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.

Circadian rhythm of cutaneous pruritus. / 皮肤瘙痒的昼夜节律.

One of the most common and significant symptoms for skin disorders is pruritus. Additionally, it serves as a significant catalyst for the exacerbation or reoccurrence of skin diseases. Pruritus seriously affects patients' physical and mental health, and even the quality of life. It brings a heavy burden to the patients, the families, even the whole society. The pathogenesis and regulation mechanisms for pruritus are complicated and have not yet been elucidated. Previous clinical studies have shown that itch worsens at night in scabies, chronic pruritus, atopic dermatitis, and psoriasis, suggesting that skin pruritus may change with circadian rhythm. Cortisol, melatonin, core temperature, cytokines, and prostaglandins are the main regulatory factors of the circadian rhythm of pruritus. Recent studies have shown that some CLOCK genes, such as BMAL1, CLOCK, PER, and CRY, play an important role in the regulation of the circadian rhythm of pruritus by regulating the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor kappa-B (NF-κB) signaling pathways. However, the mechanisms for circadian clock genes in regulation of circadian rhythm of pruritus have not been fully elucidated. Further studies on the mechanism of circadian clock genes in the regulation of circadian rhythm of pruritus will lay a foundation for elucidating the regulatory mechanisms for pruritus, and also provide new ideas for the control of pruritus and the alleviation of skin diseases.

BiVO4-Based Heterojunction Photocathode for High-Performance Photoelectrochemical Hydrogen Peroxide Production.

Photoelectrochemical (PEC) cells provide a promising solution for the synthesis of hydrogen peroxide (H2O2). Herein, an integrated photocathode of p-type BiVO4 (p-BVO) array with tetragonal zircon structure coupled with different metal oxide (MOx, M = Sn, Ti, Ni, and Zn) heterostructure and NiNC cocatalyst (p-BVO/MOx/NiNC) was synthesized for the PEC oxygen reduction reaction (ORR) in production of H2O2. The p-BVO/SnO2/NiNC array achieves the production rate 65.46 µmol L-1 h-1 of H2O2 with a Faraday efficiency (FE) of 76.12%. Combined with the H2O2 generation of water oxidation from the n-type Mo-doped BiVO4 (n-Mo:BVO) photoanode, the unbiased photoelectrochemical cell composed of a p-BVO/SnO2/NiNC photocathode and n-Mo:BVO photoanode achieves a total FE of 97.67% for H2O2 generation. The large area BiVO4-based tandem cell of 3 × 3 cm2 can reach a total H2O2 production yield of 338.84 µmol L-1. This work paves the way for the rational design and fabrication of artificial photosynthetic cells for the production of liquid solar fuel.

Engineering Surface Passivation and Hole Transport Layer on Hematite Photoanodes Enabling Robust Photoelectrocatalytic Water Oxidation.

Regulation of charge transport at the molecular level is essential to elucidating the kinetics of junction photoelectrodes across the heterointerface for photoelectrochemical (PEC) water oxidation. Herein, an integrated photoanode as the prototype was constructed by use of a 5,10,15,20-tetrakis(4-carboxyphenyl) porphyrin-cobalt molecule (CoTCPP) and ZnO on hematite (α-Fe2O3) photoanode. CoTCPP molecules serve as a typical hole transport layer (HTL), accelerating the transport of the photogenerated holes to oxygen evolution cocatalysts (OECs). Meanwhile, ZnO as the surface passivation layer (SPL) can passivate the interfacial state and reduce the level of electron leakage from hematite into the electrolyte. After the integration of OECs, the state-of-the-art α-Fe2O3/ZnO/CoTCPP/OECs photoanode exhibits a distinguished photocurrent density and excellent stability in comparison with pristine α-Fe2O3. The simultaneous incorporation of a ZnO and CoTCPP dual interlayer can effectively modulate the interfacial photoinduced charge transfer for PEC reaction. This work provides in-depth insights into interfacial charge transfer across junction electrodes and identifies the critical roles of solar PEC conversion.

Anti-Aging Drugs and the Related Signal Pathways.

Aging is a multifactorial biological process involving chronic diseases that manifest from the molecular level to the systemic level. From its inception to 31 May 2022, this study searched the PubMed, Web of Science, EBSCO, and Cochrane library databases to identify relevant research from 15,983 articles. Multiple approaches have been employed to combat aging, such as dietary restriction (DR), exercise, exchanging circulating factors, gene therapy, and anti-aging drugs. Among them, anti-aging drugs are advantageous in their ease of adherence and wide prevalence. Despite a shared functional output of aging alleviation, the current anti-aging drugs target different signal pathways that frequently cross-talk with each other. At present, six important signal pathways were identified as being critical in the aging process, including pathways for the mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), nutrient signal pathway, silent information regulator factor 2-related enzyme 1 (SIRT1), regulation of telomere length and glycogen synthase kinase-3 (GSK-3), and energy metabolism. These signal pathways could be targeted by many anti-aging drugs, with the corresponding representatives of rapamycin, metformin, acarbose, nicotinamide adenine dinucleotide (NAD+), lithium, and nonsteroidal anti-inflammatory drugs (NSAIDs), respectively. This review summarized these important aging-related signal pathways and their representative targeting drugs in attempts to obtain insights into and promote the development of mechanism-based anti-aging strategies.

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.

Water activating fresh NiMo foam for enhanced urea electrolysis.

Recently, production of hydrogen (H2) through the urea oxidation reaction (UOR) and hydrogen evolution reaction (HER) has acquired great attention because it is more environmentally friendly and energy-saving. Herein, an approach of water activation was developed for in situ growth of NiMo LDH nanosheet arrays on NiMo foam without using any binder or pressurizing or heating steps. The obtained NiMo foam electrodes showed exceptional catalytic activity and durability for both the UOR and HER. This work offers a new standpoint on designing electrodes with high activation for efficient and sustainable hydrogen production coupled with urea organic oxidation.

Unlocking the potential of a NiMo foam substrate for water splitting using an ultrafast two-step dipping strategy.

In this paper, a facile and ultrafast two-step dipping process was developed to in situ form an electrocatalyst on a NiMo foam substrate without consuming extra energy. The obtained electrode showed a porous coral-like structure decorated with nanosheets and exhibited excellent overall water splitting properties in alkaline solution. This study provides a feasible strategy for developing an environmentally friendly and energy-efficient non-noble metal electrode for hydrogen production from water splitting.

Clinical factors associated with remission of obese acanthosis nigricans after laparoscopic sleeve gastrectomy: a prospective cohort study.

BACKGROUND: Acanthosis nigricans (AN) involves skin hyperpigmentation in body folds and creases. Obesity-associated AN (OB_AN) is the most common type of AN. The skin condition of obese patients with AN can be improved through bariatric surgery, such as laparoscopic sleeve gastrectomy (LSG), after weight loss. However, the contributing factors to the remission of AN after surgery are still not fully determined. The authors aimed to assess the metabolic and pathological factors associated with remission of AN following LSG in obese individuals. METHODS: The study included 319 obese patients who underwent LSG at our hospital. The subjects were divided into obesity (OB) only (OB, n =178) or OB with AN (OB_AN, n =141) groups. The basic clinical and metabolic indices and the dermatological features via reflectance confocal microscopy and histology were collected from patients prior to and after LSG. RESULTS: OB_AN patients had higher fasting plasma glucose, homeostatic model assessment for insulin resistance, and testosterone levels than OB patients. LSG could significantly improve the biochemical and histopathological features of OB_AN patients. The remissive rate of OB_AN patients was about 86.5% (122 out of 141) after surgery. The remission of OB_AN skin lesions was positively correlated with testosterone levels ( P <0.01). In addition, there was a significant positive correlation between changes in AN scores and epidermal thickness and skin pigmentation scores after surgery ( P <0.01). CONCLUSION: The remissive rate of OB_AN after LSG is associated with improved testosterone levels and reduced epidermal thickness and skin pigmentation levels.

Interfacial phenomenon and Marangoni convection of Fe-C melt on coke substrate under in situ observation.

The interfacial phenomenon between liqiuid iron and coke is important for determining the melting efficiency in the blast furnace iron-making process. In this study, the interaction observed in the case of the iron-carbon (Fe-C) melt on coke substrate was investigated using a high-temperature vacuum wettability test equipment. The Fe-C melt did not wet and spread on the coke substrate with different graphitization degrees (r0) at a high temperature of 1450 °C. The contact angles changed from 124.5° to 105.3°, and the r0 increased from 9.30 to 50.00%, thus indicating a nonwetting state. The deepening of graphitization decreased the contact angle. Thereby, increasing the contact area between liquid iron and the carbonaceous material, which facilitated carbon dissolution. The irregular movements of Fe-C melt were observed in situ during the wetting process. The horizontal force of the droplet caused by interfacial tension and the contact angle; the Marangoni convection owing to the gradient of carbon concentration; and the impulse force caused by the generation, aggregation, and release of SiO bubbles at the interface were attributed to the driving force.

Noncoding RNA-Mediated High Expression of PFKFB3 Correlates with Poor Prognosis and Tumor Immune Infiltration of Lung Adenocarcinoma.

Background: There is growing evidence showing that 6-phosphofructo-2-kinase (PFKFB3) plays crucial roles in different types of human cancers, including LUAD; however, the specific mechanism by which PFKFB3 plays a role in LUAD remains unclear. Methods: We investigated the expression of PFKFB3 and explored the underlying mechanism as well as the correlation with immune markers using several online datasets, such as Tumor Immune Estimate Resource (TIMER), UALCAN, and the Cancer Genome Atlas (TCGA) databases, miRWalk, Targetscan, MiRDB and starBase database. Western blot and immunohistochemistry analysis were performed to verify the corresponding outcomes. Results: It was shown that the mRNA expression of PFKFB3 was lower in LUAD than in the normal tissues, while its protein expression was not consistent with the mRNA level. The expression of PFKFB3 was correlated with clinicopathological parameters and several signaling pathways. The potential long chain (lnc)RNA/microRNA/PFKFB3 axis and the possible mechanism by which tumor progression in LUAD is promoted was predicted. We obtained the LINC01798/LINC02086/AP000845.1/HAGLR-miR-17-5p-PFKFB3 axis after comprehensive analyses of expression, correlation, and survival. Moreover, the expression of PFKFB3 was positively correlated with immune cells and immune checkpoint expression, including PD-1, PD-L1 and CTLA-4. Conclusion: The present study demonstrated that noncoding RNAs mediated the upregulation of PFKFB3 and was associated with a poor prognosis and immune tumor infiltration in LUAD.

NMDA receptor activation induces damage of alveolar type II cells and lung fibrogenesis through ferroptosis.

Ferroptosis, a newly discovered type of regulated cell death, has been implicated in numerous human diseases. Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal interstitial lung disease with poor prognosis and limited treatment options. Emerging evidence has linked ferroptosis and glutamate-determined cell fate which is considered a new light on the etiology of pulmonary fibrosis. Here, we observed that N-methyl d-aspartate receptor (NMDAR) activation promoted cell damage and iron deposition in MLE-12 cells in a dose-, time-, and receptor-dependent manner. This mediated substantial Ca2+ influx, upregulated the expression levels of nNOS and IRP1, and affected intracellular iron homeostasis by regulating the expression of iron transport-related proteins (i.e., TFR1, DMT1, and FPN). Excessive iron load promoted the continuous accumulation of total intracellular and mitochondrial reactive oxygen species, which ultimately led to ferroptosis. NMDAR inhibition reduced lung injury and pulmonary fibrosis in bleomycin-induced mice. Bleomycin stimulation upregulated the expression of NMDAR1, nNOS, and IRP1 in mouse lung tissues, which ultimately led to iron deposition via regulation of the expression of various iron metabolism-related genes. NMDAR activation initiated the pulmonary fibrosis process by inducing iron deposition in lung tissues and ferroptosis of alveolar type II cells. Our data suggest that NMDAR activation regulates the expression of iron metabolism-related genes by promoting calcium influx, increasing nNOS and IRP1 expression, and increasing iron deposition by affecting cellular iron homeostasis, ultimately leading to mitochondrial damage, mitochondrial dysfunction, and ferroptosis. NMDAR activation-induced ferroptosis of alveolar type II cells might be a key event to the initiation of pulmonary fibrosis.

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.

Corylin accelerated wound healing through SIRT1 and PI3K/AKT signaling: a candidate remedy for chronic non-healing wounds.

Introduction: Chronic non-healing wound is a considerable clinical challenge and research into the discovery of novel pro-healing agents is underway as existing therapeutic approaches cannot sufficiently meet current needs. Method: We studied the effects of corylin in cell line fibroblasts and macrophages by Western blots, PCR, Flow cytometry assay, Immunofluorescence. Results: We showed that corylin, a main flavonoid extracted from Psoralea corylifolia L, reduced inflammatory responses, promoted collagen deposition, and accelerated the healing of full-thickness skin wounds in mice. Exploration of the underlying mechanisms showed that corylin activated the PI3K/AKT signaling, leading to fibroblasts' migration, proliferation, and scratch healing. Corylin also activated sirtuin 1 (SIRT1) signaling, enhanced the deacetylation and cytoplasmic translocation of NF-κB p65, and therefore reduced lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Furthermore, inhibition of PI3K/AKT and sirtuin 1 pathway with LY294002 and EX527 prevent the therapeutic potency of corylin against chronic wounds. Conclusion: In summary, our results suggested that corylin may be a candidate for the development of novel pro-healing agents.

Metal-Organic Framework Glass Catalysts from Melting Glass-Forming Cobalt-Based Zeolitic Imidazolate Framework for Boosting Photoelectrochemical Water Oxidation.

Sluggish oxygen evolution kinetics and serious charge recombination restrict the development of photoelectrochemical (PEC) water splitting. The advancement of novel metal-organic frameworks (MOFs) catalysts bears practical significance for improving PEC water splitting performance. Herein, a MOF glass catalyst through melting glass-forming cobalt-based zeolitic imidazolate framework (Co-ag ZIF-62) was introduced on various metal oxide (MO: Fe2 O3 , WO3 and BiVO4 ) semiconductor substrates coupled with NiO hole transport layer, constructing the integrated Co-ag ZIF-62/NiO/MO photoanodes. Owing to the excellent conductivity, stability and open active sites of MOF glass, Co-ag ZIF-62/NiO/MO photoanodes exhibit a significantly enhanced photoelectrochemical water oxidation activity and stability in comparison to pristine MO photoanodes. From experimental analyses and density functional theory calculations, Co-ag ZIF-62 can effectively promote charge transfer and separation, improve carrier mobility, accelerate the kinetics of oxygen evolution reaction (OER), and thus improve PEC performance. This MOF glass not only serves as an excellent OER cocatalyst on tunable photoelectrodes, but also enables promising opportunities for PEC devices for solar energy conversion.

A Series of Polymer-Supported Polyoxometalates as Heterogeneous Photocatalysts for Degradation of Organic Dye.

Photocatalytic degradation technology has developed rapidly in the treatment of organic pollutants due to its high efficiency, mild reaction conditions and easy control. In this paper, a series of heterogeneous photocatalysts, BWZ-en-R (BWZ = [BW11Z(H2O)O39]7-, Z = Zn, Cd, Mn, en = ethylenediamine, R = Merrifield resin), were prepared by using ethanediamine as a linker to immobilize Keggin-type transition elements substituting tungstoborates on Merrifield resin and characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electron microscopy and energy-dispersive X-ray spectroscopy. The photocatalytic properties of BWZ-en-R (Z = Zn, Cd, Mn) for the degradation of methyl red (MR) were investigated. The results show that the BWZ-en-R (Z = Zn, Cd, Mn) photocatalysts exhibited high photodegradation ability for MR under the irradiation of ultraviolet light, and were easily separated from the reaction media. The maximum degradation rate (%) of MR (40 mL, 25 µM, pH = 2) reached 96.4% for the BWMn-en-R photocatalyst (40 mg) after being irradiated for 30 min, making this a promising photocatalyst candidate for dye degradation. Moreover, the influences of some factors, such as the Z-substituted elements in the BWZ, the BWZ-en-R dosage and the MR initial concentration, on the photocatalytic degradation rate of MR were also examined.

Combined exposure to lead and high-fat diet induced neuronal deficits in rats: Anti-neuroinflammatory role of SIRT1.

INTRODUCTION: Lead (Pb) exposure and high-fat diet (HFD) trigger neurotoxicity, which may involve neuroinflammation. However, the mechanism by which combined Pb and HFD exposure induces nucleotide oligomerization domain-like receptor family pyrin domain 3 (NLRP3) inflammasome activation has not been fully elucidated. MATERIAL AND METHODS: The Sprague-Dawley (SD) rat model of exposure to Pb and HFD was established to reveal the influence of co-exposure on cognition and identify signaling clues that mediate neuroinflammation and synaptic dysregulation. PC12 cells was treated with Pb and PA in vitro. Silent information regulator 1 (SIRT1) agonist (SRT 1720) was employed as intervention agent. RESULTS: Our results showed that Pb and HFD exposure induced cognitive impairment and lead to neurological damage in rats. Meanwhile, Pb and HFD could stimulate the NLRP3 inflammasome assembly and activate caspase 1, releasing proinflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), further promoting neuronal cell activation and amplifying neuroinflammatory responses. Additionally, our findings suggest that SIRT1 plays a role in Pb and HFD induced neuroinflammation. However, the use of SRT 1720 agonists showed some potential in alleviating these impairments. CONCLUSION: Pb exposure and HFD intake could induce neuronal damage through activation of the NLRP3 inflammasome pathway and synaptic dysregulation, while the NLRP3 inflammasome pathway may be rescued via activating SIRT1.

Subtype-based analysis of cell-in-cell structures in non-small cell lung cancer.

Lung cancer is ranked as the leading cause of cancer-related death worldwide, and the development of novel biomarkers is helpful to improve the prognosis of non-small cell lung cancer (NSCLC). Cell-in-cell structures (CICs), a novel functional surrogate of complicated cell behaviors, have shown promise in predicting the prognosis of cancer patients. However, the CIC profiling and its prognostic value remain unclear in NSCLC. In this study, we retrospectively explored the CIC profiling in a cohort of NSCLC tissues by using the "Epithelium-Macrophage-Leukocyte" (EML) method. The distribution of CICs was examined by the Chi-square test, and univariate and multivariate analyses were performed for survival analysis. Four types of CICs were identified in lung cancer tissues, namely, tumor-in-tumor (TiT), tumor-in-macrophage (TiM), lymphocyte-in-tumor (LiT), and macrophage-in-tumor (MiT). Among them, the latter three constituted the heterotypic CICs (heCICs). Overall, CICs were more frequently present in adenocarcinoma than in squamous cell carcinoma (P = 0.009), and LiT was more common in the upper lobe of the lung compared with other lobes (P = 0.020). In univariate analysis, the presence of TiM, heCIC density, TNM stage, T stage, and N stage showed association with the overall survival (OS) of NSCLC patients. Multivariate analysis revealed that heCICs (HR = 2.6, 95% CI 1.25-5.6) and lymph node invasion (HR = 2.6, 95% CI 1.33-5.1) were independent factors associated with the OS of NSCLC. Taken together, we profiled the CIC subtypes in NSCLC for the first time and demonstrated the prognostic value of heCICs, which may serve as a type of novel functional markers along with classical pathological factors in improving prognosis prediction for patients with NSCLC.

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.

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.