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Hair is a noninvasive valuable biospecimen for the long-term assessment of endogenous metabolic disturbance. Whether the hair is suitable for identifying biomarkers of the Alzheimer's disease (AD) process remains unknown. We aim to investigate the metabolism changes in hair after β-amyloid (Aβ1-42) exposure in rats using ultra-high-performance liquid chromatography-high-resolution mass spectrometry–based untargeted and targeted methods. Thirty-five days after Aβ1-42 induction, rats displayed significant cognitive deficits, and forty metabolites were changed, of which twenty belonged to three perturbed pathways: (1) phenylalanine metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis—l-phenylalanine, phenylpyruvate, ortho-hydroxyphenylacetic acid, and phenyllactic acid are up-regulated; (2) arachidonic acid (ARA) metabolism—leukotriene B4 (LTB4), arachidonyl carnitine, and 5(S)-HPETE are upregulation, but ARA, 14,15-DiHETrE, 5(S)-HETE, and PGB2 are opposite; and (3) unsaturated fatty acid biosynthesis— eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), FA 18:3 + 1O, and FA 18:3 + 2O are downregulated. Linoleic acid metabolism belonging to the biosynthesis of unsaturated fatty acid includes the upregulation of 8-hydroxy-9,10-epoxystearic acid, 13-oxoODE, and FA 18:2 + 4O, and downregulation of 9(S)-HPODE and dihomo-γ-linolenic acid. In addition, cortisone and dehydroepiandrosterone belonging to steroid hormone biosynthesis are upregulated. These three perturbed metabolic pathways also correlate with cognitive impairment after Aβ1-42 stimulation. Furthermore, ARA, DHA, EPA, l-phenylalanine, and cortisone have been previously implicated in the cerebrospinal fluid of AD patients and show a similar changing trend in Aβ1-42 rats' hair. These data suggest hair can be a useful biospecimen that well reflects the expression of non-polar molecules under Aβ1-42 stimulation, and the five metabolites have the potential to serve as novel AD biomarkers. [ABSTRACT FROM AUTHOR]

Mercury, a toxic metal released by various human activities, exerts environmental stress through its bioaccumulation and biomagnification, particularly in marine habitats. South American fur seals (Arctocephalus australis) and sea lions (Otaria flavescens) reproduce on the Atlantic coast of Uruguay. As top predators, they can accumulate toxic levels of mercury and are often used as sentinel species for monitoring ecosystem health. Fur seals prey on pelagic species, such as fish and squid, while sea lions consume coastal-benthic prey. We analyzed the total mercury concentration (THg) in hair and the trophic habits (δ 13 C and δ 15 N) of females from both species. The average THg concentration in adult female sea lions (30.5 ± 9.3 μg/g dry weight) was significantly higher than in fur seals (6.3 ± 2.5 μg/g dry weight). Additionally, the mean δ 15 N and δ 13 C values were significantly higher in sea lion (δ 15 N: 19.2 ± 0.6‰, δ 13 C: -13.8 ± 0.2‰) compared to fur seals (δ 15 N: 16.5 ± 0.5‰, δ 13 C: -15.5 ± 0.6‰). Our results suggest that different trophic levels and feedings areas affect the THg concentration in Uruguayan Otariids. Notably, at the intraspecific level, the THg concentration in sea lions increased with δ 13 C values, suggesting a link to coastal feeding habits. This indicates that coastal feeding behaviors, compared to feeding in pelagic environments, enhance mercury bioaccumulation in Otariids along the Uruguayan coast, with the discharge of freshwater from the Río de la Plata (one of the largest estuaries in South America) basin identified as a potential mercury source. THg concentrations found in female sea lion hair are the highest reported in Otariids globally. Mercury levels exceeded toxic thresholds observed in other mammals and could pose significant health risks. Our findings may explain why sea lions were particularly affected by the avian influenza outbreak in Uruguay compared to fur seals. Monitoring the declining sea lion population is crucial, making our results significant for integrated conservation and management strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Dermal papilla cells (DPCs) are located at the bottom of the hair follicle and play a critical role in hair growth, shape, and cycle. Epidermal growth factor receptor (EGFR) and Wnt/β-catenin signaling pathways are essential in promoting keratinocyte activation as well as hair follicle formation in DPCs. Piperonylic acid is a small molecule that induces EGFR activation in keratinocytes. However, the effects of piperonylic acid on DPCs in regard to the stimulation of hair growth have not been studied. In the present study, piperonylic acid was shown to activate the Wnt/β-catenin signaling pathway in addition to the EGFR signaling pathway in DPCs. Piperonylic acid suppressed DKK1 expression, which presumably promoted the accumulation of β-catenin in the nucleus. In addition, piperonylic acid promoted cyclin D upregulation and cell growth and increased the expression of alkaline phosphatase (ALP), a DPC marker. In a clinical study, the group that applied a formulation containing piperonylic acid had a significantly higher number of hairs per unit area than the placebo group. These results identify piperonylic acid as a promising new candidate for hair loss treatment.

Background: Disruption of ALX4 causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes are not well understood. Although mice carrying distinct mutations in Alx4 have been previously reported, the perinatal lethality of homozygous mutants together with dynamic patterns of Alx4 expression in multiple tissues have hindered systematic elucidation of the cellular and molecular mechanisms involving Alx4 in organogenesis and disease pathogenesis., Results: We report generation of Alx4 f/f conditional mice and show that tissue-specific Cre-mediated inactivation of Alx4 in cranial neural crest and limb bud mesenchyme, respectively, recapitulated craniofacial and limb developmental defects as found in Alx4-null mice but without affecting postnatal survival. While Alx4-null mice that survive postnatally exhibited dorsal alopecia, mice lacking Alx4 function in the neural crest lineage exhibited a highly restricted region of hair loss over the anterior skull whereas mice lacking Alx4 in the cranial mesoderm lineage exhibited normal hair development, suggesting that Alx4 plays partly redundant roles in multiple cell lineages during hair follicle development., Conclusion: The Alx4 f/f mice provide a valuable resource for systematic investigation of cell type- and stage-specific function of ALX family transcription factors in development and disease., (© 2024 American Association for Anatomy.)

FG-4592 is a hypoxia-inducible factor inhibitor that has been approved for therapeutic use in some countries. This class of compounds can increase the oxygen carrying capacity of the blood and thus have the potential to be used as performance enhancing agents in sports. The purpose of this study was to investigate the detection of FG-4592 and metabolites in equine plasma and mane hair following a multiple dose oral administration to two Thoroughbred racehorses, to identify the best analytical targets for doping control laboratories. Urine samples were also analysed, and the results compared to previously published urine data. Liquid chromatography-high resolution mass spectrometry was used for metabolite identification in urine and plasma. Liquid chromatography-tandem mass spectrometry was used for full sample analysis of urine, plasma and hair samples and generation of urine and plasma profiles. FG-4592 and a mono-hydroxylated metabolite were detected in plasma. FG-4592 was detected with the greatest abundance and gave the longest duration of detection, up to 312 h post-administration, and would be the recommended target in routine doping samples. FG-4592 was detected in all mane hair samples collected post-administration, up to 166 days following the final dose, showing extended detection can be achieved with this matrix. To the best of the authors' knowledge, this is the first report of FG-4592 and metabolites in equine plasma and hair samples. Urine results were consistent with the previously published data, with FG-4592 offering the best target for detection and longest detection periods., (© 2024 John Wiley & Sons Ltd.)

Introduction: Living in socioeconomic disadvantage has been conceptualised as a chronic stressor, although this contradicts evidence from studies using hair cortisol and cortisone as a measure of hypothalamus-pituitary-adrenal (HPA) 1 axis activity. These studies used complete case analyses, ignoring the impact of missing data for inference, despite the high proportion of missing biomarker data. The methodological limitations of studies investigating the association between socioeconomic position (SEP) 2 defined as education, wealth, and social class and hair cortisol and cortisone are considered in this study by comparing three common methods to deal with missing data: (1) Complete Case Analysis (CCA), 3 (2) Inverse Probability Weighting (IPW) 4 and (3) weighted Multiple Imputation (MI). 5 This study examines if socioeconomic disadvantage is associated with higher levels of HPA axis activity as measured by hair cortisol and cortisone among older adults using three approaches for compensating for missing data., Method: Cortisol and cortisone levels in hair samples from 4573 participants in the 6th wave (2012-2013) of the English Longitudinal Study of Ageing (ELSA) 6 were examined, in relation to education, wealth, and social class. We compared linear regression models with CCA, weighted and multiple imputed weighted linear regression models., Results: Social groups with certain characteristics (i.e., ethnic minorities, in routine and manual occupations, physically inactive, with poorer health, and smokers) were less likely to have hair cortisol and hair cortisone data compared to the most advantaged groups. We found a consistent pattern of higher levels of hair cortisol and cortisone among the most socioeconomically disadvantaged groups compared to the most advantaged groups. Complete case approaches to missing data underestimated the levels of hair cortisol in education and social class and the levels of hair cortisone in education, wealth, and social class in the most disadvantaged groups., Conclusion: This study demonstrates that social disadvantage as measured by disadvantaged SEP is associated with increased HPA axis activity. The conceptualisation of social disadvantage as a chronic stressor may be valid and previous studies reporting no associations between SEP and hair cortisol may be biased due to their lack of consideration of missing data cases which showed the underrepresentation of disadvantaged social groups in the analyses. Future analyses using biosocial data may need to consider and adjust for missing data., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Prenatal stress physiology is often posited as a predictor of birth outcomes, including gestational age at birth and birthweight. However, research has predominantly relied on indicators in the maternal system, with few studies examining hormones of the fetal system. The current study focuses on fetal cortisol in the third trimester, as measured in neonatal hair, as a biological factor that might be associated with birth outcomes (gestational age at birth and birthweight). We report findings from two studies: a longitudinal cohort (Study 1), and a meta-analysis of the existing literature (Study 2)., Methodsstudy: Hair was collected for cortisol analysis from 168 neonates (55.95% female) shortly after birth. Gestational age at birth and birthweight were abstracted from medical records., Methodsstudy: An exhaustive search of four databases was conducted, yielding 155 total studies for screening. Papers reporting neonatal hair cortisol (collection <2 weeks postpartum) and birth outcomes among human neonates were retained for analysis, including Study 1 results ( k = 9)., Resultsstudy: Higher neonatal hair cortisol was related to longer gestation ( r = 0.28, p < .001) and higher birthweight, r = 0.16, p = .040. Sex did not moderate either association., Resultsstudy: Across the nine studies, higher neonatal hair cortisol predicted both longer gestation ( r = 0.35, p < .001, 95% confidence interval = 0.24-0.45) and higher birthweight ( r = 0.18, p = .001, 95% confidence interval = 0.07-0.28). Neonatal sex did not moderate these associations., Conclusions: Fetal cortisol exposure in the third trimester plays a role in normative maturation of the fetus, and findings reveal that higher cortisol is associated with positive birth outcomes., (Copyright © 2024 by the American Psychosomatic Society.)

Methandienone is an anabolic-androgenic steroid that is prohibited in equine sports due to its potential performance enhancing properties. Metabolism and detection of methandienone in equine urine have been investigated comprehensively in literature; however, there is a limited knowledge about its metabolites in equine plasma and no information about its detection in equine hair. Following a multi-dose oral administration of methandienone to two Thoroughbred horses, 17-epimethandienone, methyltestosterone, two mono-hydroxylated, two di-hydroxylated and three 17α-methylandrostanetriol metabolites were detected in plasma. The majority of these were present as free analytes, whilst the mono-hydroxylated metabolites and one isomer of 17α-methylandrostanetriol were partially conjugated. Estimated peak concentrations of methandienone were 6,000 and 11,100 pg/ml; meanwhile, they were 25.4 and 40.5 pg/ml for methyltestosterone. The most abundant analyte in the post-administration plasma samples of both horses was the mono-hydroxylated metabolite; however, the parent compound provided the longest detection (up to 96 h). Screening analysis of hair enabled the detection of methandienone in mane hair samples only, for up to 3 months. Its mono- and di-hydroxylated metabolites were detected with greater peak responses for up to 6 months post-administration in both mane and tail samples, showing that these metabolites could be better analytical targets for hair analysis when administered orally. A follow-up methodology with an extensive wash procedure confirmed the presence of methandienone and its metabolites in a number of post-administration hair samples. Final wash samples were also analysed to assess the degree of internal incorporation (via bloodstream) against possible external deposition (via sweat/sebum)., (© 2024 John Wiley & Sons Ltd.)

Background: In patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), momentary cortisol concentrations in blood, urine, and saliva are lower compared to healthy controls. Long-term cortisol concentration can be assessed through hair, but it is unclear whether these concentrations are also lower. Additionally, it is unknown if lower cortisol extends to other patients suffering from persistent fatigue and how hair cortisol concentration (HCC) relates to fatigue levels. Therefore, this study examines HCC in fatigued patients with ME/CFS, Q fever Fatigue Syndrome (QFS), Post-COVID-19 condition (PCC), and Juvenile Idiopathic Arthritis (JIA)., Methods: Adolescent and young adult patients with ME/CFS (n=12), QFS (n=20), PCC (n=8), JIA (n=19), and controls (n=57) were included. Patients participated in a randomized cross-over trial (RCT) targeting fatigue through lifestyle and dietary self-management strategies. HCC was measured pre-post RCT in patients and once in controls, quantified using a LC-MS/MS-based method. Fatigue severity was measured with the Checklist Individual Strength-8. HCC was compared between groups with ANOVAs. Relations between HCC, fatigue severity, and other variables were investigated using linear regression analyses., Results: The ME/CFS (p=.009) and QFS (p=.047) groups had lower HCC compared to controls. Overall, HCC was negatively associated with the presence of symptoms related to chronic fatigue syndromes (e.g., sleeping issues, often feeling tired, trouble thinking clearly; β=-0.018, p=.035), except in the QFS group (β=.063, p<.001). Baseline HCC did not predict fatigue improvement during the RCT (p=.449), and HCC increased during the trial (M dif =.076, p=.021) regardless of clinically relevant fatigue improvement (p=.658)., Conclusion: Lower cortisol concentration can also be observed in the long-term. Lower HCC is not limited to ME/CFS, as it was also observed in QFS. The role of cortisol may differ between these diagnoses and appears to be unrelated to fatigue levels., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to report., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a crucial determinant of hair follicle (HF) biology. Aldehyde dehydrogenase 2 (ALDH2) mitigates oxidative stress by detoxifying acetaldehyde. This study investigated the potential role of ALDH2 modulation in HF function and hair growth promotion., Objectives: To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion., Methods: The modulatory role of ALDH2 on HFs was investigated using an ALDH2 activator. ALDH2 expression in human HFs was evaluated through in vitro immunofluorescence staining. Ex vivo HF organ culture was employed to assess hair shaft elongation, while the fluorescence probe 2',7'- dichlorodihydrofluorescein diacetate was utilized to detect reactive oxygen species (ROS). An in vivo mouse model was used to determine whether ALDH2 activation induces anagen., Results: During the anagen phase, ALDH2 showed significantly higher intensity than that in the telogen phase, and its expression was primarily localized along the outer layer of HFs. ALDH2 activation promoted anagen phase induction by reducing ROS levels and enhancing reactive aldehyde clearance, which indicated that ALDH2 functions as a ROS scavenger within HFs. Moreover, ALDH2 activation upregulated Akt/GSK 3β/β-catenin signaling in HFs., Conclusions: Our findings highlight the hair growth promotion effects of ALDH2 activation in HFs and its potential as a promising therapeutic approach for promoting anagen induction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Vitamin D is a crucial vitamin that participates in various biological processes through the Vitamin D Receptor (VDR). While there are studies suggesting that VDR might regulate hair growth through ligand-independent mechanisms, the efficacy of Vitamin D in treating hair loss disorders has also been reported. Here, through in vivo experiments in mice, in vitro organ culture of hair follicles, and cellular-level investigations, we demonstrate that 1,25-(OH) 2 D 3 promotes mouse hair regeneration, prolongs the hair follicle anagen, and enhances the proliferation and migration capabilities of dermal papilla cells and outer root sheath keratinocytes in a VDR-dependent manner. Transcriptome analysis of VDR-knockout mouse skin reveals the involvement of HIF-1α, NLRP3, and IL-1β in these processes. Finally, we confirm that 1,25-(OH) 2 D 3 can counteract the inhibitory effects of DHT on hair growth. These findings suggest that 1,25-(OH) 2 D 3 has a positive impact on hair growth and may serve as a potential therapeutic agent for androgenetic alopecia (AGA)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hair cortisol concentrations (HCC) are measured to assess long-term HPA-axis activity and may represent a valuable non-invasive tool to evaluate chronic stress in cats. This study investigated combing as a novel, low-stress method for HCC assessment, as well as possible associations between HCC and cat characteristics in 167 owned cats. Hair was sampled at veterinary clinics through clipping and/or combing the cat, or at home by the owner combing the cat. A questionnaire was sent to cat owners, including inquiries about the cat's sex, health status, and exposure to stress. HCC was quantified using a commercial cortisol assay kit. Despite variations within and between sampling methods, Spearman's correlation and Bland-Altman plots revealed a moderate correlation between clipped and combed samples (rs = 0.61, LOA -5.51 ± 22.54). In multiple linear regression, variations in HCC were observed based on sex, health status and cat group size. No associations were found between HCC and stress as assessed by owners. Despite study limitations and remaining uncertainty regarding factors influencing HCC, combing presents a convenient approach for evaluating long-term HPA-axis activity in clinical settings. The association between health and HCC suggests alterations in cortisol levels that are related to disease processes and stress-inducing events associated with the disease., (© 2024. The Author(s).)

Synthetic cathinones are the second largest group of new psychoactive substances (NPS) monitored by the European Monitoring Centre for Drugs and Drug Addiction. Although 3-methylmethcathinone (3-MMC, C 11 H 15 NO) is legally banned in many countries, it is readily available for purchase online and on the street. Due to the scarcity of information regarding the pharmacokinetic and toxicological profile of 3-MMC, understanding its biotransformation pathways is crucial in determining its potential toxicity in humans and in the development of analytical methods for screening of human matrices. To gain more insight, Phase I and Phase II in vitro biotransformation of 3-MMC was investigated using human liver microsomes and human liver cytosol. Suspect and non-target screening approaches were employed to identify metabolites. To confirm in vitro results in an in vivo setting, human matrices (i.e., plasma, urine, saliva and hair) positive for 3-MMC (n=31) were screened. In total three biotransformation products were identified in vitro: C 11 H 15 NO 2 (a hydroxylated derivate), C 11 H 17 NO (a keto-reduced derivate) and C 10 H 13 NO (an N-desmethyl derivate). All three were confirmed as human metabolites in respectively 16 %, 52 % and 42 % of the analysed human samples. In total, 61 % of the analysed samples were positive for at least one of the three metabolites. Interestingly, three urine samples were positive for all three metabolites. The presence of 3-MMC in saliva and hair indicates its potential applicability in specific settings, e.g., roadside testing or chronic consumption analysis. To our knowledge, C 11 H 17 NO was not detected before in vivo. Although some of these metabolites have been previously suggested in vitro or in a single post mortem case report, a wide in vivo confirmation including the screening of four different human matrices was performed for the first time. These metabolites could serve as potential human biomarkers to monitor human 3-MMC consumption effectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Melatonin (MLT) is a circadian hormone that reportedly influences the development and cyclic growth of secondary hair follicles; however, the mechanism of regulation remains unknown. Here, we systematically investigated the role of MLT in hair regeneration using a hair depilation mouse model. We found that MLT supplementation significantly promoted hair regeneration in the hair depilation mouse model, whereas supplementation of MLT receptor antagonist luzindole significantly suppressed hair regeneration. By analysing gene expression dynamics between the MLT group and luzindole-treated groups, we revealed that MLT supplementation significantly up-regulated Wnt/β-catenin signalling pathway-related genes. In-depth analysis of the expression of key molecules in the Wnt/β-catenin signalling pathway revealed that MLT up-regulated the Wnt/β-catenin signalling pathway in dermal papillae (DP), whereas these effects were facilitated through mediating Wnt ligand expression levels in the hair follicle stem cells (HFSCs). Using a DP-HFSCs co-culture system, we verified that MLT activated Wnt/β-catenin signalling in DPs when co-cultured with HFSCs, whereas supplementation of DP cells with MLT alone failed to activate Wnt/β-catenin signalling. In summary, our work identified a critical role for MLT in promoting hair regeneration and will have potential implications for future hair loss treatment in humans., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

FGF5 functions as a negative regulator of the hair cycle in mammals. It is expressed in the outer root sheath of hair follicles during the late anagen phase of the hair cycle. It functions as a signaling molecule, mediating the transition of the anagen growth phase to catagen regression phase of the hair cycle. Spontaneous and engineered FGF5 mutations in mammalian animal models result in long hair phenotypes. In humans, inherited FGF5 mutations result in trichomegaly (long eyelashes). Knockdown of fgf5 in zebrafish embryos results in inner ear alterations. Alterations in FGF5 expression are also associated with various human pathologies., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Bats constitute about 22% of known mammal species; they have various ecological roles and provide many ecosystem services. Bats suffer from several threats caused by anthropization, including exposure to toxic metals and metalloids. We analyzed 75 papers in a systematic literature review to investigate how species, diet, and tissue type impact bioaccumulation. Most studies documented element accumulation in fur, liver, and kidney; at least 36 metals and metalloids have been measured in bat tissues, among the most studied were mercury and zinc. Comparisons with known toxicological thresholds for other mammals showed concerning values for mercury and zinc in bat hair, lead and some essential metals in liver, and iron and calcium in kidneys. Moreover, accumulation patterns in tissues differed depending on bat diet: insectivorous bats showed higher metal concentrations in fur than in liver and kidney while frugivorous species showed higher values in liver and kidney than in fur. Finally, among the bat species that have been studied in more than two papers, the big brown bat (Eptesicus fuscus) show values of mercury in hair and copper in liver that exceed the known thresholds; as does copper in the liver of the little brown bat (Myotis lucifugus). Most studies have been conducted in temperate North America and Eurasia, areas with the lowest bat species diversity; there is a paucity of data on tropical bat species. This review points out several information gaps in the understanding of metal contamination in bats, including a lack of measured toxicity thresholds specific for bat tissues. Data on trace element bioaccumulation and its associated health effects on bats is important for conservation of bat species, many of which are threatened., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The pathophysiology of Takotsubo syndrome (TTS) is not completely understood and the role of chronic stress is among the main mechanistic links. The aim of this study was to explore whether accumulating hair cortisol concentration (HCC), a novel biomarker of chronic stress, is associated with the occurrence of TTS., Methods: A consecutive series of 18 TTS patients and 36 age and sex matched healthy controls were included in our analysis. Hair samples were collected from participants'' vertex. The proximal 2.5 cm of hair was cut in equal parts of 0.5 cm, reflecting mean cortisol levels in time intervals of 0-15, 15-30, 30-45, 45-60 and 60-75 days prior to hair collection., Results: HCC was higher in TTS group compared to controls at any time point and increased over time starting from 75 days prior to the event. The rate of HCC increase was significantly higher in TTS patients versus controls (beta of interaction = 0.48; 95%CI: 0.36-0.60; p < 0.001)., Conclusions: The steadily increasing trend of HCC in TTS patients suggests that the additive effect of multiple stressful events over several weeks prior TTS onset may disrupt cortisol homeostasis and play a role in TTS pathophysiology., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2023. Published by Elsevier B.V.)

Background: The hypothalamic pituitary adrenal (HPA) axis is a system involved in stress and pregnancy regulation, and hair cortisol concentration (HCC) is a promising biomarker of its activity. Assessing factors that influence HCC in the prenatal period is critical to understand whether and how HPA axis (dys-)regulation influences maternal health and child development, particularly in high-risk populations from low- and middle-income countries (LMICs)., Aims: This study aimed at characterizing preconception and pregnancy HCC with respect to multiple sociodemographic, pregnancy-related, and hair-related factors., Methods: In a sample of N = 2581 pregnant women in Perú, participants from two cohort studies provided a 6 cm scalp hair sample at three prenatal timepoints. Each hair sample was cut into two segments of 3 cm that represent cortisol secretion at four times: preconception, first-, second- and third trimester of pregnancy. Hair cortisol was extracted using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spearman correlations, paired t-tests, and ANOVA were used to assess differences in log-transformed values of HCC (logHCC) across maternal sociodemographic, pregnancy-related, and hair-related factors. Multivariable linear regressions were used to examine independent associations of HCCs with selected correlates., Results: Mean logHCC values showed an increase across the four prenatal periods. Preconception BMI was consistently associated with HCC in all three trimesters, while difficulty accessing basic foods, education, hair dyeing, and infant sex showed time-specific associations with HCCs. In sensitivity analyses, we detected no substantial segment effects in the associations of HCCs with maternal characteristics., Conclusion: This study is the largest to characterize HCC in pregnant women from a LMIC. Our findings provide a foundation for the use of HCC as a biomarker of prenatal HPA axis activity for future studies. This foundation may contribute to finding valid biomarkers of stress-response systems to promote maternal and child health., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bizu Gelaye reports financial support was provided by National Institutes of Health. Bizu Gelaye reports financial support was provided by Roche Diagnostic Operations Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: Non-suicidal self-injury (NSSI) is a highly prevalent phenomenon during adolescence. Nonetheless, research on predictors of the clinical course of NSSI over time is still scarce. The present study aimed at investigating the impact of adverse childhood experiences (ACE) and hypothalamus-pituitary-adrenal (HPA) axis functioning on the longitudinal course of NSSI., Methods: In a sample of n = 51 help-seeking adolescents engaging in NSSI, diurnal cortisol secretion (CAR, cortisol awakening response; DSL, diurnal slope), hair cortisol concentrations and ACE were assessed at baseline. Clinical outcome was defined by change in the frequency of NSSI in the past 6 months measured 12 and 24 months after the baseline assessments. Mixed-effects linear regression models were used to test for effects of ACE and HPA axis functioning on the course of NSSI., Results: ACE and HPA axis functioning did not show main but interaction effects in the prediction of NSSI frequency over time: Adolescents with a low severity of ACE and either an increased CAR or a flattened DSL showed a steep decline of NSSI frequency in the first year followed by a subsequent increase of NSSI frequency in the second year., Conclusions: Our findings could be interpreted in the sense of high diurnal cortisol concentrations in the absence of ACE being favorable for clinical improvement on the short-term but bearing a risk of allostatic load and subsequent increase of NSSI frequency. In contrast, adolescents with severe ACE may benefit from elevated cortisol concentrations leading to slower but lasting decreases of NSSI frequency., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Rationale: Hair is known to preserve diet history and other physiological information during its growth period and is often used in chemical analyses. However, the growth patterns and turnover of hair vary according to the animal species or habitat, so understanding these patterns in the target animal is necessary for interpreting the results of hair analyses. In this study, we aimed to elucidate the growth pattern and dietary information of winter coat hair in captive sika deer (Cervus nippon)., Methods: Experiments involving hair-staining and shaving were conducted to elucidate the growth pattern of sika deer hair. A diet-switching experiment was conducted to ascertain what dietary information is reflected in the carbon and nitrogen stable isotope values of the deer winter coat. Hair samples collected from each body site (head, shoulder, back, and hip) were analyzed using an elemental analyser interfaced with an isotope-ratio mass spectrometer., Results: The winter coat grows from early September to early November, and then stops after that. During the growth period of the winter coat, the hair of the shoulder and back grew at a constant rate. The carbon and nitrogen stable isotope values of hair reflected the deer's feeding history during hair growth, but there seemed to be a time lag in the hip hair., Conclusions: The results suggest that the guard hair of the shoulder is suitable for hair analysis in sika deer. The obtained information on growth patterns and isotopic change of hair from captive sika deer according to diet be useful for interpreting the results of future analyses using hair samples of wild deer., (© 2024 John Wiley & Sons Ltd.)

Machine learning (ML) models have been increasingly employed to predict osteoporosis. However, the incorporation of hair minerals into ML models remains unexplored. This study aimed to develop ML models for predicting low bone mass (LBM) using health checkup data and hair mineral analysis. A total of 1206 postmenopausal women and 820 men aged 50 years or older at a health promotion center were included in this study. LBM was defined as a T-score below - 1 at the lumbar, femur neck, or total hip area. The proportion of individuals with LBM was 59.4% (n = 1205). The features used in the models comprised 50 health checkup items and 22 hair minerals. The ML algorithms employed were Extreme Gradient Boosting (XGB), Random Forest (RF), Gradient Boosting (GB), and Adaptive Boosting (AdaBoost). The subjects were divided into training and test datasets with an 80:20 ratio. The area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and an F1 score were evaluated to measure the performances of the models. Through 50 repetitions, the mean (standard deviation) AUROC for LBM was 0.744 (± 0.021) for XGB, the highest among the models, followed by 0.737 (± 0.023) for AdaBoost, and 0.733 (± 0.023) for GB, and 0.732 (± 0.021) for RF. The XGB model had an accuracy of 68.7%, sensitivity of 80.7%, specificity of 51.1%, PPV of 70.9%, NPV of 64.3%, and an F1 score of 0.754. However, these performance metrics did not demonstrate notable differences among the models. The XGB model identified sulfur, sodium, mercury, copper, magnesium, arsenic, and phosphate as crucial hair mineral features. The study findings emphasize the significance of employing ML algorithms for predicting LBM. Integrating health checkup data and hair mineral analysis into these models may provide valuable insights into identifying individuals at risk of LBM., (© 2024. The Author(s).)

Background: Frequent or prolonged exposure to stressors may jeopardize young children's health. The onset of the COVID-19 pandemic, coupled with disruptions in daily routines and social isolation resulting from public health preventive measures, have raised concerns about its potential impact on children' experienced stress, particularly for young children and vulnerable families. However, whether the pandemic was accompanied by changes in physiological stress remains unknown as perceived stress is not a good proxy of physiological stress. This study examined if preschoolers showed increasing hair steroid concentrations following the onset of the COVID-19 pandemic and whether family characteristics may have exacerbated or buffered these changes., Methods: 136 preschoolers (2-4 years) provided hair for steroid measurement (cortisol, dehydroepiandrosterone (DHEA), cortisone, cortisol-to-DHEA ratio, cortisol-to-cortisone ratio) in October-November 2019 (T0) and in July-August 2020 (T1). A 2-centimeter hair segment was analyzed, reflecting steroid production over the two months leading up to collection. Family income, conflict resolution and lack of cohesion, as well as parents' COVID-19 stress were reported by parents. Linear mixed models for repeated measures and Bayes factors were used., Results: No significant changes were noted from before to after the onset of the COVID-19 pandemic for most hair steroids. However, a moderating role of family conflict resolution was noted. Children living with parents with a better ability to resolve conflicts had lower levels of DHEA compared to those who had more difficulty managing conflicts. Additionally, lower levels of family cohesion and income were linked to some steroids, especially DHEA, suggesting that these factors may relate to children's physiological stress. Finally, boys had higher DHEA levels than girls., Conclusion: Our findings suggest that stress biomarkers were comparable from before to during the COVID-19 pandemic. This observation holds true despite the pandemic being perceived by many as a novel, unpredictable, and potentially threatening event. Findings further suggest that family characteristics are associated with hair steroid, especially DHEA, which deserves further investigation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Children's exposure to chronic stress is associated with several health problems. Measuring hair cortisol concentration is particularly useful for studying chronic stress but much is unknown about hair cortisol determinants in children and adolescents, and previous research has often not considered the simultaneous exposure of multiple variables. This research is focused on investigating the relationship between environmental, social and individual factors with hair cortisol concentration in children., Methods: The data used in this study are from the INMA prospective epidemiological cohort study. The assessment of chronic stress was made on the basis of hair samples taken at the age of 11 years in the INMA-Gipuzkoa cohort (n = 346). A metamodel summarizing the hypothesized relationships among environmental, social and individual factors and hair cortisol concentration was constructed based on previous literature. Structural Equation Modelling was performed to examine the relationships among the variables., Results: In the general model higher behavioural problems were associated with higher cortisol levels and an inverse relationship between environmental noise and cortisol levels was observed, explaining 5 % of the variance in HCC. Once stratified by sex these associations were only hold in boys, while no significant effect of any of the study variables was related with cortisol levels in girls. Importantly, maternal stress was positively related to behavioural difficulties in children. Finally, higher traffic-related air pollution and lower exposure to neighborhood greenness were related to higher environmental noise., Discussion: This study highlights that simultaneous exposure to different environmental, social and individual characteristics may determine the concentration of hair cortisol. More research is needed and future studies should include this complex view to better understanding of hair cortisol determinants in children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hair cortisol concentration (HCC) reflects the long-term activity of the hypothalamus-pituitary-adrenal (HPA) axis in response to stress. Brain-derived neurotrophic factor DNA methylation (BDNF DNA M ) may affect HCC, and sex and Val66Met may contribute to this association. Thus, the aim of this study was to investigate the associations between HCC and Brain-derived neurotrophic factor (BDNF) DNA M , and the moderating effects of Val66Met and sex. We recruited 191 healthy young participants (96 women, mean age 23.0 ± 2.6 years) and collected body samples to evaluate HCC, and to determine BDNF DNA M and Val66Met genotypes. We analyzed the effects of BDNF DNA M , sex, and Val66Met on HCC. We also evaluated the associations between BDNF DNA M and HCC in groups separated by sex and genotypes. We found a marked association of BDNF DNA M with HCC across men and women. After dividing the data by sex, a positive correlation of HCC with BDNF DNA M was found only in women. There was no substantial moderation effect of Val66Met genotypes on the association between BDNF DNA M and HCC. Therefore, BDNF DNA M was found to have positive association with HCC only in healthy young women, indicating that sex moderates the association of BDNF DNA M with long-term HPA axis activity., (© 2024 The Authors. Stress and Health published by John Wiley & Sons Ltd.)

Introduction: Substance use is highly prevalent among women experiencing intimate partner violence (IPV) and has been associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and resulting cortisol response. Posttraumatic stress disorder (PTSD) symptoms may play an important role in exacerbating the association between cortisol levels and substance use behaviors., Purpose: This study examined the role of PTSD symptoms in the relation between cortisol and past month substance use behaviors. The current study used hair cortisol as an index of past 30-day HPA-axis functioning and ecological momentary assessment (EMA) to characterize substance use behaviors more accurately over a 30-day period., Method: Participants were 90 community women who had experienced physical or sexual IPV in the past 30 days by their current male partner and used any amount of alcohol or drugs (M age = 40.71; 54.4 % white). Participants completed (a) a baseline interview, (b) EMA for 30-days, and (c) a follow up interview where they were asked to provide a hair sample for cortisol analyses. Data collection took place from 2018 to 2020., Results: PTSD severity moderated the relations between cortisol and days of drinking and binge drinking. In the context of high PTSD symptomology, women with high cortisol levels spent, on average, an additional 7.4 days drinking and 8.1 days binge drinking in the past 30 days compared to women with low cortisol levels, in a model adjusted for age., Conclusions: Results highlight the prominent role of PTSD symptoms in the association between cortisol and alcohol use among women experiencing IPV., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2024. Published by Elsevier B.V.)

Measuring trace element concentrations in tissue can be a valuable approach to monitor animal health status. Temporal variation in the absorption, transport, and storage of elements between different tissues can, however, complicate the assessment of element-health relationships. Here, we measured concentrations of selected essential (copper (Cu), zinc (Zn), selenium (Se)) and non-essential (arsenic (As), cadmium (Cd), lead (Pb)) trace elements within blood, liver, kidney, and hair of fallow deer (Dama dama; N=20) and red deer (Cervus elaphus; N=21). Using multivariate regression and structural equation models, we estimated direct and indirect linkages between tissue-specific trace element profiles and long- (body condition) and short-term (serum protein biomarkers for acute inflammation, infection, and malnutrition) health indicators. Trace element concentrations varied markedly and were weakly correlated among tissues, with the exception of Se. After accounting for sex- and site-differences in trace element concentrations, body condition of red deer was directly, and positively, associated to trace element status in liver and hair, but not in kidney. For both deer species, trace element status in blood was directly linked to serum protein status with an indirect positive association to deer body condition. For fallow deer, no direct association between trace element status and body condition was detected in any of the tissues, possibly because of elemental homeostasis, and because all individuals were in good clinical health. This study shows that hair can serve as an effective, non-invasive, biomarker in deer health assessments, yet, to fully uncover trace element-health relationships a variety of sample matrices is preferred., (© 2023. The Author(s).)

Phthalates used in the industry penetrate the environment and negatively affect humans and animals. Hair samples seem to be the best matrix for studies on long-term exposure to phthalates, but till now they were used only in investigations on humans. Moreover, the knowledge of the wild terrestrial animal exposure to phthalates is extremely limited. This study aimed to establish of concentration levels of selected phthalate metabolites (i.e. monomethyl phthalate-MMP, monoethyl phthalate-MEP, mono-isobutyl phthalate-MiBP, monobutyl phthalate-MBP, monobenzyl phthalate-MBzP, mono-cyclohexyl phthalate-MCHP, mono(2-ethylhexyl) phthalate-MEHP and mono-n-octyl phthalate-MOP) in wild boar hair samples using liquid chromatography with mass spectrometry (LC-MS) analysis. MEHP was noted in 90.7% of samples with mean 66.17 ± 58.69 pg/mg (median 49.35 pg/mg), MMP in 59.3% with mean 145.1 ± 310.6 pg/mg (median 64.45 pg/mg), MiBP in 37.0% with mean 56.96 ± 119.4 pg/mg (median < limit of detection-LOD), MBP in 35.2% with mean 19.97 ± 34.38 pg/mg (median < LOD) and MBzP in 1.9% with concentration below limit of quantification. MEP, MCHP, and MOP have not been found in wild boar hair samples during this study. The results have shown that wild boars are exposed to phthalates and hair samples may be used as a matrix during studies on levels of phthalate metabolites in wild animals., (© 2024. The Author(s).)

Background: Past studies on schizophrenia (SCZ) and the stress-sensitive neuroendocrine systems have mostly focused on a single system and traditionally utilized acute biomarkers (e.g., biomarkers from blood, urine and saliva) that poorly match the chronic course of schizophrenia in time span. Using eight biomarkers in hair, this study aimed to explore the functional characteristics of SCZ patients in the hypothalamic-pituitary-adrenocortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes and the interaction between the two axes., Methods: Hair samples were taken from 137 SCZ patients and 73 controls. The SCZ patients were diagnosed by their attending physician according to the Diagnostic and Statistical Manual of Mental Disorders IV and were clinically stable after treatment. Gender, age, BMI, frequency of hair washing, marital status, education level, family history of mental illness and clozapine dosage were concurrently collected as covariates. The 10-item perceived stress scale (PSS-10) and the social readjustment rating scale were used to assess chronic stress status in SCZ patients. Eight hair biomarkers, cortisol, cortisone, dehydroepiandrosterone (DHEA), testosterone, progesterone, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone, were measured by high performance liquid chromatography tandem mass spectrometer. Among them, cortisol, cortisone, DHEA and cortisol/DHEA reflected the functional activity of the HPA axis, and testosterone and progesterone reflected the functional activity of the HPG axis, and cortisol/cortisone reflected the activity of 11β-hydroxysteroid dehydrogenase types 2 (11β-HSD 2), and cortisol/testosterone reflected the HPA-HPG interaction., Results: SCZ patients showed significantly higher cortisone and cortisol/testosterone than controls (p<0.001, η² p =0.180 and p=0.015, η² p =0.031), lower testosterone (p=0.009, η² p =0.034), progesterone (p<0.001, η² p =0.069) and cortisol/cortisone (p=0.001, η² p =0.054). There were significant intergroup differences in male and female progesterone (p=0.003, η² p =0.088 and p=0.030, η² p =0.049) and female testosterone (p=0.028, η² p =0.051). In SCZ patients, cortisol, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone were positively associated with PSS-10 score (ps<0.05, 0.212

Duchenne muscular dystrophy (DMD) is a severe X-linked recessive genetic disorder caused by mutations in the DMD gene, which leads to a deficiency of the dystrophin protein. The main mutation types of this gene include exon deletions and duplications, point mutations, and insertions. These mutations disrupt the normal expression of dystrophin, ultimately leading to the disease. In this study, we reported a case of DMD caused by an insertion mutation in exon 59 (E59) of the DMD gene. The affected child exhibited significant abnormalities in related biochemical markers, early symptoms of DMD, and multiple gray hair. His mother and sister were carriers with slightly abnormal biochemical markers. The mother had mild clinical symptoms, while the sister had no clinical symptoms. Other family members were genetically and physically normal. Sequencing and sequence alignment revealed that the inserted fragment was an Alu element from the AluYa5 subfamily. This insertion produced two stop codons and a polyadenylate (polyA) tail. To understand the impact of this insertion on the DMD gene and its association with clinical symptoms, exonic splicing enhancer (ESE) prediction indicated that the insertion did not affect the splicing of E59. Therefore, we speculated that the insertion sequence would be present in the mRNA sequence of the DMD gene. The two stop codons and polyA tail likely terminate translation, preventing the production of functional dystrophin protein, which may be the mechanism leading to DMD. In addition to typical DMD symptoms, the child also exhibited premature graying of hair. This study reports, for the first time, a case of DMD caused by the insertion of an Alu element into the coding region of the DMD gene. This finding provides clues for studying gene mutations induced by Alu sequence insertion and expands the understanding of DMD gene mutations.

Objective: Childhood trauma may contribute to poor lifelong health in part through programming of the HPA-axis response to future life stressors. To date, empirical evidence shows an association of childhood trauma with dysregulation of the HPA-axis and blunted cortisol reactivity to acute stressors. Here, we conduct an initial examination of childhood trauma as a moderator of changes over time in perceived stress levels and HPA-axis response to a major chronic stressor in adulthood., Methods: Participants were 83 maternal caregivers of children newly diagnosed with cancer who completed the Childhood Trauma Questionnaire (CTQ), and who, over the year following their child's cancer diagnosis, had hair samples collected up to 7 times for the assessment of cortisol and completed monthly measures of perceived stress., Results: CTQ scores were in the expected range for a community sample and associated with changes in perceived stress and cortisol concentration over time (γ =.003, p =.002; γ = -.0004, p =.008, respectively) independently of age, education, treatment intensity and randomization to stress management intervention. Maternal caregivers who endorsed lower childhood trauma showed a steeper decline in perceived stress and a larger increase in cortisol levels across the year than caregivers who recalled more childhood trauma., Conclusions: Findings extend animal models and studies that examine cortisol reactivity to acute stressors and suggest that childhood trauma may program a phenotype that is more psychologically reactive but shows a blunted HPA-axis response to chronic stress. While adaptive in the short-term, this early life programming may incur long-term costs for health. Further work is warranted to examine this possibility., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% ( p < 0.01), APN + 6.20% ( p < 0.001)) and thickness (MNX + 5.14% ( p < 0.001), APN + 10.32% ( p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development.

Telomerase is present in cells with numerous or even un-limited replicative cycles, and some studies suggest it is a stemness marker. In order to determine whether this is the case for the human hair bulbs, an immunohistochemical and ultrastructural study has been carried out using antibodies against telomerase and PCNA (a cell proliferation marker). The observed labeling is similar for the two antibodies here utilized and is mainly nuclear. More frequent telomerase-positive cells are seen in the matrix epithelium of anagen hair bulbs but sparse labeled cells are also seen in the outer root sheath. In late catagen and also in telogen hair follicles only sparse labeled cells are present in the outer root sheath and few cells also in the secondary germinal epithelium formed at the base of the hair bulb in telogen. Electron microscopic immunogold shows a prevalent nuclear distribution and a lower cytoplasmic distribution in sparse cells of anagen bulb matrix that contain few keratin bundles. The nuclear localization is generally seen over the euchromatin or in areas occupied by more compact chromatin that may indicate an activity of telomerase in chromatin assemblage or dis-assemblage. The study concludes that the localization of telomerase is present in cells undergoing proliferation, namely transit amplifying cells of the outer root sheath that are sparsely detected in the lowermost secondary germinal hair bulb also in telogen., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hair follicle development and hair growth are regulated by multiple factors and multiple signalling pathways. The hair follicle, as an important skin appendage, is the basis for hair growth, and it has the functions of safeguarding the body, perceiving the environment and regulating body temperature. Hair growth undergoes a regular hair cycle, including anagen, catagen and telogen. A small amount of physiological shedding of hair occurs under normal conditions, always in a dynamic equilibrium. Hair loss occurs when the skin or hair follicles are stimulated by oxidative stress, inflammation or hormonal disorders that disrupt the homeostasis of the hair follicles. Numerous researches have indicated that oxidative stress is an important factor causing hair loss. Here, we summarize the signalling pathways and intervention mechanisms by which oxidative stress affects hair follicle development and hair growth, discuss existing treatments for hair loss via the antioxidant pathway and provide our own insights. In addition, we collate antioxidant natural products promoting hair growth in recent years and discuss the limitations and perspectives of current hair loss prevention and treatment., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Cacumen platycladi (CP) is a frequently used traditional Chinese medicine to treat hair loss. In this study, CP fermented by Lactiplantibacillus plantarum CCFM1348 increased the proliferation of human dermal papilla cells. In an in vivo assay, compared to nonfermented CP, postbiotics (fermented CP) and synbiotics (live bacteria with nonfermented CP) promoted hair growth in mice. The Wnt/β-catenin signaling pathway plays crucial roles in the development of hair follicles, including growth cycle restart and maintenance. Both postbiotics and synbiotics upregulated β-catenin, a major factor of the Wnt/β-catenin signaling pathway. Postbiotics and synbiotics also increased the vascular endothelial growth factor expression and decreased the BAX/Bcl2 ratio in the dorsal skin of mice. These results suggest that fermented CP by L. plantarum CCFM1348 may promote hair growth through regulating the Wnt/β-catenin signaling pathway, promoting the expression of growth factors and reducing apoptosis.

Background: The hair follicle development process is regulated by sophisticated genes and signaling networks, and the hair grows from the hair follicle. The Tianzhu white yak population exhibits differences in hair length, especially on the forehead and shoulder region. However, the genetic mechanism is still unclear. Isoform sequencing (Iso-seq) technology with advantages in long reads sequencing. Hence, we combined the Iso-seq and RNA-seq methods to investigate the transcript complexity and difference between long-haired yak (LHY) and normal-haired yak (NHY)., Results: The hair length measurement result showed a significant difference between LHY and NHY on the forehead and the shoulder (P-value < 0.001). The skin samples from the forehead and the shoulder of LHY and NHY were pooled for isoform sequencing (Iso-seq). We obtained numerous long transcripts, including novel isoforms, long non-coding RNA, alternative splicing events, and alternative polyadenylation events. Combined with RNA-seq data, we performed differential isoforms (DEIs) analysis between LHY and NHY. We found that some hair follicle and skin development-related DEIs, like BMP4, KRT2, IGF2R, and COL1A2 in the forehead skin; BMP1, KRT1, FGF5, COL2A1, and IGFBP5 in the shoulder skin. Enrichment analysis revealed that DEIs in both two comparable groups significantly participated in skin and hair follicle development-related pathways, like ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways. The results indicated that the hair follicle development of Tianzhu white yak may influence the hair length difference. Besides, the protein-protein interaction (PPI) network of DEIs showed COL2A1 and COL3A1 exhibited a high degree of centrality, and these two genes were suggested as potential candidates for the hair length growth of Tianzhu white yak., Conclusions: The results provided a comprehensive analysis of the transcriptome complexity and identified differential transcripts that enhance our understanding of the molecular mechanisms underlying the variation in hair length growth in Tianzhu white yak., (© 2024. The Author(s).)

In the initial stages of Alopecia Areata (AA), the predominance of hair breakage or exclamation mark hairs serves as vital indicators of disease activity. These signs are non-invasive and are commonly employed in dermatoscopic examinations. Despite their clinical salience, the underlying etiology precipitating this hair breakage remains largely uncharted territory. Our exhaustive review of the existing literature points to a pivotal role for cysteine-a key amino acid central to hair growth-in these mechanisms. This review will probe and deliberate upon the implications of aberrant cysteine metabolism in the pathogenesis of AA. It will examine the potential intersections of cysteine metabolism with autophagy, ferroptosis, immunity, and psychiatric manifestations associated with AA. Such exploration could illuminate new facets of the disease's pathophysiology, potentially paving the way for innovative therapeutic strategies., (© 2024. The Author(s).)

Background: Functional Gastrointestinal Disorders (FGIDs) present a higher prevalence in individuals with Neurodevelopmental Disorders (NDDs). The Stress System and the Gut-Brain axis (GBA) may mediate these relations. We aimed to assess the prevalence and profile of FGIDs in a clinical sample of children with Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) compared to typically developing children (TD) as well as to investigate possible relations between stress-related biomarkers and internalizing/externalizing problems in children with NDDS., Methods: In total, 120 children, aged between 4 and 12 years old, formed three groups (N = 40, each): ADHD, ASD and TD. Salivary cortisol, hair cortisol and serum leptin were measured., Results: The ASD group had more FGID problems than the TD group ( p = 0.001). The ADHD and ASD groups had higher total internalizing/externalizing problems than the TD group ( p < 0.0001, p < 0.0001, p = 0.005, respectively). Children with FGIDs showed more total, internalizing and externalizing problems compared to children without FGIDs ( p < 0.0001, p < 0.0001, p = 0.041, respectively). The ADHD group showed lower AUCg values ( p < 0.0001), while the hair cortisol was higher for the TD group ( p < 0.0001)., Conclusion: In conclusion, children with NDDs had more FGID symptoms and present higher internalizing and externalizing problems. Children with ADHD and FGIDs had more internalizing problems compared to those without FGIDs. No differences in stress-related biomarkers were shown to differentiate children with NDDs with and without FGIDs. Future prospective studies including a greater number of children may elucidate the biological pathways linking these comorbidities.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through a high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% whale oil) were topically applied to the dorsal skin of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained dorsal skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptome analysis also confirmed increases for 20% WO in filaggrin ( Flg ), a gene related to skin barrier function; fibroblast growth factor 21 ( Fgf21 ), which is involved in hair follicle development; and cysteine-rich secretory protein 1 ( Crisp1 ), a candidate gene for alopecia areata. Furthermore, the results of KEGG pathway analysis indicated that 20% WO may have lower stress and inflammatory responses than 3% MXD. Therefore, WO is expected to be a safe hair growth agent.

Objective: To summarize the dynamic and synchronized changes between the hair cycle and dermal adipose tissue as well as the impact of dermal adipose tissue on hair growth, and to provide a new research idea for the clinical treatment of hair loss., Methods: An extensive review of relevant literature both domestic and international was conducted, analyzing and summarizing the impact of dermal adipose precursor cells, mature dermal adipocytes, and the processes of adipogenesis in dermal adipose tissue on the transition of hair cycle phases., Results: Dermal adipose tissue is anatomically adjacent to hair follicles and closely related to the changes in the hair cycle. The proliferation and differentiation of dermal adipose precursor cells promote the transition of hair cycle from telogen to anagen, while mature adipocytes can accelerate the transition from anagen to catagen of the hair cycle by expressing signaling molecules, with adipogenesis in dermal adipose tissue and hair cycle transition signaling coexistence., Conclusion: Dermal adipose tissue affects the transition of the hair cycle and regulates hair growth by secreting various signaling molecules. However, the quantity and depth of existing literature are far from sufficient to fully elucidate its prominent role in regulating the hair cycle, and the specific regulatory mechanisms needs to be further studied.

Introduction: Increasing evidence supports chronic psychological stress as a risk factor for the development of type 2 diabetes. Much less is known, however, about the role of chronic stress in established diabetes., Methods: The aim of the current study was to comprehensively assess chronic stress in a sample of 73 patients with type 2 diabetes and 48 non-diabetic control participants, and to investigate associations with indicators of glycemic control (HbA1c), insulin resistance (HOMA-IR), β-cell functioning (C-peptide), illness duration, and the presence of microvascular complications. Chronic stress was measured using questionnaires [the Perceived Stress Scale (PSS), the Screening Scale of the Trier Inventory of Chronic Stress (SSCS), the Perceived Health Questionnaire (PHQ) as well as the Questionnaire on Stress in Patients with Diabetes-Revised (QSD-R)]; hair cortisol was used as a biological indicator., Results: We found that patients with type 2 diabetes had higher levels of hair cortisol in comparison to the control group ( F (1,112) = 5.3; p  = 0.023). Within the diabetic group, higher hair cortisol was associated with a longer duration of the illness ( r  = 0.25, p  = 0.04). General perceived stress did not show significant associations with metabolic outcomes in type 2 diabetes patients. In contrast, higher diabetes-related distress, as measured with the QSD-R, was associated with lower glycemic control ( r  = 0.28, p  = 0.02), higher insulin resistance ( r  = 0.26, p  = 0.03) and a longer duration of the illness ( r  = 0.30, p  = 0.01)., Discussion: Our results corroborate the importance of chronic psychological stress in type 2 diabetes. It appears, however, that once type 2 diabetes has developed, diabetes-specific distress gains in importance over general subjective stress. On a biological level, increased cortisol production could be linked to the course of the illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Buckert, Streibel, Hartmann, Monzer, Kopf, Szendrödi and Wild.)

Background/aim: Hair-follicle keratinocytes contain high levels of cysteine, which is derived from methionine, rapidly proliferate, and form the hair shaft. The high proliferation rate of hair-follicle keratinocytes resembles that of aggressive cancer cells. In the present study, we determined the effect of a methionine-deficient diet on hair loss (alopecia) in mice with or without homocysteine supplementation., Materials and Methods: Mice were fed a normal rodent diet (2020X, ENVIGO) (Group 1); a methionine-choline-deficient diet (TD.90262, ENVIGO) (Group 2); a methionine-choline-deficient diet with a 10 mg/kg/day supply of homocysteine administered by intra-peritoneal (i.p.) injection for 2 weeks (Group 3). In Group 2, mice were fed a methionine-choline-deficient diet for an additional 2 weeks but with 10 mg/kg/day of i.p. l-homocysteine and the mice were observed for two additional weeks. Subsequently, the mice were fed a standard diet that included methionine. Hair loss was monitored by photography., Results: After 14 days, hair loss was observed in Group 2 mice on a methionine-restricted diet but not in Group 3 mice on the methionine-restricted diet which received i.p. homocysteine. In Group 2, at 2 weeks after methionine restriction, hair loss was not rescued by homocysteine supplementation. However, after restoration of methionine in the diet, hair growth resumed. Thus, after 2 weeks of methionine restriction, only methionine restored hair loss, not homocysteine., Conclusion: Hair maintenance requires methionine in the diet. Future experiments will determine the effects of methionine restriction on hair-follicle stem cells., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Although hair loss contributes to various social and economic, research methods for material development are currently limited. In this study, we established a research model for developing materials for hair growth through the regulation of β -catenin. We confirmed that 100 nM tegatrabetan (TG), a β -catenin inhibitor, decreased the proliferation of human hair follicle dermal papilla cells (HFDPCs) at 72 h. In addition, TG-induced apoptosis suppressed the phosphorylation of GSK-3 β and Akt, translocation of β -catenin from the cytosol to the nucleus, and the expression of cyclin D1. Interestingly, TG significantly increased the G2/M arrest in HFDPCs. Subcutaneous injection of TG suppressed hair growth and the number of hair follicles in C57BL/6 mice. Moreover, TG inhibited the expression of cyclin D1, β -catenin, keratin 14, and Ki67. These results suggest that TG-induced inhibition of hair growth can be a promising model for developing new materials for enhancing β -catenin-mediated hair growth.

Analysis of endocannabinoids (ECs) and N-acylethanolamines (NAEs) in hair is assumed to retrospectively assess long-term EC/NAE concentrations. To inform their use, this study investigated stability of EC/NAE hair concentrations in mothers, fathers, and their children across the perinatal period as well as associations between family members. In a prospective cohort study, EC (AEA, 1-AG/2-AG) and NAE (SEA, PEA, OEA) levels were quantified in hair samples taken four times in mothers (n = 336) and their partners (n = 225) from pregnancy to two years postpartum and in offspring (n = 319) from shortly after birth to two years postpartum. Across the perinatal period, maternal and paternal hair ECs/NAEs showed poor multiple-test consistency (16-36%) and variable relative stability, as well as inconsistent absolute stability for mothers. Regarding children, hair ECs/NAEs evidenced poor multiple-test consistency (4-19%), no absolute stability, and either no or variable relative stability. Hair ECs/NAEs showed small to medium significant associations across the perinatal period within couples and parent-child dyads. Findings suggest hair ECs/NAEs during the perinatal period possess variable stability in adults, albeit more stability in fathers than mothers in this time. This highlights the need to further investigate factors associated with changes in hair ECs/NAEs across time. The first two years of life may be a dynamic phase for the endocannabinoid system in children, potentially characterized by complex within-family correspondence that requires further systematic investigation., (© 2024. The Author(s).)

Introduction: Hair cortisol level has recently been identified as a promising marker for detecting long-term cortisol levels and a marker of hypothalamic-pituitary-adrenal cortex (HPA) axis activity. However, research on the association between obesity and an altered cortisol metabolism remains controversial., Objective: This study aimed to investigate the relationship between hair cortisol levels and overweight and obesity in participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)., Methods: This was a cross-sectional study involving 2,499 participants from the second follow-up (visit 3, 2017-2019) attending research centers in Rio de Janeiro and Rio Grande do Sul states. Hair samples were collected, and cortisol levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. Cortisol levels were classified as low (< 40 pg/mg), medium (40-128 pg/mg), or high (> 128 pg/mg). The participants were classified as eutrophic, overweight, or obese according to their weight (kg) and height (m 2 ). Odds ratios (ORs) with 95% confidence intervals (95%CI) were estimated., Results: Of the 2499 individuals, 30% had eutrophic weight, 40% were overweight, and 30% were obese. Notably, cortisol levels gradually increased with increasing body weight. Among participants with high hair cortisol levels, 41.2% were classified as overweight and 34.2% as obese. Multinomial logistic regression analysis indicated that participants with high cortisol levels were 43% (OR =1.43; 95%CI: 1.02-2.03) more likely to be overweight and 72% (OR =1.72; 95%CI:1.20-2.47) more likely to be obese than participants with low hair cortisol levels. After adjustment for all covariates, high cortisol levels remained associated with obesity (OR = 1.54; 95%CI:1.02-2.31) and overweight (OR =1.33; 95%CI:0.91-1.94)., Conclusion: In the ELSA-Brazil cohort, hair stress were positively associated with overweight and obesity. These results underscore the importance of considering stress and cortisol as potential factors in obesity prevention and intervention efforts, and highlight a novel aspect of the complex relationship between stress and obesity in the Brazilian population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rodrigues, Scaranni, Pereira, da Silva, Silvares, de Araujo, Castilho, Schmidt, Fonseca, Griep and Daliry.)

The Grey allele in horses is causing premature hair greying and susceptibility to melanoma. The causal mutation is a 4.6 kb tandem duplication in intron 6 of the Syntaxin 17 gene. A recent study demonstrated that the most common allele at the Grey locus ( G3 ) involves three tandem copies of this sequence, whilst a more rare allele ( G2 ) has two tandem copies and the wild-type allele ( G1 ) only one copy. The G3 allele is causing fast greying and high incidence of skin melanoma, whereas the G2 allele is causing slow greying and no obvious increase in melanoma incidence. Further somatic copy number expansion has been documented in melanoma tissue from Grey horses. Functional studies showed that this intronic sequence acts as a weak melanocyte-specific enhancer that becomes substantially stronger by the copy number expansion. The Grey mutation is associated with upregulated expression of both Syntaxin 17 and the neighbouring NR4A3 gene in Grey horse melanomas. It is still an open question which of these genes is most important for the phenotypic effects or if causality is due to the combined effect of upregulation of both genes. Interestingly, RNAseq data in the Human Protein Atlas give support for a possible role of NR4A3 because it is particularly upregulated in human skin cancer, and it belongs to a cluster of genes associated with skin cancer and melanin biosynthesis. The Grey mutation and its association with melanoma provide a possibility to study the path to tumour development in numerous Grey horses carrying exactly the same predisposing mutation., Competing Interests: The author reports no conflicts of interest., (© 2024 The Author(s). Published by Upsala Medical Society.)

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

Objective: We compared hair cortisol (HC) with classic tests of the hypothalamic-pituitary-adrenal (HPA) axis in chronic kidney disease (CKD) and assessed its association with kidney and cardiometabolic status., Design and Methods: A cross-sectional study of 48 patients with CKD stages I-IV, matched by age, sex, and BMI with 24 healthy controls (CTR) was performed. Metabolic comorbidities, body composition, and HPA axis function were studied., Results: A total of 72 subjects (age 52.9 ± 12.2 years, 50% women, BMI 26.2 ± 4.1 kg/m 2 ) were included. Metabolic syndrome features (hypertension, dyslipidaemia, glucose, HOMA-IR, triglycerides, waist circumference) and 24-h urinary proteins increased progressively with worsening kidney function (p < 0.05 for all). Reduced cortisol suppression after 1-mg dexamethasone suppression (DST) (p < 0.001), a higher noon (12:00 h pm) salivary cortisol (p = 0.042), and salivary cortisol AUC (p = 0.008) were seen in CKD. 24-h urinary-free cortisol (24-h UFC) decreased in CKD stages III-IV compared with I-II (p < 0.001); higher midnight salivary cortisol (p = 0.015) and lower suppressibility after 1-mg DST were observed with declining kidney function (p < 0.001). Cortisol-after-DST cortisol was >2 mcg/dL in 23% of CKD patients (12.5% in stage III and 56.3% in stage IV); 45% of them had cortisol >2 mcg/dL after low-dose 2-day DST, all in stage IV (p < 0.001 for all). Cortisol-after-DST was lineally inversely correlated with eGFR (p < 0.001). Cortisol-after-DST (OR 14.9, 95% CI 1.7-103, p = 0.015) and glucose (OR 1.3, 95% CI 1.1-1.5, p = 0.003) were independently associated with eGFR <30 mL/min/m 2 ). HC was independently correlated with visceral adipose tissue (VAT) (p = 0.016). Cortisol-after-DST (p = 0.032) and VAT (p < 0.001) were independently correlated with BMI., Conclusion: Cortisol-after-DST and salivary cortisol rhythm present progressive alterations in CKD patients. Changes in cortisol excretion and HPA dynamics in CKD are not accompanied by significant changes in long-term exposure to cortisol evaluated by HC. The clinical significance and pathophysiological mechanisms explaining the associations between HPA parameters, body composition, and kidney damage warrant further study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Boswell, Vega-Beyhart, Blasco, Quintana, Rodríguez, Díaz-Catalán, Vilardell, Claro, Mora, Amor, Casals and Hanzu.)