Homocysteine in androgenetic alopecia: A case control study and observational experiments on mice.

OBJECTIVE: To investigate the relationship between homocysteine (HCY) and androgenetic alopecia (AGA). METHODS: A case control study and two observational experiments on mice were conducted. In the first part, a total of 528 Chinese AGA patients and 500 age-matched healthy controls were included. Serum HCY levels of AGA and controls were compared. In the second part, eight mice were divided into two groups. Both groups of mice had their hair removed. AGA group received a DHT injection, and the other as control group. HCY levels in hair follicles (HFs) were detected by ELISA and compared. In the third part, twelve mice were divided into three groups and fed with different concentrations of methionine. After 4 weeks, serum HCY levels, parameters related to hair growth through observation and HE staining, and expression of immunohistochemistry (IHC) hair-growth-related markers Ki67, VEGF, IGF-1, Krt27, FGF9, and TGF-ß1 were compared among the three groups. RESULTS: In the first part, HCY levels were higher in AGA than the controls of both genders. However, there was no difference in HCY levels between groups with varying severity. Rates of hyperhomocysteinemia was higher in AGA patients than the controls. Logistic regression analysis showed serum HCY levels was positively correlated with the incidence of AGA. In the second part, HCY of the HFs in the AGA group was significantly higher than that in the control group. The third part showed that the increase in serum HCY levels inhibited the growth of mice hair, with the less expressed stimulative markers Ki67, VEGF, IGF-1, Krt27, and FGF9, while there was no difference in the expression of inhibitory markers TGF-ß1. CONCLUSION: There is a potential relationship between HCY and AGA. HCY had an inhibitory effect on hair growth. Further studies are necessary to explore the specific mechanism.

IGFBP-rP1 is a potential therapeutic target in androgenic alopecia.

The available interventions for androgenic alopecia (AGA), the most common type of hair loss worldwide, remain limited. The insulin growth factor (IGF) system may play an important role in the pathogenesis of AGA. However, the exact role of IGF binding protein-related protein 1 (IGFBP-rP1) in hair growth and AGA has not been reported. In this study, we first found periodic variation in IGFBP-rP1 during the hair cycle transition in murine hair follicles (HFs). We further demonstrated that IGFBP-rP1 levels were lower in the serum and scalp HFs of individuals with AGA than in those of healthy controls. Subsequently, we verified that IGFBP-rP1 had no cytotoxicity to human outer root sheath cells (HORSCs) and that IGFBP-rP1 reversed the inhibitory effects of DHT on the migration of HORSCs in vitro. Finally, a DHT-induced AGA mouse model was created. The results revealed that the expression of IGFBP-rP1 in murine HFs was downregulated after DHT treatment and that subcutaneous injection of IGFBP-rP1 delayed catagen occurrence and prolonged the anagen phase of HFs in mice with DHT-induced AGA. The present work shows that IGFBP-rP1 is involved in hair cycle transition and exhibits great therapeutic potential for AGA.

Association analysis of the IKZF4 gene with Alopecia Areata in the Chinese Han population.

Objective: The IKZF4(Ikaros family zinc finger 4) gene encodes Eos, a zinc finger transcription factor that belongs to the Ikaros family. High expression of Eos on Treg cells is important for the suppression of autoimmune responses and immune homeostasis. It has been suggested that the SNP in IKZF4 may influence the pathogenesis of AA(alopecia areata). The purpose of this study was to explore the relationship between IKZF4 polymorphism and AA in the Chinese Han population. Methods: We examined 459 patients and 434 controls in this study. The rs1701704 polymorphism was evaluated using HRM analysis and direct sequencing. Results: The prevalence of the C/C, A/C, and A/A genotypes in AA patients was 7.4%, 37.5% and 55.1%, respectively. There were significant differences in genotype distribution and allele frequencies between AA and the control group (P < .0001). The frequency of the C allele in the AA group was significantly higher (P < .0001), and the frequencies of the C allele and C/C genotype in patients with family history were higher (P < .0001; P = .001). Conclusions: The rs1701704 SNP of IKZF4 may be a genetic marker for assessing the risk of AA in the Chinese Han population.

Work from home or office during the COVID-19 pandemic: The different chain mediation models of perceived organizational support to the job performance.

With the coronavirus pandemic in 2019 (COVID-19), work from home (WFH) has become a frequent way of responding to outbreaks. Across two studies, we examined how perceived organizational support influences job performance when employees work in office or work from home. In study 1, we conducted a questionnaire survey of 162 employees who work in office. In study 2, we conducted a questionnaire survey of 180 employees who work from home. We found that perceived organizational support directly affected job performance when employees work in office. When employees work from home, perceived organizational support could not affect job performance directly. However, it could influence job performance indirectly through the separate mediating effects of job satisfaction and work engagement. These findings extend our understanding of the association of perceived organizational support and job performance and enlighten enterprises on improving employees' job performance during the COVID-19 pandemic.

MicroRNA-1246 Inhibits NFATc1 Phosphorylation and Regulates T Helper 17 Cell Activation in the Pathogenesis of Severe Alopecia Areata.

BACKGROUND: We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. OBJECTIVE: To explore the role and mechanism of miR-1246 in severe AA. METHODS: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+IL-17+ cells proportion. ELISA was used to measure cytokine levels. RESULTS: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples. NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+IL-17+ cells proportion and the IL-17F level. CONCLUSION: miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.

The association between experience-based risky choice and mathematical ability.

Mathematical ability has always been considered an important influencing factor in description-based risky choices. Experience-based risky choices, which occur frequently in daily life, are very different from description-based risky choices. The association between experience-based risky choice and mathematical ability remains unknown. This study adopts the feedback paradigm for experience-based risky choice to explore the association between multiple mathematical abilities and experience-based risky choice. The results show that, in experience-based risky choice, mathematical ability did not influence the decision to pursue higher expected value, but it did influence preference for risky. Thus, our study contributes to a more comprehensive view of mathematical ability and risky choice.

Randomized trial of microneedling combined with 2% minoxidil topical solution for the treatment of female pattern hair loss in a Chinese population.

OBJECTIVE: To evaluate the efficacy and safety of 2% minoxidil combined with microneedling in the treatment of female pattern hair loss. METHODS: Forty female patients with female pattern hair loss were randomly divided into two groups with 20 patients each. The control group was treated with 2% minoxidil. The combined treatment group was treated with weekly microneedling in addition to daily minoxidil. The treatment period of both groups was 24 weeks. RESULTS: There were no significant differences in age or duration of disease between the two groups of patients. The effective rate in the combined treatment group was 85%, which was significantly higher than that of the control group (45%). The hair counts were also higher in the combined treatment group. All of the adverse reactions observed during the treatment period were mild. No severe adverse event was observed in either group. CONCLUSION: Microneedling combined with minoxidil had better efficacy for female pattern hair loss during the treatment period and follow-up. Microneedling combined with minoxidil therapy was safe and effective.

How Noise Can Influence Experience-Based Decision-Making under Different Types of the Provided Information.

Pervasive noise undermines many cognitive processes. Across two studies, we examined how noise influences experience-based decision-making and whether the nature of the information provided moderates this influence. Study 1 used the repeated choice paradigm and found that noise can significantly reduce people's performance in experience-based decision-making by increasing the likelihood of choosing the option with the lower expected value. This negative influence can be attenuated when experience-congruent suggestions are provided, but significantly worsened when experience-incongruent suggestions are provided. Study 2 investigated how noise influences decision-making performance in two experience-incongruent conditions differing in error salience. By replicating noise's general negative effect, we found that the noise effect could be attenuated when incongruent suggestions were obvious. We suggest that noise can undermine the information updating and integration process, which is necessary for experience-based decision-making. We also discuss the principles for designing better information aids based on these findings.

How Social Support Impact Teachers' Mental Health Literacy: A Chain Mediation Model.

Teachers have an important social role, and their mental health literacy is very important to their own abilities as educators and to the growth and development of those they educate. This study explored the mechanism underlying the influence of social support on teachers' mental health literacy by conducting a questionnaire survey of 573 teachers. The results showed that social support can influence teachers' mental health literacy not only through the separate effects of life satisfaction and coping tendency but also through the chain mediation effect of life satisfaction and coping tendency; however, the direct effect of social support on the teachers' mental health literacy is not significant. This study is conducive to understanding the internal mechanism underlying the relationship between social support and mental health literacy. It reminded us that when formulating mental health literacy promotion programs for teachers, we should not only provide adequate social support to improve but also should pay attention to improvements in their coping tendencies and life satisfaction.

The PD-1/PD-L1 pathway in murine hair cycle transition: a potential anagen phase regulator.

Programmed cell death protein-1 (PD-1) is primarily recognized as an inhibitory receptor involved in the regulation of immunological tolerance. However, recent studies have indicated that PD-1/PD-L1 signaling could also regulate the functions of nonimmune cells and may be involved in regulating hair biology. In this study, we showed in a mouse model of depilation-induced hair cycling that PD-1/PD-L1 are expressed in the murine epidermis and hair follicle (HF) in a hair cycle-dependent manner. During HF morphogenesis, PD-1 expression was strongly decreased during the anagen phase compared with the catagen and telogen phases. PD-L1 expression was enhanced during the catagen phase compared with the anagen and telogen phases. Moreover, direct blockade of PD-L1 not only accelerated hair anagen phase onset but also delayed catagen progression. In conclusion, our findings indicated that PD-1/PD-L1 signaling may act as a negative regulator of hair cycle transition. Anti-PD-1/PD-L1 therapy may thus be a promising strategy for treating anagen-reduced hair loss.

Serum 25 hydroxyvitamin D levels in alopecia areata, female pattern hair loss, and male androgenetic alopecia in a Chinese population.

BACKGROUND: It has been suggested that low vitamin D levels may affect the development of hair loss. AIMS: Our aim was to evaluate the serum 25-hydroxy vitamin D [25(OH)D] status in Chinese patients with alopecia areata (AA), female pattern hair loss (FPHL), and male androgenetic alopecia (MAGA) compared with healthy individuals. METHODS: We performed a case-control study including 443 AA patients, 657 FPHL patients, 777 MAGA patients, and 2070 normal controls (1064 male and 1006 female healthy individuals) from 2015 to 2017 to analyze the correlation of serum 25(OH)D levels and hair loss in a Chinese population. RESULTS: Serum 25(OH)D levels stratified by age, sex, and season were compared between patients and healthy individuals. AA patients' serum 25(OH)D levels were statistically lower than that of controls (P < .0001, α = .05). Serum 25(OH)D levels of FPHL patients (P < .0001, α = .05) and MAGA patients (P = .0005, α = .05) were also significantly lower than counterpart control subjects. CONCLUSION: Our findings suggest an association between serum 25(OH)D levels and alopecia areata, female pattern hair loss, or male androgenetic alopecia in a Chinese population.

Hyperuricemia is associated with androgenetic alopecia in men: A cross-sectional case-control study.

BACKGROUND: Early androgenetic alopecia (AGA) is patterned hair loss occurring before 30 years. Early AGA is frequently reported in men and carries the risk of obesity, metabolic syndrome, and cardiovascular diseases. Hyperuricemia used to be a minor component of metabolic syndrome. Recently, increasing number of studies has proved that hyperuricemia is an independent risk factor for many cardiovascular diseases and psoriasis. However, none of these studies have examined the relationship between hyperuricemia and AGA. AIMS: To determine the association between hyperuricemia and AGA in men. METHODS: A cross-sectional case-control study was conducted. The medical charts and photographs of men with a clinical diagnosis of AGA were reviewed. The clinical and laboratory data of AGA and control groups were compared. RESULTS: Men with AGA (n = 1312) had higher mean uric acid level (6.25 mg/dL vs 5.97 mg/dL; P < .001) and higher prevalence of hyperuricemia (25.0% vs 15.6%; P < .001) than those without AGA (n = 2624). There was no statistically significant association between AGA severity and hyperuricemia (P = .295). CONCLUSIONS: Men with early AGA have a higher prevalence of hyperuricemia.

Genome-wide expression profiling of long non-coding RNAs and competing endogenous RNA networks in alopecia areata.

BACKGROUND: Long non-coding RNAs (lncRNAs) regulate gene expression in concert with microRNAs (miRNAs) and mRNAs. This study was designed to explore the potential roles of lncRNAs and their related competing endogenous RNA (ceRNA) networks in alopecia areata (AA). METHODS: This study comprised six participants (three AA patients and three healthy individuals) whose serum lncRNA profiles were evaluated by lncRNA sequencing. Following differential expression analysis, and function enrichment analysis, a lncRNA-miRNA-mRNA network was then constructed using various bioinformatics tools and validated using quantitative reverse-transcription PCR (qRT-PCR). RESULTS: We identified 220 mRNAs and 166 lncRNAs that were differentially expressed in AA patients. The differentially expressed mRNAs were predominantly associated with cytokine-cytokine receptor interactions, MAPK signaling and Ras signaling pathways. The differentially expressed lncRNAs were primarily associated with cytokine-cytokine receptor interactions, chemokine signaling pathways, axon guidance, and legionellosis. In addition, qRT-PCR analyses verified the upregulation of AC005562.1, AF131217.1, and RP11-251G23.5 and downregulation of RP11-231E19.1 in AA patients. CONCLUSION: We constructed a complex ceRNA network for AA and discovered that various RP11 lncRNAs including RP11-251G23.5 and RP11-231E19 may play a crucial role in the pathogenesis of AA via the regulation of the cytokine-cytokine receptor interaction pathway, which could serve as a therapeutic target for alopecia areata in clinical interventions.

Identification of blood microRNA alterations in patients with severe active alopecia areata.

BACKGROUND: Alopecia areata (AA) is a common inflammatory disease characterized by cellular infiltration of T cells targeting the anagen-stage hair follicle. Lack of efficacious treatment for AA may be due to little knowledge about its exact cellular mechanism. Studies have demonstrated that microRNAs (miRNAs) play an important role in the regulation of inflammatory skin diseases such as atopic dermatitis and psoriasis. However, little is known about the role of miRNAs in AA. OBJECTIVE: The present study aimed to explore the blood miRNAs alterations in patients with severe active AA. METHODS: We constructed a bipartite miRNA-messenger RNA (mRNA) regulatory network by the validated miRNA-mRNA relationships. Subsequently, the miRNA-miRNA synergistic network was formed in consideration of the Gene Ontology function enrichment of coregulated target genes. Lastly, the functional network was identified by the ingenuity pathway analysis. RESULTS: By using an Agilent microarray that covers 2549 human miRNAs, we identified 36 significantly differentially expressed miRNAs in severe active AA patients. miRNA target gene prediction and functional annotation analysis showed significant enrichment in several pathways including the ribosome, cancer, cell cycle, insulin signaling, transforming growth factor-ßsignaling, and p53 signaling pathways. Analysis of the three kinds of network showed that miR-185-5p, miR-125b-5p, and miR-186-5p might play important and synergistic roles in the active phase of AA. According to the receiver operating characteristic curve analysis, several miRNAs were selected for the quantitative real-time polymerase chain reaction validation. Among the miRNAs, miR-210 and miR-1246 had high prediction with high accuracy. CONCLUSION: Blood dysregulated miRNAs are potentially associated with the severe active AA. These miRNAs could function synergistically and might be promising targets for the development of novel treatments for AA in the future.

Differential expression patterns of specific long noncoding RNAs and competing endogenous RNA network in alopecia areata.

BACKGROUND: Long noncoding RNAs (lncRNAs) regulate gene expression by acting with microRNAs (miRNAs) and indirectly interact with messenger RNA (mRNAs). However, the roles of specific lncRNA and its related competing endogenous RNAs (ceRNA) network in alopecia areata (AA) are not fully understood. METHODS: The blood lncRNA profiles were obtained by microarray from 10 samples, including five alopecia areata samples and five normal samples. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in alopecia areata. RESULTS: We found 154 differentially expressed lncRNAs and 46 differentially expressed genes (DEGs). The functional enrichment indicated that the DEGs mainly regulated the pathways of focal adhesion, Mucin type O-glycan biosynthesis, and so on. The differentially expressed lncRNA (DElncRNA) involved in the pathway of thyronamine and iodothyronamine metabolism and so on. Through integrated lncRNA-mRNA and miRNA-mRNA pairs, the ceRNA network was constructed, thereafter, six ceRNA subnetworks were identified and subnetwork 1 were found to be significantly associated with the occurrence of alopecia areata. CONCLUSION: Our results showed blood lncRNA expression patterns and a complex ceRNA network in alopecia areata. However, futher studies on blood and tissue verification of these lncRNAs and relative pathways are needed.

Exploring the dynamic changes between pulmonary and cutaneous sarcoidosis based on gene expression.

Sarcoidosis is a disease involving the growth of abnormal inflammatory granulomas and affecting multisystems. It has an unknown etiology. The lung and the skin are the most commonly involved organs. Although large amounts of research have focused on the pathogenesis of sarcoidosis, little is known about the link between cutaneous sarcoidosis and pulmonary sarcoidosis. Moreover, the gene expression profiles provide a novel way to find diagnostic or prognostic biomarkers. Therefore, the aim of this study was to analyze the differentially expressed genes (DEGs) in pulmonary sarcoidosis and cutaneous sarcoidosis patients and to compare them to healthy individuals. DEGs and their biological functions are dynamically dysregulated, and several common disease-related genes and mutual disease progression-related genes were identified which linked pulmonary sarcoidosis and cutaneous sarcoidosis together. The biological functional pathways regulated by these DEGs may allow to define the common mechanism shared by different type of sarcoidosis, providing novel insight into the common pathogenesis of sarcoidosis and opening the way to the development of new therapeutic strategies.

Low-concentration hydrogen peroxide can upregulate keratinocyte intracellular calcium and PAR-2 expression in a human keratinocyte-melanocyte co-culture system.

Hydrogen peroxide (H2O2) may have a biphasic effect on melanin synthesis and melanosome transfer. High H2O2 concentrations are involved in impaired melanosome transfer in vitiligo. However, low H2O2 concentration promotes the beneficial proliferation and migration of melanocytes. The aim of this study was to explore low H2O2 and its mechanism in melanosome transfer, protease-activated receptor-2 (PAR-2) expression and calcium balance. Melanosomes were fluorescein-labeled for clear visualization of their transfer. The expression of protease-activated receptor-2 (PAR-2) in keratinocytes was determined by western blot analysis. Flow cytometry was employed to evaluate the effects of H2O2 on calcium levels in keratinocytes. Fluorescence microscopy showed the upregulation of melanosome transfer into keratinocytes following 0.3 mM H2O2 treatment in the co-cultures rather than in the untreated control groups, which was associated with higher expression of PAR-2 protein and increased calcium concentration. The addition of a PAR-2 antagonist inhibited the positive activity of H2O2 and calcium flow in keratinocytes. When calcium flow was blocked by a calcium chelator, the addition of H2O2 did not increase the PAR-2 expression level in keratinocytes, therefore, inhibiting dendrite formation and melanosome transfer. Low H2O2 concentration promotes melanosome transfer with increased PAR-2 expression level and calcium concentration in keratinocytes. In addition, the interaction between melanocytes and keratinocytes is more beneficial to enhance calcium levels in keratinocytes which mediate melanin transfer. Moreover, low H2O2 concentration promotes dendrite formation, in which extracellular calcium and Par-2 were involved.

Polymorphic CAG Repeat Numbers in the Androgen Receptor Gene of Female Pattern Hair Loss in a Han Chinese Population.

OBJECTIVE: To investigate the association of CAG repeat numbers in the androgen receptor (AR) gene with female pattern hair loss (FPHL) in a Chinese population. METHODS: A total of 200 Han Chinese patients with FPHL (142 Ludwig II and 58 Ludwig III cases) and 200 healthy controls were enrolled in this study. The polymorphism of CAG repeat numbers was analyzed by the fluorescent amplified fragment length polymorphism technique. RESULTS: The CAG biallelic mean length was 23.73 ± 2.04 repeats in Han Chinese FPHL patients and 23.90 ± 2.13 repeats in healthy controls, without any significant difference between the two groups (p = 0.481). In addition, neither the shorter nor the longer CAG repeat numbers were significantly different between FPHL and control subjects (p = 0.726, p = 0.383). CONCLUSION: The polymorphism of CAG repeat numbers of the AR gene may not be the genetic marker of FPHL in a Chinese population.

Identification of Differentially Expressed Genes in Kawasaki Disease Patients as Potential Biomarkers for IVIG Sensitivity by Bioinformatics Analysis.

Kawasaki disease (KD) is a leading cause of acquired heart disease predominantly affecting infants and young children. Intravenous immunoglobulin (IVIG) is applied as the most favorable treatment against KD, but IVIG resistant remains exist. Although several clinical scoring systems have been developed to identify children at highest risk of IVIG resistance, there is a need to identify sufficiently sensitive biomarkers for IVIG treatment. Some differentially expressed genes (DEGs) could be the promising potential biomarkers for IVIG-related sensitivity diagnosis. We employed a systematic and integrative bioinformatics framework to identify such kind of genes. The performance of the candidate genes was evaluated by hierarchical clustering, ROC analysis and literature mining. By analyzing three datasets of KD patients, 34 DEGs of the three groups have been found to be associated with IVIG-related sensitivity. A module of 12 genes could predict resistant group patients with high accuracy, and a module of ten genes could predict responsive group patients effectively with accuracy of 96 %. And three of them are most likely to serve as drug targets or diagnostic biomarkers in the future. Compared with unsupervised hierarchical clustering analysis, our modules could distinct IVIG-resistant patients efficiently. Two groups of DEGs could predict IVIG-related sensitivity with high accuracy, which are potential biomarkers for the clinical diagnosis and prediction of IVIG treatment response in KD patients, improving the prognosis of patients.

Association of Single Nucleotide Polymorphisms in the CYP19A1 Gene with Female Pattern Hair Loss in a Chinese Population.

BACKGROUND: It has been suggested that the single nucleotide polymorphism (SNP) of the CYP19A1 gene encoding aromatase may affect the development of female pattern hair loss (FPHL). OBJECTIVE: Our aim was to investigate the association of CYP19A1 gene SNPs with FPHL in a Chinese population. METHODS: Two hundred Chinese Han patients with FPHL and 200 controls were enrolled into our study. SNaPshot technology was used to detect CYP19A1 gene candidate SNPs. RESULTS: The allele frequencies and distributions of rs6493497 and rs7176005 were significantly different between FPHL and control subjects (p < 0.001 and p < 0.001 vs. p < 0.001 and p = 0.003). CONCLUSION: The rs6493497 and rs7176005 SNPs of the CYP19A1 gene may be genetic markers that influence the risk of FPHL in this Chinese population.