Pigmentary Changes Research Articles

A retrospective clinico epidemiological study of pattern of dermatosis involving trigeminal distribution in a tertiary care center

Trigeminal nerve is the principal sensory nerve of face. Many dermatological conditions known occur in relation to trigeminal nerve distribution clinically presenting as unilateral facial lesions with strict midline demarcation. To study the clinical pattern and epidemiological determinants of dermatoses along trigeminal nerve among the patients of both the sexes, involving all the age groups. Thirty two patients presenting with skin lesions along trigeminal nerve presenting to Dermatology department of a tertiary care center, Bangalore, Karnataka, are selected for the study. Study design is retrospective hospital record based study conducted from January 2023 to January 2024. In this study, out of 32 patients most common dermatoses along trigeminal nerve were infection of which herpes zoster was seen thirteen (40.62%) patients, followed by nevi (n=6, 18.75%), pigmentary disorders (n=5, 15.62%), vascular disorder (n=4, 12.5%) and auto inflammatory disorder (n=4, 12.5%) was seen. Most common branch affected was ophthalmic followed maxillary branch .Females were more common and mean age was 24 years. Small sample size and rare clinical cases are included Studies focusing on the pattern of dermatoses involving the trigeminal nerve contribute to the advancement of medical knowledge and facilitate the development of novel diagnostic techniques and therapeutic modalities. By elucidating the underlying pathophysiological mechanisms and identifying potential risk factors, research in this field can lead to the development of more effective treatment strategies tailored to the specific needs of patients.

Understanding dermatological health challenges in rural communities - An epidemiological study

Skin diseases contribute to significant morbidity to the patients which have geographical variation. There are many hospital-based studies describing the distribution of dermatoses but social and preventive health camps conducted in rural areas often give the real portrait of the dermatological burden in entire population. To provide a detailed overview of the prevalence of skin diseases in a rural area. This is cross sectional study conducted in people attending preventive health camps in Pudukottai district over a period of 3months. Patients with various dermatological complaints are diagnosed clinically and details recorded using a proforma tailored for recording dermatology conditions. Statistical analysis was made according to patient profile, final diagnosis and appropriate treatment suggested. Awareness about the preventive measures were educated.In our study, among the 5870 patients attending the dermatology campy, 1468 had dermatological complaints. Males outnumbered females and the most common age group is 40-60years. Non-infectious dermatoses were predominant, some of them include eczema, appendageal and pigmentary disorders. Infectious dermatoses are the second common, among them the fungal infections top the list followed by bacterial and arthropod infections. Planning of the health programmes should be tailored to the individual needs of a community. This study provides valuable insights into the epidemiology of dermatological conditions in the studied rural population. Further researches are warranted to enhance diagnostic, therapeutic and preventive strategies for these conditions.

Identification of a novel ST3GAL5 variant in a Chinese boy with GM3 synthase deficiency and literature review of variants in the ST3GAL5 gene

Abstract Background GM3 synthase deficiency (GM3SD) is an autosomal recessive disorder resulting from mutations in the ST3GAL5 gene. It is characterized by intellectual disability, microcephaly, psychomotor and developmental delay, hearing and visual impairments, and changes in skin pigmentation. This study aims to broaden the genetic mutation spectrum of GM3SD through the report of a de novo mutation and a comprehensive summary of GM3SD phenotype to aid in genetic counseling and prenatal diagnosis. Results Compound heterozygous variants in ST3GAL5 (NM_003896.4: c.1000delC, p.Arg334Glufs*15 and c.207-1G > T, p.Cys70Glufs*81) were identified via trio-whole exome sequencing (trio-WES) and confirmed pathogenic through functional experiments. Notably, c.207-1G > T was a newly discovered variant. Additionally, previously reported GM3SD mutations were classified into R288X and non-R288X, revealing that R288X mutations were more likely to manifest developmental, emotional abnormalities, and severe feeding difficulties. Conclusions This study reveals a novel mutation in ST3GAL5 and provides a comprehensive overview of GM3SD phenotype, aiding in the diagnosis and genetic counseling of GM3SD in clinical practice.

Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments

Mitochondria regulate several physiological functions through mitochondrial Ca2+ dynamics. However, role of mitochondrial Ca2+ signaling in melanosome biology remains unknown. Here, we show that pigmentation requires mitochondrial Ca2+ uptake. In vitro gain and loss of function studies demonstrate that mitochondrial Ca2+ uniporter (MCU) is crucial for melanogenesis while MCU rheostat, MCUb negatively control melanogenesis. Zebrafish, MCU+/- and MCUb-/- mice models show that MCU complex drives pigmentation in vivo. Mechanistically, MCU silencing activates transcription factor NFAT2 to induce expression of keratin (5, 7, and 8) filaments. Interestingly, keratin5 in turn augments mitochondrial Ca2+ uptake and potentiates melanogenesis by regulating melanosome biogenesis and maturation. Hence this signaling module acts as a negative feedback loop that fine-tunes both mitochondrial Ca2+ signaling and pigmentation. Notably, mitoxantrone, an FDA approved drug that inhibits MCU, reduces pigmentation thereby highlighting therapeutic potential of targeting mitochondrial Ca2+ uptake for clinical management of pigmentary disorders. Taken together, we reveal an MCU-NFAT2-Keratin5 driven signaling axis that acts as a critical determinant of mitochondrial Ca2+ uptake and pigmentation. Given the vital role of mitochondrial Ca2+ signaling and keratin filaments in cellular physiology, this feedback loop could be operational in a variety of other patho-physiological processes.

Exploring mechanisms of skin aging: insights for clinical treatment

The skin is the largest organ in the human body and is made up of various cells and structures. Over time, the skin will age, which is not only influenced by internal factors, but also by external environmental factors, especially ultraviolet radiation. Aging causes immune system weakening in the elderly, which makes them more susceptible to dermatosis, such as type 2 inflammatory mediated pruritus. The immune response in this condition is marked by senescent cells consistently releasing low amounts of pro-inflammatory cytokines through a senescence-associated secretory phenotype (SASP). This continuous inflammation may accelerate immune system aging and establish a connection between immune aging and type 2 inflammatory skin diseases. In addition, two chronic pigmentation disorders, vitiligo and chloasma, are also associated with skin aging. Aged cells escape the immune system and accumulate in tissues, forming a microenvironment that promotes cancer. At the same time, “photoaging” caused by excessive exposure to ultraviolet radiation is also an important cause of skin cancer. This manuscript describes the possible links between skin aging and type 2 inflammation, chronic pigmentation disorders, and skin cancer and suggests some treatment options.

A prospective, double‐blinded, randomized head‐to‐head clinical trial of topical adapinoid (oleyl adapalenate) versus retinol

AbstractBackgroundRetinoids, such as retinol, are widely investigated and utilized in skin care products as a treatment for photoaging but their use is limited by tolerability. Adapinoid (oleyl adapalenate, OA) is a novel third generation retinoid that is a pro‐drug of adapalene, but there is little research on its effects on photoaging or its tolerability.ObjectivesThe purpose of this study is to compare the effects and tolerability of OA 0.5% to retinol 0.5% cream regarding visible signs of facial photoaging including facial wrinkles, fine lines and pigmentation.MethodsIn this 12‐week, double‐blind, randomized clinical trial, 48 eligible participants were recruited and enroled from the Greater Sacramento region. The study consisted of a baseline and follow‐up visits at weeks 4, 8 and 12. Participants were randomized to receive either topical OA 0.5% or retinol 0.5% for 12 weeks. The primary outcome was changes in the appearance of wrinkle severity at 12 weeks. Secondary outcome measures include changes in erythema, skin pigmentation, skin hydration and transepidermal water loss (TEWL).ResultsOA improved wrinkle severity by 9.45% (p < 0.0001) at week 12, whereas retinol improved wrinkle severity by 4.11% (p < 0.001) compared to baseline. When comparing the two treatment groups at week 12, the OA group improved significantly more than the retinol group (p = 0.001). OA decreased pigment intensity at week 12 by 3.88% (p < 0.0001), whereas retinol decreased pigment intensity by 3.15% (p < 0.03) compared to baseline. OA‐based improvement in pigment intensity at week 12 was not significantly different from retinol (p = 0.62). OA reduced facial erythema by 13.39% (p < 0.05) at week 12, whereas the retinol group did not have a significant change. OA use led to a 14.92% decrease in TEWL by week 12 (p = 0.07), whereas the retinol group had no significant change. OA was better tolerated than retinol when assessed at all follow‐up visits.ConclusionsOA 0.5% is superior to retinol 0.5% in improving wrinkle severity and similar in improvement of pigment intensity. OA is better tolerated than retinol. Overall, the use of OA as a precursor to adapalene may be an effective method to improving the tolerability of retinoids while maintaining efficacy.Trial RegistrationThis study was registered on www.clinicaltrials.gov (NCT05778760).

Giant Centella asiatica, a novel cultivar rich in madecassoside and asiaticoside, suppresses α‑melanocyte‑stimulating hormone‑induced melanogenesis through MC1R binding.

The present study investigated the anti‑melanogenesis effects of Giant Centella asiatica (GCA), a new cultivator of Centella asiatica (CA) cataloged by the Korea Forest Service in 2022, and compared its efficacy with that of traditional CA. GCA has a high yield per unit area and enhanced antioxidant properties. The anti‑melanogenic effects of GCA were investigated using B16F10 melanoma cells and a 3D human skin‑equivalent model. Key molecular mechanisms were elucidated through western blotting, cAMP assays and molecular docking studies. Focus was addressed on the effect of GCA on skin whitening by comparing the ability of a GCA extract to inhibit melanin production in B16F10 melanoma cells and a 3D human skin‑equivalent model to that of CA. The results showed that the GCA extracts more effectively reduced melanin production, which was attributed to their higher content of two active components, madecassoside and asiaticoside. Further investigation revealed that GCA primarily inhibited melanogenesis through the PKA‑cAMP response element‑binding (CREB)‑microphthalmia‑associated transcription factor (MITF) axis, a key regulatory pathway in melanin synthesis. Notably, the present study, to the best of our knowledge, is the first to demonstrate that madecassoside and asiaticoside, the two principal compounds in GCA, directly bound to MC1R, which contributed to the significant skin‑whitening effects. Moreover, GCA reduced melanin production in a 3D human skin‑equivalent model, showing efficacy within a complex skin environment. These results demonstrated the superior effectiveness of GCA to that of CA for skin anti‑melanogenesis, indicating its potential as a promising natural material for targeting pigmentation disorders.

Tetranychus ludeni (Acari: Tetranychidae) infestation triggers a spatiotemporal redox response dependent on soybean genotypes.

The redox homeostasis and photosynthetic pigments changes vary with Tetranychus ludeni infestation, with longer-cycle genotypes showing greater tolerance and efficiency in antioxidant defense. Infestations of Tetranychus ludeni Zacher (Tetranychidae) have been frequently observed in soybean plants. In this context, understanding the oscillation of redox homeostasis is crucial for detecting and assessing the stress levels caused in the plants by these organisms. The impacts of these infestations on redox metabolism and photosynthetic pigments are currently unknown. Therefore, we examined the hypothesis that T. ludeni infestations in soybean plants can influence redox homeostasis and photosynthetic pigments in a spatiotemporal manner, varying between different infestation times, modules and genotypes. For this purpose, soybean plants of the genotypes Monsoy, maturity group 5.7, and Brasmax, maturity group 6.3, grown in a controlled environment, were exposed to infestation and evaluated at two periods: 14 and 24days. A variation in the distribution of T. ludeni within the infested plants over time increased the activity of ascorbate peroxidase and catalase, especially in Monsoy, reducing the content of hydrogen peroxide and superoxide, which prevented lipid peroxidation in the apical region in both genotypes. In the basal region, low chlorophyll indices corroborated by the yellow coloration of trifoliate leaves, high levels of membrane stability loss, and accumulation of hydrogen peroxide and superoxide characterized senescent trifoliate leaves in Brasmax, 24days post infestation. Thus, the infestation of T. ludeni has a complex and significant impact on the redox metabolism of soybean plants, especially in shorter-cycle genotypes such as Brasmax. Furthermore, the oscillation of homeostasis can be considered as a good biochemical marker for selecting more suitable genotypes that are less sensitive and prone to infestations.

Lichen Planus: Health Related Quality of Life, Dermoscopic Features and Clinical Variants in Uganda

Background: Lichen planus is a chronic, lichenoid inflammatory disorder affecting skin, mucous and appendages that can negatively impact patients’ quality of life. The clinical variants and dermoscopic feature vary based on skin type and race. Such an understanding can ease the diagnosis of lichen planus among dark skinned people. Aims and Objective: The goal of this study was to assess the quality of life and to describe the clinical variants and dermoscopic features among adult patients with lichen planus attending a Regional Referral Hospital skin clinic. Methods: A cross-sectional study was conducted from January to June 2024. A questionnaire was used to collect patients’ data, a standardized tool (DLQI) to assess the quality of life, dermoscopy for describing dermoscopic features and data analyzed using Stata version 17.0. Results: We enrolled 52 adult patients, the median age was 34.5 IQR= 25 – 47. There was a significant relationship between itch X2(1, n = 52) =17.5102, p<.001), embarrassment X2(1, n = 52) =9.5510, p<.002) with patients’ impaired quality of life. More patients had a very large effect on their quality of life (36.54%). The most common variants were classical (50%) and hypertrophic (23.08%). On dermoscopy 104 lesions were examined, (25.96%) of lesions had a violet, (22.11%) gray, (15.38%) gray-blue and (15.38%) gray-violet background. The pigmentary changes seen were mostly brown (69.23%). Wickham’s striae patterns were reticulate (21.15%) and diffuse (14.42%). Limitation: A single study site. Conclusions: lichen planus exerts a very large effect on patient’s quality of life. Itchy skin and a feeling of embarrassment significantly affected the quality of life. Classical and hypertrophic were the most common forms of lichen planus. The most lesions had violaceous or a grayish background, and had brown pigments with a reticulate and diffuse wickham’s striae patterns. Routine screening of quality of life should be practiced on patients with lichen planus.

Dermoscopy of Lichen Planus Pigmentosus and Histopathological Correlation: A Case Series

Introduction: Lichen planus pigmentosus (LPP) is an acquired pigmentary disorder affecting the dark-skinned population. There is a wide range of differentials with substantial clinicopathological overlap. Dermoscopy may contribute to the better characterization of this dermatosis. Objective: This study aimed to describe dermoscopic features of LPP with a histopathological correlation. Methods: LPP lesions of 23 patients were studied using a polarized dermoscopy, followed by histological evaluation. Results: The most common dermoscopic finding was dots and/or globules (n=23) in different patterns: speckled (n=4), dotted (n=2), reticular (n=4), diffuse (n=9), hem-like (n=1), and circular (n=2). Other patterns were exaggerated pseudo-reticular pattern (n=12), sparing of follicular openings (n=23), targetoid appearance (n=3), blue-white veil (n=5), rosettes (n=5), erythema (n=4), and telangiectasia (n=7). Histological findings included pigment incontinence (n=23), the severity being mild (n=8) and severe (n=15). We found a statistically significant association between the intensity of pigmentary incontinence on the histological examination and the presence of blotches in dermoscopy (p=0.046); and between blue-white veil and rosettes in flexural areas (p=0.01). Also, a statistical relationship was found between severe pigment density (reticulated and diffused patterns) and a short disease duration (p=0.016). Conclusion: We described LPP dermoscopic changes according to disease progression. We found that blotches are indicative of long-duration disease and could be specific dermoscopic features of LPP. We demonstrated that a blue-white veil associated with rosettes could be pathognomonic features of LPP inversus.

Evaluation of Safety and Efficacy of Chemical Peels With and Without Sonophoresis on Selected Skin Parameters—A Prospective Comparative Study

Background: Skin is the largest organ in the human body. Some skin parameters like moisturization and sebum secretion play a vital role in the skin’s functioning. This study aims to assess the effects of topical chemical peels of different concentrations and pH, applied manually and with ultrasounds, on the level of hydration, erythema, pigmentation, and sebum secretion of the skin. Methods: The study involved 90 Caucasian females, aged 25 to 59, with dry, dehydrated skin, skin with erythema or pigmentation disorders. The patients were randomly divided into three equal groups. The subjects from Group A were applied 10% mandelic acid with 25% gluconolactone of pH 4.0 manually. In Group B, 40% mandelic acid of pH 1.5 was used. The subjects from Group C were applied 10% mandelic acid with 25% gluconolactone of pH 4.0 via sonophoresis. A series of six procedures in weekly intervals was performed. Skin functional parameters (skin hydration, erythema, and melanin indicators) were taken before the first procedure, after 14 days, 28 days, and 42 days. Results: In Group A, the level of moisturization of the skin increased statistically significantly (p = 0.0100) however, the sebum secretion and erythema did not change. In Group B, the level of moisturization improved statistically significantly, as well as erythema (p = 0.0001). Sebum secretion in the final measurement increased. The moisturization and erythema in Group C did not differ statistically significantly. On the other hand, the sebum secretion increased significantly. Conclusions: Very superficial chemical peels significantly alter selected skin parameters. AHAs and PHAs applied using the ultrasound method do not affect the level of hydration, erythema, or pigmentation of the skin.

Evaluation of auditory system in vitiligo patients: A case-control study

BackgroundVitiligo is a common acquired pigmentary disorder characterized by well-defined areas of depigmentation due to loss of melanocytes. Vitiligo can affect melanocytes in the auditory system and potentially hearing. ObjectiveThe aim of this study was to investigate hearing changes in vitiligo patients. MethodsTwenty-six with vitiligo patients and 26 demographically matched healthy controls were included in this study. Audiological function was evaluated using pure tone audiometry (PTA), speech audiometry and tympanometry tests in all subjects. ResultsThe mean hearing threshold of the left ear at frequencies of 250 and 8000 Hz in vitiligo patients was significantly higher than the control group. Sensorineural hearing loss (SNHL) was seen in 14 (53.8 %) vitiligo patients and 5(19.2 %) control group (p < 0.05). Most affected patients (10/14; 71 %) had bilateral hearing loss especially in high frequency (8000 Hz). A significant association was identified between vitiligo and SNHL (OR 4.9; 95 % CI, 1.41–16.98, P = 0.01). There was a statistically significant correlation between hearing impairment and age in both groups. Gender, severity, activity and duration of vitiligo had no a significant effect on the results of audiometric tests. ConclusionThis study confirmed that the auditory system was affected in vitiligo patients. Vitiligo patients might be at a higher risk for auditory abnormalities at a younger age than control subjects. Auditory evaluation of vitiligo patients should be considered for early detection of hearing loss.

Mining and analysis of adverse event signals of vandetanib based on the FAERS database.

By analyzing the signal mining of vandetanib AEs, it provides a reference for the rational clinical use of the drug. This study provides signal detection and analysis of AEs associated with vandetanib using the FAERS from Q2 2011 to Q1 2023. Disproportionality analyses were conducted using the ROR and the MHRA method, with AEs categorized and described based on SOC and PT from the MedDRA. A total of 1,721 AEs reports identified vandetanib as the primary suspect. The analyses yielded 187 AEs signals across 20 SOCs categories, with 47 signals not previously reported in the vandetanib labeling. Additionally, the study analyzes factors influencing AEs. The results are as follows: There are significant differences in Investigations based on gender and nationality (p < 0.05); skin and subcutaneous tissue disorders and gastrointestinal disorders exhibit differences based on gender, age, and nationality (p < 0.05). Common AEs signals identified align with those documented in the drug labeling. However, AEs such as tumor lysis syndrome, skin discoloration, and pigmentary disorders, which are not listed in the labeling, warrant special attention. It is essential that abnormalities in patients' skin and laboratory indicators are closely monitored and addressed promptly to safeguard medication safety.

Skin senescence-from basic research to clinical practice.

The most recognizable implications of tissue aging manifest themselves on the skin. Skin laxity, roughness, pigmentation disorders, age spots, wrinkles, telangiectasia or hair graying are symptoms of physiological aging. Development of the senescent phenotype depends on the interaction between aging cells and remodeling of the skin's extracellular matrix (ECM) that contains collagen and elastic fiber. Aging changes occur due to the combination of both endogenous (gene mutation, cellular metabolism or hormonal agents) and exogenous factors (ultraviolet light, environmental pollutants, and unsuitable diet). However, overproduction of mitochondrial reactive oxygen species (ROS) is a key factor driving cellular senescence. Aging theories have disclosed a range of diverse molecular mechanisms that are associated with cellular senescence of the body. Theories best supported by evidence include protein glycation, oxidative stress, telomere shortening, cell cycle arrest, and a limited number of cell divisions. Accumulation of the ECM damage is suggested to be a key factor in skin aging. Every cell indicates a functional and morphological change that may be used as a biomarker of senescence. Senescence-associated β-galactosidase (SA-β-gal), cell cycle inhibitors (p16INK4a, p21CIP1, p27, p53), DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS), senescence-associated heterochromatin foci (SAHF), shortening of telomeres or downregulation of lamina B1 constitute just an example of aging biomarkers known so far. Aging may also be assessed non-invasively through measuring the skin fluorescence of advanced glycation end-products (AGEs). This review summarizes the recent knowledge on the pathogenesis and clinical conditions of skin aging as well as biomarkers of skin senescence.

First description of leucism in the deep-sea angular rough shark (Oxynotus centrina) and the first documented pigment disorder in family Oxynotidae Gill, 1912.

The capture of a rare, critically endangered adult angular rough shark, Oxynotus centrina (Linnaeus, 1758), with abnormal coloration is reported in this paper. The shark exhibited a partial reduction in pigmentation, resulting in an overall pale appearance with white-greyish patches. Since the retinal pigmentation appeared normal, the shark was considered leucistic. This represents the first documented case of leucism in this species and the first colour disorder reported in the family Oxynotidae Gill, 1912. Despite the atypical appearance, the physical health of the shark seemed unaffected, supporting the notion that pigment disorders in deep-sea sharks do not inherently impair survival and growth. Full morphometric characteristics are presented and compared with those of a normal individual of the same sex caught in the same area, showing no differences.

Response mechanisms of submerged macrophytes and epiphytic biofilms to single and coexisting per-and poly-fluoroalkyl substances and antibiotics stress

Combined pollutants of per- and poly-fluoroalkyl substances (PFAS) and antibiotics are commonly found in aquatic environments. This study aimed to investigate the effects of PFAS (perfluorobutyric acid (PFBA) and perfluorooctanoic acid (PFOA)) and antibiotics (tetracycline (TC) and chloramphenicol (CAP)) on Vallisneria natans (V. natans) and their epiphytic biofilms. The changes in photosynthetic pigments and oxidative damage in V. natans were altered by these pollutants. For example, the total chlorophyll was increased from 4.64 to 8.10 mg/L due to the combined pollutant of PFOA and TC. When exposed to the combined pollutant of PFBA and TC, a concentration of malondialdehyde of 28.4 nmol/g was measured, which was significantly higher than that in the control group. For combined toxicity, the PFAS and antibiotics primarily exhibited antagonistic effects within V. natans. The glycine, serine, and threonine metabolism pathways were mainly affected by the combined stress of PFBA and TC. Single pollutants of TC and CAP were found to inhibit the uptake of nutrients by V. natans, while the coexisting antibiotics enhanced the inhibitory effects of PFBA and PFOA in combined pollutant treatments. The growth of microorganisms in the epiphytic biofilms was significantly promoted by PFBA and PFOA, whereas their growth was notably inhibited by CAP. The composition of biofilms could be altered by single and combined pollutants, with antibiotics being more likely than PFAS to change the microbial communities within the biofilms. When exposed to TC and CAP, the ACE indices decreased from 1171.5 to 466.4 and 703.8, respectively.

Stress Responses to Bark Beetle Infestations among Pine (Pinus sylvestris), Fir (Abies alba), and Beech (Fagus sylvatica) Trees

Insect infestation triggers multiple defense responses in plants, both locally at the infection site and systemically throughout the plant, including the production of feeding deterrents, toxins, defensive proteins, enzymes, and secondary metabolites. Our study aimed to compare the endogenous levels of antioxidative enzymes, photosynthetic pigments, phytohormones, total phenols, and flavonoids in bark-beetle-infested and uninfested trees. We evaluated the surviving trees in bark-beetle-infested stands, assessing both the condition and defense of uninfested and infested beech (Fagus sylvatica), pine (Pinus sylvestris), and fir (Abies alba) trees. Sampling was performed at six affected sites in the Czech Republic, targeting trees that were resilient to significant health deterioration caused by abiotic and biotic factors. The results showed different levels of most of the measured compounds in the three species. Among all the tested species, photosynthetic pigment levels showed the strongest association with infestation status, which was generally lower in the infested plants. For chlorophyll a, extremely significant reductions were observed from 123 ± 20.6 to 101 ± 17.9 μg/g dry weight (DW) in pine, from 231 ± 33.1 to 199 ± 22.2 μg/g DW in beech, and from 60 ± 5.66 to 51.3 ± 6.27 μg/g DW in fir. In contrast, enzymatic activities indicated only isolated instances of significant association, whereas antioxidative properties (total phenolic content, flavonoids, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity) were not significantly associated with infestation status. There was a statistically significant increase in glutathione reductase activity in infested fir and pine trees. However, this difference was not statistically significant in beech. In contrast, a significant increase in superoxide dismutase activity was detected in infected beech trees. Phytohormones have emerged as the most diverse group of analyzed compounds. Cytokinins were the most distinct, with many of them being significantly increased in infested pines, whereas both beech and fir showed only one significant association. Additionally, derivatives of jasmonic acid also showed a distinct pattern of change associated with bark beetle infestation, with the levels of three out of the four analyzed jasmonates being significantly decreased in infested pines, whereas no effects were observed in beeches and firs. Notably, many phytohormones were significantly elevated in the infested pine, whereas both beech and fir exhibited only one significant association. Overall, the data showed that pines responded differently to bark beetles than to beeches or firs. The greatest changes in phytohormones were observed in pine, whereas the most significant changes in photosynthetic pigments were observed in beech and fir trees.

Modulatory effects of oxytocin on normal human cultured melanocyte proliferation, migration, and melanogenesis

Melanocytes are specialized melanin-producing neural crest-derived cells. Melanocyte proliferation and melanin production (i.e., melanogenesis) are crucial for determining skin color. Disruption of these processes can cause pigmentary skin disorders, including hypo-pigmentary disorders such as vitiligo and hyper-pigmentary disorders such as melasma. Understanding these processes is important for discovering new targets to tackle these skin disorders. Therefore, this study aimed to investigate the effects of oxytocin (OXT) on melanocyte functions. Normal Human Cultured Melanocytes (NHCM) were treated with different OXT doses to investigate OXT effects and mechanisms on NHCM proliferation, migration, and on melanogenesis. OXT significantly increased NHCM proliferation and migration in a dose-dependent manner after 72 h of treatment. In addition, OXT dose-dependently upregulated melanogenesis-related microphtalmia-associated transcription factor, tyrosinase, tyrosinase-related protein (TYRP)-1, and TYRP-2 expression accompanied by an increased trend in melanosome number and maturation stage. Furthermore, OXT at concentrations (62.5–125 nM) increased melanin production. These findings suggest the involvement of OXT receptor (OXTR). In addition, this study demonstrates that OXT stimulates melanocyte proliferation, migration, with a tendency toward melanosome maturation, while it modulates melanin production in a dose-dependent manner. Thus, OXT system including its receptor OXTR may be a potential therapeutic target for skin pigmentary disorders.

Acute toxicity of salicylic acid and its derivatives on the diatom Phaeodactylum tricornutum: Physico-Biochemical and transcriptomic insights

Salicylate pollutants (SAs) poses a serious threat to marine ecosystems as emerging contaminants. However, the toxic effects of SAs on marine phytoplankton, as well as the potential mechanisms and their ecological risks linked with them, are remain largely unknown. In this study, we aimed to evaluate the toxic effects of salicylic acid (SA) and its 5-substituted derivatives (5-sSA) on the marine diatom Phaeodactylum tricornutum, as well as the potential molecular mechanism involved in the toxicity. Physiological assays conducted on P. tricornutum revealed significant changes in photosynthetic pigments, chlorophyll fluorescence parameters, and antioxidant enzyme activities. The results showed that exposure of P. tricornutum to SAs caused a significant decline in chlorophyll contents and damage to the photosystem II (PSII) core resulting in the decline of photosynthesis. Although the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were enhanced, oxidative damage occurred. Transcriptome analysis showed that a large number of differentially expresses genes (DEGs) were significantly enriched in metabolic pathways such as porphyrin metabolism, terpenoid backbone biosynthesis, and carbon fixation in photosynthetic organisms after SA and 5-BrSA treatments. In addition, key genes in transcriptomic metabolic pathways were further analyzed and validated using weighted correlation network analysis (WGCNA) and real-time fluorescence quantitative PCR (qPCR). Considering the above results, SAs mainly inhibit the processes of photosynthesis by repressing the expression of genes involved in secondary metabolite synthesis and photosynthetic carbon sequestration pathways, thus exerting toxic effects on algal cells. The results of the study will provide key data for understanding the ecological risk and toxicity mechanisms of SA pollutants.

Prevalence and spectrum of manifestations of tamoxifen retinopathy as assessed by multimodal and ultra-widefield retinal imaging

Background/ObjectivesTamoxifen has well-known retinal toxicity, but the epidemiology of this toxicity is poorly defined. This study aims to 1) evaluate the prevalence of tamoxifen retinopathy in a major northeastern metropolitan area based on multimodal retinal imaging and 2) determine whether the additional peripheral retina captured in ultra-widefield (UWF) imaging aids in the diagnosis of tamoxifen retinopathy. MethodsThis retrospective cohort study examined female patients initiated on tamoxifen for at least 12 months prior to their first retinal exam. Two independent graders performed blinded review of spectral-domain optical coherence tomography (OCT) images for evidence of macular toxicity and UWF images for signs of central and peripheral toxicity. A one-tailed two-proportion Z-test determined whether peripheral pigmentary changes were more prevalent in the tamoxifen cohort than age- and gender-matched controls. Results241 eyes from 123 patients were included in the tamoxifen cohort, and 258 eyes from 132 patients were included in the control cohort. Two patients demonstrated definitive tamoxifen retinopathy, for a prevalence of 1.6%. One patient demonstrated crystalline maculopathy on OCT and UWF imaging, while another demonstrated pseudocystic cavitations on OCT imaging. Neither patient had peripheral findings on UWF imaging. Peripheral pigmentary changes were not significantly more prevalent in the tamoxifen cohort. ConclusionsThese findings suggest that UWF imaging does not contribute to diagnosis of tamoxifen retinopathy, and OCT may be the most valuable tool in diagnosing tamoxifen retinopathy. Our prevalence (1.6%) diverges from higher rates in studies screening with similarly advanced retinal imaging. Further large population studies are needed.