Roles of gut microbiota in androgenetic alopecia: insights from Mendelian randomization analysis.

Background: Androgenetic alopecia (AGA) is the most common type of androgen-associated hair loss. Previous studies have indicated an association between the gut microbiota and AGA. To delve deeper, we executed a two-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between the gut microbiota and AGA. Methods: A two-sample MR investigation was utilized to delve into the intricate interplay between gut microbiota and AGA. Information regarding 211 gut microbial taxa was sourced from the MiBioGen consortium. The summary statistics of the genome-wide association studies (GWAS) for AGA were obtained from the FinnGen biobank, which included 195 cases and 201,019 controls. Various analytical approaches, including Inverse Variance Weighting (IVW), Weighted Median, MR-Egger, Weighted Mode, and Simple Mode were employed to evaluate the causal impact of gut microbiota on AGA. Sensitivity analyses were subsequently conducted to affirm the robustness of the findings. Results: A two-sample MR investigation unveiled the genus Olsenella, genus Ruminococcaceae UCG-004, and genus Ruminococcaceae UCG-010 were identified as risk factors associated with AGA. In contrast, the family Acidaminococcaceae and genus Anaerofilum, along with the genus Ruminiclostridium 9, demonstrated a protective effect. The sensitivity analyses provided additional assurance that the findings of the current study were less susceptible to the influence of confounding variables and biases. Conclusion: The MR study has established a link between specific gut microbiota and AGA, offering evidence for the identification of more precisely targeted probiotics. This discovery has the potential to aid in the prevention, control, and reversal of AGA progression.

Acquired perforating dermatosis: A clinicopathologic study, and the features of dermoscopy and reflective confocal microscopy of 37 cases.

BACKGROUND: Acquired perforating dermatosis (APD) is a rare skin condition characterized by degenerated materials eliminated from the dermis. Several retrospective studies on APD have been reported; however, few data are available on Chinese APD and their features on dermoscopy and reflective confocal microscope (RCM) assays. OBJECTIVE: The aim of this study was to retrospectively evaluate the clinical and histopathologic data of 37 acquired perforating dermatosis cases, and assess their features on dermoscopy and RCM. METHODS: Thirty-seven APD patients were retrospectively enrolled in our study. We characterized the clinical histopathological features, concomitant diseases, treatment responses, and the dermoscopy and RCM findings. RESULTS: Pruritus was the most common symptom, with the lower extremities as the most predilection sites (86.5%, n = 32; 91.9%, n = 34, respectively). Concomitant diseases were found in 34 patients (92.6%), among which diabetes mellitus was the most common, followed by thyroid nodules, allergic dermatosis, and chronic renal insufficiency. Dermoscopy and RCM assays were performed in 11 patients. The typical RCM images were hyperreflective cord-like structures from the epidermis to dermis. Dermoscopy features of fully developed lesions showed central ulceration with peripheral hairpin-like or loop-like capillaries with characteristic garland arrangements. CONCLUSION: APD is an uncommon skin disorder associated with various systemic conditions in Chinese individuals. Thyroid disorders are an overlooked complication and may play an important role in the development of APD. The results of this study indicate that noninvasive dermoscopy and RCM examination are helpful in the rapid diagnosis and early intervention of APD.

Fulvic Acid Attenuates Atopic Dermatitis by Downregulating CCL17/22.

The main pathogenic factor in atopic dermatitis (AD) is Th2 inflammation, and levels of serum CCL17 and CCL22 are related to severity in AD patients. Fulvic acid (FA) is a kind of natural humic acid with anti-inflammatory, antibacterial, and immunomodulatory effects. Our experiments demonstrated the therapeutic effect of FA on AD mice and revealed some potential mechanisms. FA was shown to reduce TARC/CCL17 and MDC/CCL22 expression in HaCaT cells stimulated by TNF-α and IFN-γ. The inhibitors showed that FA inhibits CCL17 and CCL22 production by deactivating the p38 MAPK and JNK pathways. After 2,4-dinitrochlorobenzene (DNCB) induction in mice with atopic dermatitis, FA effectively reduced the symptoms and serum levels of CCL17 and CCL22. In conclusion, topical FA attenuated AD via downregulation of CCL17 and CCL22, via inhibition of P38 MAPK and JNK phosphorylation, and FA is a potential therapeutic agent for AD.

Atopic dermatitis is associated with abnormal stool form: a population-based cross-sectional study in college students.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Bristol Stool Form Scale (BSFS) is a widely used stool scoring method that could indirectly reflect intestinal function. OBJECTIVES: To evaluate the associations of AD with BSFS. METHODS: This was a population-based cross-sectional study of freshmen in five universities of China. AD diagnosis was performed by dermatologists according to the guideline from the American Academy of Dermatology. BSFS and covariates were collected through an online questionnaire survey. Chronic itch scores were assessed by the numeric rating scales and grouped into quartiles (Q). Mixed logistic regression models were used. Subgroup analysis was conducted by covariates. P value < 0.05 was considered statistically significant. RESULTS: The prevalence of hard stools and loose stools were 8.9% and 7.6%, respectively (20,049 participants). After adjusting covariates, AD was significantly associated with hard stools (OR = 1.38, P < 0.001) and loose stools (OR = 1.24, P = 0.037). In subgroup analysis of hard stool, a stronger effect was observed in intake of milk (> 3 days/week), yogurt (> 3 days/week), pork (< 1 day/week), and higher itch scores (Q4). CONCLUSION: This study found the relationship between AD and abnormal stool forms, and the association with hard stools might be modified by dietary factor.

Association of exposure to artificial light at night with atopic diseases: A cross-sectional study in college students.

The impact of artificial light at night (ALAN) exposure on health has become increasingly prominent. However, little is known about the effect of ALAN exposure on atopic diseases. In this study, a cross-sectional analysis of incoming students was conducted in 5 geographically disperse universities which locate in Changsha (south), Wuhan (central), Xiamen (east), Urumchi (west), and Hohhot (north), respectively. All incoming students who consented to participate were recruited, followed by a health examination and a questionnaire survey. Prevalent atopic diseases were diagnosed by clinicians. Mean ALAN (nanoWatts/cm2/sr) during their adolescence was obtained from the remote sensing observed nighttime light data matching with their residence information, which was obtained from survey. Mixed generalized linear models (log-binomial) were used to estimate the associations, in terms of prevalence ratio (PR) with 95% confidence interval (CI). A total of 20106 participants were included in the analysis. Based on previous work, we chose factors including socioeconomic status, behavioural factors, major air pollutants, and air climatic parameters for adjustment. After full adjustment, the PR for atopic diseases was 1.35 (95% CI: 1.27-1.42; P < 0.001). The effect size of ALAN was the largest for asthma (PR = 1.80; 95% CI: 1.48-2.19; P < 0.001), followed by atopic rhinitis (PR = 1.42; 95% CI: 1.33-1.51; P < 0.001), and atopic dermatitis (PR = 1.20; 95% CI: 1.06-1.35; P = 0.003). Subgroup analyses by covariates showed consistent results. This study revealed that exposure to ALAN during adolescence may contribute to a higher risk of atopic diseases in young adulthood.

Association of antibiotics use in preschool age with atopic and allergic skin diseases in young adulthood: a population-based retrospective cohort study.

BACKGROUND: Overuse and misuse of antibiotics is a public health problem in low-income and middle-income countries. Although the association of antibiotics with atopic and allergic diseases has been established, most studies focused on prenatal exposure and the occurrence of disease in infants or young children. OBJECTIVE: To investigate the association of preschool use of antibiotics with atopic and allergic skin diseases in young adulthood. DESIGN: Population-based retrospective cohort. SETTING AND PARTICIPANTS: The first-year college students (n=20 123) from five universities were investigated. The sampled universities are located in Changsha, Wuhan, Xiamen, Urumqi and Hohhot, respectively. METHODS: We conducted a dermatological field examination and a questionnaire survey inquiring the participants about the frequency of upper respiratory tract infection (URTI) and the preschool antibiotics use (prior to 7 years old). The two-level probit model was used to estimate the associations, and adjusted risk ratio (aRR) and 95% CI were presented as the effect size. RESULTS: A total of 20 123 participants with complete information was included in the final analysis. The frequent antibiotics use intravenously (aRR 1.36, 95% CI 1.14 to 1.62) and orally (aRR 1.18, 95% CI 1.01 to 1.38) prior to 7 years old was significantly associated with atopic dermatitis in young adulthood. Similar trends could be observed in allergic skin diseases among those who use antibiotics orally and intravenously, with RRs of 1.16 (95% CI 1.01 to 1.34) and 1.33 (95% CI 1.13 to 1.57), respectively. CONCLUSIONS: Preschool URTI and antibiotics use significantly increases the risk of atopic and allergic skin diseases in young adulthood.

A novel model of myocardial infarction based on atherosclerosis in mice.

RATIONALE: Coronary artery ligation to induce myocardial infarction (MI) and ischemia injury in mice is typically performed in normal mice, but This is not consistent with disease progression. There should be atherosclerosis (AS) first, followed by MI. OBJECTIVE: We tried a novel model to induce MI that was established on atherosclerosis in mice. This approach was much more consistent with disease progression. METHODS: In this study, Mice lacking apolipoprotein E (ApoE-/-) were randomly divided into four groups. The mice of the control and MI groups were fed normal diet for 24-weeks, while the mice of AS and AS + MI groups were fed high-fat diet (HFD). After 23 weeks, the mice of MI and AS + MI groups were ligated with coronary arteries. A week later, after echocardiography, analysis of plaque and myocardium were conducted on aortic and heart, then the serum, aorta and heart tissues were further detected. RESULTS: Our results showed that AS model mice exhibited significant body weight gain, dyslipidemia and atherosclerotic lesions formation which were in accordance with the pathological changes of AS. Co-treatment with AS and MI led to higher operative mortality and heart pathological were in accordance with the pathological changes of MI. In addition, Echocardiography and NT pro-BNP revealed co-treatment with AS and MI led to deterioration of cardiac function. AS also aggravated myocardial inflammatory cell infiltration and fibrosis post-MI. CONCLUSIONS: Together, it is feasible to establish myocardial infarction model based on atherosclerosis model.

Helianthus Annuus L. Alleviates High-Fat Diet Induced Atherosclerosis by Regulating Intestinal Microbiota, Inhibiting Inflammation and Restraining Oxidative Stress.

Helianthus Annuus L. (HAL) is composed of flavonoids and polysaccharides. Flavonoids have demonstrated beneficial effects on atherosclerosis (AS). The objective of this study was to investigate the anti-atherosclerosis effect and the related mechanism of HAL. In this study, the AS model induced by high-fat diet (HFD) mice that lacked apolipoprotein E (Apoe[Formula: see text] received feed containing 5% HAL for 24 weeks. After administration, the analysis of plaque on aorta was conducted, and the possible mechanisms were further explored. With HAL treatment, the size of atherosclerotic lesions in HFD-induced AS model mice was reduced. HAL ameliorated dyslipidemia and decreased the combined ratio. HAL up-regulated concentrations of superoxide dismutase (SOD), nitric oxide (NO) and glutathione peroxidase (GSH-Px) and down-regulated concentrations of malondialdehyde (MDA) in the aorta. In addition, 16S rRNA analysis showed that HAL also reduced diversity of the intestinal microbiota, decreased the Firmicutes-to-Bacteroidetes ratio, and increased the relative abundance of probiotics such as Akkermansia muciniphila and Lactobacillus. In the end, HAL decreased the permeability of intestine by increasing the levels of occludin and tight junction protein 1 (ZO-1) in the colon, consequently decreasing concentration of interleukin (IL)-6, IL-1[Formula: see text] and tumor necrosis factor-alpha (TNF-[Formula: see text] in serum and mRNA expressions in the aorta. Data showed that HAL alleviates AS by restraining oxidative stress, regulating intestinal microbiota, decreasing intestinal permeability and inhibiting inflammation. Our findings provided novel insights into the role and mechanism of anti-atherogenic potential of HAL.

Acquired Perforating Dermatosis Induced by PD-1 Inhibitor: A Case Report.

ABSTRACT: Acquired perforating dermatoses (APDs) are a group of diverse skin disorders in patients with systemic disease, most commonly chronic renal failure and diabetes mellitus. APD induced by medication has seldom been reported. Anti-PD-1 monoclonal antibody has recently been used as a broad-spectrum, effective, durable, and relatively safe antitumor therapy for various malignancies. Thus far, known side effects involving skin have included rash, pruritus, and vitiligo. Here, we present a rare case of a unilateral linear eruption with histopathologic features of APD in a 36-year-old man during treatment with Terepril monoclonal antibody. To the best of our knowledge, APD induced by the PD-1 inhibitor has not been described in the medical literature.

Behavior of Nutritional Supplements Use in Association With Inflammatory Skin Diseases in Chinese College Students.

Objectives: It is understudied how frequently adolescents use nutritional supplements (NS) and whether the corresponding behavior is associated with skin diseases that may cause unpleasant symptoms and disfigurement. The current study aimed to investigate the prevalence of NS use in Chinese college students and its association with inflammatory skin diseases. Methods: This was a university-based epidemiologic investigation that included 20,138 students who underwent dermatological examinations. A questionnaire survey was conducted to inquire about the use of NS along with related information. Skin diseases were diagnosed by dermatologists during the health examination. Logistic regression models were used for analysis. Adjusted odds ratios (aORs) were presented as the effect size. Results: Survey responses from a total of 20,138 participants were analyzed. Specifically, 18.3% of the participants reported the use of NS in the past year. The use of vitamin C was most frequently reported, accounting for a proportion of 12.9%, followed by vitamin B and mineral supplements. The use of NS was found to be associated with female sex, Han ethnicity, higher annual household income, and a series of healthy lifestyles such as more physical activity, less second-hand smoke exposure, less alcohol consumption, and higher intake of milk and yogurt (p < 0.001). Participants with chronic urticaria (aOR = 1.3; 95% CI, 1.0-1.7), atopic dermatitis (aOR = 1.4; 95% CI, 1.2-1.6), or acne (aOR = 1.17; 95% CI, 1.04-1.31) were more likely to use NS, especially herbs (aOR = 2.7; 95% CI, 1.2-3.7), followed by vitamin B (aOR = 1.6; 95% CI, 1.2-2.0) and mineral supplements (aOR = 1.4; 95% CI, 1.0-2.0). Conclusion: College students with inflammatory skin diseases are more likely to use NS.

Glycogen phosphorylase B promotes cell proliferation and migration through PI3K/AKT pathway in non-small cell lung cancer.

OBJECTIVE: Glycogen phosphorylase B (PYGB), the rate-determining enzyme in glycogen degradation, plays a critical role in progression of various tumors. The present study focused on the potential molecular mechanism toward PYGB in non-small cell lung cancer (NSCLC) progression. METHODS: Expression of PYGB in NSCLC tissues and cell lines was evaluated via quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. Cell viability, proliferation and apoptosis were investigated using 3-(4,5-Dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay, 5-bromo-2-deoxyuridine (BrdU) and flow cytometry, respectively. Cell migration and invasion ability were detected by wound healing and transwell invasion assays, respectively. The in vivo effect of PYGB on NSCLC tumor growth was determined via subcutaneous xenotransplanted tumor model. RESULTS: PYGB was upregulated in NSCLC tissues and cell lines, suggesting a poor prognosis in NSCLC patients. In vitro functional assays indicated that knockdown of PYGB suppressed cell viability, proliferation, migration and invasion, while promoted cell apoptosis in NSCLC. Mechanistically, we found that overexpression of PYGB could activate phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, while these effects were effectively reversed by knockdown of PYGB. In vivo tumorigenesis and PI3K/AKT signaling pathway were also inhibited by PYGB knockdown. CONCLUSIONS: Knockdown of PYGB suppressed NSCLC progression, suggesting PYGB as a novel biomarker and potential molecular therapeutic target for further investigation in NSCLC.

Associations of second-hand smoke exposure with hand eczema and atopic dermatitis among college students in China.

Smoking has been identified as a risk factor for atopic dermatitis and hand eczema, but less is known about the association of exposure to second-hand smoke (SHS) with hand eczema. The study aimed to investigate the association of SHS exposure with hand eczema and atopic dermatitis in a group of adolescents. We conducted a cross-sectional study among first-year college students. SHS exposure was measured by a self-administered questionnaire. Skin diseases were diagnosed by dermatologists in the field survey. Mixed models were used to estimate the associations. A total of 20,129 participants that underwent skin examination and a questionnaire survey were included in the analyses. The prevalence rates of atopic dermatitis and hand eczema were 3.86% and 3.35%, respectively. Crude and adjusted estimates consistently showed that exposure to SHS was significantly associated with atopic dermatitis and hand eczema in a dose-response manner. Attention deficit/hyperactivity disorder mediated minimal or no effect of SHS on hand eczema and atopic dermatitis. Subgroup analysis by type of hand eczema, and sensitivity analysis by excluding data with center effect showed consistent results. Exposure to SHS is an independent but modifiable risk factor for hand eczema and atopic dermatitis in adolescents.

The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget's disease.

Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways - including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD.

Prevalence and patient-reported outcomes of noncommunicable skin diseases among college students in China.

BACKGROUND: The prevalence and health-related quality of life of skin disease have been understudied in adolescents. OBJECTIVE: To investigate the prevalence and relevant patient-reported outcomes of noncommunicable skin diseases in college students. METHODS: First-year college students from 5 universities in China were investigated in the cross-sectional study. Skin diseases were diagnosed by dermatologists in the field survey. Itch and pain, symptoms of depression and anxiety, and sleep quality were measured by validated tools. RESULTS: A total of 28,364 students consented to participate and completed the survey. The prevalence of acne, eczema, chronic urticaria, psoriasis, and vitiligo was 10.3%, 5.8%, 2.6%, 0.16%, and 0.23%, respectively. Eczema and chronic urticaria were associated with lower health utility estimates. Most diseases, but not psoriasis and vitiligo, were associated with the symptoms of depression and sleep disturbance. Itch intensity predicted other patient-reported outcome scores better in healthy controls than in individuals with skin diseases. Sex difference in the associations of skin diseases with patient-reported outcomes was not identified. LIMITATIONS: Cross-sectional study design and limited generalizability to the nonstudent population. CONCLUSION: Skin diseases are associated with moderately impaired emotional well-being, sleep quality, and quality of life, partly attributable to cutaneous symptoms.

Chlamydia muridarum plasmid induces mouse oviduct pathology by promoting chlamydial survival and ascending infection and triggering host inflammation.

BACKGROUND: Infection with plasmid-free Chlamydia trachomatis and Chlamydia muridarum fails to induce severe pathology, however, the mechanisms underlying this phenotype are unclear. OBJECTIVES: To elucidate the mechanisms of chlamydial plasmid-mediated pathology in mouse oviducts. MATERIALS & METHODS: BALB/c mice were intravaginally infected with either plasmid-competent or plasmid-free C. muridarum strains. To compare the survival and ascending infection of these strains, vaginal swabs and genital tract tissues were collected and cultured with HeLa cells to monitor the recovery of live organisms. In addition, Chlamydia strains were intrabursally inoculated into the oviducts of mice to assess pathogenicity. Cytokine levels in the vaginal swabs collected from both the plasmid-competent and plasmid-free C. muridarum-infected mice were detected using Bio-Plex Pro Mouse Cytokine, Chemokine, and Growth Factor Assays. RESULTS: The plasmid-competent C. muridarum strain induced hydrosalpinx formation in mouse oviducts following intravaginal inoculation, however, this was not the case for the plasmid-free C. muridarum strain. The lack of hydrosalpinges in response to the plasmid-free C. muridarum strain correlated with its significantly reduced ability to survive and disseminate to the upper genital tract. Furthermore, the plasmid-free C. muridarum failed to induce hydrosalpinx formation in mice, even when the strain was intrabursally injected into oviducts. A comparison of the cytokine levels in mouse vaginal secretions showed that the plasmid-free C. muridarum strain induced less IL-15, LIF, MIP-2, IL-1α, IL-1ß, TNF-α, and RANTES. CONCLUSION: C. muridarum plasmid contributes to oviduct pathology by promoting bacterial survival and ascending infection, and triggering host inflammatory responses.