UV-light absorbance ability, metal ion chelation capacity, antimicrobial action, redox behaviors, and scavenging properties. Based on these characteristics, melanins might be applied in different industrial fields like food packaging, environmental bioremediation, and bioelectronic fields. The actual melanin manufacturing process is not environmentally friendly as it is based on extraction and purification from cuttlefish. Synthetic melanin is available on the market, but it is more expensive than animal-sourced pigment and it requires long chemical procedures. The biotechnological production of microbial melanin, instead, might be a valid alternative. Streptomycetes synthesize melanins as pigments and as extracellular products. In this review, the melanin biotechnological production processes by different Streptomyces strains have been revised according to papers in the literature. The different fermentation strategies to increase melanin production such as the optimization of growth conditions and medium composition or the use of raw sources as growth substrates are here described. Diverse downstream purification processes are also reported as well as all the different analytical methods used to characterize the melanin produced by Streptomyces strains before its application in different fields.

A Cyclam Salt as an Antifungal Agent: Interference with Candida spp. and Cryptococcus neoformans Mechanisms of Virulence.

The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.

Skin Anti-Aging Potential through Whitening and Wrinkle Improvement Using Fermented Oil Derived from Hermetia illucens Larvae.

As the aging population increases, so has interest among emerging seniors in anti-aging ingredients that enhance functionality by incorporating fermentation with natural materials. In this study, fermentation conditions for enhancing the functionality of Hermetia illucens larvae oil (HIO) were established, and its anti-aging potential was evaluated. First, the lipase activity and amount of lipid degradation products of the fermentation strains were measured in order to select Lactobacillus gasseri and Lactiplantibacillus plantarum as the strains with high fermentation ability. A fermentation period of 28 d and a fermentation method that uses only the strain culture medium were established by evaluating the fermentation degree after fermenting HIO with the selected strains. The whitening functionality test results of fermented HIO (FHIO) showed an increase of approximately 20% in extracellular tyrosinase inhibition activity compared with HIO. Additionally, within melanocytes, there was a 12% increase in tyrosinase inhibition activity and a 26% enhancement in melanin production inhibition ability. For wrinkle-improving functionality, it was observed that, for fibroblasts, there was a 10% increase in collagen production, a 9% increase in collagenase inhibition ability, and an 8% increase in elastase inhibition ability. Therefore, FHIO was confirmed to be an effective cosmetic raw material, with high functionality for anti-aging within the senior generation. This is achieved through increased whitening and wrinkle-improving functionality.

Production and characterization of melanin pigment from black fungus Curvularia soli AS21 ON076460 assisted gamma rays for promising medical uses

Owing to the growing need for natural materials in different fields, studying melanin production from biological sources is imperative. In the current study, the extracellular melanin pigment was produced by the fungus Curvularia soli AS21 ON076460. The factors that affect the production of melanin were optimized by the Plackett-Burman design (P-BD). The effect of gamma irradiation on melanin productivity was investigated. The maximum melanin yield (3.376 mg/L) was elicited by a stimulus of gamma irradiation at 1.0 kGy. The results evoked that, Curvularia soli AS21 ON076460 melanin exhibited excellent antimicrobial activity against all tested bacteria and fungi. Klebsiella pneumoniae ATCC 13883 and P. digitatum were mostly affected by melanin registering the inhibition zone diameters of 37.51 ± 0.012 and 44.25 ± 0.214 mm, respectively. Moreover, Curvularia soli AS21 ON076460 melanin indicated a significant antiviral efficacy (77% inhibition) of Herpes simplex virus (HSV1). The melanin pigment showed antioxidant activities with IC50 of 42 ± 0.021 and 17 ± 0.02 µg/mL against DPPH and NO, respectively. Melanin had cytotoxic action against human breast cancer and skin cancer cell lines (Mcf7and A431) as well as exerting a low percentage of cell death against normal skin cell lines (Hfb4). Melanin was effective in wound management of human skin cells by 63.04 ± 1.83% compared with control (68.67 ± 1.10%). The novelty in the study is attributed to the possibility of using gamma rays as a safe method in small economic doses to stimulate melanin production from the fungi that have been isolated. In summary, melanin produced from fungi has significant biological activities that encourage its usage as a supportive medical route.

Genomic Insights into Moderately Thermophilic Methanotrophs of the Genus Methylocaldum.

Considering the increasing interest in understanding the biotic component of methane removal from our atmosphere, it becomes essential to study the physiological characteristics and genomic potential of methanotroph isolates, especially their traits allowing them to adapt to elevated growth temperatures. The genetic signatures of Methylocaldum species have been detected in many terrestrial and aquatic ecosystems. A small set of representatives of this genus has been isolated and maintained in culture. The genus is commonly described as moderately thermophilic, with the growth optimum reaching 50 °C for some strains. Here, we present a comparative analysis of genomes of three Methylocaldum strains-two terrestrial M. szegediense strains (O-12 and Norfolk) and one marine strain, Methylocaldum marinum (S8). The examination of the core genome inventory of this genus uncovers significant redundancy in primary metabolic pathways, including the machinery for methane oxidation (numerous copies of pmo genes) and methanol oxidation (duplications of mxaF, xoxF1-5 genes), three pathways for one-carbon (C1) assimilation, and two methods of carbon storage (glycogen and polyhydroxyalkanoates). We also investigate the genetics of melanin production pathways as a key feature of the genus.

Dendropanax morbifera Leveille Extract-Induced Alteration of Metabolic Profile in Whitening Effects

This study aimed to evaluate the potential of Dendropanax morbifera Leveille (D. morbifera) extract as a natural melanin depigmentation agent to achieve skin whitening. Treating α-MSH-stimulated B16-F10 cells with the extract effectively inhibited melanin production and tyrosinase activity. The cellular metabolic profiles were analyzed to understand the mechanisms underlying the whitening-related metabolic processes. We identified 29 metabolites that were significantly altered in the α-MSH-stimulated B16-F10 cells. The melanin-synthesis-related pathways that were downregulated included phenylalanine, tyrosine, and tryptophan biosynthesis and phenylalanine metabolism. Simultaneously, alanine, aspartate, and glutamate metabolism; arginine and proline metabolism; arginine biosynthesis; butanoate metabolism; glutathione metabolism; and glyoxylate and dicarboxylate metabolism were upregulated. We found that the optimal extract concentration of 0.2 mg/mL showed the highest efficacy in reversing the alterations to the metabolite levels and metabolic pathways. Moreover, D. morbifera extract exerted low cytotoxicity and high efficacy in inhibiting melanin production. Thus, D. morbifera extract is a potential melanin inhibitor with application in the development of whitening cosmetics.