The Roles of Exosomes in Regulating Hair Follicle Growth.

Alopecia is considered a widespread yet troubling health issue, with limited treatment options. As membranous structures derived from cells carrying proteins, nucleic acids and lipids, exosomes functionally medicate intercellular communication and alter the responses of recipient cells, resulting in disease restraint or promotion. Exosomes have broad prospects in diagnosis and treatment of diseases. Studies using animal models and at the cellular level have clearly shown that exosomes from several types of cells, including dermal papilla cells and mesenchymal stem cells, have a notable capacity to promote hair growth, suggesting that exosomes may provide a new option to treat alopecia. Here, we present a thorough review of the most recent progress in the application of exosomes to hair growth.

Paeoniflorin regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in oxidative stressed melanocytes.

BACKGROUND: The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. OBJECTIVES: This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway. METHODS: Human Oxidative Stress Plus array was used to identify the differentially expressed genes between H2O2 + PF group and H2O2 only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1). RESULTS: PF increased the expressions of PDLIM1, RhoA and ROCK1 in H2O2-induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in H2O2-induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated H2O2-induced PIG1, and ROCK1 and Nrf2 in PF-pretreated H2O2-induced PIG3V. CONCLUSIONS: PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in H2O2-induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1.

GWAS of Chronic Spontaneous Urticaria Reveals Genetic Overlap with Autoimmune Diseases, Not Atopic Diseases.

Although chronic spontaneous urticaria (CSU) is a common disease, GWASs of CSU are lacking. We aimed to identify susceptibility SNPs by performing a GWAS in Chinese Han adults with CSU. The discovery cohort included 430 CSU cases and 482 healthy controls. The GWAS findings were validated in 800 CSU cases and 900 healthy controls. Genetic, functional enrichment, and bioinformatic analyses of genome-wide significant SNPs were performed to assess the association between CSU and autoimmunity or atopy. Five genome-wide significant SNPs were identified: rs434124/LILRA3, rs61986182/IGHG1/2, rs73075571/TDGF1, rs9378141/HLA-G, and rs3789612/PTPN22. The first four SNPs were in linkage disequilibrium with autoimmune-related diseases‒associated SNPs and were cis-expression quantitative trait loci in immune cells. The five SNPs-annotated genes were significantly enriched in immune processes. Higher polygenic risk scores and allele frequencies of rs3789612∗T, rs9378141∗C, and rs73075571∗G were significantly associated with autoimmune-related CSU phenotypes, including positive antithyroglobulin IgG, positive anti-FcεRIα IgG, total IgE <40 IU/ml, and positive antithyroid peroxidase IgG but not with atopic or allergic sensitized CSU phenotypes. This GWAS of CSU identifies five risk loci and reveals that CSU shares genetic overlap with autoimmune diseases and that genetic factors predisposing to CSU mainly manifest through associations with autoimmune traits.

Combined therapy of 5-aminolevulinic acid photodynamic therapy and intense pulsed light for rosacea.

Rosacea is difficult to treat. Therefore, new alternative modalities are necessary to demonstrate. The present study was conducted to assess the efficacy and safety of the combined therapy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and intense pulsed light (IPL) for rosacea to provide a new treatment option for rosacea. The study was conducted from November 2017 to April 2019 at the Department of Dermatology, The First Hospital of China Medical University. Patients aged 18-65 years and diagnosed clinically as erythematotelangiectatic (ET) or papulopustular (PP) rosacea were enrolled. Three times of ALA-PDT at 10 days interval followed by 3 times of IPL at 3-4 weeks interval were defined as 1 session and applied to the whole face of each patient. ALA-PDT: 5% ALA, red light (fluency dose 60-100 mW/cm2, 20 min); IPL: 560/590/640 nm, double/triple-pulse mode, pulse width 3.0 to 4.5 ms, delay time 30-40 ms, energy fluency 14-17 J/cm2. Ten patients were enrolled in the study. Among them, 4 patients received only 1 session, while 6 patients received 2 sessions. After all treatments, 50% of patients achieved 75-100% improvement, and 30% achieved 50-75% improvement. Forty percent of patients were graded very satisfaction and 30% graded moderate satisfaction. All noninvasive measurements showed no significant differences among all time points (p > 0.05). The side effects were pain, burning sensation, itching, erythema, desquamation, slight edema, slight exudation, and hyperpigmentation. All of which were tolerable and recovered in a few days. The combined therapy of ALA-PDT and IPL showed an effective option for rosacea with a safety profile.

Investigation of optimal energy or density of a fractional CO2 laser system in the treatment of stable non-segmental vitiligo.

BACKGROUND: Fractional carbon dioxide (CO2) laser has been considered to be an add-on to conventional treatments of vitiligo. OBJECTIVE: This study aimed to evaluate the optimal energy and density of the fractional CO2 laser system in stable non-segmental vitiligo (NSV) patients. METHOD: 48 patients were treated with fractional CO2 laser and sequential phototherapies of narrowband ultraviolet B (NB-UVB), after the CO2 laser treatment, a compound betamethasone solution was topically applied. For the fractional CO2 laser, coverages of 8% and 12.6% were set as low density (Ld) and high density (Hd), and energies of 60 mJ and 80 mJ were set as low energy (Le) and high energy (He), respectively. The patients were randomly assigned to Group A (HeHd), Group B (HeLd) or Group C (LeLd). RESULTS: Either after 3 or 6 months of enrollment, the efficacy of Group C was better than Group B (p < 0.05). No difference was seen between Group A and Group B or Group A and Group C (p > 0.05). More patients complained higher pain score in Group A as compared with Group C (p < 0.05). CONCLUSION: The optimal parameters of the fractional CO2 laser were energy at 60 mJ and density at 8%.

Prediction of Prognostic Risk Factors in Patients with Invasive Candidiasis and Cancer: A Single-Centre Retrospective Study.

Background: Invasive candidiasis is a common cancer-related complication with a high fatality rate. If patients with a high risk of dying in the hospital are identified early and accurately, physicians can make better clinical judgments. However, epidemiological analyses and mortality prediction models of cancer patients with invasive candidiasis remain limited. Method: A set of 40 potential risk factors was acquired in a sample of 258 patients with both invasive candidiasis and cancer. To begin, risk factors for Candida albicans vs. non-Candida albicans infections and persistent vs. nonpersistent Candida infections were analysed using classic statistical methods. Then, we applied three machine learning models (random forest, logistic regression, and support vector machine) to identify prognostic indicators related to mortality. Prediction performance of different models was assessed by precision, recall, F1 score, accuracy, and AUC. Results: Of the 258 patients both with invasive candidiasis and cancer included in the analysis. The median age of patients was 62 years, and 95 (36.82%) patients were older than 65 years, of which 178 (66.28%) were male. And 186 (72.1%) patients underwent surgery 2 weeks before data collection, 100 (39.1%) patients stayed in ICU during hospitalisation, 99 (38.4%) patients had bacterial blood infection, 85 (32.9%) patients had persistent invasive candidiasis, and 41 (15.9%) patients died within 30 days. The usage of drainage catheter and prolonged length of hospitalisation are the dominant risk factors for non-Candida albicans infections and persistent Candida infections, respectively. Risk factors, such as septic shock, history of surgery within the past 2 weeks, usage of drainage tubes, length of stay in ICU, total parenteral nutrition, serum creatinine level, fungal antigen, stay in ICU during hospitalisation, and total bilirubin level, were significant predictors of death. The RF model outperformed the LR and SVM models. Precision, recall, F1 score, accuracy, and AUC for RF were 64.29%, 75.63%, 69.23%, 89.61%, and 91.28%. Conclusions: In this study, the machine learning-based models accurately predicted the prognosis of cancer and invasive candidiasis patients. The algorithm could be used to help clinicians in high-risk patients' early intervention.

Machine-learning based prediction and analysis of prognostic risk factors in patients with candidemia and bacteraemia: a 5-year analysis.

Bacteraemia has attracted great attention owing to its serious outcomes, including deterioration of the primary disease, infection, severe sepsis, overwhelming septic shock or even death. Candidemia, secondary to bacteraemia, is frequently seen in hospitalised patients, especially in those with weak immune systems, and may lead to lethal outcomes and a poor prognosis. Moreover, higher morbidity and mortality associated with candidemia. Owing to the complexity of patient conditions, the occurrence of candidemia is increasing. Candidemia-related studies are relatively challenging. Because candidemia is associated with increasing mortality related to invasive infection of organs, its pathogenesis warrants further investigation. We collected the relevant clinical data of 367 patients with concomitant candidemia and bacteraemia in the first hospital of China Medical University from January 2013 to January 2018. We analysed the available information and attempted to obtain the undisclosed information. Subsequently, we used machine learning to screen for regulators such as prognostic factors related to death. Of the 367 patients, 231 (62.9%) were men, and the median age of all patients was 61 years old (range, 52-71 years), with 133 (36.2%) patients aged >65 years. In addition, 249 patients had hypoproteinaemia, and 169 patients were admitted to the intensive care unit (ICU) during hospitalisation. The most common fungi and bacteria associated with tumour development and Candida infection were Candida parapsilosis and Acinetobacter baumannii, respectively. We used machine learning to screen for death-related prognostic factors in patients with candidemia and bacteraemia mainly based on integrated information. The results showed that serum creatinine level, endotoxic shock, length of stay in ICU, age, leukocyte count, total parenteral nutrition, total bilirubin level, length of stay in the hospital, PCT level and lymphocyte count were identified as the main prognostic factors. These findings will greatly help clinicians treat patients with candidemia and bacteraemia.

Effects of Oral Carotenoids on Oxidative Stress: A Systematic Review and Meta-Analysis of Studies in the Recent 20 Years.

Carotenoids protect organs, tissues, and cells from the damaging action of singlet oxygen, oxygen radicals, and lipid peroxides. This systematic review was sought to evaluate the influence of oral carotenoids on antioxidant/oxidative markers, blood carotenoids levels, and lipid/lipoprotein parameters in human subjects. A comprehensive review of relevant literature was conducted in PubMed, Web of Sciences, and the Cochrane library, from 2000 to December 2020. Randomized controlled trials, case-controlled trials, or controlled trials were identified. A total of eighteen trials were included, with the target populations being healthy subjects in 16 studies, athletes in 1 study, and pregnant women in 1 study. The meta-analysis results showed that carotenoids complex supplementation significantly increased the levels of antioxidative parameters ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) [standardized mean difference (SMD) = 0.468; 95% CI: 0.159-0.776, p = 0.003; SMD = 0.568; 95% CI: 0.190-0.947, p = 0.003] and decreased the blood triglyceride (TG) level (SMD = -0.410, 95% CI: -0.698 to -0.122, p = 0.005). Oral carotenoids supplement significantly increased the blood levels of ß-carotene (SMD = 0.490, 95% CI: 0.123-0.858, p = 0.009), α-tocopherol (SMD = 0.752, 95%CI: 0.020-1.485, p = 0.044), and the intaking durations were 8 weeks. The levels of antioxidative enzymes and other lipid/lipoprotein parameters were not different between subjects receiving carotenoids and controls (p > 0.05). In conclusion, our systematic review showed that the carotenoids complex is beneficial for alleviating potential oxidative stress via interacting with free radicals or decreasing blood TG levels. The intaking duration of carotenoids should be 8 weeks to reach enough concentration for function.

Sporothrix schenckii regulates macrophage inflammatory responses via the c-JUN-induced Dab2 transcription.

Macrophages, which serve as a bridge between innate and adaptive immunity, play an important role in sporotrichosis. Sporothrix schenckii infections can produce immune responses such as macrophage polarization and inflammatory factor secretion. In the early stages of inflammation, the expression of DAB2 in macrophages is increased, which controls the secretion of inflammatory factors and affects the polarization of macrophages. However, the expressions and mechanisms of DAB2 in sporotrichosis are not clear. In this study, we examined the expression of DAB2 and its regulation of inflammatory factors under conditions of Sporothrix schenckii infection. Our results indicated that the Sporothrix schenckii infection increased the expression of DAB2 and revealed a mixed M1/M2-like type of gene expression in BMDMs with the inhibited Il-6, Il1-ß and Arg-1 and induced Tnf-α, Il-10 and Mgl-1. The deficiency of Dab2 gene suspended the changes of cytokines. In addition, JNK activity in BMDMs was inhibited by Sporothrix schenckii infection, leading to an increase in c-JUN. We also identified c-JUN as a transcription factor for Dab2 through chromatin immunoprecipitation and luciferase reporter assays. In an in vivo mouse model, sporotrichosis-induced skin lesions were accompanied with an upregulation of c-JUN and inhibition of JNK activity, which were in accord with findings from in vitro experiments. Taken together, these findings indicate that in the early stages of Sporothrix schenckii infection there is a promotion of DAB2 expression through the JNK/c-JUN pathway, effects that can then control the expression of inflammatory factors.

A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.

Machine-learning based prediction of prognostic risk factors in patients with invasive candidiasis infection and bacterial bloodstream infection: a singled centered retrospective study.

BACKGROUND: Invasive candidal infection combined with bacterial bloodstream infection is one of the common nosocomial infections that is also the main cause of morbidity and mortality. The incidence of invasive Candidal infection with bacterial bloodstream infection is increasing year by year worldwide, but data on China is still limited. METHODS: We included 246 hospitalised patients who had invasive candidal infection combined with a bacterial bloodstream infection from January 2013 to January 2018; we collected and analysed the relevant epidemiological information and used machine learning methods to find prognostic factors related to death (training set and test set were randomly allocated at a ratio of 7:3). RESULTS: Of the 246 patients with invasive candidal infection complicated with a bacterial bloodstream infection, the median age was 63 years (53.25-74), of which 159 (64.6%) were male, 109 (44.3%) were elderly patients (> 65 years), 238 (96.7%) were hospitalised for more than 10 days, 168 (68.3%) were admitted to ICU during hospitalisation, and most patients had records of multiple admissions within 2 years (167/246, 67.9%). The most common blood index was hypoproteinemia (169/246, 68.7%), and the most common inducement was urinary catheter use (210/246, 85.4%). Moreover, the most frequently infected fungi and bacteria were Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis by machine learning method are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, C-Reactive protein (CRP), leukocyte count, neutrophil count, Procalcitonin (PCT), and total bilirubin level. CONCLUSION: Our results showed that the most common candida and bacteria infections were caused by Candida parapsilosis and Acinetobacter baumannii, respectively. The main predictors of death prognosis are serum creatinine level, age, length of stay, stay in ICU during hospitalisation, serum albumin level, CRP, leukocyte count, neutrophil count, PCT and total bilirubin level.

IgE and IgG Anti-Thyroid Autoantibodies in Chinese Patients With Chronic Spontaneous Urticaria and a Literature Review.

Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients (r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels (P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.

A multicenter retrospective analysis of the clinical and pathological characteristics of 1188 cases of actinic keratosis in different ultraviolet radiation intensity areas of China.

BACKGROUND: Actinic keratosis (AK) is a precancerous disease, caused by ultraviolet radiation (UV). OBJECTIVE: To analyze the clinical and pathological characteristics of AK in four areas with different ultraviolet radiation intensities. METHODS: 1188 diagnosed AK patients, from January 2000 to July 2015, in dermatology department of four hospitals were collected. The UV intensity of hospital located cities from high to low is Kunming, Yinchuan, Shenyang and Nanjing. The information comes from medical records, and the pathological types and Keratinocyte Intraepithelial Neoplasia (KIN) grades were checked by two experienced pathologists. All information was conducted a retrospective multicenter research. RESULTS: The patients were mainly middle-aged and elderly female, which was in direct contrast to the majority of men in European. The age of onset in Kunming group was lower than that in Yinchuan Group (p = 0.013) and Nanjing Group (p < 0.01). The course of disease in Kunming group was significantly shorter than that in Nanjing Group (p < 0.001). The lesions were almost located in the exposed area. The proportion of unexposed areas in Shenyang group was significantly higher than that in other groups (p < 0.001). There were statistical differences in pathological morphological classification among the four groups. These differences were not affected by age and gender. The number of KIN III grade patients in Shenyang group was significantly higher than that in other three groups (p < 0.05). CONCLUSION: The Asian patients were mainly female. The clinical characteristics of AK are closely related to UV intensity, and environmental pollution, lifestyle, religious beliefs and other factors are also related.

Efficacy and safety of Resveratrol combined with Ablative Fractional CO2 laser system in the treatment of skin photoaging.

OBJECTIVE: To evaluate the efficacy and safety of resveratrol combined with ablative fractional CO2  laser system (AFL) treating skin photoaging. METHODS: Thirty-two subjects were assigned to the treatment group (TG) or the control group (CG), respectively, applied test product (resveratrol essence) or control product twice daily for 6 months. Each subject was given an AFL treatment or no laser treatment on left or right side of the face randomly. Subjective evaluations by investigators and subjects themselves were conducted after treatment. Melanin index, erythema index, and cuticle moisture content were conducted at baseline and after treatments. Adverse events (AEs) were evaluated during the study period. RESULTS: All subjects in TG achieved improvements of their photoaging signs compared to pre-treatment both the laser side and the non-laser side at 6 months (p < 0.05). On the laser side, TG produced a better improvement than CG at 6 months (p < 0.05). On the laser side, the difference values of MI in TG at the 2 months after enrollment (M2), M3, and M4 were more obvious than those in CG (p < 0.05). On the non-laser side, the difference values of MI in TG at M3, M4, M5, and M6 were more obvious than those of CG (p < 0.05). Subjects in TG were more likely to have tingling and had a faster subsidence of erythema mild edema, and pigmentation induced by AFL compared to CG. CONCLUSION: The resveratrol can improve photoaging alone and add an efficacy to the AFL treatment and subside the AEs induced by AFL.

TMT-Based Quantitative Proteomic Analysis Reveals the Effect of Bone Marrow Derived Mesenchymal Stem Cell on Hair Follicle Regeneration.

Hair loss (HL) is a common chronic problem of poorly defined etiology. Herein, we explored the functionality of bone marrow-derived mesenchymal stem cell (BMSC) and conditioned medium (MSC-CM) as regulators of hair follicle proliferation and regeneration, and the mechanistic basis for such activity. BMSC were cultured and identified in vitro through the induction of multilineage differentiation and the use of a CCK-8 kit. The dorsal skin of mice was then injected with BMSC and MSC-CM, and the impact of these injections on hair cycle transition and hair follicle stem cell (HFSC) proliferation was then evaluated via hematoxylin and eosin (H&E) staining and immunofluorescent (IF) staining. We then conducted a tandem mass tags (TMT)-based quantitative proteomic analysis of control mice and mice treated with BMSC or MSC-CM to identify differentially expressed proteins (DEPs) associated with these treatments. Parallel reaction monitoring (PRM) was utilized as a means of verifying our proteomic analysis results. Herein, we found that BMSC and MSC-CM injection resulted in the transition of telogen hair follicles to anagen hair follicles, and we observed the enhanced proliferation of HFSCs positive for Krt15 and Sox9. Our TMT analyses identified 1,060 and 770 DEPs (fold change＞1.2 or＜0.83 and p ＜ 0.05) when comparing the BMSC vs. control and MSC-CM vs. control groups, respectively. Subsequent PRM validation of 14 selected DEPs confirmed these findings, and led to the identification of Stmn1, Ncapd2, Krt25, and Ctps1 as hub DEPs in a protein-protein interaction network. Together, these data suggest that BMSC and MSC-CM treatment can promote the proliferation of HFSCs, thereby facilitating hair follicle regeneration. Our proteomics analyses further indicate that Krt25, Cpm, Stmn1, and Mb may play central roles in hair follicle transition in this context and may represent viable clinical targets for the treatment of HL.