Evaluation of the inflammatory parameters as potential biomarkers of systemic inflammation extent and the disease severity in psoriasis patients.

The disease severity of psoriasis is mainly assessed subjectively via  psoriasis area and severity index (PASI) and body surface area (BSA), while an optimal measure of cutaneous response, may overlook systemic inflammation in psoriasis patients. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), monocyte to high density lipoprotein ratio (MHR), and systemic immune-inflammation index (SII) exhibit notable associations with the inflammation severity in multiple diseases. The aim of this retrospective study was to explore the associations between inflammatory parameters and the skin lesions' severity of psoriasis. After analysis, we found that patients with psoriasis had higher NLR, MLR, PLR, MHR, and SII levels compared to the control group. At baseline, the parameters of NLR (r = 0.124, P = 0.003), MLR (r = 0.153, P < 0.001), MHR (r = 0.217, P < 0.001) and SII (r = 0.141, P = 0.001) had a positive correlation with PASI in psoriasis patients. At the same time, we analyzed the patients who received different systemic therapy. We observed a significant decrease in NLR, PLR, MLR, and SII in psoriasis patients after treatment. Notably, TNF-α inhibitors and IL-17A inhibitors subgroups showed a more significant reduction than IL-23/IL-12/23 inhibitors and MTX medication. Additionally, we found the change of NLR (r = 0.194, P < 0.001), PLR (r = 0.104, P = 0.014), MLR (r = 0.191, P < 0.001), MHR (r = 0.106, P = 0.012), and SII (r = 0.228, P < 0.001) had a positive correlation with the change of PASI in psoriasis patients. In conclusion, this study suggests that NLR, MLR, and SII may serve as useful biomarkers for assessing systemic inflammation extent and disease severity in psoriasis patients.

A BET inhibitor, NHWD-870, can downregulate dendritic cells maturation via the IRF7-mediated signaling pathway to ameliorate imiquimod-induced psoriasis-like murine skin inflammation.

Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of dendritic cells (DCs), which are primarily responsible for initiating an immune response. The bromodomain and extraterminal domain (BET) family plays a pivotal role in the transcriptional regulation of inflammation and its inhibitors can downregulate DCs maturation and activation. Here we investigated the effect of NHWD-870, a potent BET inhibitor, on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS) and IMQ. Application of NHWD-870 significantly ameliorated IMQ-triggered skin inflammation in mice, and markers associated with DC maturation (CD40, CD80 and CD86) were decreased in skin lesions, spleen and lymph nodes. Additionally, NHWD-870 reduced LPS or IMQ induced DCs maturation and activation in vitro, with lower expression of inflammatory cytokines [interleukin (IL)-12, IL-23, tumor necrosis factor-α, IL-6, IL-1ß, chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10]. In addition, we found that interferon regulatory factor 7 (IRF7) significantly increased during DCs maturation, and inhibition of IRF7 could impair BMDCs maturation and activation. What's more, IRF7 was highly expressed in both psoriatic patients and IMQ-induced psoriasis-like mice. Single-cell RNA sequencing of normal and psoriatic skin demonstrated that IRF7 expression was increased in DCs of psoriatic skin. While NHWD-870 could inhibit IRF7 and phosphorylated-IRF7 expression in vivo and in vitro. These results indicate that NHWD-870 suppresses the maturation and activation of DCs by decreasing IRF7 proteins which finally alleviates psoriasis-like skin lesions, and NHWD-870 may be a potent therapeutic drug for psoriasis.

[Corrigendum] Downregulation of CD147 induces malignant melanoma cell apoptosis via the regulation of IGFBP2 expression.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the ß­actin bands shown for the western blots portrayed in Fig. 4A and E on p. 2403 appeared to be strikingly similar, albeit that the bands were inverted with respect to their orientation and the dimensions of the bands differed slightly. After re­examining their original data, the authors have realized that these data in Fig. 4 had inadvertently been assembled incorrectly. The revised version of Fig. 4, showing the correct data for all the experiments in Fig. 4E, is shown on on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree to its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 53: 2397­2408, 2018; DOI: 10.3892/ijo.2018.4579].

Lactate dehydrogenase predicts disease progression outcome in COVID-19 patients treated with Azvudine.

Background: Azvudine has been approved in China for the treatment of COVID-19 patients. Previous studies have suggested a correlation between high levels of lactate dehydrogenase (LDH) and the severity of COVID-19. However, the impact of LDH levels in COVID-19 patients receiving Azvudine treatment remains unclear. Methods: In this retrospective cohort study, we analyzed the data of 351 hospitalized COVID-19 patients who were consecutively treated with Azvudine, with or without high LDH levels. The clinical features, treatment strategies and prognosis data were collected and analyzed. Results: Among the 351 hospitalized patients with COVID-19 treated with Azvudine (119 with high-LDH levels), the median age was 69 years (range 58-78), and 213 (60.7%) were male. Common symptoms included cough (86.0%), expectoration (73.5%), fever (69.8%), polypnea (47.6%) and poor appetite (46.4%). Patients with high LDH levels exhibited significantly elevated leucocyte and neutrophil counts, elevated level of myocardial enzymes, as well as higher levels of inflammatory markers such as interleukin-6, interleukin-10, procalcitonin, C reactive protein, ferritin, and prolonged erythrocyte sedimentation rate upon admission. COVID-19 patients with high-LDH levels had higher rates of corticosteroid therapy, non-invasive and invasive mechanical ventilation, worsened and death (2.5% vs. 0%). The Cox proportional hazard model demonstrated that high LDH levels (adjusted hazard ratio = 5.27; 95% confidence interval: 1.19, 14.50) were associated with a more unfavorable composite disease progression outcome among COVID-19 patients treated with Azvudine, after accounting for potential confounding variables. Conclusion: High-LDH levels predict a worse composite disease progression outcome in COVID-19 patients treated with Azvudine.

Causal Associations Between Gut Microbiota and Psoriasis: A Mendelian Randomization Study.

INTRODUCTION: Previous studies have proposed a possible gut-skin axis, and linked gut microbiota to psoriasis risks. However, there is heterogeneity in existing evidence. Observational research is prone to bias, and it is hard to determine causality. Therefore, this study aims to evaluate possible causal associations between gut microbiota (GM) and psoriasis. METHODS: With published large-scale GWAS (genome-wide association study) summary datasets, two-sample Mendelian randomization (MR) was performed to sort out possible causal roles of GM in psoriasis and arthropathic psoriasis (PsA). The inverse variance weighted (IVW) method was taken as the primary evaluation of causal association. As complements to the IVW method, we also applied MR-Egger, weighted median. Sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept test, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) global test, and leave-one-out analysis. RESULTS: By primary IVW analysis, we identified nominal protective roles of Bacteroidetes (odds ratio, OR 0.81, P = 0.033) and Prevotella9 (OR 0.87, P = 0.045) in psoriasis risks. Bacteroidia (OR 0.65, P = 0.03), Bacteroidales (OR 0.65, P = 0.03), and Ruminococcaceae UCG002 (OR 0.81, P = 0.038) are nominally associated with lower risks for PsA. On the other hand, Pasteurellales (OR 1.22, P = 0.033), Pasteurellaceae (OR 1.22, P = 0.033), Blautia (OR 1.46, P = 0.014), Methanobrevibacter (OR 1.27, P = 0.026), and Eubacterium fissicatena group (OR 1.21, P = 0.028) are nominal risk factors for PsA. Additionally, E. fissicatena group is a possible risk factor for psoriasis (OR 1.22, P = 0.00018). After false discovery rate (FDR) correction, E. fissicatena group remains a risk factor for psoriasis (PFDR = 0.03798). CONCLUSION: We comprehensively evaluated possible causal associations of GM with psoriasis and arthropathic psoriasis, and identified several nominal associations. E. fissicatena group remains a risk factor for psoriasis after FDR correction. Our results offer promising therapeutic targets for psoriasis clinical management.

Global trends in the health economics field of PD-1/PD-L1 inhibitors: A bibliometric and visualized study.

Inhibitors of programmed cell death protein 1 and its associated ligand (PD-L1) are widely used in cancer treatment. However, medical costs and benefits of PD-1/PD-L1 inhibitors need attention owing to differences in response rates among individuals. This study explored global trends in the health economics field of PD-1/PD-L1 inhibitors to enhance their worldwide development. Bibliometric analysis of all documents currently indexed in Web of Science Core Collection from inception to 2022 was performed. Publication year, authors, countries, institutes, and journals were analyzed by Bibliometrix package (version 3.2.1) in R (version 4.1.3). CiteSpace (version 6.1.R6) and VOSviewer (version 1.6.18) were used to analyze burst words, co-authorship of institutes, co-cited journals, and co-cited references, while figures were mainly drawn by Ggplot2 package (version 3.3.5) in R (version 4.1.3) and SCImago Graphica Beta (version 1.0.23). A total of 2020 documents related to the health economics of PD-1/PD-L1 inhibitors were identified, and 1,204 documents met the selection criteria for inclusion in the study. A rapid increase in the number of publications since 2019 was observed, but this increase stopped in 2022, revealing research saturation in the field. Value in Health (166 publications, 13.79% of total documents) had the most publications, while New England Journal of Medicine (2,890 co-citations) was the most co-cited journal. The United States was the leading contributor in this field with 506 publications and the top two productive institutes globally. The main hot topics included the cost-effectiveness of treatment with PD-1 and/or PD-L1 inhibitors, and the comparison between the cost-effectiveness of PD-/PD-L1 inhibitors and other drugs. There were substantial differences between developed and developing countries in the health economics field of PD-1 and/or PD-L1 inhibitors. The cost-effectiveness analysis of combined treatment with PD-1/PD-L1 inhibitors and other drugs warrants further attention. Findings from this study may provide governments and pharmaceutical companies with a strong reference for future research.

The HLA-Cw*06 allele may predict the response to methotrexate (MTX) treatment in Chinese arthritis-free psoriasis patients.

MTX in genetically distinctive Chinese psoriatic patients remains less explored. The present study aimed to determine the impact of HLA-Cw*06 on MTX response in a Chinese psoriasis patient population. A total of 204 patients with psoriasis were enrolled in this study. Clinical data and DNA samples from all patients were collected. The allele of HLA-Cw*06 genotyping was detected using direct Sanger sequencing. This study enrolled 204 patients with psoriasis, including 47 (23.04%) psoriatic arthritis patients, 157 (76.96%) patients free of psoriatic arthritis. Overall, 110 (53.92%) of all patients carried the HLA-Cw*06 allele. This frequency in patients with arthritis-free psoriasis was higher than that in those with psoriatic arthritis (58.59 vs. 38.30%, P = 0.014). After 8 weeks of MTX treatment, the arthritis-free psoriasis patients, who tested positive for the HLA-Cw*06 allele, showed significant improvement compared to those who tested negative (For PASI50, 78.57 vs. 55.22%, P = 0.02, and for PASI75, 51.11 vs. 34.33%, P = 0.036). The psoriatic arthritis-free patients who carried the HLA-Cw*06 allele in combination with the ABCB1 rs1045642 CC genotype showed the highest improvement. A regression model containing HLA-Cw*06, rs1045642T > C, and initial PASI scores was used to construct the efficacy prediction model of MTX, which yielded AUC values of 73.2 and 75.6% for PASI50 and PASI75 to MTX, respectively, in arthritis-free psoriasis patients. The HLA-Cw*06 allele is associated with optimal response to MTX treatment in arthritis-free Chinese psoriasis patients. When combined with clinical indicators, the polymorphism explained more than 75% of the individual efficacy differences.

HLA-DQA1 and DQB1 Alleles are Associated with Acitretin Response in Patients with Psoriasis.

BACKGROUND: Psoriasis vulgaris is an immune-mediated inflammatory skin disease. Although the pathogenesis of psoriasis is unclear, genetic susceptibility, such as HLA-C*06:02, is believed to be a major risk factor. However, there is a paucity of knowledge regarding the relationship between genetics and the response to systemic treatment of psoriasis. We hypothesized that genetic variations in human leukocyte antigen (HLA) genes may act as predictors of acitretin treatment in psoriasis. The aim of our study was to explore the presence of HLA gene variants in patients with moderate-to-severe psoriasis receiving acitretin treatment. METHODS: A total of 100 Han Chinese patients with psoriasis completed the study. 24 patients including 16 responders and 8 non-responders underwent deep sequencing by MHC targeted region capture and 76 samples were genotyped by Sanger sequencing (SBT) based HLA typing for validation. RESULTS: Regressions with adjustment for age, sex, body mass index (BMI), and baseline psoriasis area and severity index (PASI) revealed that two HLA alleles (HLA-DQA1*:02:01, DQB*:02:02) were associated with the response to acitretin. The DQA1*0201-positive patients showed a better response to acitretin compared to the DQA1*0201-negative patients (relative risk (RR) = 10.34, 95% confidence interval (CI): 2.62-40.77, p = 0.001), and the DQB1*0202-positive patients manifested a better response to acitretin when compared to the DQB1*0202-negative patients (RR = 21.01, 95% CI: 2.53-174.27, p = 0.005). CONCLUSIONS: Our observations support the potential role of HLA-DQA1*:02:01 and DQB*:02:02 as pharmacogenetic markers of the acitretin response in patients with psoriasis.

Predicting the Risk of Psoriatic Arthritis in Plaque Psoriasis Patients: Development and Assessment of a New Predictive Nomogram.

Objective: This study aimed to develop a risk of psoriatic arthritis (PsA) predictive model for plaque psoriasis patients based on the available features. Methods: Patients with plaque psoriasis or PsA were recruited. The characteristics, skin lesions, and nail clinical manifestations of the patients have been collected. The least absolute shrinkage was used to optimize feature selection, and logistic regression analysis was applied to further select features and build a PsA risk predictive model. Calibration, discrimination, and clinical utility of the prediction model were evaluated by using the calibration plot, C-index, the area under the curve (AUC), and decision curve analysis. Internal validation was performed using bootstrapping validation. The model was subjected to external validation with two separate cohorts. Results: Age at onset, duration, nail involvement, erythematous lunula, onychorrhexis, oil drop, and subungual hyperkeratosis were presented as predictors to perform the prediction nomogram. The predictive model showed good calibration and discrimination (C-index: 0.759; 95% CI: 0.707-0.811). The AUC of this prediction model was 0.7578092. Excellent performances of the C-index were reached in the internal validation and external cohort validation (0.741, 0.844, and 0.845). The decision curve indicated good effect of the PsA nomogram in guiding clinical practice. Conclusion: This novel PsA nomogram could assess the risk of PsA in plaque psoriasis patients with good efficiency.

Reductive Effect of Acitretin on Blood Glucose Levels in Chinese Patients With Psoriasis.

Background: Psoriasis is a skin condition associated with increased risks of developing metabolic diseases, such as diabetes and hyperlipidaemia. Retinoid drugs, including acitretin, are commonly used to treat psoriasis due to its low cost and tolerable side effects. Objective: This study aimed to explore the influence of acitretin on patients' metabolism levels, especially lipid and glucose. Methods: In this retrospective study, a total of 685 psoriatic patients and 395 age/sex matched controls were enrolled. The demographic and biochemical indexes of each participant were recorded. Acitretin (30 mg/d) combined with the topical ointment calcipotriol was used to treat the psoriatic patients, and the glucose and lipid profiles of patients before and after acitretin treatment were analyzed. Results: The blood glucose levels of 685 psoriasis patients were significantly higher than that of the control group (P < 0.001), while the blood lipid levels showed no difference between psoriatic patients and the matched controls. Triglyceride and low-density lipoprotein levels were significantly increased in 247 patients (P < 0.05) after 8 weeks of treatment with acitretin. Interestingly, there was a remarkable downward trend in body mass index (BMI) and blood glucose levels (P < 0.05) after acitretin treatment. Additionally, expression of both GLUT1 and GLUT4 in HaCaT and HepG2 cells were significantly increased when treated with acitretin. Compared to acitretin-free cells, the uptake of 2-NBDG was significantly higher in HaCaT and HepG2 cells after incubation with 5000 ng/mL acitretin for 36 h. Conclusion: Acitretin plays a significant role of reducing the blood glucose level in psoriasis patients. The mechanism of lowering blood glucose may be through increasing glucose intake by cells, thereby reducing glucose levels in the peripheral blood.

Resveratrol-induced apoptosis is associated with regulating the miR-492/CD147 pathway in malignant melanoma cells.

Resveratrol (RES) as a natural phytoalexin has anti-tumor effects on various cancers through its pro-apoptotic activities. Our aim was to determine that RES induces apoptosis in melanoma cells by regulating miR-492 resulting in decreased CD147 expression. We treated A375 and SK-MEL-28 melanoma cells via RES at different concentrations and time-points. The results have shown that the inhibition rate of A375 and SK-MEL-28 was significantly increased after RES treatment. Subsequently, we investigated cell apoptosis by flow cytometry, as well as detected apoptotic-associated proteins including PARP, Caspase-3, Bcl-2, and Bax by western blotting. Meanwhile, the expression of miR-492 and CD147 was analyzed. We found that RES remarkably induces apoptosis in melanoma cells, along with an upregulation of miR-492 and the inhibition of CD147 expression. Furthermore, the detection of luciferase reporter activity confirmed that miR-492 could target CD147 mRNA, and transfected with mimic miR-492 in cells reduced CD147 expression. We also performed the rescued experiment by using a miR-492 inhibitor in melanoma cells. The results showed that the ability of induced apoptosis by RES in melanoma cells was to be attenuated via inhibiting miR-492 expression resulting in CD147 augment. Finally, we determined that the effect of RES-induced apoptosis in melanoma cells is associated with, at least in part, its ability to regulate the miR-492/CD147 pathway.

Polyethylene Glycol Ointment Alleviates Psoriasis-Like Inflammation Through Down-Regulating the Function of Th17 Cells and MDSCs.

Objective: To explore the possible mechanism of improving the imiquimod (IMQ)-induced psoriasis-like inflammation by using polyethylene glycol (PEG) ointment. Methods: We evaluated the appearance of psoriasis lesions by Psoriasis Area and Severity Index (PASI), observed the epidermal proliferation by histopathological staining and immunohistochemical staining, and explored the key molecules and signaling pathways of improving psoriasis-like inflammation treated with PEG ointment by RNA sequencing. Finally, we verified the expression of inflammatory cells and inflammatory factors by flow cytometry, immunohistochemical staining, and Q-PCR. Results: PEG ointment could improve the appearance of psoriasis lesions and the epidermis thickness of psoriasis mouse, inhibit the proliferation of keratinocytes, and down-regulate the relative mRNA levels of IL-23, IL-22, IL-6, IL-17C, IL-17F, S100A7, S100A8, S100A9, CXCL1, CXCL2, and IL-1ß in the skin lesions of psoriasis mouse by down-regulating the numbers of myeloid-derived suppressor cells (MDSCs) and T helper 17 (Th17) cells. Conclusion: PEG ointment could improve the IMQ-induced psoriasis-like inflammation by down-regulating the functions of Th17 cells and MDSCs.

Human H1 receptor (HRH1) gene polymorphism is associated with the severity of side effects after desloratadine treatment in Chinese patients with chronic spontaneous uticaria.

H1 nonsedating antihistamines, such as desloratadine, are first-line treatment options for chronic spontaneous urticaria (CSU). However, desloratadine induces various degrees of sedation side effect in CSU patients, and no biomarkers currently exist for predicting the severity of such side effect. Herein, we evaluated the association between HRH1 gene rs901865 polymorphism and the severity of sedation side effect following desloratadine therapy in patients with CSU. We found that 20 of the 114 patients (17.50%) showed sedation side effect after desloratadine treatment, and 3 patients (2.63%) experienced serious sleepiness. The frequency of HRH1 rs901865 G allele was significantly higher in patients who experienced sedation than in patients with rs901865 A allele (p = 0.0009). Moreover, patients with the rs901865 G/G genotype suffered a more serious sedation side effect than patients with the rs901865 G/A genotype (p = 0.005). These results provide evidence that the HRH1 rs901865 G/G polymorphism is associated with severe sedation side effect after desloratadine treatment. Thus, the HRH1 rs901865 allele may potentially be used as a biomarker for predicting the severity of sedation side effect in patients suffering from CSU and treated with desloratadine.

Retinoids as an Immunity-modulator in Dermatology Disorders.

The skin is the largest epithelial surface protecting the body from invading microbes. Vitamin A plays vital roles in the host defence of the skin, including promoting epithelial cell integrity, proliferation, and differentiation and even mediating immune responses. Furthermore, vitamin A derivatives, retinoid drugs, are widely used to treat skin diseases, such as acne and psoriasis. However, the immunoregulatory mechanisms of retinoids in dermatology have not been systematically described. In this paper, we discuss the immunological functions of retinoids during disease treatment, especially in skin disorders caused by exogenous infections.

Efficacy of the combination of superficial shaving with photodynamic therapy for recalcitrant periungual warts.

BACKGROUND: Periungual warts are a viral infectious disease that occurs in a particular location. It is difficult to eliminate completely, and recurrence is common. Photodynamic therapy (PDT) as an option that has been widely recommended to treat viral warts. However, there are always a few patients with poor efficacy after PDT treatment. We have considered that the reason is the limitation of PDT penetrating deep into tissue. Thus, we combined superficial shaving with PDT to treat recalcitrant periungual warts. METHODS: Twenty-three patients had a total of 61 periungual wart lesions. All patients had recalcitrant periungual warts that had failed to respond to various treatments that had poor curative effects. After local injection of anesthesia, the lesions were shaved in situ, and PDT was performed immediately. A total of three sessions of PDT were applied for each patient after only one superficial shaving. The overall clinical response rate, recurrence rates, cosmetic outcomes, adverse events, patient satisfaction and quality of life were assessed. The potential risk factors have also been recorded. RESULTS: We achieved a 96% success rate (defined as more than 50% on clearance) in our 23 patients using combination superficial shaving with PDT after treatment for 3 months. At the 12-month follow-up, 21 patients (91%) had excellent cosmetic outcomes. All patients had satisfactory therapeutic effects and significant improvement in the quality of life. Pain during the illumination process was the main adverse event, but all patients were able to tolerate it. We also found that frequent or continuous hand activity, such as playing Mah-jong, may be a potential risk factor for periungual warts. CONCLUSION: Our results offer promise for combining superficial shaving with PDT as an effective and safe therapy for patients with periungual warts, especially for those periungual warts that are recurrent, have multiple lesions, and thickness corneum stratum of lesions. For nails that are not suitable for routine surgery, combined superficial shaving with PDT is recommended.

Abnormal Serum Copper and Zinc Levels in Patients with Psoriasis: A Meta-Analysis.

BACKGROUND: Copper and zinc are important trace elements involved in the development of psoriasis. However, reports regarding changes in serum copper and zinc levels in patients with psoriasis have been inconsistent. AIMS: This meta-analysis was designed to analyze changes in serum copper and zinc levels between patients with psoriasis and a healthy population. MATERIALS AND METHODS: English and Chinese literature from international and national electronic databases from 1988 to May 2016 was analyzed. Studies that performed a comparative analysis of serum copper and zinc levels between patients with psoriasis and healthy controls were included in the meta-analysis. The random-effects model was used to calculate the overall combined estimates of serum copper and zinc levels between patients with psoriasis and healthy individuals. Results: Fifteen references were included in this study, including 1324 patients with psoriasis and 1324 healthy controls. Compared with healthy controls, serum copper levels were significantly increased (Z = 4.02, P < 0.0001; standardized mean difference [SMD], 1.23; 95% confidence interval [CI], 0.63 to 1.82), and serum zinc levels were significantly decreased (Z = 2.95, P < 0.0001; SMD, -1.35; 95% CI, -2.25 to - 0.45) in patients with psoriasis. CONCLUSIONS: In conclusion, increased serum copper and decreased serum zinc levels were generally observed in patients with psoriasis. Treatments to normalize the serum copper and zinc levels may improve the outcome of psoriasis patients.

Calcium release-activated calcium modulator 1 as a therapeutic target in allergic skin diseases.

Allergic skin disease is the most common skin condition, and considerably affects patients' life quality because of its recurrence and pruritus. Numbers of studies point out that immune cells, including mast cells and T cells, play pathogenic roles in allergic skin diseases, and share similarities in the activation and secretion of cytokines. Calcium Release-Activated Calcium Modulator 1(CRACM1/ORAI1) is a subtype of Ca2+ membrane channel, causing Ca2+ influx into the cells. As a second messenger, Ca2+ is an essential element that regulates immune responses, especially in the development and function of T and B cells. Thus, ORAI1 is considered to participate in allergic diseases. However, the specific mechanism of ORAI1 in skin disorders is still unclear. In order to investigate the roles of ORAI1 in allergic skin disorders, we reviewed the related articles and concluded that ORAI1 could be a potential therapeutic target for allergic skin diseases.

Trace Elements Homeostatic Imbalance in Psoriasis: a Meta-Analysis.

Studies point out that trace elements take vital roles in immunological and inflammatory reactions, such as psoriasis, while the conclusions are controversial. The purpose of this study was to analyze the existing literatures and explore the relationship between the risk of psoriasis and four trace elements zinc (Zn), copper (Cu), iron (Fe), and selenium (Se). We identified 42 studies through the databases PubMed, Embase, Cochrane Library, Google Scholar, and Web of knowledge. After the meta-analysis, the serum zinc, iron, and selenium levels showed no remarkable difference between psoriasis and controls. The people with psoriasis showed a higher level of zinc in lesion tissue (standard mean difference (SMD) = 14.43; 95% confidence interval (CI), 7.89-20.97; P < 0.0001), and a higher level of serum copper than controls (SMD = 18.23; 95% CI, 5.06-31.40; P = 0.007). Our findings indicated that the trace element of copper and zinc levels are in a homeostatic imbalance in psoriasis patients when compared with controls, which raise the question whether this imbalance can be taken as the therapy target for psoriasis.

C-reactive protein (CRP) rs3093059C predicts poor mizolastine response in chronic spontaneous urticaria patients with elevated serum CRP level.

Chronic spontaneous urticaria (CSU) is a frequent disorder with recurrent itchy wheals and/or angioedema, and nearly 35% patients respond poorly to non-sedating H1 antihistamine treatment. CRP gene encodes the C-reactive protein, which is involved in the pathogenesis of CSU. To investigate the impacts of CRP polymorphisms on the susceptibility and therapeutic efficacy in the South Han CSU patients, we enrolled 145 CSU patients in our study. After 4-week non-sedating H1 antihistamine monotherapy treatment, more than 50% reduction of the severity score is considered as effective, or else non-effective. The CRP rs3093059T/C and rs2794521G/A genotypes of patients were determined by Sequenom MassARRAY. Functional studies including relative luciferase assay and ß-hexosaminidase assay were conducted in HEK293T cells or RBL-2H3 cells to explore the function of variants. Forty (62.50%) CSU patients were effective when treated with mizolastine, and 55 (72.4%) patients were effective in the desloratadine group. We found that the patients carried with rs3093059TT genotype were significantly associated with good response (OR = 4.20, P = 0.015), had lower serum CRP, IL-6 and TNF-α levels than the CT/CC genotypes. In vitro, the rs3093059C allele exhibited significantly higher luciferase activity than wild allele (P < 0.001). From the ß-hexosaminidase assay, we observed the inhibiting degranulation effects by mizolastine and this effect is weakened when with a higher dose CRP in RBL-2H3 cells. Our findings suggested that CSU patients carrying the rs3093059C allele may respond poorly to mizolastine with elevated serum CRP level.

The role of lysophosphatidic acid in the physiology and pathology of the skin.

Lysophosphatidic acid (LPA) is the simplest phospholipid found in nature. LPA is mainly biosynthesized in tissues and cells by autotoxin and PA-PLA1α/PA-PLA1ß and is degraded by lipid phosphate phosphatases (LPPs). It is an important component of biofilm, an extracellular signal transmitter and intracellular second messenger. After targeting to endothelial differentiation gene (Edg) family LPA receptors (LPA1, LPA2, LPA3) and non-Edg family LPA receptors (LPA4, LPA5, LPA6), LPA mediates physiological and pathological processes such as embryonic development, angiogenesis, tumor progression, fibrogenesis, wound healing, ischemia/reperfusion injury, and inflammatory reactions. These processes are induced through signaling pathways including mitogen-activated protein kinase (MAPK), phosphatidylinositol-3-kinase (PI3K)/Akt, protein kinase C (PKC)-GSK3ß-ß-catenin, Rho, Stat, and hypoxia-inducible factor 1-alpha (HIF-1α). LPA is involved in multiple physiological and pathological processes in the skin. It not only regulates skin function but also plays an important role in hair follicle development, skin wound healing, pruritus, skin tumors, and scleroderma. Pharmacological inhibition of LPA synthesis or antagonization of LPA receptors is a new strategy for the treatment of various skin disorders. This review focuses on the current understanding of the pathophysiologic role of LPA in the skin.