-
Pharmaceutics Jul 2023Photothermal therapy (PTT) and sonodynamic therapy (SDT) are becoming promising therapeutic modalities against various tumors in recent years. However, the single...
Photothermal therapy (PTT) and sonodynamic therapy (SDT) are becoming promising therapeutic modalities against various tumors in recent years. However, the single therapeutic modality with SDT or PTT makes it difficult to achieve a satisfactory anti-tumor outcome due to their own inherent limitations, such as poor tissue penetration for the near-infrared (NIR) laser and the limited cytotoxic reactive oxygen species (ROS) generated from conventional sonosensitizers irradiated by ultrasound (US). Here, we successfully biosynthesized melanin with a controllable particle size with genetically engineered bacteria harboring a heat-inducible gene circuit. The biosynthetic melanin with 8 nm size and chlorin e6 (Ce6) was further encapsulated into liposomes and obtained SDT/PTT dual-functional liposomes (designated as MC@Lip). The resulting MC@Lip had an approximately 100 nm particle size, with 74.71% ± 0.54% of encapsulation efficiency for melanin and 94.52% ± 0.78% for Ce6. MC@Lip exhibited efficient O production and photothermal conversion capability upon receiving irradiation by US and NIR laser, producing significantly enhanced anti-tumor efficacy in vitro and in vivo. Especially, US and NIR laser irradiation of tumors received with MC@Lip lead to complete tumor regression in all tested tumor-bearing mice, indicating the great advantage of the combined use of SDT and PTT. More importantly, MC@Lip possessed good photoacoustic (PA) and fluorescence dual-modal imaging performance, making it possible to treat tumors under imaging guidance. Our study provides a novel approach to synthesize a melanin nanoparticle with controllable size and develops a promising combined SDT/PTT strategy to treat tumors.
PubMed: 37631273
DOI: 10.3390/pharmaceutics15082058 -
Frontiers in Immunology 2023Melanin, a ubiquitous dark pigment, plays important roles in the immune system, including scavenging reactive oxygen species formed in response to ultraviolet radiation...
Melanin, a ubiquitous dark pigment, plays important roles in the immune system, including scavenging reactive oxygen species formed in response to ultraviolet radiation absorption, absorbing metals, thermal regulation, drug uptake, innate immune system functions, redox, and energy transduction. Many tissue types, including brain, heart, arteries, ovaries, and others, contain melanin. Almost all cells contain precursors to melanin. A growing number of diseases in which there is a loss of melanin and/or neuromelanin are increasingly thought to have infectious etiologies, for example, Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body Dementia (LBD), and vitiligo. AD, PD, LBD, and vitiligo have been linked with herpesvirus, which enters melanosomes and causes apoptosis, and with gut dysbiosis and inflammation. Herpesvirus is also linked with gut dysbiosis and inflammation. We theorize that under normal healthy states, melanin retains some of the energy it absorbs from electromagnetic radiation, which is then used to fuel cells, and energy from ATP is used to compliment that energy supply. We further theorize that loss of melanin reduces the energy supply of cells, which in the case of AD, PD, and LBD results in an inability to sustain immune system defenses and remove the plaques associated with the disease, which appear to be part of the immune system's attempt to eradicate the pathogens seen in these neurodegenerative diseases. In addition, in an attempt to explain why removing these plaques does not result in improvements in cognition and mood and why cognitions and moods in these individuals have ebbs and flows, we postulate that it is not the plaques that cause the cognitive symptoms but, rather, inflammation in the brain resulting from the immune system's response to pathogens. Our theory that energy retained in melanin fuels cells in an inverse relationship with ATP is supported by studies showing alterations in ATP production in relationship to melanin levels in melanomas, vitiligo, and healthy cells. Therefore, alteration of melanin levels may be at the core of many diseases. We propose regulating melanin levels may offer new avenues for treatment development.
Topics: Humans; Lewy Body Disease; Alzheimer Disease; Parkinson Disease; Vitiligo; Dysbiosis; Melanins; Ultraviolet Rays; Inflammation; Adenosine Triphosphate
PubMed: 37841274
DOI: 10.3389/fimmu.2023.1228530 -
Inflammation Apr 2024Vitiligo is a skin disease characterized by selective loss of melanocytes, which seriously affects the appearance and causes great psychological stress to patients. In...
Vitiligo is a skin disease characterized by selective loss of melanocytes, which seriously affects the appearance and causes great psychological stress to patients. In this study, we performed a comprehensive analysis of two vitiligo microarray datasets from the GEO database using bioinformatics tools to identify 297 up-regulated mRNAs and 186 down-regulated mRNAs, revealing important roles for pathways related to melanin synthesis, tyrosine metabolism, and inflammatory factors, such as "PPAR signaling pathway", "tyrosine metabolism", "nonalcoholic fatty liver disease (NAFLD) pathway", "melanogenesis", and "IL-17 signaling pathway". Combining the Search Tool for Interacting Chemicals (STITCH) database 5.0 and the drug-gene interaction database 3.0 (DGIdb), we identified that the PPAR-γ agonist rosiglitazone may promote melanin synthesis via EDNRB. Next, we investigated the mechanism of rosiglitazone and PPAR-γ pathway in promoting melanin production. Consistent with the results of bioinformatics analysis, the expression levels of PPAR-γ, EDNRB, and TYR were significantly reduced in human non-segmental vitiligo skin along with the reduction of MITF, a key gene for epidermal melanogenesis. Meanwhile, rosiglitazone increased melanin synthesis capacity in melanocytes and zebrafish by activating PPAR-γ and upregulating TYR, TYRP-1, and TYRP-2. Conversely, treatment of melanocytes with the PPAR-γ antagonist GW resulted in inhibition of melanin synthesis and expression of melanin-related factors. At the same time, simultaneous treatment of rosiglitazone with GW reversed the inhibitory effect of GW on melanin synthesis. In this study, we identified that rosiglitazone, an important insulin sensitizer, promotes melanin synthesis in melanocytes by increasing PPAR-γ activity and upregulating the expression levels of EDNRB and TYR. These findings may provide new ideas for exploring the pathogenesis and potential therapeutic targets of non-segmental vitiligo.
Topics: Vitiligo; Humans; PPAR gamma; Rosiglitazone; Melanocytes; Animals; Melanins; Zebrafish; Receptor, Endothelin B; Computational Biology; Signal Transduction
PubMed: 38159176
DOI: 10.1007/s10753-023-01937-9 -
Journal of Ornithology 2024Although the evolutionary ecology of melanin pigments and melanin-based coloration has been studied in great details, particularly in birds, little is known about the...
Although the evolutionary ecology of melanin pigments and melanin-based coloration has been studied in great details, particularly in birds, little is known about the function of melanin stored inside the body. In the barn owl , in which individuals vary in the degree of reddish pheomelanin-based coloration and in the size of black eumelanic feather spots, we measured the concentration in melanin pigments in seven organs. The eyes had by far the most melanin then the skin, pectoral muscle, heart, liver, trachea, and uropygial gland. The concentration in eumelanin was not necessarily correlated with the concentration in pheomelanin suggesting that their production can be regulated independently from each other. Redder barn owls had more pheomelanin in the skin and uropygial gland than white owls, while owls displaying larger black feather spots had more eumelanin in the skin than small-spotted owls. More data are required to evaluate whether melanin-based traits can evolve as an indirect response to selection exerted on melanin deposition in organs.
PubMed: 38496038
DOI: 10.1007/s10336-023-02137-w -
Dermatology Practical & Conceptual Oct 2023Individuals with melanin-rich skin account for the majority of the world's population. However, literature data regarding dermatoscopic characteristics of skin cancer in... (Review)
Review
INTRODUCTION
Individuals with melanin-rich skin account for the majority of the world's population. However, literature data regarding dermatoscopic characteristics of skin cancer in skin of color (SoC) are scarce. The dermatoscopic characteristics of cutaneous tumors might differ among skin types due to heterogeneity in composition and pigmentation.
OBJECTIVES
To summarize literature data on the dermatoscopic findings of skin neoplasms, according to the skin color and race.
METHODS
The literature search was performed using PubMed database up to December 30, 2022 and was conducted with the use of terms referring to dermatoscopy, race (Caucasians, Hispanics, Asians, and Black/African) and skin cancer types (BCC, SCC, keratoacanthoma, Bowen's disease and melanoma).
RESULTS
In total, 30 race-specific records were included. 9 SoC records for BCCs (2 BCC studies in Hispanics, 1 BCC study in Black individuals and 6 BCC studies in Asians ), 9 SoC records for SCCs ( 1 SCC study in Hispanics, 1 SCC study in Black individuals and 7 SCCs in Asian population) and 8 SoC records for melanoma (2 melanoma studies in Hispanics, 1 melanoma study in Blacks and 5 melanoma studies in Asians) were compared with 4 records that involved only Caucasian population, according to their participant section as well as with studies on dermatoscopy characteristics without focusing on race origins and phototype of the patient. In Hispanics and in both fair and dark-skinned Asians, BCCs were more often pigmented or at least with pigmented structures on dermoscopy. Squamous cell carcinoma (SCC) and keratoacanthoma were the least studied in SoC patients. Bowen's disease in SoC patients can be pigmented in a higher frequency compared to Caucasians, with glomerular vessels and a squamous surface being the most common dermatoscopic findings. The most frequent pattern of melanomas in SoC individuals were the parallel ridge pattern in palmoplantar region.
CONCLUSION
Based on a review of studies including Caucasians, Hispanics, Asians and Blacks /Africans, SoC patients present with more frequent and unique dermatoscopy features of skin cancers.
PubMed: 37874992
DOI: 10.5826/dpc.1304S1a311S -
International Journal of Molecular... Mar 2024Melanins are complex, polymeric pigments with interesting properties like UV-light absorbance ability, metal ion chelation capacity, antimicrobial action, redox... (Review)
Review
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 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 strains before its application in different fields.
Topics: Animals; Melanins; Actinomycetales; Streptomyces; Chemical Phenomena; Biotechnology
PubMed: 38474259
DOI: 10.3390/ijms25053013 -
Pharmaceuticals (Basel, Switzerland) Apr 2024Melanins are biopolymeric pigments formed by a multi-step oxidation process of tyrosine in highly specialized cells called melanocytes. Melanin pigments are mainly found... (Review)
Review
Melanins are biopolymeric pigments formed by a multi-step oxidation process of tyrosine in highly specialized cells called melanocytes. Melanin pigments are mainly found in the skin, iris, hair follicles, and inner ear. The photoprotective properties of melanin biopolymers have been linked to their perinuclear localization to protect DNA, but their ability to scavenge metal ions and antioxidant properties has also been noted. Interactions between drugs and melanins are of clinical relevance. The formation of drug-melanin complexes can affect both the efficacy of pharmacotherapy and the occurrence of adverse effects such as phototoxic reactions and discoloration. Because the amount and type of melanin synthesized in the body is subject to multifactorial regulation-determined by both internal factors such as genetic predisposition, inflammation, and hormonal balance and external factors such as contact with allergens or exposure to UV radiation-different effects on the melanogenesis process can be observed. These factors can directly influence skin pigmentation disorders, resulting in hypopigmentation or hyperpigmentation of a genetic or acquired nature. In this review, we will present information on melanocyte biology, melanogenesis, and the multifactorial influence of melanin on pharmacological parameters during pharmacotherapy. In addition, the types of skin color disorders, with special emphasis on the process of their development, symptoms, and methods of treatment, are presented in this article.
PubMed: 38675481
DOI: 10.3390/ph17040521 -
Frontiers in Neuroendocrinology Jul 2023Hypothalamic melanin-concentrating hormone (MCH) neurons participate in many fundamental neuroendocrine processes. While some of their effects can be attributed to MCH... (Review)
Review
Hypothalamic melanin-concentrating hormone (MCH) neurons participate in many fundamental neuroendocrine processes. While some of their effects can be attributed to MCH itself, others appear to depend on co-released neurotransmitters. Historically, the subject of fast neurotransmitter co-release from MCH neurons has been contentious, with data to support MCH neurons releasing GABA, glutamate, both, and neither. Rather than assuming a position in that debate, this review considers the evidence for all sides and presents an alternative explanation: neurochemical identity, including classical neurotransmitter content, is subject to change. With an emphasis on the variability of experimental details, we posit that MCH neurons may release GABA and/or glutamate at different points according to environmental and contextual factors. Through the lens of the MCH system, we offer evidence that the field of neuroendocrinology would benefit from a more nuanced and dynamic interpretation of neurotransmitter identity.
Topics: Hypothalamic Hormones; Pituitary Hormones; Neurons; Melanins; Hypothalamus; Glutamic Acid; Neurotransmitter Agents; gamma-Aminobutyric Acid
PubMed: 37149229
DOI: 10.1016/j.yfrne.2023.101069 -
Frontiers in Fungal Biology 2024Fungal melanin is an underexplored natural biomaterial of great biotechnological interest in different areas. This study investigated the physical, chemical,...
INTRODUCION
Fungal melanin is an underexplored natural biomaterial of great biotechnological interest in different areas. This study investigated the physical, chemical, electrochemical, and metal-binding properties of melanin extracted from the metallotolerant black fungus strain IRTA-M2-F10.
MATERIALS AND METHODS
Specific inhibitory studies with tricyclazole and biochemical profiling of whole cells by synchrotron radiation-based Fourier-transform infrared spectral microscopy (SR-FTIRM) were performed. An optimized extraction protocol was implemented, and purified fungal melanin was characterized using an array of spectrophotometric techniques (UV-Vis, FTIR, and EPR) and by cyclic voltammetry (CV) experiments. The metal-binding capacity of melanin extracts was also assessed by using Cr(VI) as a model heavy metal.
RESULTS
Inhibitory studies indicated that 1,8-dihydroxynaphthalene may be the main precursor molecule of melanin (DHN-melanin). The biochemical characterization of fungal melanin extracts were benchmarked against those from two melanins comprising the precursor molecule L-3,4-dihydroxiphenylalanine (DOPA-melanin): extracts from the ink of the cephalopod and DOPA-melanin synthesized in the laboratory. The CV results of melanin extracts incubated with and without cell suspensions of the electroconductive bacterium were indicative of novel semiquinone/hydroquinone redox transformations specific for each melanin type. These interactions may play an important role in cation exchange for the adsorption of metals and in microbial interspecies electron transfer processes.
DISCUSSION
The obtained results provided further evidence for the DHN-nature of melanin. The FTIR profiling of melanin extracts exposed to Cr(VI), compared to unexposed melanin, resulted in useful information on the distinct surface-binding properties of fungal melanin. The parameters of the Langmuir and Freundlicht isotherms for the adsorption of Cr(VI) were determined and compared to bibliographic data. Altogether, the inherent properties of fungal melanin suggest its promising potential as a biomaterial for environmental applications.
PubMed: 38812984
DOI: 10.3389/ffunb.2024.1390724 -
Brain : a Journal of Neurology Apr 2024Degeneration of the noradrenergic system is now considered a pathological hallmark of Parkinson's disease, but little is known about its consequences in terms of...
Degeneration of the noradrenergic system is now considered a pathological hallmark of Parkinson's disease, but little is known about its consequences in terms of parkinsonian manifestations. Here, we evaluated two aspects of the noradrenergic system using multimodal in vivo imaging in patients with Parkinson's disease and healthy controls: the pigmented cell bodies of the locus coeruleus with neuromelanin sensitive MRI; and the density of α2-adrenergic receptors (ARs) with PET using 11C-yohimbine. Thirty patients with Parkinson's disease and 30 age- and sex-matched healthy control subjects were included. The characteristics of the patients' symptoms were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Patients showed reduced neuromelanin signal intensity in the locus coeruleus compared with controls and diminished 11C-yohimbine binding in widespread cortical regions, including the motor cortex, as well as in the insula, thalamus and putamen. Clinically, locus coeruleus neuronal loss was correlated with motor (bradykinesia, motor fluctuations, tremor) and non-motor (fatigue, apathy, constipation) symptoms. A reduction of α2-AR availability in the thalamus was associated with tremor, while a reduction in the putamen, the insula and the superior temporal gyrus was associated with anxiety. These results highlight a multifaceted alteration of the noradrenergic system in Parkinson's disease since locus coeruleus and α2-AR degeneration were found to be partly uncoupled. These findings raise important issues about noradrenergic dysfunction that may encourage the search for new drugs targeting this system, including α2-ARs, for the treatment of Parkinson's disease.
Topics: Humans; Parkinson Disease; Tremor; Carbon Radioisotopes; Positron-Emission Tomography; Norepinephrine; Locus Coeruleus; Magnetic Resonance Imaging; Melanins
PubMed: 37787503
DOI: 10.1093/brain/awad338