Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

STAT2/Caspase3 in the diagnosis and treatment of psoriasis.

BACKGROUND: Psoriasis is a classic chronic recurrent inflammatory skin disease characterized by skin inflammation and abnormal biological behaviour of keratinocytes. Although Signal Transducer And Activator Of Transcription 2 (STAT2) was found to play an important role in the Janus kinase (JAK)-STAT signalling pathway and contribute to the pathogenesis of psoriasis, its exact role in psoriasis remains unclear. METHODS: Using bioinformatics analysis, we identified the key pathways that significantly impacted psoriatic lesions. After identifying the critical molecule gene differentially expressed in multiple public databases using the Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis, clinical samples were collected to validate the gene's significance. Its functions and underlying mechanism were also investigated in vitro. Lastly, we evaluated the diagnostic and therapeutic power of the target gene using the receiver operating characteristic curve (ROC), and gene association was assessed using Spearman correlation. RESULTS: A significant correlation was found between cysteine-aspartic acid protease3 (Caspase3) and STAT2, and functional enrichment analysis revealed that they were both significantly up-regulated in psoriatic skin lesions compared to non-lesional tissues. Functional analysis revealed that Caspase3 functioned downstream of STAT2 in psoriasis. Lastly, we found that Caspase3 and STAT2 could be potential biomarkers for diagnosing and treating psoriasis. CONCLUSIONS: In summary, STAT2 overexpression contributes to psoriasis progression by regulating Capase3 phosphorylation to induce excessive apoptosis of keratinocytes. Meanwhile, STAT2 and Capase3 were identified as promising biomarkers for the diagnosis and treatment of psoriasis and could be used for individualized treatments.

Protective roles of tRNA-derived small RNA tRF-Ile-AAT-019 in pathological progression of psoriasis.

Psoriasis is a chronic recurrent inflammatory skin disease that is characterized by abnormal proliferation and differentiation of keratinocytes (KCs), angiogenesis and skin inflammation. Transfer RNA fragments (tRFs) are tRNA-derived small RNAs (tsRNAs), which possess regulatory functions in many diseases. Their potential roles in the pathological development of psoriasis have not been established. We first identified differentially expressed (DE) tRFs from psoriatic skin lesions using small RNA sequencing, and collected additional clinical samples for validation. Then, we investigated the function and mechanism of target tRFs in vitro. As a result of our investigation: we identified 234 DE transcripts in psoriatic skin lesions compared with normal controls. Further functional analysis showed the downregulation of tRF-Ile-AAT-019 in psoriatic lesions plays a critical role in pathogenesis since it could target 3'UTR of the serine protease serpin protein E1 (SERPINE1) gene. We next demonstrated that tRF-Ile-AAT-019 could suppress SERPINE1, thus leading to decreased expressions of vascular endothelial growth factor but increased expressions of keratinocytes (KCs) differentiation markers including Keratin1 and Involucrin. In conclusion, tRF-Ile-AAT-019 plays a protective role in the pathological progression of psoriasis via targeting SERPINE1, resulting in regulation of KCs differentiation and vascular proliferation biomarkers and providing a potential novel targeting pathway for the disease treatment.

Ozone therapy for skin diseases: Cellular and molecular mechanisms.

Ozone is a highly reactive oxidant molecule consisting of triatomic oxygen atoms. Ozone therapy can be achieved using ozonated hydrotherapy, ozonated oil, ozone autohemotherapy, and other innovative dosage forms of ozone products. Ozone is frequently used as a complementary therapy for various cutaneous diseases, including infectious skin diseases, wound healing, eczema, dermatitis, psoriasis, axillary osmidrosis, diabetic foot, and pressure ulcers. In addition, several studies have reported the superior potential of ozone therapy for improving skin and gut microbiomes, as well as antitumour and antiaging treatment. Ozone therapy is an emerging treatment strategy that acts via complex mechanisms, including antioxidant effects, immunomodulatory capacity, and modulation of local microcirculation. Studies assessing the mechanism of ozone have gradually expanded in recent years. This review article aims to summarise and explore the possible molecular biological mechanisms of ozone in cutaneous diseases and provide compelling theoretical evidence for the application of ozone in cutaneous diseases.

Ozonated oil alleviates dinitrochlorobenzene-induced allergic contact dermatitis via inhibiting the FcεRI/Syk signaling pathway. / 医用臭氧油通过抑制FcεRI/Syk信号通路缓解DNCB诱导的变应性接触性皮炎（英文）.

OBJECTIVES: Ozone is widely applied to treat allergic skin diseases such as eczema, atopic dermatitis, and contact dermatitis. However, the specific mechanism remains unclear. This study aims to investigate the effects of ozonated oil on treating 2,4-dinitrochlorobenzene (DNCB)-induced allergic contact dermatitis (ACD) and the underling mechanisms. METHODS: Besides the blank control (Ctrl) group, all other mice were treated with DNCB to establish an ACD-like mouse model and were randomized into following groups: a model group, a basal oil group, an ozonated oil group, a FcεRI-overexpressed plasmid (FcεRI-OE) group, and a FcεRI empty plasmid (FcεRI-NC) group. The basal oil group and the ozonated oil group were treated with basal oil and ozonated oil, respectively. The FcεRI-OE group and the FcεRI-NC group were intradermally injected 25 µg FcεRI overexpression plasmid and 25 µg FcεRI empty plasmid when treating with ozonated oil, respectively. We recorded skin lesions daily and used reflectance confocal microscope (RCM) to evaluate thickness and inflammatory changes of skin lesions. Hematoxylin-eosin (HE) staining, real-time PCR, RNA-sequencing (RNA-seq), and immunohistochemistry were performed to detct and analyze the skin lesions. RESULTS: Ozonated oil significantly alleviated DNCB-induced ACD-like dermatitis and reduced the expressions of IFN-γ, IL-17A, IL-1ß, TNF-α, and other related inflammatory factors (all P<0.05). RNA-seq analysis revealed that ozonated oil significantly inhibited the activation of the DNCB-induced FcεRI/Syk signaling pathway, confirmed by real-time PCR and immunohistochemistry (all P<0.05). Compared with the ozonated oil group and the FcεRI-NC group, the mRNA expression levels of IFN-γ, IL-17A, IL-1ß, IL-6, TNF-α, and other inflammatory genes in the FcεRI-OE group were significantly increased (all P<0.05), and the mRNA and protein expression levels of FcεRI and Syk were significantly elevated in the FcεRI-OE group as well (all P<0.05). CONCLUSIONS: Ozonated oil significantly improves ACD-like dermatitis and alleviated DNCB-induced ACD-like dermatitis via inhibiting the FcεRI/Syk signaling pathway.

Advanced Biomarkers: Therapeutic and Diagnostic Targets in Urticaria.

Urticaria is a type of skin disease characterized by rapid onset of hives (superficial dermis edema, erythema, pruritus, or burning sensation). According to whether the natural course exceeds 6 weeks, urticaria can be divided into acute and chronic urticaria (CU). At present, the evaluation of CU activity mainly depends on the Urticaria Activity Score (UAS), but the evaluation indicators are relatively single, and we need more reliable experimental data for evaluation. We typically summarize advanced biomarkers and several related pathogenic pathways discovered in recent years on urticaria, including the cell adhesion/chemotaxis pathway, interleukin (IL)-6/Janus tyrosine kinase/STAT pathway, IL-17/IL-23 pathway, basophil- and mast cell-related pathway, coagulation/fibrinolysis-related pathways, single-nucleotide polymorphism, and some other pathways. This review aims to find appropriate biomarkers so that we can evaluate disease activity, discover novel therapeutic targets, and predict the patients' response more accurately to therapeutic agents.

Efficacy of topical acidified aliphatic ester for treatment of axillary osmidrosis by rebalancing skin microecology.

This study investigated the mechanism and efficacy of topical acidified aliphatic ester for treatment of axillary osmidrosis (AO). A total of 32 AO patients were enrolled in this study. In the initial pilot study, 20 patients were double-blindly, randomly divided into acidified aliphatic ester or aliphatic ester treatment groups, followed by efficacy evaluation after 4 weeks. Then, all patients (n = 32) were treated with topical acidified aliphatic ester for 16 weeks. Efficacy was evaluated at every 4 weeks, and at 3- and 6-month follow-ups. Changes of pH values and microecology at targeting sites were analyzed. In the first cohort (n = 20) of pilot study, acidified aliphatic ester showed significantly higher curative rate (60% vs 10%, P < .05) and effective rate (90% vs 30%; P < .05) than aliphatic ester. For the next 16 weeks, 25 of 32 cases completed treatment. Curative rate showed gradual and significant increases from 64% to 96% during the treatment courses (P = .001); it slightly but insignificantly decreased at 3- and 6- month follow-ups. Abundance of Corynebacterium and Anaerobic bacteria decreased while Staphylococcus increased after treatments. Axillary pH values negatively correlated with Staphylococcus abundance (r = -.40, P = .01) and positively with Corynebacterium abundance (r = .64, P = .01). We concluded that topical acidified aliphatic ester could effectively alleviate conditions of AO patients by reducing value of axillary pH and rebalancing axillary microecology.

In vivo reflectance confocal microscopy for monitoring actinic keratosis treated with 5-aminolevulinic acid photodynamic therapy.

BACKGROUND: Actinic keratosis (AK) occurs frequently in sun-exposed skin while its diagnosis and treatment were still in exploration. MATERIALS AND METHODS: Thirty two patients with facial AK lesions were selected and examined with reflective confocal microscopy (RCM) firstly, followed by biopsy at the same site. RCM was used to observe AK lesions before 5-aminolevulinic acid photodynamic therapy (ALA-PDT) treatment, after the first treatment, after 4 treatments, and at 1 and 6 months follow-up. Retrospective analysis of RCM images was performed. RESULTS: Thirty two AK cases showed initial RCM microscopic features including disorderly arranged epidermal cells (100%), atypical keratinocytes (100%), and blurry border between the epidermis and dermis (100%). 4 patients quitted trail. After treatments, 24 cases showed basically regular arrangement of epidermal cells, absent atypical keratinocytes, and clear border between epidermis and dermis, while 4 cases improved little. At 1 and 6 months follow-up, 23 cases remained relapse-free while 1 case developed recurrent symptoms. Effective rate of 4 ALA-PDT treatments for AK was 100%; recurrence and cure rates were 4.2% and 82.1%, respectively. CONCLUSION: ALA-PDT is effective to treat AK, while RCM can be recommended for in vivo evaluating and monitoring the effect of ALA-PDT on AK.

The diagnostic value of in vivo reflectance confocal microscopy in actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a pre-neoplastic skin damage caused by sun exposure with a risk of transforming squamous cell carcinoma (SCC) ranging from 0.1%-20%, while it should be differentiated with many diseases such as seborrheic keratosis (SK), discoid lupus erythematosus (DLE), Bowen's disease, and basal cell carcinoma(BCC) et al. Reflectance confocal microscopy (RCM) as a non-invasive method is showing an increasing diagnostic accuracy. Currently, there are a few studies that summarized the characteristics of AK with RCM. AIM: The study aimed to find the diagnostic value of diagnosing actinic keratosis by reflectance confocal microscopy. METHODS: A total of 92 patients with clinical suspicious diagnosis of actinic keratosis were enrolled in this study, and RCM device imaged their lesions. Fifty-three of these patients underwent skin biopsies to confirm the diagnosis. We retrospectively analyzed the results of RCM and histological diagnosis and then summarized the RCM characteristics of biopsy-confirmed lesions. RESULTS: Based on RCM images, 76 of 92 (82.6%) patients were diagnosed with AK, 9 of 92 (9.8%) patients could not be diagnosed by the dermatologist according to RCM. Of all 53 biopsied lesions, 42 (79.2%) were AK, 1 was seborrheic keratosis, 3 were basal cell carcinoma, three were discoid lupus erythematosus, 1 was Bowen's disease, and three were squamous cell carcinoma. CONCLUSION: The value of RCM in the diagnosis and differential diagnosis of AK is good and worthy of clinical application.

Application of blended teaching model based on SPOC and TBL in dermatology and venereology.

BACKGROUND: In this study, we applied the small private online course (SPOC) and team-based learning (TBL) blended teaching model to dermatology and venereology to ensure a higher quality learning experience for clinical medical students. METHODS: A total of 52 fifth-grade clinical undergraduates from Xiangya School of Medicine of Central South University were randomly divided into an experimental (n = 26) and a control group (n = 26). In March 2018, we used the SPOC and TBL blended teaching model in the experimental group and explored the effects of innovative teaching in the dermatology and venereology course, compared with the control group receiving the conventional teaching method. We analyzed the two groups' theoretical assessment scores and questionnaire results to evaluate the efficiency of the new pedagogy. RESULTS: Students in the experimental group had a better understanding than the control group of the dermatology and venereology content and higher scores on the case analysis questions in the final theoretical examination. The results revealed that the majority of the experimental group students agreed that the novel teaching model blended with SPOC&TBL helped them significantly stimulate motivation and develop their ability in self-directed learning, independent thinking, literature retrieval, presentation board, teamwork, communication, and systematic clinical thinking. The teaching satisfaction survey of the two groups showed that the students' satisfaction in the experimental group was significantly higher than in the control group (p < 0.05). CONCLUSIONS: The SPOC&TBL teaching model is better than the traditional one in enriching students' professional knowledge and cultivating their comprehensive ability. It can effectively promote educational quality, improve students' learning effects, and enhance their satisfaction. This method has broad application prospects.

Ozone therapy promotes the differentiation of basal keratinocytes via increasing Tp63-mediated transcription of KRT10 to improve psoriasis.

Psoriasis is a chronic immune-mediated inflammatory dermatosis. Recently, ozone therapy has been applicated to psoriasis treatment; however, the mechanism by which ozone therapy improves psoriasis remains unclear. The excessive proliferation and the differentiation of basal keratinocytes have been considered critical issues during pathological psoriasis process, in which keratin 6 (KRT6) and KRT10 might be involved. In the present study, KRT6, IL-17 and IL-22 protein within psoriasis lesions was decreased, while KRT10 and Tp63 protein in psoriasis lesions was increased by ozone treatment in both patient and IMQ mice psoriatic tissues. In the meantime, ozone treatment down-regulated KRT6 mRNA and protein expression while up-regulated KRT10 mRNA and protein expression within IL-22 treated primary KCs; the cell viability of KCs was suppressed by ozone treatment. Moreover, Tp63 bound to KRT10 promoter region to activate its transcription in basal keratinocytes; the promotive effects of ozone on Tp63 and KRT10 were significantly reversed by Tp63 silence. Both TP63 and KRT10 mRNA expression were significantly increased by ozone treatment in psoriasis lesions; there was a positive correlation between Tp63 and KRT10 expression within tissue samples, suggesting that ozone induces the expression of Tp63 to enhance the expression of KRT10 and the differentiation of keratinocytes, therefore improving the psoriasis. In conclusion, the application of ozonated oil could be an efficient and safe treatment for psoriasis; ozone promotes the differentiation of keratinocytes via increasing Tp63-mediated transcription of KRT10, therefore improving psoriasis.

Icaritin inhibits lung cancer-induced osteoclastogenesis by suppressing the expression of IL-6 and TNF-a and through AMPK/mTOR signaling pathway.

Bone metastasis is one of the common phenomena in the late stage of lung cancer. Inhibition of bone metastasis can improve the survival of lung cancer patients. However, the current drugs for the treatment of bone metastasis have shown little effect on overall survival. Therefore, there is an urgent necessity to identify novel drugs capable of preventing and treating bone metastasis of lung cancer. Our study determined that icaritin (ICT) can inhibit lung cancer-mediated osteoclastogenesis and induce the apoptosis of osteoclasts. Exposure to ICT increased the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK), reduced the activation of mammalian target of rapamycin (mTOR) and decreased the expression of bcl-2. The bioactivity of ICT on osteoclastogenesis was associated with the regulation of the AMPK/mTOR signaling pathway. Blocking AMPK significantly increased osteoclast differentiation, decreased osteoclast apoptosis and canceled the effects of ICT on the phosphorylation of AMPK as well as the inhibition of mTOR and bcl-2. Furthermore, ICT decreased the levels of IL-6 and TNF-α in osteoclasts, while the AMPK inhibitor compound C significantly abolished the inhibitory effects of ICT on IL-6 and TNF-α. Thus, the present study demonstrated that ICT may be a potential natural agent for the treatment of bone metastasis in patients with lung cancer.

[Serum levels of ANP signaling in different degree of allergic asthmatics and its role in the pathogenesis ofallergic asthma].

OBJECTIVE: To investigate the relationship between the severity of allergic asthma and the levels of atrial natriuretic peptide (ANP), and to analyze the potential role of ANP signaling in the pathogenesis of asthma.
 METHODS: We recruited 96 subjects, including 23 healthy volunteers, 25 stable allergic asthmatics, 21 mild allergic asthmatics and 27 moderate allergic asthmatics, from the Affiliated Hospital of Guilin Medical University. ANP, IFN-γ and IL-4 levels in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expressions of natriuretic peptide receptor A (NPRA), transcription factor T-bet and GATA3 were measured by RT-PCR and Western blot.
 RESULTS: The levels of ANP in serum and the expressions of NPRA mRNA and protein in the peripheral blood mononuclear cell (PBMC) from the mild asthma group or the moderate group were elevated compared with those in the stable asthma group or the mild group, respectively (P<0.05). Consistently, expressions of GATA3 and levels of IL-4 showed the same tendency (P<0.05). In addition, levels of ANP in serum were positively correlated with the severity of asthma, whereas negatively correlated with the ratio of T-bet/GATA3 and IFN-γ/IL-4 (r=-0.85, P<0.05; r=-0.88, P<0.05, respectively).
 CONCLUSION: Levels of ANP signaling in serum were significantly increased with the severity of allergic asthma, suggesting a close relation with the pathogenesis of asthma; ANP signaling may play a role in the pathogenesis of allergic asthma through inducing the Th2-type immune response.

[The role of SDF-1/CXCR4 on airway inflammation and airway remodeling in a rat asthma model].

OBJECTIVE: To explore the roles of stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor 4 (CXCR4) on airway inflammation and airway remodeling in rat asthma models. METHODS: Eighteen female SD rats were randomly divided into 3 groups (n = 6): control group, asthmatic 4 weeks group and asthmatic 8 weeks group. The rats were sensitized and inhaled ovalbumin (OVA). After the asthma model was successfully established, the airway pressure was measured. The methods of HE staining and Image-Pro Plus image analysis software were used to detect the changes of eosinophils (EOS), the perimeter of inner bronchial lumen, the wall area, the area of bronchial smooth muscle and the number of smooth muscle cells of airway walls. RT-PCR and Western-blot were used to detect the expression of SDF-1 and CXCR4 in lung tissues among the 3 groups.Immunohistochemistry was used to detect the expression of SDF-1 in airway walls. RESULTS: Compared with the control group, the airway responsiveness, the count of EOS, the area of bronchial wall, the area of bronchial smooth muscle, the number of smooth muscle cells of airway walls in the asthmatic 4 weeks and asthmatic 8 weeks were significantly increased, and significant difference between the 2 asthmatic groups was also observed in the above indexes (P < 0.01) .RT-PCR showed that compared with the control group (SDF-1 was 0.146 ± 0.003 and CXCR4 was 0.281 ± 0.002) , the expression of SDF-1 (0.583 ± 0.004 and 0.724 ± 0.008) and CXCR4 (0.467 ± 0.003 and 0.655 ± 0.002) in lung tissues in the asthmatic 4 weeks and asthmatic 8 weeks were significantly increased (P < 0.01) . In addition, compared with the asthmatic 4 weeks group, the expression of SDF-1 and CXCR4 in lung tissues in the 8 weeks asthmatic group were significantly increased (P < 0.01) . Compared with the control group (0.180 ± 0.009) , the expression of SDF-1 in airway walls in the asthmatic 4 weeks and asthmatic 8 weeks groups (0.270 ± 0.006 and 0.350 ± 0.009) were significantly increased (P < 0.01) . In addition, compared with the asthmatic 4 weeks group, the expression of SDF-1 in airway walls in the 8 weeks asthmatic group was significantly increased (P < 0.01) . The expression of SDF-1 and CXCR4 was correlated positively with the airway responsiveness, the number of EOS, the area of bronchial wall, the area of bronchial smooth muscle and the number of smooth muscle cells of airway walls (P < 0.01). CONCLUSIONS: SDF-1/CXCR4 axis may play a key role in airway inflammation and airway remodeling of asthma.

[Effects of different types of interferon on the expression of HCV replication-related microRNA].

OBJECTIVE: To explore the effects of different types of interferon (IFN) on the expression of hepatitis C virus(HCV) replication-related miRNAs in human hepatocytes. METHODS: The levels of miRNAs in Huh7 cells treated with types I (IFN-α, IFN-ß), II (IFN-γ) and III (IFN-λ1) interferons (IFNs) were determined by real-time quantitative polymerase chain reaction (PCR). The levels of various miRNAs were compared among different IFN treatment groups. RESULTS: The expression of miRNA-196, miRNA-296, miRNA-351, miRNA-431 and miRNA-448 in IFN-α, IFN-ß and IFN-λ1 treated groups was higher than that in control group (474.5 ± 57.7, 436.0 ± 37.8, 431.3 ± 43.5 vs 99.5 ± 2.4; 389.5 ± 44.0, 416.3 ± 36.7, 284.8 ± 20.9 vs 99.0 ± 0.8; 453.3 ± 51.1, 473.8 ± 24.0, 522.0 ± 40.3 vs 99.5 ± 2.1; 288.3 ± 44.9, 294.3 ± 29.9, 450.0 ± 29.5 vs 100.5 ± 2.4; 319.0 ± 35.4, 357.0 ± 27.5, 446.5 ± 61.2 vs 99.8 ± 1.0; all P < 0.05). The expression of miRNA-196, miRNA-351 and miRNA-448 in IFN-γ-treated group (271.3 ± 29.6, 140.5 ± 27.5, 177.8 ± 23.4) was higher than that in control group (all P < 0.05). But the expression of miRNA-431 and miRNA-296 had no significant difference between IFN-γ treated group and control group (both P > 0.05). The expression of miRNA-122 at difference concentrations (10, 100, 1 000 U/ml) of IFN-α, IFN-ß, IFN-γ and IFN-λ1 (10, 100, 1 000 ng/ml) was lower than that in control group (49.3 ± 4.9, 32.0 ± 3.7, 24.5 ± 3.7 vs 99.5 ± 2.1; 53.5 ± 1.9, 35.5 ± 2.7, 25.8 ± 4.0 vs 98.8 ± 1.3; 60.8 ± 7.1, 43.8 ± 4.0, 33.5 ± 4.2 vs 99.3 ± 2.6; 50.0 ± 2.9, 35.5 ± 3.3, 22.3 ± 3.8 vs 100.3 ± 1.5; all P < 0.01). CONCLUSIONS: Different types of IFN increase the expression of miRNAs that inhibit HCV replication and decrease the expression of miRNA-122 that supports HCV replication. Thus the regulation of HCV replication-related miRNA expression is a general anti-HCV mechanism by different types of IFN. However, the regulation pattern by type II IFN is different from those by other types of IFNs, implying that type II IFN has different anti-HCV mechanisms from other types of IFN at miRNA level.

The therapeutic effect of sufficient oxygen-rich PRP injection in facial rejuvenation by multiple objective evaluations in 26 cases.

Background: Ozone can enhance the expression of some growth factors (GFs) in platelet rich plasma (PRP), recent study showed oxygen-rich PRP (ozonized PRP) have better therapeutic effects on bone and joint diseases. PRP injection has been widely used in the treatment of facial rejuvenation, but the efficacy of sufficient oxygen-rich PRP in facial rejuvenation has not been studied. Objective: Firstly, we examined whether ozone treatment can increase the concentration of GFs of PRP in vitro. And then a variety of subjective and objective detection methods were used to evaluate the effect of sufficient(10-12 mL each time for the injection of face and neck) oxygen-rich (ozonized PRP) PRP injection in facial rejuvenation by follow-up for 6 months. At last, we investigated the satisfaction, side effects and pain score of the treatment through a questionnaire survey. Methods: The concentration of main GFs in PRP treated with different dose of ozone in vitro was measured by ELISA. Clinical picture, the collagen thickness of dermis by reflectance confocal microscope(RCM), skin conditions (including spots, ultraviolet (UV) spots, brown spots, red area, pores, wrinkles, texture and porphyrin) by VISIA were collected before treatment and each month follow-up visit after treatment until 6-month follow-up period was finished. Patients' satisfaction, side effects and pain score were collected at the end of follow-up period. Results: PRP treated by high-dose ozone (57 µg/mL, ozone/PRP volume ratio:1/1) in vitro showed a significant increase in endothelial growth factor (EGF) and transforming growth factor-ß (TGF-ß) compared to baseline(P < 0.05). Collagen thickness of forehead, cheek and neck improved significantly compare to the baseline until to the 6 months after treatment. Spots, UV spots, brown spots, red area and texture improved significantly compare to the baseline(P < 0.05). All of participants reported improvement and have a median pain score of 4.19. No serious adverse events were observed. Conclusions: Ozone treatment can increase the concentration of GFs such as EGF and TGF-ß in PRP in vitro. Sufficient oxygen-rich PRP injection may be an effective and promising method to treat facial rejuvenation.

Critical role of epigenetic modification in the pathogenesis of atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease characterised by recurrent eczema-like lesions and severe pruritus, along with drying and decrustation of skin. Current research relates the pathogenesis of atopic dermatitis mainly to genetic susceptibility, abnormal skin barrier function, immune disorders, Staphylococcus aureus colonisation, microbiological dysfunction and vitamin D insufficiency. Epigenetic modifications are distinct genetic phenotypes resulting from environment-driven changes in chromosome functions in the absence of nuclear DNA sequence variation. Classic epigenetic events include DNA methylation, histone protein modifications and non-coding RNA regulation. Increasing evidence has indicated that epigenetic events are involved in the pathogenesis of atopic dermatitis by their effects on multiple signalling pathways which in turn influence the above factors. This review primarily analyses the function of epigenetic regulation in the pathogenesis of atopic dermatitis. In addition, it tries to make recommendations for personalised epigenetic treatment strategies for atopic dermatitis in the future.

WTAP-Mediated N6-Methyladenosine of RNAs Facilitate the Pathophysiology of Atopic Dermatitis.

N6-methyladenosine (m6A) is the most abundant dynamic and reversible internal chemical modification of RNA in eukaryotic cells and is essential in multiple pathophysiological processes. However, it has not been reported in atopic dermatitis (AD). We used Arraystar m6A-mRNA epitranscriptomic microarray to screen for differentially expressed genes and their m6A levels and m6A-related enzymes in patients with AD. We confirmed that the m6A RNA methyltransferase WTAP and 2 candidate differentially expressed genes (S100A9 and SERPINB3) were significantly upregulated in keratinocytes in public data and epidermal lesions of patients with AD. In vitro cell experiments confirmed that WTAP influenced the expression of the 2 candidate differentially expressed genes and promoted primary human epidermal keratinocyte proliferation while inhibiting human epidermal keratinocyte differentiation. Furthermore, we showed that WTAP, S100A9, and SERPINB3 expression correlated with AD severity. Our findings revealed that WTAP-mediated m6A modification promoted the expression of S100A9 and SERPINB3 to aggravate human epidermal keratinocyte proliferation and dysdifferentiation contributing to the pathophysiological development of AD.

Robust dual-cross-linked networks enable stable silicon anodes.

The simultaneous attainment of long cycle life and high energy in Si anodes remains challenging. Herein, we introduce the concept of primary building units as organizing units to construct durable and conductive electrode architectures, which helps to facilitate the coalescence of Si nanoparticles with conductive pathways and prevent nanoparticle aggregation.

Topical Ozone Accelerates Diabetic Wound Healing by Promoting Re-Epithelialization through the Activation of IGF1R-EGFR Signaling.

Ozonated oil increases the healing of chronic diabetic wounds, but the underlying mechanisms remain unclear. We investigated the effect of topical ozonated oil on wound healing in mice with diabetes with diet-induced obesity and further elucidated the role of EGFR and IGF1R signaling in diabetic wound healing. We found that topical ozonated oil accelerated wound healing; increased phosphorylation of IGF1R, EGFR, and VEGFR; and improved vascularization at the wound leading edge in mice with diabetes with diet-induced obesity. Exposure of normal epidermal keratinocytes to ozonated medium (20 µM for 2 hours daily) increased cell proliferation and migration distance by increasing phosphorylation of IGF1R and EGFR and downstream phosphoinositide 3-kinase, protein kinase B, and extracellular signal-regulated kinase. These findings shed light on the mechanism for topical ozone action in chronic wounds and support its potential therapeutic application.