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Clinical, Cosmetic and Investigational... 2024Melasma is a common challenge in the field of pigmentary skin disorders, exerting a significant emotional and psychosocial burden on patients. The persistent and... (Review)
Review
Melasma is a common challenge in the field of pigmentary skin disorders, exerting a significant emotional and psychosocial burden on patients. The persistent and recurring nature of melasma complicates its management in routine clinical practice. This comprehensive review outlines a stepwise, practical approach encompassing diagnostic, preventive and therapeutic strategies for the management of melasma. A thorough exploration of aggravating and exacerbating factors, including sun exposure, hormonal imbalances, photosensitizing medication and cosmetics, is essential for a holistic assessment of the disease. With an emphasis on consistent and effective photoprotection, initial topical treatment modalities target the melanin production and/or the transfer of melanosomes to keratinocytes. Topical tyrosine inhibitors emerge as the first choice for reducing and preventing hyperpigmentation, with compounds such as thiamidol or tranexamic acid (TXA) being preferred for their safety profile over hydroquinone (HQ), kojic acid and arbutin. Combination with chemical peels can further enhance the therapeutic efficacy, even in cases with resistant melasma. In more severe cases, laser- and light-based interventions may be considered, but with the caveat of the likelihood of recurrence within 3-6 months. Assisted TXA delivery, via either fractional non-ablative laser or microneedling techniques, can further improve clinical outcomes. In conclusion, an optimal melasma management strategy is a multimodal approach, which includes effective photoprotection and a mix of different topical treatments targeting melanin synthesis, the anti-inflammatory environment, senescence and vascularity. Complementary procedures, such as chemical peels, and laser, light-based or microneedling procedures, with or without TXA, can further expedite melanin clearance in more severely affected instances. Individual discussions with patients regarding treatment expectations, recurrence likelihood and potential side effects are paramount to a comprehensive and successful therapeutic journey.
PubMed: 38800358
DOI: 10.2147/CCID.S372456 -
Clinical, Cosmetic and Investigational... 2024The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many... (Review)
Review
The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many pathological processes, such as tumors and autoimmune diseases. Recent studies also demonstrated that the defective functions of ER may lead to pigmentary diseases. Vitiligo is a depigmenting ailment skin disorder whose pathogenesis is now found to be associated with ER. However, the detailed mechanism is still unclear. In this review, we try to link the association between ER with its inter- and intra-organellar interactions in vitiligo pathogenesis and focus on the function, mechanism, and clinical potential of ER with vitiligo. Expand ER is found in melanocytes of vitiligo and ER stress (ERS) might be a bridge between oxidative stress and innate and adaptive immunity. Meanwhile, the tight association between ER and mitochondria or melanosomes in organelles levels, as well as genes and cytokines, is the new paradigm in the pathogenesis of vitiligo. This undoubtedly adds a new aspect to the understanding of vitiligo, facilitating the design of targeted therapies for vitiligo.
PubMed: 38774812
DOI: 10.2147/CCID.S459070 -
Nature Communications May 2024Fossil feathers have transformed our understanding of integumentary evolution in vertebrates. The evolution of feathers is associated with novel skin ultrastructures,...
Fossil feathers have transformed our understanding of integumentary evolution in vertebrates. The evolution of feathers is associated with novel skin ultrastructures, but the fossil record of these changes is poor and thus the critical transition from scaled to feathered skin is poorly understood. Here we shed light on this issue using preserved skin in the non-avian feathered dinosaur Psittacosaurus. Skin in the non-feathered, scaled torso is three-dimensionally replicated in silica and preserves epidermal layers, corneocytes and melanosomes. The morphology of the preserved stratum corneum is consistent with an original composition rich in corneous beta proteins, rather than (alpha-) keratins as in the feathered skin of birds. The stratum corneum is relatively thin in the ventral torso compared to extant quadrupedal reptiles, reflecting a reduced demand for mechanical protection in an elevated bipedal stance. The distribution of the melanosomes in the fossil skin is consistent with melanin-based colouration in extant crocodilians. Collectively, the fossil evidence supports partitioning of skin development in Psittacosaurus: a reptile-type condition in non-feathered regions and an avian-like condition in feathered regions. Retention of reptile-type skin in non-feathered regions would have ensured essential skin functions during the early, experimental stages of feather evolution.
Topics: Animals; Feathers; Dinosaurs; Fossils; Biological Evolution; Skin; Reptiles; Melanosomes; Animal Scales; Epidermis; beta-Keratins
PubMed: 38773066
DOI: 10.1038/s41467-024-48400-3 -
Communications Biology May 2024Limited studies using animal models with a few natural mutations in melanophilin (Mlph) provided partial functions of Mlph in melanosome trafficking. To investigate...
Limited studies using animal models with a few natural mutations in melanophilin (Mlph) provided partial functions of Mlph in melanosome trafficking. To investigate cellular functions of Mlph, especially ZnF motif of Mlph, we analyzed all three Mlph knockout (KO) quail lines, one and two base pair (bp) deletions as models for total KO, and three bp deletion causing deletion of one Cysteine (C84del) in the ZnF motif. All quail lines had diluted feather pigmentation with impaired dendritogenesis and melanosome transport in melanocytes. In vitro studies revealed capability of binding of the ZnF motif to PIP3, and impairment of PI3P binding and mislocalization of MLPH proteins with ZnF motif mutations. The shortened melanocyte dendrites by the C84del mutation were rescued by introducing WT Mlph in vitro. These results revealed the diluted feather pigmentation by Mlph mutations resulted from congregation of melanosomes in the cell bodies with impairment of the dendritogenesis and the transport of melanosomes to the cell periphery.
Topics: Animals; Feathers; Melanocytes; Pigmentation; Melanosomes; Quail; Mutation; Adaptor Proteins, Signal Transducing
PubMed: 38760591
DOI: 10.1038/s42003-024-06284-5 -
The EMBO Journal May 2024Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode of intercellular communication by melanosomes, large EVs...
Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode of intercellular communication by melanosomes, large EVs secreted by melanocytes for melanin transport. Unlike small EVs, which are disintegrated within the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell as "second-hand" EVs. We show that melanoma-secreted melanosomes passaged through epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. This process leads to macrophage polarization into pro-tumor or pro-immune cell infiltration phenotypes. Melanosomes that are transferred through fibroblasts can carry AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in vivo. In melanoma patients, macrophages that are co-localized with AKT1 are correlated with disease aggressiveness, and immunotherapy non-responders are enriched in macrophages containing melanosome markers. Our findings suggest that interactions mediated by second-hand extracellular vesicles contribute to the formation of the metastatic niche, and that blocking the melanosome cues of macrophage diversification could be helpful in halting melanoma progression.
PubMed: 38719996
DOI: 10.1038/s44318-024-00103-7 -
Medicina 2024Melanotic schwannoma (MS) is a rare and infrequent subtype of schwannoma characterized by cytoplasmic deposits of melanosomes (melanin). Unlike the other schwannomas, it...
Melanotic schwannoma (MS) is a rare and infrequent subtype of schwannoma characterized by cytoplasmic deposits of melanosomes (melanin). Unlike the other schwannomas, it could have malignant transformation. Due to distinctive characteristics and atypical behavior from classic schwannomas subtypes, MS were renamed and reclassified as "melanocytic malignant neural sheath tumor" in the 5th ed. of the World Health Organization's classification of central nervous system tumors in 2021. We present two cases of MS that underwent complete surgical resection.
Topics: Adult; Female; Humans; Middle Aged; Mediastinal Neoplasms; Nerve Sheath Neoplasms; Neurilemmoma
PubMed: 38683517
DOI: No ID Found -
International Journal of Molecular... Apr 2024Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment,... (Review)
Review
Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been fully investigated and the molecular analysis has been performed. Moreover, the role of paracrine factors derived from epidermis has also been studied. However, the role of dermis has not been fully studied. Thus, in this review, dermis-derived factors including soluble and insoluble components were overviewed and discussed in normal and abnormal circumstances. Dermal factors play an important role in the regulation of melanogenesis in the normal and abnormal mammalian skin.
Topics: Melanins; Melanocytes; Humans; Animals; Skin; Dermis; Epidermis; Melanogenesis
PubMed: 38674144
DOI: 10.3390/ijms25084560 -
Scientific Reports Apr 2024The Eocene Geiseltal Konservat-Lagerstätte (Germany) is famous for reports of three dimensionally preserved soft tissues with sub-cellular detail. The proposed mode of...
The Eocene Geiseltal Konservat-Lagerstätte (Germany) is famous for reports of three dimensionally preserved soft tissues with sub-cellular detail. The proposed mode of preservation, direct replication in silica, is not known in other fossils and has not been verified using modern approaches. Here, we investigated the taphonomy of the Geiseltal anurans using diverse microbeam imaging and chemical analytical techniques. Our analyses confirm the preservation of soft tissues in all body regions but fail to yield evidence for silicified soft tissues. Instead, the anuran soft tissues are preserved as two layers that differ in microstructure and composition. Layer 1 comprises sulfur-rich carbonaceous microbodies interpreted as melanosomes. Layer 2 comprises the mid-dermal Eberth-Katschenko layer, preserved in calcium phosphate. In addition, patches of original aragonite crystals define the former position of the endolymphatic sac. The primary modes of soft tissue preservation are therefore sulfurization of melanosomes and phosphatization of more labile soft tissues, i.e., skin. This is consistent with the taphonomy of vertebrates in many other Konservat-Lagerstätten. These findings emphasize an emerging model for pervasive preservation of vertebrate soft tissues via melanosome films, particularly in stagnation-type deposits, with phosphatization of more labile tissues where tissue biochemistry is favorable.
Topics: Fossils; Animals; Anura; Germany; Melanosomes
PubMed: 38654038
DOI: 10.1038/s41598-024-55822-y -
Investigative Ophthalmology & Visual... Apr 2024To undertake the first ultrastructural characterization of human retinal pigment epithelial (RPE) differentiation from fetal development to adolescence.
PURPOSE
To undertake the first ultrastructural characterization of human retinal pigment epithelial (RPE) differentiation from fetal development to adolescence.
METHODS
Ten fetal eyes and three eyes aged six, nine, and 17 years were examined in the temporal retina adjacent to the optic nerve head by transmission electron microscopy. The area, number, and distribution of RPE organelles were quantified and interpreted within the context of adjacent photoreceptors, Bruch's membrane, and choriocapillaris maturation.
RESULTS
Between eight to 12 weeks' gestation (WG), pseudostratified columnar epithelia with apical tight junctions differentiate to a simple cuboidal epithelium with random distribution of melanosomes and mitochondria. Between 12 to 26 WG, cells enlarge and show long apical microvilli and apicolateral junctional complexes. Coinciding with eye opening at 26 WG, melanosomes migrate apically whereas mitochondria distribute to perinuclear regions, with the first appearance of phagosomes, complex granules, and basolateral extracellular space (BES) formation. Significantly, autophagy and heterophagy, as evidenced by organelle recycling, and the gold standard of ultrastructural evidence for autophagy of double-membrane autophagosomes and mitophagosomes were evident from 32 WG, followed by basal infoldings of RPE cell membrane at 36 WG. Lipofuscin formation and deposition into the BES evident at six years increased at 17 years.
CONCLUSIONS
We provide compelling ultrastructural evidence that heterophagy and autophagy begins in the third trimester of human fetal development and that deposition of cellular byproducts into the extracellular space of RPE takes place via exocytosis. Transplanted RPE cells must also demonstrate the capacity to subserve autophagic and heterophagic functions for effective disease mitigation.
Topics: Humans; Retinal Pigment Epithelium; Adolescent; Autophagy; Microscopy, Electron, Transmission; Child; Lipofuscin; Exocytosis; Extracellular Space; Gestational Age; Female; Male; Fetal Development; Mitochondria; Cell Differentiation
PubMed: 38648041
DOI: 10.1167/iovs.65.4.32 -
PNAS Nexus Apr 2024Colors are well studied in bird plumage but not in other integumentary structures. In particular, iridescent colors from structures other than plumage are undescribed in...
Colors are well studied in bird plumage but not in other integumentary structures. In particular, iridescent colors from structures other than plumage are undescribed in birds. Here, we show that a multilayer of keratin and lipids is sufficient to produce the iridescent bill of . Furthermore, that the male bill is presented to the female under different angles during display provides support for the hypothesis that iridescence evolved in response to sexual selection. This is the first report of an iridescent bill, and only the second instance of iridescence in birds in which melanosomes are not involved. Furthermore, an investigation of museum specimens of an additional 98 species, showed that this evolved once, possibly twice. These results are promising, as they suggest that birds utilize a wider array of physical phenomena to produce coloration and should further stimulate research on nonplumage integumentary colors.
PubMed: 38638835
DOI: 10.1093/pnasnexus/pgae138