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Objective To investigate the clinical manifestations,diagnosis,treatment,and laboratory examination characteristics of 8 pemphigus patients with high titers of anti-desmoglein antibodies in remission. Methods A retrospective study was conducted for the pemphigus patients diagnosed and treated in the department of dermatology from January 2013 to September 2020.The patients should have the serum anti-desmoglein antibodies ≥150 U/ml in remission or the antibody levels dropped less than 20%(calculated based on the maximum detection limit of 150 U/ml)of their initial ones detected before treatment,and the clinical and laboratory data of patients eligible for the inclusion criteria were collected. Results Among the 134 pemphigus patients with available follow-up data during this period,a total of 8 patients met the criteria,with the follow-up period of 21-85 months and the remission duration of 18-70 months.They all received less than or equal to 10 mg/d prednisone and had high titers of anti-desmoglein antibodies.At their first visit,the number of patients with positive anti-desmoglein 1/desmoglein 3 antibodies was 7.Two patients still had high titers of anti-desmoglein 1 antibodies 19 months and 21 months after they achieved remission,and 5 patients had high titers of anti-desmoglein 3 antibodies in 18-70 months.There was one patient showing high titers of both antibodies,especially for anti-desmoglein 1 antibodies.This patient relapsed after 19 months' remission while other patients were still in clinical remission. Conclusions Some pemphigus patients showed persistent high titers of anti-desmoglein antibodies in remission.Anti-desmoglein 3 antibodies were more common to keep positive,while high titer of anti-desmoglein 1 antibodies was less observed.The high titer of anti-desmoglein 1 antibodies had a correlation with recurrence.For the pemphigus patients with long-term clinical remission but high antibody titer,the dosages of corticosteroids should be adjusted carefully according to their actual clinical manifestations and the positive antibody type.For the patients with high titer of anti-desmoglein 1 antibodies,the dosage reduction of corticosteroids should be appropriately slower.

Background: Current epidemiological studies suggest a significant correlation between Alzheimer's disease (AD) and bullous pemphigoid (BP). However, the autoimmune response against BP180 in patients with AD has not been fully understood. investigated., Methods: We randomly enrolled 48 patients with AD and 50 sex- and age-matched healthy controls. We detected the presence/absence and the level of anti-BP180/BP230 immunoglobulin G (IgG) autoantibodies in the patients' serum to determine whether said antibodies possess reactivity against the BP180 protein in the human brain and skin., Results: The enzyme-linked immunosorbent assay (ELISA) results revealed that the positive rate of anti-BP180 autoantibodies in patients with AD (23/48, 47.9%) was significantly higher than that in controls (4/50, 8.0%; P<0.0001). These ELISA-positive patients were further examined through immunoblotting. Sera from nine patients with AD (9/23, 39.1%) and one control (1/4, 25.0%) reacted with human cutaneous recombinant full-length BP180 and BP180-noncollagenous 16A (NC16A). Sera from 11 (11/23, 47.8%) patients with AD reacted with a 180-kDa protein from the human brain extract, but none of the controls' sera recognized the corresponding protein band. The majority of the patients in the anti-BP180-positive AD group were men (14/23, 60.9%) who were older (74.0 years) compared with those in the control group (6/25, 24.0%; P<0.05) (72.2 years; P<0.01)., Conclusions: Anti-BP180 autoantibodies are present in AD and recognize human recombinant full-length BP180 and a 180-kDa protein from the human brain extract, suggesting that BP180 is a shared autoantigen in AD and BP and may help clarify the mechanism to explain why a high risk of BP exists in AD. Elderly male patients with AD are significantly more likely to develop BP180 serum autoreactivity compared with other patients with AD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5343). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Marine fungi with their successful pharmacological effects were considered to be the treasure of ocean medicines concerning the striking ability of their secondary metabolites. Literature over literature has been published on fungi derived bioactive molecules to probe its therapeutic potential. Marine fungi have an implicit to cede future medicines against life-threatening diseases, such as cancer and several emerging inflammations. The biological actions of many marine fungi-derived secondary metabolites are still unlocked, for an assorted number of bioactive compounds by which they interact with human diseases are discussed here with comprehensive diagrams. This knowledge is one of the main tracks to be established specifically for the successful transformation of bioactive compounds to medicines. Marine fungi produce a diverse range of biochemical substances with precious carbon scaffolds, which are the main component interplaying with human diseases at distinctive spots. Specific diseases having a flair to fight at distinctive targets within the body can lead to a new trend of raising the chances of developing targeted drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This report illustrated isolation and identification of 42 compounds comprising five (spicatainoids A-E) undescribed eremophilanolide type sesquiterpenoids and one undescribed nor-eremophilane (spicatainoid F) from Ligularia subspicata.. Among all the isolated new compounds, 4 is reported as the first enantiomeric form of novel eremophilanolide type sesquiterpenoid. Comprehensive analysis of HRESIMS, 1D/2D NMR, experimental circular dichroism (CD), calculated ECD analysis, and X-ray crystallographic (XRD) analysis validated the complete configuration and confirmation of these isolated compounds. All the isolated compounds were tested for the anti-inflammatory potential by measuring the amount of nitric oxide production. Among the tested compounds, 4 was the most effective with 90% NO-inhibition activity. Compounds 1, 2, 3, 9, 10 18, 29, 34, 35 exhibited moderate inhibitory effects against the production of NO, while other compounds displayed no activity even at the concentration of 50 μM. Additionally, compounds 1, 3 and 4 presented moderate anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in LPS-stimulated N9 cells. The IC 50 values of compounds 1, 3 and 4 were calculated 39.6 ± 2.7, 42.5 ± 3.8 and 27.60 ± 1.9 μΜ., (Copyright © 2020. Published by Elsevier B.V.)

Background: Compound Dan Zhi tablet (DZT) is a commonly used traditional Chinese medicine formula. It has been used for the treatment of ischemic stroke for many years in clinical. However, its pharmacological mechanism is unclear., Purpose: The aim of the current study was to understand the protective effects and underlying mechanisms of DZT on ischemic stroke., Methods: Fifteen representative chemical markers in DZT were determined by ultra-performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). The protective effect of DZT against ischemic stroke was studied in a rat model of middle cerebral artery occlusion (MCAO), and the mechanism was further explored through a combination of network pharmacology and experimental verification., Results: Quantitative analysis showed that the contents of phenolic acids, furan sulfonic acids, tanshinones, flavonoids, saponins and phthalides in DZT were calculated as 7.47, 0.788, 0.627, 0.531 and 0.256 mg/g, respectively. Phenolic acids were the most abundant constituents. Orally administered DZT (1.701 g kg -1 ) significantly alleviated the infarct size and neurological scores in MCAO rats. The network analysis predicted that 53 absorbed active compounds in DZT-treated plasma targeted 189 proteins and 47 pathways. Ten pathways were associated with anti-platelet activity. In further experiments, DZT (0.4 and 0.8 mg mL -1 ) markedly inhibited in vitro prostaglandin G/H synthase 1 (PTGS1) activity. DZT (0.4 and 0.8 mg mL -1 ) significantly inhibited in vitro platelet aggregation in response to ADP or AA. DZT (113 and 226 mg kg -1 , p.o.) also produced a marked inhibition of ADP- or AA-induced ex vivo platelet aggregation with a short duration of action. DZT decreased the level of thromboxane A 2 (TXA 2 ) in MCAO rats. In the carrageenan-induced tail thrombosis model and ADP-induced acute pulmonary thromboembolism mice model, DZT (113 and 226 mg kg -1 , p.o.) prevented thrombus formation. Importantly, DZT (113 and 226 mg kg -1 , p.o.) exhibited a low bleeding liability., Conclusion: DZT protected against cerebral ischemic injury. The inhibition of TXA 2 level, platelet aggregation and thrombosis formation might involve in the protective mechanism., (Copyright © 2020. Published by Elsevier GmbH.)

N 6 -methyladenosine (m 6 A) methylation, as the most prevalent internal RNA modification, has been revealed to play critical roles in various biological functions. In this study, we performed m 6 A transcriptome-wide profiling in three kinds of skin tissue: involved psoriatic skin (PP), uninvolved psoriatic skin (PN), and healthy control skin samples (NN). The findings revealed that transcripts of PP contained the fewest m 6 A peaks and lowest m 6 A peak density. The greatest differences of m 6 A methylation were observed in the PP vs. NN and PP vs. PN comparisons. Intriguingly, in these comparisons, hypermethylated m 6 A was mainly enriched within the CDSs and 3'UTRs, while hypomethylated m 6 A was not only enriched within CDSs and 3'UTRs, but also within 5'UTRs. GO and KEGG pathway analyses indicated that hypermethylated transcripts in PP were particularly associated with response-associated terms, cytokine production, and olfactory transduction. Meanwhile, hypomethylated transcripts in PP were mainly associated with development-related processes and the Wnt signaling pathway. In addition, we discovered that 19.3-48.4% of the differentially expressed transcripts in psoriasis vulgaris were modified by m 6 A, and that transcripts with lower expression were more preferentially modified by m 6 A. Moreover, upregulation of gene expression was often accompanied by upregulation of m 6 A methylation, suggesting a regulatory role of m 6 A in psoriasis vulgaris gene expression., (Copyright © 2020 Wang and Jin.)

Purpose: To determine the effectiveness and safety of trabeculectomy along with amniotic membrane transplantation (AMT) for glaucoma., Methods: This systematic review was performed using RevMan 5.3. We searched PubMed, EMBASE, and the Cochrane Library and included studies published until September 2019. The treatment group included patients with AMT and trabeculectomy (group A), and the control group had only trabeculectomy (group B). We only included randomized controlled trials. The outcomes were intraocular pressure (IOP), complete success rate, number of antiglaucoma medications, and complications., Results: Five studies, including 174 eyes (87 eyes in the AMT group and 87 eyes in the control group), were eligible in this review. The parameters had no significant difference in heterogeneity between the AMT and control groups preoperatively. In the AMT group, the mean IOP was significantly lower at 3 and 12 months after operation ( P  < 0.0001 and P  = 0.02, respectively), while the number of complete successes in the AMT group was significantly higher at 6 and 12 months ( P  = 0.02 and P  = 0.003, respectively) compared with the control group. Complications, including a flat anterior chamber and hyphema, appeared to be decreased in the AMT group compared to the control group ( P  = 0.02 and P  = 0.02, respectively). No differences were observed in the number of antiglaucoma medications, hypotony, encapsulated bleb, or choroidal detachment., Conclusion: Compared with only trabeculectomy, it is more efficient and safer to add AMT to trabeculectomy during glaucoma filtering surgery., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Tian-yi Shen et al.)

Although T cells are considered as the central component in immune-mediated diseases, supportive evidence has demonstrated that B cells also contribute to the progression of these diseases. B cells are divided into various subsets according to their secreted cytokines. Different B cell subsets play diverse roles in immune-mediated dermatoses. Regulatory B cells (Bregs) are defined functionally by their ability to secrete IL-10, which has been revealed to contribute to immunological tolerance. Drugs that deplete B cells, such as rituximab, are now used for the treatment of several immune-mediated dermatoses. In this review, we present and discuss the current knowledge on the roles of B cells in several immune-mediate dermatoses including psoriasis, pemphigus, bullous pemphigoid, and dermatomyositis, atopic dermatitis., (Copyright © 2020. Published by Elsevier Ltd.)

Objectives: Both thymic stromal lymphopoietin (TSLP) and dendritic cells (DCs) are involved in many autoimmune diseases, but the potential roles of TSLP and DCs in bullous pemphigoid (BP) have not been clarified. We sought to explore the contributions of TSLP and DCs in patients with BP., Methods: TSLP levels in sera and blister fluids were measured by enzyme-linked immunosorbent assay. The TSLP expression in the BP lesional skin was detected by immunohistochemical staining. Infiltration of DCs, marked by DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), and its relationship with TSLP and TSLP receptors was evaluated by immunofluorescence staining., Results: We found that TSLP levels in sera and in blister fluids of patients with BP were higher compared to the control groups. In patients with BP, TSLP levels in sera correlated with TSLP levels in blisters. The expression of TSLP in the BP lesional skin was higher compared to the healthy controls' skin. Greater numbers of TSLP-positive cells were observed in the epidermis of patients with BP compared to the healthy controls. Greater numbers of DC-SIGN-positive cells were present in the BP lesional skin compared to the skin of controls. The expression of TSLP was highly upregulated in DC-SIGN-positive cells, and most DC-SIGN-positive cells expressed TSLP receptors., Conclusions: We conclude that TSLP may activate DC-SIGN-positive DCs directly, which may be involved in the pathogenesis of BP., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2020 Si-Zhe Li et al.)

Background: Diagnoses of Skin diseases are frequently delayed in China due to lack of dermatologists. A deep learning-based diagnosis supporting system can facilitate pre-screening patients to prioritize dermatologists' efforts. We aimed to evaluate the classification sensitivity and specificity of deep learning models to classify skin tumors and psoriasis for Chinese population with a modest number of dermoscopic images., Methods: We developed a convolutional neural network (CNN) based on two datasets from a consecutive series of patients who underwent the dermoscopy in the clinic of the Department of Dermatology, Peking Union Medical College Hospital, between 2016 and 2018, prospectively. In order to evaluate the feasibility of the algorithm, we used two datasets. Dataset I consisted of 7192 dermoscopic images for a multi-class model to differentiate three most common skin tumors and other diseases. Dataset II consisted of 3115 dermoscopic images for a two-class model to classify psoriasis from other inflammatory diseases. We compared the performance of CNN with 164 dermatologists in a reader study with 130 dermoscopic images. The experts' consensus was used as the reference standard except for the cases of basal cell carcinoma (BCC), which were all confirmed by histopathology., Results: The accuracies of multi-class and two-class models were 81.49% ± 0.88% and 77.02% ± 1.81%, respectively. In the reader study, for the multi-class tasks, the diagnosis sensitivity and specificity of 164 dermatologists were 0.770 and 0.962 for BCC, 0.807 and 0.897 for melanocytic nevus, 0.624 and 0.976 for seborrheic keratosis, 0.939 and 0.875 for the "others" group, respectively; the diagnosis sensitivity and specificity of multi-class CNN were 0.800 and 1.000 for BCC, 0.800 and 0.840 for melanocytic nevus, 0.850 and 0.940 for seborrheic keratosis, 0.750 and 0.940 for the "others" group, respectively. For the two-class tasks, the sensitivity and specificity of dermatologists and CNN for classifying psoriasis were 0.872 and 0.838, 1.000 and 0.605, respectively. Both the dermatologists and CNN achieved at least moderate consistency with the reference standard, and there was no significant difference in Kappa coefficients between them (P > 0.05)., Conclusions: The performance of CNN developed with relatively modest number of dermoscopic images of skin tumors and psoriasis for Chinese population is comparable with 164 dermatologists. These two models could be used for screening in patients suspected with skin tumors and psoriasis respectively in primary care hospital.

Etanercept biosimilar recombinant human tumour necrosis factor-α receptor II: IgG Fc fusion protein (rhTNFR-Fc, trade name Yisaipu) has shown good efficacy in the treatment of moderate-to-severe plaque psoriasis. To compare the efficacy and safety of rhTNFR-Fc plus methotrexate (MTX) and rhTNFR-Fc plus placebo in Chinese patients with moderate-to-severe plaque psoriasis. In this multicentre, randomized, placebo-controlled trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned in a 1:1 ratio to receive rhTNFR-Fc plus MTX or rhTNFR-Fc plus placebo. The primary endpoint was the proportion of patients achieving Psoriasis Area and Severity Index improvement of at least 75% (PASI 75) from baseline at week 24. Adverse events (AEs) were recorded to evaluate safety. Efficacy analysis was performed using the intent-to-treat principle. A total of 466 patients were enrolled and randomly received rhTNFR-Fc plus MTX (combination group, n = 233) or rhTNFR-Fc plus placebo (monotherapy group, n = 233). PASI 75 at week 24 was significantly higher in the combination group than in the monotherapy group (81.86% vs. 65.50%, p < 0.001). Similar results were observed in other PASI improvement scores at week 12 [PASI 75, 62.39% vs. 44.54% (p < 0.001); PASI 50, 87.17% vs. 75.55% (p = 0.001); and PASI 90, 34.07% vs. 18.78% (p < 0.001)] and week 24 [PASI 50, 92.48% vs. 85.59% (p = 0.019); and PASI 90, 64.16% vs. 42.36% (p < 0.001)]. Significantly more patients had a static Physicians' Global Assessment of clear or almost clear in the combination group than in the monotherapy group at week 12 (26.46% vs. 12.50%, p < 0.001) and week 24 (62.38% vs. 40.83%, p < 0.001). The most common AEs in the two groups were upper respiratory tract infection and abnormal liver function. The combination therapy of rhTNFR-Fc plus MTX was an effective therapy for moderate-to-severe plaque psoriasis with an acceptable safety and tolerability profile, indicating that it was feasible and well tolerated for patients.

Introduction: Pustular psoriasis is a group of skin diseases characterized by neutrophil infiltration in the epidermis and formation of sterile pustules. Conventional treatments, such as retinoids and immunosuppressive drugs, have improved the clinical manifestations; however, many patients suffer from drug-related toxicity or are resistant to therapy., Areas Covered: In this review, the authors focus on the efficacy and safety of these biologics, including anti-IL-1β (gevokizumab and canakinumab), anti-IL-1 R (anakinra), anti-IL-36 R (BI 655130), anti-tumor necrosis factor-α (etanercept, infliximab, and adalimumab), anti-IL-12/23 (ustekinumab), anti-IL-17A (secukinumab and ixekizumab), anti-IL-17RA (brodalumab), anti-IL-2 R (basiliximab), anti-IL-6 R (tocilizumab), and anti-IL-23 (risankizumab and guselkumab), for treating pustular psoriasis., Expert Opinion: Patients with pustular psoriasis treated with biologics demonstrated positive responses. Anti-TNF-α is the most available biologics for the treatment of pustular psoriasis, and anti-IL-12/23 and anti-IL-17A might be considered as the first- or second-line therapy for moderate-to-severe and refractory pustular psoriasis. Anti-IL-17A can be used in the pustular psoriasis patients who failed to respond to anti-TNF agents and anti-IL-12/23. Therapeutic efficacy of biologics in pustular psoriasis might have no association with IL-36 RN mutation status.

Tripterygium wilfordii Hook F (TwHF) is a traditional Chinese herb used in many medicinal applications, but the treatment of bullous pemphigoid (BP) with TwHF has never been reported. The aim of this study was to evaluate the efficacy and safety of TwHF in BP patients. A retrospective study was performed from January 2015 to September 2019 in the Department of Dermatology, Peking Union Medical College Hospital. A total of 10 patients with mild to moderate BP and treated with TwHF were enrolled in the study with 10 mild or moderate BP patients treated with systemic glucocorticoid randomly selected as controls. In the TwHF group, a major response was seen in seven patients, a minor response in one and no response was seen in two patients. In the glucocorticoid group, a major response was seen in nine patients and a minor response in one patient. Two patients experienced treatment failure. The time to disease control in the TwHF group (34 ± 11 days) was longer as compared to the glucocorticoid group (18 ± 8 days, P < .05). Ten patients relapsed during the follow-up period. The adverse events in the TwHF group were lower than those in the glucocorticoid group (13 vs 19). Low-dose TwHF may be effective and safe for treating mild and moderate BP., (© 2020 Wiley Periodicals LLC.)

Psoriasis is a common inflammatory disease that can involve the skin, joints, or both. The abnormalities of innate immunity play crucial roles in the pathogenesis of psoriasis. Neutrophils are the most abundant leukocytes in the circulation. Emerging evidences have demonstrated that neutrophils may play a role in autoimmune diseases. The neutrophil-to-lymphocyte ratio (NLR), the activity of neutrophils, and the number of NETotic cells were significantly higher in psoriasis patients compared to healthy controls. The number of low-density granulocytes (LDGs) in the blood of psoriasis patients was significantly higher than those in the control blood. Furthermore, neutrophils may play important roles in the cardiovascular risk in psoriasis. However, the exact role of neutrophils in psoriasis remains unclear. In this review, we highlight the role of neutrophils in the pathogenesis of psoriasis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Wen-Ming Wang and Hong-Zhong Jin.)

Untargeted mass spectrometry analysis is one of the most challenging and meaningful steps in the rapid structural elucidation of the highly complex and diverse constituents of traditional Chinese medicine. Specifically, it is a laborious and time-consuming way to identify unknown compounds. Herein, a workflow was proposed to expedite the annotations of the chemical structures in Pheretima aspergillum (E. Perrier) (Di-Long, DL). First, ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOFMS) was performed to obtain the untargeted mass spectral data. Then, the spectral data were uploaded to the Global Natural Products Social Molecular Networking (GNPS) platform to create a network and extract the Mass2Motifs (co-occurring fragments and neutral losses) using unsupervised substructure annotation topic modeling (MS2LDA). Finally, a structural analysis was performed using the proposed workflow of MS2LDA in combination with mass spectral molecular networking and in silico fragmentation prediction. As a result, a total of 124 compounds from DL were effectively characterized, of which 89 (7 furan sulfonic acids, 57 phospholipids and 25 carboxamides) were identified as potentially new compounds from DL. The results presented in this article significantly improve the understanding of the chemical composition of DL and provide a solid scientific basis for the future study of the quality control, underlying pharmacology and mechanism of DL. Moreover, the proposed workflow was used for the first time to accelerate the annotations of unknown molecules from TCM. Furthermore, this workflow will increase the efficiency of characterizing the 'unknown knowns' and elucidation of the 'unknown unknowns' from TCM, which are crucial steps of discovering the natural product drugs in TCM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Psoriasis is a highly prevalent condition that affects the quality of life of affected individuals. Several studies have indicated an association between psoriasis and metabolic syndrome (MS). However, the results were inconsistent. The objective of this study was to evaluate the relationship between psoriasis and MS., Material and Methods: Electronic databases (PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane) were searched systematically for published studies up to November 2, 2018. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between psoriasis and MS. The heterogeneity of the study was estimated with the I 2 statistic and analyzed by meta-regression and subgroup analyses., Results: Twenty-two studies with a total of 137,053 participants were included in this meta-analysis. Psoriasis was associated with MS and the combined OR (95% CI) was 2.02 (1.67-2.43). The results showed high heterogeneity ( I 2 = 83.60%, p < 0.001) and no publication bias among the included studies ( p = 0.119). The source of controls may have influenced the heterogeneity according to the meta-regression. There was no heterogeneity in studies with matched non-psoriasis control groups according to the subgroup analysis., Conclusions: Psoriasis was associated with MS. The source of the control group was an influencing factor on heterogeneity in this study. Treating for MS in patients with psoriasis might improve psoriasis and reduce the risk of cardiovascular disease., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

N 6 -methyladenosine (m 6 A) is the most important modification of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) in higher eukaryotes. Modulation of m 6 A modifications relies on methyltransferases and demethylases. The discovery of binding proteins confirms that the m 6 A modification has a wide range of biological effects and significance at the molecular, cellular, and physiological levels. In recent years, techniques for investigating m 6 A modifications of RNA have developed rapidly. This article reviews the biological significance of RNA m 6 A modifications in the innate immune response, adaptive immune response, and viral infection., Competing Interests: The authors confirm that there are no conflicts of interest., (Copyright © 2020 Ya-Nan Wang et al.)

Background: Psoriasis is a common chronic inflammatory skin disease that features the abnormal proliferation of keratinocytes. This proliferation could partly result from disturbances in vitamin A metabolism. Changes in psoriasis patients of the levels of retinol-binding protein 4 (RBP4), a carrier of retinol (vitamin A); transmembrane protein stimulated by retinoic acid 6 (STRA6); and other retinol metabolic molecules have not yet been fully established. Therefore, we investigated vitamin A-related proteins in mice with imiquimod (IMQ)-induced psoriasis., Methods: Thirty mice were divided into four study groups: two groups underwent IMQ application for 3 or 6 days (groups A and B, respectively), and two groups underwent Vaseline application for 3 or 6 days (groups C and D, respectively). Blood and skin samples from both lesional and non-lesional areas of the mice were analyzed using enzyme-linked immunosorbent assays, hematoxylin and eosin staining, immunochemistry, real-time reverse transcription polymerase chain reaction, and RNA sequencing., Results: IMQ-treated mice developed erythema, scales, and skin thickening. Compared with the control groups, IMQ-treated groups had the following changes: 1) interleukin (IL)-17A, IL-23, and tumor necrosis factor (TNF)-α levels were raised significantly in both serum and lesional skin (all p  < 0.001); 2) retinol levels in lesional skin increased slightly ( p  = 0.364), but no change was evident in serum retinol levels; 3) STRA6 was upregulated in both lesional skin ( p  = 0.021) and serum ( p  = 0.034); 4) RBP4 levels were elevated in serum ( p  = 0.042), but exhibited only an increasing trend ( p  = 0.273) in lesional skin; and 5) proteins and enzymes that mediate retinoic acid formation and transformation were upregulated in lesional skin., Conclusions: As the demand for vitamin A in psoriatic mice increased, retinol underwent relocation from the circulation to target tissues. RBP4, STRA6, and the transformation from retinol to retinoic acid were upregulated, which may be part of the mechanism of psoriasis skin lesion formation. We propose that a positive feedback mechanism was formed that maintained the severity of psoriasis., Competing Interests: Competing interestsThe authors declare they have no competing interests., (© The Author(s). 2020.)

Competing Interests: Competing interests: None declared.

Mounting evidence has demonstrated that acute pancreatitis (AP) is one of the causes of multiple organ damage. NADPH (nicotinamide adenine dinucleotide phosphate) act as a substrate of NADPH oxidase (NOX) to generate reactive oxygen species (ROS), but the role NADPH oxidase signaling pathway plays in AP-induced acute lung injury remains unclear. Apocynin, an inhibitor of NOX, is highly effective in suppressing the production of ROS. Here, we used rat model of severe acute pancreatitis (SAP) to explore whether the NOX inhibitor apocynin produced protective effects in against SAP-induced lung injury via inhibition of inflammation and oxidation. We observed that apocynin significantly attenuated severe acute pancreatitis-induced increase of NOX2, NOX4 and ROS expressions in lung tissues. In addition, the phosphorylation and degradation of IκBα, and the nuclear localization of NF-κB p65 in SAP-induced lung injury were also inhibited after using apocynin. Simultaneously, down-regulation of NOX suppressed the levels of inflammasome proteins including NLRP3, ASC, pro-Caspase-1 and cleaved-Caspase-1 in the lung. Serum levels of TNF-α, interleukin (IL)-1β and IL-6 were also reduced. Our findings suggest that beyond anti-oxidative effects, apocynin may also have anti-inflammatory effects by suppressing NLRP3 inflammasome activation and NF-κB signaling in acute pancreatitis. Therefore, apocynin may have therapeutic potential in the treatment of SAP and SAP-induced lung injury., (Copyright © 2019 Elsevier B.V. All rights reserved.)

B cells are a heterogeneous population, which have distinct functions of antigen presentation, activating T cells, and secreting antibodies, cytokines as well as protease. It is supposed that the balance among these B cells subpopulation (resting B cells, activated B cells, Bregs, and other differentiated B cells) will determine the ultimate role of B cells in tumor immunity. There has been increasing evidence supporting opposite roles of B cells in tumor immunity, though there are no general acceptable phenotypes for them. Recent years, a new designated subset of B cells identified as Bregs has emerged from immunosuppressive and/or regulatory functions in tumor immune responses. Therefore, transferring activated B cells would be possible to become a promising strategy against tumor via conquering the immunosuppressive status of B cells in future. Understanding the potential mechanism of double-edge role of B cells will help researchers utilize activated B cells to improve their anti-tumor response. Moreover, the molecular pathways related to B cell differentiation are involved in its tumor-promoting effect, such as NF-κB, STAT3, BTK. So, we review the molecular and signaling pathway mechanisms of B cells involved in both tumor-promoting and tumor-suppressive immunity, in order to help researchers optimize B cells to fight cancer better.

Objective Psoriasis is an immune-mediated inflammatory disease. Despite advances in the study of its pathogenesis, the exact development mechanism of psoriasis remains to be fully elucidated. Hyperproliferative epidermis plays a crucial role in psoriasis. This study aimed to investigate the effects of interleukin-36 β (IL-36 β ) on keratinocyte dysfunction in vitro . Methods Human keratinocyte cell lines, HaCaT cells, were treated with 0 (control), 50 or 100 ng/ml IL-36 β respectively for 24 h. Cell viability was determined with a cell counting kit-8 assay. Flow cytometry was used to assess the effects of IL-36 β on apoptosis and cell cycle distribution. Expressions of the differentiation markers, such as keratin 10 and involucrin, were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). Expressions of the inflammatory cytokines, IL-1 β and IL-6 were tested by ELISA. Results CCK8 assay showed the survival rate had no significant difference between the control and treated group ( P > 0.05). Flow cytometry analysis showed cell cycle arrest at S phase in the IL-36 β -treated groups compared with the control group ( P < 0.05). RT-qPCR verified the decreased mRNA expressions of keratin 10 and involucrin in the IL-36 β -treated groups compared with the negative control ( P < 0.01). ELISA showed 100 ng/ml IL-36 β enhanced levels of IL-1 β and IL-6 in culture supernatants of HaCaT cells compared with the negative control ( P < 0.05). Conclusion Taken together, these findings suggest that IL-36 β could induce cell cycle arrest at S phase, inhibit keratin 10 and involucrin expressions and promote inflammatory activity in HaCaT cell lines.

Background: Due to advances in high-frequency ultrasound technology, it is easier to detect fine structures of skin lesions. The aim of this study was to examine the ultrasonographic features and use recurrence risk stratification to assess the diagnostic performance of pre-operative ultrasound examination of basal cell carcinoma (BCC)., Methods: This was a retrospective study. Forty-six BCC lesions underwent pre-operative ultrasound examination using 50- and 20-MHz probes. Ultrasonographic shape, margin, internal echoes, hyper-echoic spots, posterior echoes, and depth of the lesion were evaluated and correlated with the risk of recurrence based on histological features., Results: Forty-two patients had 46 skin lesions in total. The high-risk (n = 6) and low-risk (n = 40) groups exhibited considerable overlap in the ultrasonographic manifestations and no significant difference in margin (χ = 3.231, P = 0.072), internal echo (χ = 1.592, P = 0.207), or posterior echo (P = 0.169). However, high-risk BCCs tended to be irregular in shape than low-risk lesions (χ = 4.313, P = 0.038). Both types presented hyper-echoic spots (χ = 1.850, P = 0.174). Additionally, 78% of low-risk lesions were confined to the dermis (31/40), and 100% of high-risk lesions infiltrated into the sub-cutaneous tissue, resulting in a significant difference between the two groups (χ = 10.951, P = 0.001). Ultrasound detected sub-clinical lesions in five patients., Conclusions: High-frequency ultrasound can provide important information for pre-operative evaluation of risk in BCC foci and reveal hidden lesions. The technique may play a crucial role in guiding therapeutic options for BCC.

Background: Injectable hyaluronic acid fillers have been widely applied in the clinical treatment of facial wrinkles. However, further information and clinical evidence concerning dermal changes and hyaluronic acid filler longevity after injection and diffusion pattern are limited., Methods: The authors evaluated the longevity and diffusion pattern of two hyaluronic acid fillers generated by different cross-linking technologies used in the treatment of nasolabial folds using high-frequency ultrasound. Forty-one subjects were treated with Restylane 2 and the remaining 41 were treated with Dermalax DEEP. Wrinkle severity rating scale score and high-frequency ultrasound evaluation of nasolabial folds were performed before and after the injection of hyaluronic acid filler. The ultrasound images were acquired and analyzed to determine dermal thickness and the shape and distribution of hyaluronic acid filler., Results: At 2 and 24 weeks from baseline, increased dermal thickness induced by hyaluronic acid filler treatment was not significantly different between groups. At 48 weeks after injection, increased dermal thicknesses of the Restylane 2 group (0.14 ± 0.12 mm) were much lower than those of the Dermalax DEEP group (0.20 ± 0.13 mm). Ultrasound examination revealed that hyaluronic acid materials form well-demarcated and hypoechogenic areas. Restylane 2 tended to form a more diffuse pattern, with multiple smaller bubbles, whereas Dermalax DEEP developed into a more localized configuration, with larger clumps., Conclusions: This study is the first long-term assessment of nasolabial fold correction that reveals the performance of different hyaluronic acid materials in vivo and validates high-frequency ultrasound as a simple and rapid modality. Hyaluronic acid fillers generated by different cross-linking technologies display differential diffusion patterns in skin tissues., Clinical Question/level of Evidence: Therapeutic, II.

Psoriasis is a chronic disfiguring skin condition which may be induced or exacerbated by stress. Heat shock proteins (HSPs), as molecular chaperones, play a central role in protein folding and cellular protein homeostasis. The many different functions of HSPs in the cell depend on the specific HSP involved. HSPs play crucial roles in inflammation and immune reactions, and have emerged as promising therapeutic targets. In this review, we compile current lines of evidence concerning the roles and molecular mechanisms of HSPs that lead to the occurrence and development of psoriasis.

Six rare guaiane-type sesquiterpene dimers xylopins A-F, having three different connecting modes through two direct C-C bonds, were isolated from the roots of Xylopia vielana . Their absolute configurations were established by NOESY analysis, Cu Kα X-ray crystallography, and experimental and calculated electronic circular dichroism spectra. Flow cytometry demonstrated the fact that compound 6 arrested the cell cycle at G2 phase and concentration-dependently induced apoptosis of DU145 cells. Furthermore, the EPT2-TGC cell model, zebrafish study and western blot analysis illustrated compound 6 could induce apoptosis by efficiently inhibiting the Wnt/β-catenin signaling pathway via decreasing the expression of β-catenin., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Exosomes are membrane vesicles of endocytic origin that can mediate communication between cells and the transport of cellular components such as microRNAs, mRNAs, proteins and DNA. Recently, exosomes have been under investigation for their significant roles in both healthy physiology and disease states. Herein, we review the role of exosomes in chronic inflammatory skin diseases and skin tumors, especially focusing on systemic lupus erythematosus, psoriasis, atopic dermatitis, bullous pemphigoid and melanoma. Moreover, we emphasize the involvement of changes in exosome cargo in the regulation of these diseases., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pterostilbene (PTS) mainly enriched in small fruits such as berries and grapes exerts an antioxidant effect. However, the protective effects of PTS against endoplasmic reticulum stress (ERS) have not yet been elucidated in mouse preimplantation embryo. ERS plays an important role in regulating the pathological and physiological processes, including embryonic development. We explored the protective effect of PTS on the tunicamycin (TM)-induced ERS in mouse preimplantation embryos. In vitro, culture medium was supplemented with different concentrations of TM and PTS. Our result indicated that treatment of zygotes with 0.5 μg/ml TM significantly decreased the development of day 4 blastocysts (P < 0.05), whereas 0.25 μM PTS supplementation improved the development rate of blastocysts. Moreover, TM treatment significantly increased (P < 0.05) the apoptotic index and reduced the total cell number of the blastocyst, whereas PTS treatment counteracted these effects. Additionally, TM potently increased expression levels of ERS-related proteins, such as GRP78, ATF6, PERK, p-Perk, IRE1, ATF4, and CHOP (P < 0.05). However, PTS and PTS + TM treatment decreased expression levels of ERS-related proteins (P < 0.05). Furthermore, expression level of the anti-apoptotic protein and gene BCL2 significantly decreased (P < 0.05) in TM-treated embryo but increased by PTS treatment (P < 0.05), whereas expression levels of the pro-apoptotic protein and gene BAX increased (P < 0.05) with TM but significantly decreased (P < 0.05) with co-treatment with PTS. In summary, PTS treatment significantly increased the development potential of mouse embryo by reduction of ERS.

Five new guaiane dimers, xylopidimers A-E ( 1-5 ), were isolated and identified from the roots of Xylopia vielana . The structures of 1-5 were elucidated by spectroscopic analysis and further confirmed by single-crystal X-ray diffraction. On the basis of the results of single-crystal X-ray analysis, 1-5 showed different carbon skeletons. Among these compounds, the unique connecting patterns of 1 and 2 caused significant differences on their carbon skeletons, which have not been reported. Moreover, 3-5 were also three new guaiane dimers. Among these compounds, 4 exhibited potent inhibitory activity against the production of nitric oxide with an IC 50 value of 4.59 μM in RAW264.7 cells stimulated by lipopolysaccharide., Competing Interests: The authors declare no competing financial interest.

Elicitation by chemical means including heavy metals is one of a novel technique for drug discoveries. In this review, the effect of heavy metals on animal, plants and microorganisms for the production of novel compounds with the unique structures has been discussed. The number of parameters such as metal concentration, type, dose, treatment schedule, duration of metal exposure, and nutrient composition are significant factors altering the secondary metabolites production. The detailed illustrated diagram representing the mode of action of metal stress has also been discussed. This is the first article reporting all the novel compounds produced from plants and microorganisms in response to metal-stress with their pharmacological potential. This new technique opens the new way for drug discovery from natural products., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: The present study carried out a meta-analysis to investigate whether the interleukin-1 receptor antagonist (IL-1RN) VNTR polymorphism and three IL-10 single-nucleotide polymorphisms (SNPs) rs1800896, rs3021097, and rs1800872 are associated with psoriasis risk., Methods: Wanfang, China National Knowledge Infrastructure, Medline, and PubMed databases were searched for potential studies published until 2 November 2017. Forest plots were generated., Results: Thirteen case-control studies were included in the review. The results of meta-analyses revealed no association of the IL-1RN*2 allele with psoriasis in the overall populations (odds ratio [OR] = 1.16, 95% confidence intervals [CI]: 0.89-1.50, p = 0.279), Asians (OR = 1.27, 95% CI: 0.73-2.23, p = 0.403), and Caucasians (OR = 1.04, 95% CI: 0.88-1.23, p = 0.669). Under the allelic model, there was no statistically significant association of psoriasis with the IL-10 SNPs rs1800896 (G allele vs. A allele: OR = 1.03, 95% CI: 0.90-1.18, p = 0.639), rs3021097 (C allele vs. T allele: OR = 1.17, 95% CI: 0.88-1.56, p = 0.288), and rs1800872 (C allele vs. A allele: OR = 1.01, 95% CI: 0.81-1.25, p = 0.951). No publication bias was found by Egger's test and Begg's funnel plots., Conclusion: Current published studies fail to support an association of the IL-1RN VNTR polymorphism and IL-10 SNPs rs1800896, rs3021097, and rs1800872 with psoriasis risk., (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Five new guaiane-type sesquiterpenoid dimers vielopsides A-E, connecting patterns through two direct CC bonds (C-2 to C-2', C-4 to C-1'), were isolated from the roots of Xylopia vielana. Their absolute configurations were established by NOE analysis, the Cu Kα X-ray crystallographic and circular dichroism (CD) experiment. Among them, compound 5 showed moderate activity IC 50 values of 33.8 μM on NO production in RAW 264.7 macrophages., (Copyright © 2018. Published by Elsevier B.V.)

Four unprecedented guaiane dimers, xylopsides A-D (1-4), were isolated and identified from the roots of Xylopia vielana. The structures of 1-4 were elucidated by spectroscopic analysis, Cu Kα X-ray crystallography and CD spectra. 1-4 showed two bridged pentacyclic skeletons between two guaiane-type sesquiterpenes, which were characterized as two different bridged ring systems. Among these compounds, 4 exhibited a moderate inhibitory activity against the production of nitric oxide with an IC50 value of 25.7 μM in RAW264.7 cells stimulated by LPS.

A hospital-based cross-sectional study was performed, including 117 psoriatic patients and 117 controls matched for age, gender, and body mass index. Psoriatic patients had higher levels of serum uric acid (6.25 ± 1.62 vs 5.71 ± 1.35 mg/dl; P=0.019) and significantly greater prevalence of hyperuricemia (31.6% vs 16.2%; P=0.009) than individuals without psoriasis. Psoriatic patients had significantly higher serum uric acid than controls in subjects without metabolic syndrome. Multivariate logistic regression analysis showed that psoriasis can be a strong predictor of hyperuricemia (odds ratio 2.61; 95% confidence interval 1.34-5.00; P=0.004).

Psoriasis usually combines with metabolic diseases,and the prevalence of cardiovascular disease remarkably increases in psoriatic patients. Adipokines,which play an important role in the cardiovascular diseases,also express abnormally in psoriasis and may induce or exacerbate the skin lesion. The adipokines associated with psoriasis and cardiovascular disease include adiponectin,leptin,resistin,omentin,visfatin,chemerin,and retinoid binding protein 4 (RBP-4). The levels of adiponectin and omentin apparently decrease in psoriatic patients compared to healthy controls,and thus they may play protective roles for psoriasis. Similarly,adiponectin plays a protective role in cardiovascular disease,but the role of retina in cardiovascular disease is still controversial. However,the concentrations of leptin,resistin,visfatin,chemerin,and RBP-4 in patients with psoriasis or cardiovascular disease are significantly higher than those of the controls;therefore,they may serve as the pathogenic factors for both diseases. Low adiponectin,leptin,visfatin,and chemerin levels may induce or aggravate psoriasis by activating plasmacytoid dendritic cells or T cells,as demonstrated in in vitro experiments. However,in vitro experiments also have shown that visfatin may inhibit cardiomyocyte apoptosis.

Herein, we report a case of a 34-year-old woman with systemic sclerosis (SSc)-rheumatoid arthritis (RA) overlap syndrome (OS) complicated with Sweet's syndrome. OS has been defined as entities satisfying classification criteria of at least two connective tissue diseases (CTD) occurring at the same or at different times in the same patient. The CTD include RA, SSc, systemic lupus erythematosus (SLE), polymyositis, and dermatomyositis. Sweet's syndrome also known as acute febrile neutrophilic dermatosis was first described by Robert Sweet in 1964. Sweet's syndrome is characterized by fever, neutrophilia, erythematous skin lesions, and a diffuse dermal infiltrate of mature neutrophils. There are sets of associations that we will discuss in this article between OS and Sweet's syndrome.

Six new guaiane dimers, xyloplains A-F (1-6), with connecting patterns through two direct C-C bonds (C-1 to C-3', C-2 to C-1'), were isolated from the roots of Xylopia vielana . Their structures were elucidated clearly using extensive analysis of 1D NMR and 2D NMR, combined with Cu-Kα X-ray diffraction and circular dichroism (CD) experiments. In additon, all of the isolates were tested for anti-inflammatory activity by measuring the amount of nitric oxide produced. To our delight, compounds 2 and 6 exhibited moderate inhibitory activity against the production of nitric oxide with IC 50 value of 34.5 and 31.1 μM, respectively, in RAW264.7 cells stimulated by LPS., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)