Research Progress on the Correlation of Atopic Dermatitis with Gut Microbiota.

Atopic dermatitis (AD) is a common skin disease, the pathogenesis of which has not been fully elucidated. The gut microbiota is the largest micro-ecosystem in the human body that affects the immune system and skin barrier function. Recent studies have shown that in addition to the environmental factors, skin barrier, genetic factors and immune response, gut microbiota disturbance may also cause AD. This review described the correlation of AD with gut microbiota and existing research status of AD treatment via targeting gut microbiota.

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.

Characteristics of gut microbiota and serum metabolism in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15%-30% of children and 10% of adults globally, with its incidence being influenced by genetic, environmental, and various other factors. While the immune plays a crucial role in the development, the composition of gut microbiota and serum metabolites also contribute to its pathogenesis. SUBJECT: Study the characteristics of gut microbiota and serum metabolites in patients with atopic dermatitis METHOD: In this study, we collected stool and serum samples from 28 AD patients and 23 healthy individuals (NC) for metagenomic sequencing of gut microbiota and non-targeted metabolomic sequencing of serum. RESULT: Our results revealed a lower diversity of gut microbiota in the AD group compared to the NC group. The predominant Phylum in AD patients were Bacteroidetes, Pseudomonas, and Verrucomicrobia, with the most dominant bacterial genus being Faecalibacterium. At the species level, Prevotella copri and Faecalibacterium prausnitzii were found to be the most abundant bacteria. Significant differences in serum metabolite profiles were observed between NC and AD patients, with noticeable variations in metabolite expression levels. The majority of metabolites in the serum of AD patients exhibited low expression, while a few showed high expression levels. Notably, metabolites such as Cholesterol glucuronide, Styrene, Lutein, Betaine, Phosphorylcholine, Taurine, and Creatinine displayed the most pronounced alterations. CONCLUSION: These findings contribute to a further understanding of the complexities underlying this disease.

Photodynamic therapy for recalcitrant plantar warts: Case reports and a literature review.

Plantar wart is one of the most recalcitrant types of cutaneous warts with a high recurrence rate. Recalcitrant plantar warts are resistant to traditional treatments such as cryotherapy. Photodynamic therapy (PDT) is a modern, non-invasive method utilized to treat benign and malignant skin disorders. Several previous studies have reported the effective application of PDT treatment for plantar warts. We reported three cases of recalcitrant plantar warts successfully treated with PDT.

The role of aryl hydrocarbon receptor in vitiligo: a review.

Vitiligo is an acquired autoimmune dermatosis characterized by patchy skin depigmentation, causing significant psychological distress to the patients. Genetic susceptibility, environmental triggers, oxidative stress, and autoimmunity contribute to melanocyte destruction in vitiligo. Due to the diversity and complexity of pathogenesis, the combination of inhibiting melanocyte destruction and stimulating melanogenesis gives the best results in treating vitiligo. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that can regulate the expression of various downstream genes and play roles in cell differentiation, immune response, and physiological homeostasis maintenance. Recent studies suggested that AhR signaling pathway was downregulated in vitiligo. Activation of AhR pathway helps to activate antioxidant pathways, inhibit abnormal immunity response, and upregulate the melanogenesis gene, thereby protecting melanocytes from oxidative stress damage, controlling disease progression, and promoting lesion repigmentation. Here, we review the relevant literature and summarize the possible roles of the AhR signaling pathway in vitiligo pathogenesis and treatment, to further understand the links between the AhR and vitiligo, and provide new potential therapeutic strategies.

Erratum: FAM72A promotes glioma progression by regulating mitophagy through the Pink1/Parkin signaling pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.82949.].

The efficiency and safety of low-dosage isotretinoin therapy for Chinese acne vulgaris patients.

BACKGROUND: Acne vulgaris is one of the most common skin conditions in dermatology clinics. Accumulating evidence has implicated oral low-dosage isotretinoin was an effective treatment for acne with fewer side effects. Currently, the data on low-dosage isotretinoin use in Chinese is limited. AIMS: To investigate the efficiency and safety of low-dosage isotretinoin therapy for Chinese acne patients. METHODS: Three hundred and eighty-eight patients treated with low-dosage isotretinoin (0.2-0.4 mg/kg/d) and who completed the course (120 mg/kg) were enrolled. Medical information on the severity, duration, adverse effects, and outcome of acne was reviewed. RESULTS: The majority (90.2%, n = 350) of patients achieved complete remission, and on average, patients received 13.5 months of treatment. The time between isotretinoin start and the clear date between the mild and moderate groups was not significantly different (74 ± 24 vs. 84 ± 24 days). However, it took longer to resolve for the severe acne group (112 ± 25 days). Follow-up 1 year after completion of the isotretinoin course, 37/350 (10.6%) patients relapsed, but there was no difference in the severity of acne. There were 133 (34.3%), 40 (10.3%), and 14 (2.6%) patients who developed hypercholesterolemia, hypertriglyceridemia, and high LDL, respectively. Thirty-two (8.2%) and 28 patients (7.2%) had elevated serum levels of alanine and aspartate aminotransferases. No values above grade 2 were detected. CONCLUSIONS: This study reaffirms the efficacy and safety of low-dosage oral isotretinoin in Chinese patients with acne vulgaris. Lab investigation could be performed after 2 months of therapy in healthy patients with normal baseline liver function and lipid panel tests.

A Modified NAR Scoring Model Incorporating Immune Infiltration Characteristics to Better Predict Long-Term Survival Following Neoadjuvant Radiotherapy in Rectal Cancer.

(1) Background: The neoadjuvant rectal (NAR) score has been developed as a prognostic tool for survival in locally advanced rectal cancer (LARC). However, the NAR score only incorporates weighted cT, ypT, and ypN categories. This long-term follow-up study aims to modify a novel prognostic scoring model and identify a short-term endpoint for survival. (2) Methods: The prognostic factors for overall survival (OS) were explored through univariate and multivariate analyses. Based on Cox regression modeling, nomogram plots were constructed. Area under the curve (AUC) and concordance indices were used to evaluate the performance of the nomogram. Receiver operating characteristic (ROC) analysis was conducted to compare the efficiency of the nomogram with other prognostic factors. (3) Results: After a long-term follow-up, the 5-year OS was 67.1%. The mean NAR score was 20.4 ± 16.3. Multivariate analysis indicated that CD8+ T-cell, lymphovascular invasion, and the NAR score were independent predictors of OS. The modified NAR scoring model, incorporating immune infiltration characteristics, exhibited a high C-index of 0.739 for 5-year OS, significantly outperforming any individual factor. Moreover, the predictive value of the nomogram was superior to the AJCC stage and pathological complete regression at 3-year, 5-year, and 10-year time points, respectively. Over time, the model's predictions of long-term survival remained consistent and improved in accuracy. (4) Conclusions: The modified NAR scoring model, incorporating immune infiltration characteristics, demonstrates high accuracy and consistency in predicting OS.

Curcumin Alleviates Epidermal Psoriasis-Like Dermatitis and IL-6/STAT3 Pathway of Mice.

Background: To further investigate why curcumin (CUR) can attenuate psoriasis-like dermatitis of mice. Methods and Results: Sixteen mice were randomized into four groups. The control group used carrier cream, and the model and the CUR group were applied with topical 5% imiquimod in the naked mice skin once a day for 6 days (62.5 mg/day/mice). Meanwhile, the control and model mice were given the same dose of saline by oral means, while mice in the CUR groups received oral drug doses of 50 and 100 mg/kg once a day for 6 days, respectively. CUR could largely improve imiquimod-induced lesions of mice. By using the ELISA and qPCR, we found that the protein and mRNA levels of epidermal TNF-α and IL-6 were inhibited by CUR. The phosphorylation levels of STAT3 and its downstream associated protein levels (eg, Cyclin D1, Bcl-2 and Pim1) in skin tissues of different groups were also inhibited by CUR. Furthermore, the results of immunohistochemistry also showed the repressed effect of CUR for the expression of TNF-α, IL-6 and p-STAT3 in psoriasis-like lesions of mice. Conclusion: CUR can effectively ameliorate the featured lesions of psoriasis mice, which may be closely associated with the involvement of IL-6/STAT3 signaling.

Curcumin alleviates imiquimod-induced psoriasis-like inflammation and regulates gut microbiota of mice.

BACKGROUND: As a polyphenolic compound originated from the food spice turmeric, curcumin (CUR) has various pharmacological effects, such as anti-inflammatory, antioxidation, antiproliferative, and antiangiogenic activities. Psoriasis is centered on the overproduction of Th1- and Th2-related cytokines (e.g., interleukin [IL]-23, IL-17, TNF-α, IL-22), which is involved in the occurrence and development of its pathogenesis. However, whether CUR is involved in the treatment of psoriasis and its specific mechanisms are not fully understood. METHODS: In this study, we detected the therapeutic effect of CUR (100 mg/kg/day) on IMQ-induced dermatitis in mice, analyzed by PASI scores, ELISA, HE staining, immunofluorescence. Moreover, we further confirmed the alteration in the relative abundance of the gut microbiota through 16sRNA to explore whether CUR could regulate the gut microbiota of IMQ-induced mice. RESULT: Through intragastric administration, CUR can alleviate psoriasis-like lesions of mice by decreasing PASI scores, reducing the level of IL-6, IL-17A, IL-22, IL-23, TNF-α, and TGF-ß1, promoting the expression of IL-10. Moreover, 16sRNA sequencing revealed that CUR could regulate the alteration in the abundance alteration of gut microbiota related to inflammation, such as Alistipes, Mucispirillum, and Rikenella at genus level. The correlation analysis further confirmed the close association between important microflora and psoriasis-like inflammation indicators. CONCLUSIONS: CUR exerts the effect of alleviating dermatitis of psoriatic mice by regulating Th-17 related inflammatory factors. Moreover, the changes in gut microbiota via CUR may be another factor of relieving IMQ-induced lesions in mice. Therefore, CUR may be a highly promising candidate for the treatment of psoriasis.

Aberrant KAT2A accumulations render TRIM22-low melanoma sensitive to Notch1 inhibitors via epigenetic reprogramming.

BACKGROUND: Aberrant ubiquitin-proteasome system (UPS) triggers various disorders of biological events and contributes to progression of tumorigenesis. The tripartite motif containing 22 (TRIM22) was demonstrated to participate in the progression of multiple malignancies. Nevertheless, the role of TRIM22 in melanoma is still indefinite. This project aims to investigate the biological function of TRIM22 in melanoma and provide novel therapeutical targets. METHODS: Bioinformatic algorithms were used to investigate prognostic significance of TRIM22. The in vitro or in vivo assays were used to explore the functions of TRIM22 in melanoma. The Co-Immunoprecipitation (Co-IP) and in vivo ubiquitination assays were used to assess regulations of TRIM22 on lysine acetyltransferase 2 A (KAT2A). The Chromatin immunoprecipitation (ChIP) assays and luciferase reporter assay were utilized to explore epigenetic regulations of KAT2A on Notch1. RESULTS: Here, we utilized the bioinformatic methods to confirm that TRIM22 is decreased in melanoma than normal tissues. Patients with low TRIM22 levels had shorter survival months than those with high TRIM22 levels. Targeting TRIM22 favors melanoma cell migration, proliferation, and tumor development in vitro and in vivo. Mechanistically, TRIM22 interacts with KAT2A and promotes its degradation in a ubiquitination-dependent manner. Melanoma cells with TRIM22 deficiency depended on KAT2A to enhance malignant progression, including proliferation, migration, and in vivo growth. KEGG analysis determined the positive correlation between KAT2A and Notch signaling. Chromatin Immunoprecipitation (ChIP) assays implicated that KAT2A directly binds to the promoter region of Notch1 and mediates the enrichment of H3K9ac modification. KAT2A activates Notch1 transcriptional levels and sustains the stemness feature of melanoma cells. Nocth1 inhibitor (IMR-1) effectively suppresses the growth of TRIM22low melanoma in vitro and in vivo but fails to inhibit TRIM22high melanoma. CONCLUSION: Together, our study illustrates the mechanism by which the TRIM22-KAT2A-Notch1 axis promotes melanoma progression, and demonstrates that KAT2A/Nocth1 confers an epigenetic vulnerability in TRIM22low melanoma.

A modified melanoma-molGPA scoring model: assessment of survival after and efficacy of different radiotherapy modalities in patients with melanoma brain metastases.

PURPOSE: Patients with malignant melanoma brain metastases (MBMs) have poor prognoses. For MBMs, the Melanoma-molGPA is the most widely used predictive score, but its predictive value remains uncertain in patients fully treated with radiotherapy. We identified MBMs prognostic factors and modified the prognostic scoring model. METHODS: We retrospectively analyzed patients diagnosed with MBMs between December 2010 and November 2021 for prognostic factors influencing overall survival (OS) by univariate and multivariate analyses. Nomogram plots were based on Cox regression modeling. We evaluated overall survival (OS) using Kaplan-Meier survival curves and log-rank tests. RESULTS: The median OS (mOS) was 7.9 months. On multivariate analysis, BRAF mutation status (p < 0.001), number of brain metastases (BM) (p < 0.001), presence of liver metastases (p < 0.001), brain metastases with a midline shift (p = 0.003), Karnofsky Performance Score (p = 0.02), and lymphocyte-to-monocyte ratio (p < 0.0001) were independent OS predictors. These were incorporated into a modified risk-stratification model. Overall, whole-brain radiotherapy (WBRT) did not significantly affect mOS (mOS, 6.89 vs. 8.83 months; p = 0.07). After risk stratification using our model, WBRT resulted in no significant survival benefit in the low-risk group (mOS 10.07 vs. 13.1 months; p = 0.71) but significantly worse prognosis in the high-risk group (mOS, 2.37 vs. 6.92 months; p = 0.026). CONCLUSION: We propose a modified model that accurately distinguishes the prognosis of patients with MBMs and guides decision-making for radiotherapy. Based on this novel model, WBRT should be cautiously selected for high-risk patients.

CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity.

The interaction of PD-L1 with PD-1 is a major immune checkpoint that limits effector T cell function against cancer cells; monoclonal antibodies that block this pathway have been approved in multiple tumor indications. As a next generation therapy, small molecule inhibitors of PD-L1 have inherent drug properties that may be advantageous for certain patient populations compared to antibody therapies. In this report we present the pharmacology of the orally-available, small molecule PD-L1 inhibitor CCX559 for cancer immunotherapy. CCX559 potently and selectively inhibited PD-L1 binding to PD-1 and CD80 in vitro, and increased activation of primary human T cells in a T cell receptor-dependent fashion. Oral administration of CCX559 demonstrated anti-tumor activity similar to an anti-human PD-L1 antibody in two murine tumor models. Treatment of cells with CCX559 induced PD-L1 dimer formation and internalization, which prevented interaction with PD-1. Cell surface PD-L1 expression recovered in MC38 tumors upon CCX559 clearance post dosing. In a cynomolgus monkey pharmacodynamic study, CCX559 increased plasma levels of soluble PD-L1. These results support the clinical development of CCX559 for solid tumors; CCX559 is currently in a Phase 1, first in patient, multicenter, open-label, dose-escalation study (ACTRN12621001342808).

FAM72A promotes glioma progression by regulating mitophagy through the Pink1/Parkin signaling pathway.

Background: There is growing evidence that aberrant expression of FAM72A contributes to biological dysfunction, especially mitochondrial dysfunction. However, its role in most tumors remains unclear, especially in glioma. Methods: Herein, a high-throughput sequencing approach was used here to identify FAM72A as the target molecule. Next, we detected the protein and mRNA expression levels of FAM72A in normal brain tissue (NBT) as well as different grades of glioma tissue. CCK-8, colony formation, Transwell assays, and Western blotting, were all used to determine the molecular effects of FAM72A on glioma cells. Results: FAM72A was significantly upregulated in glioma, was significantly correlated with WHO grade and was associated with poor clinical outcomes. In functional assays, FAM72A was shown to promote glioma cell growth. Subsequent mechanistic studies indicated that FAM72A promoted glioma progression by regulating mitophagy through the Pink1/Parkin signaling pathway. In addition, FAM72A promoted mitophagy and maintained Pink1 stability through the Pink1/Parkin signaling pathway. Finally, FAM72A promoted tumor immune escape by upregulating PD-L1 expression. Conclusion: All of these data indicate that FAM72A confers an aggressive phenotype and poor prognosis on gliomas. Targeting FAM72A might represent a new therapeutic strategy for glioma.

Benvitimod inhibits MCM6-meditated proliferation of keratinocytes by regulating the JAK/STAT3 pathway.

BACKGROUND: Benvitimod (Tapinarof), as a small-molecule topical therapeutical aryl hydrocarbon receptor (AHR)-modulating agent, is in clinical development for treating psoriasis and atopic dermatitis. Benvitimod reduces proinflammatory cytokines in psoriasis by specifically binding and activation of AHR. However, whether benvitimod can inhibit keratinocyte proliferation remains unclear. Minichromosome maintenance protein 6 (MCM6) is a key element of the prereplication complex (pre-RC) assembly which is one of the essential steps in the initiation of DNA replication for cell proliferation. OBJECTIVES: This study aimed to determine whether benvitimod could reduce the excessive proliferation of psoriatic keratinocytes by inhibiting MCM6. METHODS: We examined the inhibitory effect of benvitimod on MCM6-mediated proliferation of keratinocytes by HaCaT cells in vitro and an IMQ-induced psoriatic model of mice in vivo. RESULTS: Epidermal MCM6 expression was enhanced in the skin lesions of psoriatic patients. The experiments further revealed that MCM6 was required for the proliferation of keratinocytes and governed by the IL-22/STAT3 pathway. In addition, the antiproliferation effect of benvitimod is achieved by the inhibition of p-JAK1 and p-JAK2, which further restrained the activation of STAT3 in keratinocytes. Lastly, benvitimod could repressed imiquimod-induced skin lesions and the expression of epidermal MCM6 and p-STAT3 in mice. Moreover, knockdown of AHR in keratinocytes enhanced the activation of JAK1 and JAK2. CONCLUSION: The findings reveal that benvitimod could decrease MCM6-mediated proliferation of keratinocytes by affecting the JAK/STAT3 pathway, thereby serving as a new treatment modality for psoriasis.

Impact of physical self-efficacy on physical activity and physical health among university students / 预防医学

Objective@#To investigate the impact of physical self-efficacy on physical activity and physical health among university students, so as to provide insights into formulation of the strategy to improve physical activity and physical health among university students.@*Methods@#Freshmen and sophomores were sampled from a university in Guangzhou City using a convenience sampling method from December 2021 to April 2022. Students' demographics and types of sport exercises were collected using questionnaire surveys. Physical self-efficacy was tested using the Physical Self-efficacy Scale, and physical activity was measured using the International Physical Activity Questionnaire-Short, while physical health was evaluated using the school physical health standard test. The associations of physical self-efficacy with physical activity and physical health were examined using a multivariable logistic regression model. @*Results@#Totally 4 171 questionnaires were allocated, and 3 811 valid questionnaires were recovered, with a effective recovery rate of 91.37%. The respondents included 1 582 males (41.51%) and 2 229 females (58.49%), and included 1 967 freshmen (51.61%) and 1 844 sophomores (48.39%). The median score of physical self-efficacy was 36 (interquartile range, 7) points, and there were 1 777 students reaching the national standard of physical activity (46.63%) and 1 112 students with excellent and good physical health (29.18%). Multivariable logistic regression analysis showed that physical self-efficacy was a promoting factor for the proportion of reaching the national standard of physical activity (OR=1.054, 95%CI: 1.043-1.064) and excellent and good physical health (OR=1.109, 95%CI: 1.096-1.122) after adjustment for gender, grade, specialty and source of students. @*Conclusion@#The improvement of physical self-efficacy may increase the proportion of reaching the national standard of physical activity and excellent and good physical health among university students.

Nodular and diffuse spindle cell infiltration in keloidal scleroderma: a case report.

Keloidal scleroderma is a variant of scleroderma that presents as firm keloidal nodules or plaques. Due to the similarity in morphology and pathology, it is often distinguished from a hypertrophic scar or keloid. We report a case of keloidal scleroderma with rare nodular and diffuse spindle cell infiltration in histopathology. Recognition of this unusual histopathological feature may help clinicians improve their knowledge and avoid misdiagnosis.

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.