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Microbiology Spectrum Jun 2024and are both known urease producers and have the potential to cause hyperammonemia. We hypothesized that the risk of hyperammonemia is increased by renal failure,...
and are both known urease producers and have the potential to cause hyperammonemia. We hypothesized that the risk of hyperammonemia is increased by renal failure, burden of cryptococcal infection, and fungal strain characteristics. We performed a retrospective review of plasma ammonia levels in patients with cryptococcal infections. Risk factors for hyperammonemia were statistically compared between patients with and without hyperammonemia (>53 µmol/L). Cryptococcal cells from three patients included in the study were recovered from our biorepository. Strain characteristics including urease activity, ammonia production, growth curves, microscopy, melanin production, and M13 molecular typing were analyzed and compared with a wild-type (WT) strain. We included 29 patients, of whom 37.9% had hyperammonemia, 59% had disseminated cryptococcal infection (DCI), and 41% had isolated central nervous system infection. Thirty-eight percent of patients had renal failure and 28% had liver disease. Renal failure was associated with 4.4 times (95% confidence interval [CI] 1.5, 13.0) higher risk of hyperammonemia. This risk was higher in DCIs (RR 6.2, 95% CI 1.0, 40.2) versus isolated cryptococcal meningitis (RR 2.5, 95% CI, 0.40, 16.0). Liver disease and cryptococcal titers were not associated with hyperammonemia. from one patient with extreme hyperammonemia demonstrated a 4- to 5-fold increase in extracellular urease activity, slow growth, enlarged cell size phenotypes, and diminished virulence factors. Hyperammonemia was strongly associated with renal failure in individuals with DCI, surpassing associations with liver failure or cryptococcal titers. However, profound hyperammonemia in one patient was attributable to high levels of urease secretion unique to that cryptococcal strain. Prospective studies are crucial to exploring the significance of this association.IMPORTANCE produces and secretes the urease enzyme to facilitate its colonization of the host. Urease breaks down urea into ammonia, overwhelming the liver's detoxification process and leading to hyperammonemia in some hosts. This underrecognized complication exacerbates organ dysfunction alongside the infection. Our study investigated this intricate relationship, uncovering a strong association between the development of hyperammonemia and renal failure in patients with cryptococcal infections, particularly those with disseminated infections. We also explore mechanisms underlying increased urease activity, specifically in strains associated with extreme hyperammonemia. Our discoveries provide a foundation for advancing research into cryptococcal metabolism and identifying therapeutic targets to enhance patient outcomes.
PubMed: 38842310
DOI: 10.1128/spectrum.03902-23 -
International Journal of Radiation... Jun 2024Acute radiation dermatitis (ARD) is the most common side effect reported by patients undergoing radiotherapy (RT). Currently, the assessment of the severity of the...
BACKGROUND
Acute radiation dermatitis (ARD) is the most common side effect reported by patients undergoing radiotherapy (RT). Currently, the assessment of the severity of the reaction is based on the visual assessment of the skin, which is a subjective method, depending on many factors.
PURPOSE
The main aim of this study was to investigate the usefulness of hyperspectral imaging (HSI) in the assessment of ARD and finding physiological factors that could be correlated with the ARD.
METHOD
In this clinical pilot trial, weekly acquisitions of hyperspectral camera images of irradiated skin were performed for 5 weeks of RT and at the post-treatment follow-up visit which took place 30-40 days after the last fraction of RT. At the same time, the severity of radiodermatitis was assessed based on the criteria of the National Cancer Institute Common Terminology for Adverse Events (NCI-CTCAE). The content and concentration of chromophores in irradiated skin were quantitatively determined using a hyperspectral camera RESULT: The use of hyperspectral imaging supported by image analysis and processing methods allowed for the determination of the content and distribution of hemoglobin and melanin in the irradiated skin. It was found that the hemoglobin concentration is correlated with the subjective assessment made according to NCI-CTCAE protocol.
CONCLUSIONS
HSI is a sensitive and specific method of analyzing the concentration of chromophores in the skin, including hemoglobin. A clear correlation was found between hemoglobin concentration and CTCAE v.5 scale thanks to which HSI can be considered as an objective method of skin assessment during RT.
PubMed: 38838992
DOI: 10.1016/j.ijrobp.2024.05.027 -
Poultry Science May 2024The earlobe is a featherless, exposed thickening located beneath the ear canal of chickens, which plays a visual signaling role in age, performance, mental vitality,...
The earlobe is a featherless, exposed thickening located beneath the ear canal of chickens, which plays a visual signaling role in age, performance, mental vitality, reproduction, and other aspects. However, despite its importance, there have been few studies on the color differences and formation mechanisms of chicken earlobes, particularly the structurally blue earlobes characteristic of the Jiangshan black-bone chicken. In this study, we explored the physiological mechanisms that may influence the formation of differently colored earlobes using 3 types of earlobes from Jiangshan black-bone chickens: light peacock green (Green group), dark peacock green (Blue group), and dark reddish purple (Black group). All 3 earlobe colors exhibited positive melanin Masson-Fontana staining, and the thickness of collagen fibers in the dermis decreased in the order of Green, Blue, and Black groups. A total of 1,953 differentially expressed genes (DEGs) were detected in the 3 earlobes through mRNA sequencing, among which the GO term "collagen trimer" was significantly enriched in DEGs between groups. Additionally, 716 differentially expressed proteins (DEPs) were identified in the 3 earlobes using 4D-DIA proteomics, with the term "collagen fibril organization" being significantly enriched in DEPs between the Green and Black groups. Integrated analysis of transcriptome and proteome data revealed that 12 DEGs and DEPs were commonly differentially expressed between the Green and Black groups, including the gene LUM (corneal keratan sulfate proteoglycan), which was significantly enriched in the "collagen fibril organization" GO term. In conclusion, our study suggests that LUM plays a crucial role in the formation of peacock green earlobes in Jiangshan black-bone chickens. The high level of LUM in peacock green (Green and Blue groups) may affect collagen nanostructures, leading to a stronger effect of melanin-supported dermal collagen on the production of non-iridescent structural colors through coherent scattering, resulting in a bright structural blue color in Jiangshan black-bone chickens. In contrast, the low expression of LUM in dark reddish purple (Black group) reduces the reflection of non-iridescent structural colors, making the earlobe color appear almost black, similar to melanin.
PubMed: 38838590
DOI: 10.1016/j.psj.2024.103864 -
PloS One 2024Pathological angiogenesis and vascular instability are observed in diabetic retinopathy (DR), diabetic macular edema (DME), and wet age-related macular degeneration... (Comparative Study)
Comparative Study
PURPOSE
Pathological angiogenesis and vascular instability are observed in diabetic retinopathy (DR), diabetic macular edema (DME), and wet age-related macular degeneration (wAMD). Many receptor tyrosine kinases (RTKs) including vascular endothelial growth factor receptors (VEGFRs) contribute to angiogenesis, whereas the RTK TIE2 is important for vascular stability. Pan-VEGFR tyrosine kinase inhibitors (TKIs) such as vorolanib, sunitinib, and axitinib are of therapeutic interest over current antibody treatments that target only one or two ligands. This study compared the anti-angiogenic potential of these TKIs.
METHODS
A kinase HotSpot™ assay was conducted to identify TKIs inhibiting RTKs associated with angiogenesis and vascular stability. Half-maximal inhibitory concentration (IC50) for VEGFRs and TIE2 was determined for each TKI. In vitro angiogenesis inhibition was investigated using a human umbilical vein endothelial cell sprouting assay, and in vivo angiogenesis was studied using the chorioallantoic membrane assay. Melanin binding was assessed using a melanin-binding assay. Computer modeling was conducted to understand the TIE2-axitinib complex as well as interactions between vorolanib and VEGFRs.
RESULTS
Vorolanib, sunitinib, and axitinib inhibited RTKs of interest in angiogenesis and exhibited pan-VEGFR inhibition. HotSpot™ assay and TIE2 IC50 values showed that only axitinib potently inhibited TIE2 (up to 89%). All three TKIs effectively inhibited angiogenesis in vitro. In vivo, TKIs were more effective at inhibiting VEGF-induced angiogenesis than the anti-VEGF antibody bevacizumab. Of the three TKIs, only sunitinib bound melanin. TKIs differ in their classification and binding to VEGFRs, which is important because type II inhibitors have greater selectivity than type I TKIs.
CONCLUSIONS
Vorolanib, sunitinib, and axitinib exhibited pan-VEGFR inhibition and inhibited RTKs associated with pathological angiogenesis. Of the three TKIs, only axitinib potently inhibited TIE2 which is an undesired trait as TIE2 is essential for vascular stability. The findings support the use of vorolanib for therapeutic inhibition of angiogenesis observed in DR, DME, and wAMD.
Topics: Axitinib; Humans; Sunitinib; Angiogenesis Inhibitors; Imidazoles; Pyrroles; Indoles; Human Umbilical Vein Endothelial Cells; Receptors, Vascular Endothelial Growth Factor; Indazoles; Animals; Protein Kinase Inhibitors; Receptor, TIE-2; Neovascularization, Pathologic
PubMed: 38833447
DOI: 10.1371/journal.pone.0304782 -
Cureus May 2024The most common aesthetic issue that affects people's smiles is gingival pigmentation, especially in those with high smile lines. This pigmented gingiva is thought to be...
The most common aesthetic issue that affects people's smiles is gingival pigmentation, especially in those with high smile lines. This pigmented gingiva is thought to be naturally occurring melanin pigments that add to the gingiva's endogenous pigmentation. The goal of plastic periodontal surgery known as "gingival depigmentation" is to lighten the dark gingiva by scraping off the gingival epithelium. Gingival depigmentation has been performed with a variety of techniques, including bur abrasion, scraping, partial thickness flap, cryotherapy, electrocautery, and laser. The present case comprised a split-mouth design in which depigmentation using an electrosurgical unit and soft tissue trimming bur was used for the maxillary sections, and evaluated the difference in pain felt by the patient and healing of the surgical site between the sites treated with the electrosurgical unit and bur abrasion method. A visual analog scale (VAS) was used to quantify pain felt by the patient on the seventh day, whereas healing was assessed on the seventh day and at a one-month interval visually. The results of this study showed that the electrocautery-treated site showed better results in terms of pain experienced by the patient and also with the surgical site healing.
PubMed: 38826928
DOI: 10.7759/cureus.59455 -
ACS Omega May 2024This report details some of our observations regarding the impact of cysteine on the air-mediated oxidation of catecholamines, particularly epinephrine. The intent was...
This report details some of our observations regarding the impact of cysteine on the air-mediated oxidation of catecholamines, particularly epinephrine. The intent was to synthesize light-colored, pheomelanin-like materials. Pheomelanin is commonly described as a material generated from a mixture of catecholamines and cysteine. However, we observed that (1) the presence of cysteine resulted in a concentration-dependent delay in the onset of color formation and (2) the presence of cysteine resulted in darker, more eumelanin-like materials. These effects were particularly impactful in the case of epinephrine. More elaborate studies involving other amino acids or scaled-up reactions were conducted with epinephrine as the precursor. These studies show that other amino acids, , methionine or serine, could lead to darker materials, but none were as impactful as cysteine. Although our results are in contrast to typical descriptions regarding the impact of cysteine on the synthesis of melanin, they may reflect crucial differences between the synthesis of pheomelanin.
PubMed: 38826551
DOI: 10.1021/acsomega.4c00889 -
Journal of Oleo Science 2024Hair is important to our appearance as well as to protect our heads. Human hair mainly consists of proteins (80-85%), melanin pigments (0-5%), water (10-13%), and lipids... (Review)
Review
Hair is important to our appearance as well as to protect our heads. Human hair mainly consists of proteins (80-85%), melanin pigments (0-5%), water (10-13%), and lipids (1-6%). The physicochemical properties of hair have been studied for over 100 years. However, they are not yet thoroughly understood. In this review, recent progress and the latest findings are summarized from the following three perspectives: structural characteristics, delivery and distribution of active ingredients, and hair as a template. The structural characteristics of hair have been mainly investigated by microscopic and/or spectroscopic techniques such as atomic force microscopy integrated with infrared spectroscopy (AFM-IR) and rheological measurements. The distribution of active ingredients has been generally evaluated through techniques such as nanoscale secondary ion mass spectrometry (NanoSIMS). And finally, attempts to explore the potential of hair to be used as a substrate for flexible device fabrication will be introduced.
Topics: Hair; Humans; Microscopy, Atomic Force; Melanins; Chemical Phenomena; Spectrometry, Mass, Secondary Ion; Rheology; Spectrophotometry, Infrared; Lipids; Water; Proteins
PubMed: 38825536
DOI: 10.5650/jos.ess23203 -
Bioorganic & Medicinal Chemistry Letters May 2024The tyrosinase (TYR) enzyme catalyses sequential reactions in the melanogenesis pathway: l-tyrosine is oxidised to yield L-3,4-dihydroxyphenylalanine (l-dopa), which in...
The tyrosinase (TYR) enzyme catalyses sequential reactions in the melanogenesis pathway: l-tyrosine is oxidised to yield L-3,4-dihydroxyphenylalanine (l-dopa), which in turn is converted to dopaquinone. These two reactions are the first two steps of melanin biosynthesis and are rate limiting. The accumulation or overproduction of melanin may cause skin hyperpigmentation and inhibitors of TYR are thus of interest to the cosmeceutical industry. Several TYR inhibitors are used to treat skin hyperpigmentation, however, some are ineffective and possess questionable safety profiles. This emphasises the need to develop novel TYR inhibitors with better safety and efficacy profiles. The small molecule, 3-hydroxycoumarin, has been reported to be a good potency TYR inhibitor (IC = 2.49 µM), and based on this, a series of eight structurally related 3-hydroxyquinolin-2(1H)-one derivatives were synthesised with the aim to discover novel TYR inhibitors. The results showed that four of the derivatives inhibited TYR from the champignon mushroom Agaricus bisporus (abTYR) with IC < 6.11 µM. The most potent inhibitor displayed an IC value of 2.52 μM. Under the same conditions, the reference inhibitors, thiamidol and kojic acid, inhibited abTYR with IC values of 0.130 and 26.4 μM, respectively. Based on the small molecular structures of the active 3-hydroxyquinolin-2(1H)-one inhibitors which are amenable to structure optimisation, it may be concluded that this class of compounds are good leads for the design of TYR inhibitors for cosmeceutical applications.
PubMed: 38823727
DOI: 10.1016/j.bmcl.2024.129823 -
The Journal of Poultry Science 2024Iris color is a prominent phenotypic feature of quail. To understand the mechanism of melanin deposition related to quail iris color, iris tissues were selected from...
Iris color is a prominent phenotypic feature of quail. To understand the mechanism of melanin deposition related to quail iris color, iris tissues were selected from Beijing white and Chinese yellow quail for transcriptome analysis. Differentially expressed genes (DEGs) associated with pigmentation were identified using RNA sequencing and validated by quantitative real-time polymerase chain reaction (RT-qPCR). The identified single nucleotide polymorphisms were studied using bioinformatics and iris color correlation analyses. A total of 485 DEGs were obtained, with 223 upregulated and 262 downregulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Thirty-two genes were annotated using the GO database. Three important pigment synthesis pathways (Notch signaling, melanogenesis, and tyrosine metabolism) were identified in quail iris tissue (). The expression levels of solute carrier family 45 member 2 (), tyrosinase-related protein 1, vitamin D receptor, opsin 5, and docking protein 5 were significantly different between Beijing white and Chinese yellow quail, as verified by RT-qPCR. The c.1061C>T mutation in , which caused a single amino acid change at position 354 (threonine to methionine), was significantly associated with iris color in Beijing white and Chinese yellow quail, and might be the main reason for the different iris colors between these two quail species.
PubMed: 38818526
DOI: 10.2141/jpsa.2024015 -
Behavioral Ecology : Official Journal... 2024Melanin-based color polymorphism is predicted to evolve and maintain through differential fitness of morphs in different environments, and several empirical studies...
Melanin-based color polymorphism is predicted to evolve and maintain through differential fitness of morphs in different environments, and several empirical studies indicate that life history strategies, physiology, and behavior vary among color morphs. Sex allocation theory predicts that parents should adjust their sex allocation based on differential costs of raising sons and daughters, and therefore, color morphs are expected to modify their brood sex ratio decisions. In color polymorphic tawny owls (), the pheomelanistic brown morph is associated with higher energy requirements, faster growth, and higher parental effort than the gray morph. As hypothesized, we find that brown tawny owl mothers produced more daughters in early broods and more males in late broods, whereas gray mothers did the opposite. At fledging, daughters of early broods and of brown mothers were heavier than those of late broods or gray mothers. Hence, larger and more costly daughters appeared to benefit more than males from being born to brown mothers early in the season. Brown mothers breeding later in the season produced more cheap sons, while gray mothers face fewer challenges under limited resources and favor daughters. These findings suggest that environmental conditions influence brood sex allocation strategies of genetically determined color morphs differently.
PubMed: 38818250
DOI: 10.1093/beheco/arae039