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Cutaneous warts caused by human papillomavirus are benign proliferative lesions that occur at any ages in human lives. Updated, comprehensive and systematic evidence-based guidelines to guide clinical practice are urgently needed.We collaborated with multidisciplinary experts to formulate this guideline based on evidences of already published literature, focusing on 13 clinical questions elected by a panel of experts. We adopted Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to form classification of recommendations as well as the improved Delphi method to retain respective recommendations with a consensus degree of over 80%.Our guideline covered aspects of the diagnosis and treatment of cutaneous warts such as diagnostic gold standard, transmission routes, laboratory tests, treatment principle, clinical cure criterion, definitions, and treatments of common warts, flat warts, plantar warts, condyloma acuminatum, and epidermodysplasia verruciformis. Recommendations about special population such as children and pregnant women are also listed. In total, 49 recommendations have been obtained.It is a comprehensive and systematic evidence-based guideline and we hope this guideline could systematically and effectively guide the clinical practice of cutaneous warts and improve the overall levels of medical services.

This study aimed to assess and compare the clinical efficacy and safety of a triple combination treatment using 2940 nm Er:YAG laser, triamcinolone acetonide solution combined with either 308 nm excimer laser or 0.1% tacrolimus for the treatment of stable segmental vitiligo. Patients with stable segmental vitiligo were randomly divided into two groups and received a 5-month treatment with 2940 nm Er:YAG laser followed by triamcinolone acetonide and, either 308 nm excimer laser (Group A, N = 8) or 0.1% tacrolimus (Group B, N = 13). General information and imaging data were collected before and at 1 month after treatments. Marked repigmentation and overall repigmentation rates were analyzed and any adverse skin reactions were recorded. Both treatments significantly reduced the percent of skin lesions per total body surface area (p 0.05) and no significant differences in repigmentation were observed between the two groups (p 0.05). The marked repigmentation rate of Group A was 42.11% and overall repigmentation rate was 94.74%, while for Group B these rates were 51.16% and 100%, respectively. There were no significant differences in the number of fingertip units at each time point (p 0.05). While there was a significant effect for time on the number of fingertip units without considering other factors (p 0.05), the time x treatment interaction was not significant (p 0.05). One Group A patient developed adverse reactions consisting of erythema, burning sensation and blisters and one Group B patient developed mild erythema and burning sensations. Both treatments demonstrated a high level of efficacy and safety in the treatment of stable segmental vitiligo.

The distinction between Keratoacanthoma (KA) and Cutaneous Squamous Cell Carcinoma (cSCC) is critical yet usually challenging to discriminate clinically and histopathologically. One approach to differentiate KA from cSCC is through assessing the immunohistochemical staining patterns of the three indicators, β-catenin, C-Myc, and CyclinD1, which are critical molecules that play important roles in the Wnt/β-catenin signaling pathway. Ki-67, as a proliferation biomarker for human tumor cells, was also assessed as an additional potential marker for differentiating KA from cSCC. In this report, these four indicators were analyzed in 42 KA and 30 cSCC cases with the use of the computer automated image analysis system. Computer automated image analysis is a time-based and cost-effective method of determining IHC staining in KA and cSCC samples. We found that C-Myc staining was predominantly localized in the nuclei of basal cells within KA patients, whereas cSCC staining was predominantly localized in the nuclei of diffuse cells. This C-Myc staining pattern has a sensitivity of 78.6% and a specificity of 66.7% for identifying KA. Moreover, positive rates of distinct expression patterns of C-Myc and Ki-67 may also serve as a means to clinically distinguish KA from cSCC. Taken together, our results suggest that these markers, in particular C-Myc, may be useful in differentiating KA from cSCC.

Macrophages, which serve as a bridge between innate and adaptive immunity, play an important role in sporotrichosis. Sporothrix schenckii infections can produce immune responses such as macrophage polarization and inflammatory factor secretion. In the early stages of inflammation, the expression of DAB2 in macrophages is increased, which controls the secretion of inflammatory factors and affects the polarization of macrophages. However, the expressions and mechanisms of DAB2 in sporotrichosis are not clear. In this study, we examined the expression of DAB2 and its regulation of inflammatory factors under conditions of Sporothrix schenckii infection. Our results indicated that the Sporothrix schenckii infection increased the expression of DAB2 and revealed a mixed M1/M2-like type of gene expression in BMDMs with the inhibited Il-6, Il1-β and Arg-1 and induced Tnf-α, Il-10 and Mgl-1. The deficiency of Dab2 gene suspended the changes of cytokines. In addition, JNK activity in BMDMs was inhibited by Sporothrix schenckii infection, leading to an increase in c-JUN. We also identified c-JUN as a transcription factor for Dab2 through chromatin immunoprecipitation and luciferase reporter assays. In an in vivo mouse model, sporotrichosis-induced skin lesions were accompanied with an upregulation of c-JUN and inhibition of JNK activity, which were in accord with findings from in vitro experiments. Taken together, these findings indicate that in the early stages of Sporothrix schenckii infection there is a promotion of DAB2 expression through the JNK/c-JUN pathway, effects that can then control the expression of inflammatory factors.

Background. Hyperthermia in combination with DnaJA4-knockout (KO) obviously affects the anti-viral immunity of HaCaT cells. The mechanisms of this process are not yet fully explored. However, it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia. Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia. Methods. Wild-type (WT) and DnaJA4-KO HaCaT cells were isolated at either 37°C (unheated) or 44°C (hyperthermia) for 30 min followed by testing under conditions of 37°C and assessing at 6, 12, and 24 h after hyperthermia. The cytoskeleton was observed with immunofluorescence. Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein. Results. DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells. F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells (6364.33 ± 989.10 vs. 4272.67 ± 918.50, P

Interleukin (IL)‑18, a pro‑inflammatory cytokine, plays an important role in a number of skin diseases. The aim of the present study was to investigate the role of IL‑18 in the development of atopic dermatitis (AD). For this purpose, mice were divided into 4 groups (n=5/group) as follows: i) The wild‑type (WT) controls; ii) IL18 knockout (KO) controls; iii) MC903‑treated WT mice; and iv) MC903‑treated KO mice. MC903 (4 nmol in ethanol) was topically applied daily for 15 consecutive days to the exposed skins of mice. AD‑like symptoms and severity were evaluated by the scoring of AD (SCORAD). Serum immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP) levels were determined with the use of an enzyme‑linked immunosorbent assay. Immunohistochemistry was used to assess the expression of IL‑1β, signal transducer and activator of transcription (STAT)3 and filaggrin (FLG) in the skin lesions. RT‑qPCR was performed to assess the mRNA levels of IL‑1β, IL‑4, IL‑9, STAT3, corticotropin‑releasing hormone receptor (CRHR)1, CRHR2, TSLP and caspase‑1 in the skin lesions. It was demonstrated that IL‑18 may function as a pleiotropic pro‑inflammatory cytokine in the development of AD‑like lesions. IL‑18 KO reduced aggravated AD‑like lesions induced by MC903, in part by upregulating Th2 cytokines. IL‑18 promoted the expression of FLG in the epidermis and CRHR2 in AD‑like lesions, but downregulated the serum levels of IgE. On the whole, the findings of the present study demonstrate that IL‑18 deficiency alleviates AD‑induced lesions in mice.

Background Hyperthermia upregulates DNAJA4, a member of heat shock proteins (HSPs) 40 family, in human keratinocytes and HPV-infected tissue. DNAJA4 deficiency enhances growth arrest induced by hyperthermia. Clusterin (CLU) and phosphorylated ERK (p-ERK) play a role in regulating cell proliferation and apoptosis, under environmental stress. Objectives To examine the downstream molecules and signalling pathways of DNAJA4 and assess their roles in cell cycle and apoptosis of keratinocytes in response to hyperthermia. Methods Wild-type and DNAJA4-knockout (KO) HaCaT cells were exposed to either 44 °C (hyperthermia) or 37 °C (control) for 30 min. The expression levels of CLU and p-ERK were determined by RT-PCR and Western blotting. RNAi and PD98059 were used to inhibit the expression of CLU and p-ERK, respectively. Cell viability, cell cycle and apoptosis were analysed by MTS assay and flow cytometry. Fresh biopsy samples of human normal foreskin or condyloma acuminatum (CA) were utilized to examine the expression of CLU and p-ERK after ex vivo culture at 44 °C. Results The expression of CLU and p-ERK was significantly increased by hyperthermia treatment at 44 °C in HaCaT cells, foreskin and HPV-infected tissues. In HaCaT cells subjected to hyperthermia, DNAJA4 deficiency further augmented the expression of CLU and p-ERK. CLU deficiency enhanced the p-ERK expression. Hyperthermia-induced CLU and p-ERK exerted protective roles mainly through inhibiting apoptosis and maintaining cell cycle, respectively. Conclusions In keratinocytes, CLU and p-ERK are induced by hyperthermia, an effect which can be further enhanced by DNAJA4 deficiency. CLU deficiency also increases p-ERK expression. Both CLU and p-ERK are critical protective factors of human keratinocytes from hyperthermia-induced injury.

Purpose. To evaluate the regulating effect of Notch-Hes1 signaling on IL-17A+γδ+T cell expression and IL-17A secretion in mouse psoriasis-like skin inflammation. Materials and Methods. Experimental mice were randomly divided into control group, model group (5% imiquimod- (IMQ-) treated mice), and intervention group (IMQ and γ-secretase inhibitor DAPT cotreated mice). The severity of psoriasis-like skin inflammation was evaluated by target lesion score based on the clinical psoriasis area and severity index (PASI). Flow cytometry detected IL-17A+γδ+T cell percentage. Quantitative real-time RT-PCR detected Hes1 mRNA expression. Enzyme-linked immunosorbent assay and western blot measured IL-17A serum concentration and protein expression. Additionally, splenic single cells from model mice were treated by DAPT to further evaluate the inhibitory effect of blocking Notch-Hes1 signaling on IL-17A+γδ+T cell differentiation and IL-17A secretion. Results. The spleen index, IL-17A+γδ+T cell percentage, Hes1 mRNA expression, IL-17A serum concentration, and protein expression were all significantly higher in model mice than control mice, while dramatically reduced in intervention mice by DAPT treatment, which also obviously alleviated the target lesion score, epidermal hyperplasia, and dermal inflammatory cell infiltration of intervention mice. In vitro study demonstrated that DAPT treatment could result in dose-dependent decrease of IL-17A+γδ+T cell percentage and IL-17A secretion in splenic single cells of model mice.

To evaluate the efficacy and safety of resveratrol combined with ablative fractional COThirty-two subjects were assigned to the treatment group (TG) or the control group (CG), respectively, applied test product (resveratrol essence) or control product twice daily for 6 months. Each subject was given an AFL treatment or no laser treatment on left or right side of the face randomly. Subjective evaluations by investigators and subjects themselves were conducted after treatment. Melanin index, erythema index, and cuticle moisture content were conducted at baseline and after treatments. Adverse events (AEs) were evaluated during the study period.All subjects in TG achieved improvements of their photoaging signs compared to pre-treatment both the laser side and the non-laser side at 6 months (p 0.05). On the laser side, TG produced a better improvement than CG at 6 months (p 0.05). On the laser side, the difference values of MI in TG at the 2 months after enrollment (M2), M3, and M4 were more obvious than those in CG (p 0.05). On the non-laser side, the difference values of MI in TG at M3, M4, M5, and M6 were more obvious than those of CG (p 0.05). Subjects in TG were more likely to have tingling and had a faster subsidence of erythema mild edema, and pigmentation induced by AFL compared to CG.The resveratrol can improve photoaging alone and add an efficacy to the AFL treatment and subside the AEs induced by AFL.

Psoriasis is an immune‑mediated cutaneous disorder with a high incidence and prevalence. Patients with psoriasis may experience irritation, pain and psychological problems. The cause and underlying molecular etiology of psoriasis remains unknown. In an attempt to achieve a more comprehensive understanding of the molecular pathogenesis of psoriasis, the gene expression profiles of 175 pairs of lesional and corresponding non‑lesional skin samples were downloaded from 5 data sets in the Gene Expression Omnibus (GEO) database. Integrated differentially expressed genes (DEGs) were obtained with the use of R software. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed using the DAVID online analysis tool. The protein‑protein interaction (PPI) network was constructed on the STRING platform and hub genes were calculated with the use of Cytoscape software. Finally, GEO2R was used to determine the expression of the hub genes in scalp psoriasis. A total of 373 genes from the 5 data sets were identified as DEGs, including 277 upregulated and 96 downregulated genes. GO analysis revealed that immune responses and epidermal differentiation/development were the most enriched terms in biological processes, extracellular space/matrix was the most enriched term in cellular components, and endopeptidase inhibitor activity was the most enriched term in molecular functions. In the KEGG pathway enrichment, DEGs were mainly enriched in the metabolic and viral infection‑associated pathways. A total of 17 hub genes were calculated, including CSK2, CDC45, MCM10, SPC25, NDC80, NUF2, AURKA, CENPE, RRM2, DLGP5, HMMR, TTK, IFIT1, RSAD2, IFI6, IFI27 and ISG20, among which interferon‑α‑inducible genes were revealed to display a similar expression pattern as that obtained in scalp psoriasis. This comprehensive bioinformatic re‑analysis of GEO data provides new insights on the molecular pathogenesis of psoriasis and the identification of potential therapeutic targets for the treatment of psoriasis.

Background:. As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis. Methods:. WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline; n = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC). Results:. Acanthosis (98.46 ± 14.12 vs. 222.68 ± 71.10 μm, P

Background: Sarcoidosis and tuberculosis share similarities in clinical manifestations and histopathological features. We aimed to identify the microRNA (miRNA) profiles of the lymph nodes of individuals with sarcoidosis and of those with tuberculous lymphadenitis to investigate the value of miRNAs in the differential diagnosis of sarcoidosis and tuberculous lymphadenitis.Methods: The miRNA profiles of the lymph nodes of individuals with sarcoidosis, those with tuberculous lymphadenitis (TBLN) and controls were detected by miRNA microarray analysis in the age- and sex-matched development group of the controls (n = 3), patients with TBLN (n = 3) and patients with sarcoidosis (n = 3), and the results were validated by quantitative real-time polymerase chain reaction in the validation group of the controls (n = 30), TBLN (n = 30) and patients with sarcoidosis (n = 31). The relationship between miRNA expression and the clinical parameters of sarcoidosis was analyzed.Results: miR-145, miR-185-5p, miR-301, miR-425-5P, miR-449b and miR-885-5P were differentially expressed between individuals with sarcoidosis and controls (P < 0.0001, P < 0.0001, P = 0.0008, P = 0.0002, P = 0.0018, and P < 0.0001, respectively), and the same six miRNAs were differentially expressed between individuals with tuberculous lymphadenitis and controls (P = 0.0002, P = 0.0004, P = 0.0238, P = 0.0006, P = 0.0149, and P = 0.0045, respectively). miR-185-5p was differentially expressed between individuals with tuberculous lymphadenitis and those with sarcoidosis (P = 0.0101). The area under the receiver operating characteristic curve calculated for miR-185-5p was 0.6860, and the sensitivity and specificity of miR-185-5p for the differential diagnosis of sarcoidosis from TBLN were 61 and 80%, respectively. The levels of miR-145, miR-301, miR-425-5P, and miR-885-5P were positively correlated with CD4+/CD8+ T lymphocytes in bronchoalveolar lavage fluid.Conclusions: miRNAs in lymph nodes show similar expression patterns between individuals with sarcoidosis and those with tuberculous lymphadenitis, which were experimentally selected. miR-185-5p in the lymph nodes can be used as an auxiliary marker for the differential diagnosis of sarcoidosis and tuberculous lymphadenitis.

Additional file 1: Supplementary Figure 1. Sensitivity test of PCR. PCR reactions were performed on 6 kinds of HPV type plasmids (HPV1, HPV2, HPV3, HPV4, HPV27 and HPV 57) with universal HPV primers. (A) 108 copies/μl, (B) 107 copies/μl and (C) 106 copies/μl plasmid concentrations were selected for three PCR tests.

Background Hyperthermia is an effective treatment against cancer and human papillomavirus (HPV) infection. Previous studies have shown that heat shock proteins are crucial to the action of hyperthermia. Objectives To examine the effects of hyperthermia in combination with DNAJA4-deficiency on human keratinocytes and Condyloma acumunatum (CA) tissues. Methods HaCaT cells were subjected to 44 °C (compared to 37 °C) waterbath for 30 min for stimulation. Foreskin or CA tissues obtained from patients undergoing circumcision or pathological examination were bisected and subjected to similar treatments. DNAJA4-knockout (KO) HaCaT cells were generated with CRISPR/Cas9 technology. mRNA and protein expressions were determined using rt-qPCR and western-blotting. Cell cycle distribution, apoptosis and senescence were analyzed by flow cytometry. Results DNAJA4 was induced in HaCaT cells, foreskin and CA tissues subjected to hyperthermia at both transcriptional and translational levels. NF-kB, 3 was activated by hyperthermia in HaCaT cells, and further enhanced by DNAJA4-deficiency. Transcription of TNF-α 4 ; IL-1B, 5 TNFAIP3 6 and IL-8 7 were induced in HaCaT cells subjected to hyperthermia. DNAJA4-knockout promoted transcriptions of TNF-α and IL-1B, whereas decreased that of TNFAIP3 and IL-8. Reduced cell survival, proliferation and viability were demonstrated using flow cytometry and MTS assays. Furthermore, NF-kB inhibitors reversed most of the phenotypes observed. Conclusions Hyperthermia reduced HaCaT cell proliferation and promoted cytokine expressions responsible for anti-viral activity, mainly through a NF-kB dependent pathway. DNAJA4-deficiency enhanced the activation of NF-kB by hyperthermia in HaCaT cells, indicating that DNAJA4 may be a promising therapeutic target for use in the treatment of cutaneous HPV infections.

Background Th17 cells and its effective cytokine IL-17A play an important role in the pathogenesis of abnormal immune responses in psoriasis. Notch1 signaling has been implicated in Th17 cell differentiation and function. In this study, our aim was to evaluate the possible inhibitory effect of Notch1 signaling inhibitor, γ-secretase inhibitor DAPT, on psoriatic Th17 cell differentiation and function in a mouse model of psoriasis-like skin inflammation. Methods Mouse psoriasis-like skin inflammation model was established by topical 5% imiquimod (IMQ) application, and experimental mice were divided into control group, IMQ-treated group and IM + DAPT-treated group. DAPT and the equivalent amount of Dimethyl sulfoxide was intraperitoneally injected in IMQ + DAPT-treated group and the other two experimental groups respectively. Skin tissues of the three experimental groups were acquired and stained with haematoxylin and eosin (HE). Splenic single-cells and serum were collected to detect the percentage of Th17 cells, the mRNA expression levels of Notch1 and its target gene Hes-1, Th17-specific transcription factor RORγt and its effective cytokines IL-17A, as well as IL-17A serum concentration. In addition, splenic CD4+ T cells from IMQ-treated mice were isolated and treated by DAPT to further measure the inhibitory effect of DAPT on the Th17 cell differentiation and IL-17A secretion in vitro. Results DAPT treatment alleviated the severity of IMQ-induced mouse psoriasis-like skin inflammation and decreased the scores of erythema, scaling and thickening. HE stain reveals obviously reduced epidermal hyperplasia and dermal inflammatory cells infiltration in IMQ + DAPT-treated mice. The increased expression of splenic Th17 cell percentage, along with Notch1, Hes-1, RORγt and IL-17A mRNA and IL-17A serum concentration in IMQ-treated mice were significantly decreased when experimental mice were treated by IMQ and DAPT combinedly. Data obtained from in vitro study in IMQ-treated mice also demonstrated that blocking Notch1 signaling by DAPT can result in a dose-dependent decrease of Th17 cell proportion, mRNA expression of Notch1, Hes-1, RORγt and IL-17A as well as IL-17A secretion in splenic CD4+ T cells. Conclusion These data suggest that Notch1 inhibition by DAPT can effectively alleviate the severity of mouse psoriasis-like skin inflammation by regulating the differentiation and function of Th17 cells, indicating that DAPT might be a potential therapeutic candidate for the treatment of psoriatic inflammation.

Psoriasis is a chronic inflammatory skin disease characterized by well‑defined scaly papules and plaques. Interleukin (IL)‑17 is involved in its pathogenesis and promotes the proliferation of epidermal keratinocytes through signal transducer and activator of transcription 3 (STAT3) activation. Shikonin, a natural naphthoquinone isolated from Lithospermum erythrorhizon, possesses anti‑inflammatory and immunosuppressive properties and can suppress IL‑17‑induced vascular endothelial growth factor expression by inhibiting the JAK/STAT3 pathway. In the present study, MTS, iCELLigence and RT‑qPCR were used to determine the optimal concentration and duration of IL‑17 or shikonin acting on HaCaT cells. The changes in the expression levels of genes associated with the IL‑6/STAT3 pathway in differentially treated cells were analyzed via RT2Profiler™ PCR Array. Small interfering RNA was used to silence the expression levels of the target gene CCAAT/enhancer‑binding protein δ (CEBPD). Western blotting and immunohistochemistry were used to evaluate the effect of shikonin on imiquimod‑induced psoriasis in mice and the expression levels of CEBPD. Shikonin reversed IL‑17‑mediated downregulation of the tumor suppressor CEBPD in HaCaT cells. Moreover, low levels of CEBPD in the imiquimod‑induced mouse model of psoriasis were restored by shikonin treatment, which ameliorated excessive keratinocyte proliferation. Taken together, these findings suggest that CEBPD plays a key role in the pathogenesis of psoriasis and can be targeted by shikonin as a potential therapeutic strategy.

Human skin or mucosa exposes cells to both an internal and exogeneous thermal environment and the cells survive within a certain range of temperature. Exogeneous hyperthermia has been applied for the treatment of various types of cancers, fungal disease, and warts.To determine whether different cellular components in the skin adapt to hyperthermic conditions differentially and further elucidate the mechanisms involved.Cell lines derived from normal and tumour epithelial cells were treated with hyperthermic conditions and tested for viability (using an MTS assay), apoptosis (using a FITC-conjugated annexin V apoptosis detection kit), and changes in intracellular calcium (using a calcium-sensitive fluorescent single-wavelength dye, Fluo-4 AM).Thermo-resistance of different cell types was different when cells were subjected to heat at 45̊C for 30 minutes. Stronger effects of hyperthermia were noted on cell viability and apoptosis in epidermal cells relative to their malignant counterparts, except for cell lines harbouring human papillomavirus (HPV). Hyperthermia had a much greater effect on cell viability and apoptosis in a HPV-negative cell line compared to HPV-positive cell lines. We further found that hyperthermia treatment resulted in a strong calcium influx which led to apoptotic cells. However, no obvious increase in apoptosis was observed in cells treated with the CRAC channel selective inhibitor, BTP2, before application of hyperthermia in all cell types, except three cervical cell lines harbouring HPV.We propose that hyperthermia results in a CRAC-related strong calcium influx which induces apoptosis, with the exception of HPV-positive cells.

Melanoma is an aggressive cancer, the incidence of which is increasing worldwide. Limited therapies are currently available, particularly following metastasis. The aim of the present study was to investigate the inhibiting effect of methionine enkephalin (MENK) on human melanoma via opioid receptors. The results of the present study revealed that MENK markedly regulates the proliferation of A375 cells, causing cell cycle arrest in G0/G1 phase and a decrease in the percentage of cells in S and G2/M phases. Reverse transcription‑quantitative polymerase chain reaction demonstrated that MENK treatment increased opioid receptor expression in A375 cells. Furthermore, the expression level of survivin, an inhibitory apoptotic protein, was 1.1% of the level in the control group in the MENK group following 48 h of treatment. In conclusion, the results of the present study revealed, to the best of our knowledge for the first time, that MENK may inhibit growth and induce apoptosis of A375 cells, and describes a potential mechanism underlying these effects. Therefore, MENK should be investigated as a primary therapy for human melanoma cancer and as an adjuvant to other chemotherapies. Further studies are required to develop an optimal strategy for the use of MENK for the treatment of human cancers.

Introduction Mild local hyperthermia at 44°C has been proven efficacious in the treatment of cutaneous warts induced by human papillomavirus (HPV), while its effect on cervical intraepithelial neoplasia (CIN) caused by high risk type of HPVs has not been reported. Patient concerns Three patients with low grade CIN and positive high risk HPV types (HPV 16, 31, 52, 56, 58) are reported in this study. Diagnosis The diagnosis was based on identification of HPV types and abnormal cytological findings. Interventions The 3 patients were treated with local hyperthermia from ceramic heating (surface temperature, 44°C) to cervix. The treatment was delivered once a day for 3 consecutive days, plus two similar treatments 10 ± 3 days later, with each session lasting 30 minutes. HPV and cytology test were performed 3 months thereafter. Outcomes All the 3 patients recovered to normal cytological findings. Two of the patients were negative for HPV, the remaining patient with pre-treatment HPV 56 and 58 positivity changed to HPV58 positive alone. Conclusion This pilot observation inspires that mild local hyperthermia be recommended as a new method in the treatment of CIN patients with persistent HPV infection, once validated by qualified RCT.

Candida albicans (C. albicans) is an opportunistic human fungal pathogen that colonises the skin. Both keratinocytes and macrophages play crucial roles in host defence against C. albicans. However, the interaction of keratinocytes with macrophages during C. albicans colonisation has not been well studied. In this study, macrophages were cultured in conditioned medium from keratinocytes treated with heat-inactivated C. albicans (CM-C. albicans), macrophage migration and polarised activation and were then assessed by a Transwell assay, flow cytometry, quantitative real-time PCR (qPCR), Western blot and an enzyme-linked immunosorbent assay (ELISA). The results showed that CM-C. albicans-stimulated macrophages display significantly increased migration and phagocytosis, and they display an upregulation of proinflammatory cytokines (tumour necrosis factor alpha (TNF-a), interleukin (IL)-12 and nitric oxide (NO)). Markers characteristic of M1 macrophages, such as human leukocyte antigen (HLA)-DR, CD86 and inducible nitric oxide synthase (iNOS), are upregulated, whereas markers of M2 macrophages, such as mannose receptor (MR) and Arginase 1 (Arg1), are not affected. Additionally, the levels of TNF-a, IL-12 and monocyte chemotactic protein 1 (MCP-1) in CM-C. albicans are markedly upregulated, whereas the levels of IL-4 and IL-10 are not affected. And the CM-C. albicans-induced M1 macrophage polarisation, proinflammatory cytokine production and phagocytosis could be blocked by an anti-TNF-a neutralising antibody. This study showed that keratinocytes may promote macrophage recruitment and M1 polarisation during C. albicans colonisation at least in part by secreting TNF-a.

Previous studies on the correlation between positive autologous serum skin test (ASST) responses and the clinical features of patients with chronic spontaneous urticaria (CSU) have provided conflicting results. To evaluate the significance of ASST responses in CSU, a variety of databases were searched from inception to March 2018 to identify relevant studies on CSU. Data were analyzed with use of the Cochrane Collaboration's Review Manager 5.2. Multiple relevant factors of CSU were evaluated by calculating the weighted mean difference, odds ratio and 95% confidence interval. The results indicated that CSU cases with positive ASST responses had higher urticaria activity scores and higher levels of total serum immunoglobulin E than CSU cases with negative responses in the ASST. In addition, a positive ASST response was more likely to be accompanied with the presence of thyroid autoantibodies and angioedema. An increased prevalence of CSU was identified in females, who were more likely to have a positive response in the ASST. It was also indicated that a greater incidence of positive ASST responses was present in CSU patients as compared with that in healthy controls. No statistically significant differences were obtained between positive and negative ASST responses with regard to age and duration of disease. Based on these results, it was concluded that the ASST provides an effective means of predicting urticaria activity and recurrence in CSU patients.

In the present study, a novel pH-responsive amphiphilic copolymer, 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[methoxy(polyethylene glycol)] conjugated poly(β-amino esters) (DSPE- b -PEG- b -PAE- b -PEG- b -DSPE), was designed and successfully synthesized via Michael-type step polymerization. The chemical structure of the pentablock copolymer was confirmed with proton nuclear magnetic resonance ( 1 H-NMR) and Fourier transform infrared (FT-IR) spectroscopy. The copolymer was able to self-assemble into core/shell polymeric micelles in aqueous solution at low concentrations, and its critical micelle concentration (CMC) value was 4.5 mg l −1 determined by fluorescence spectrophotometry. The p K b value of the copolymer was about 6.5, confirmed by acid–base titration, indicating the pH-sensitivity of the polymeric micelle. The hydrodynamic diameter, distribution and zeta potential of the polymeric micelles at different pH conditions were monitored by dynamic light scattering (DLS). Doxorubicin (DOX) was encapsulated into the core of the micelles with a high drug loading content (15.9%) and entrapment efficacy (60.4%). In vitro experiments demonstrated that the release behaviour of DOX from the DOX-loaded polymeric micelles (DOX-PMs) was pH-triggered. When the pH decreased from 7.4 to 5.0, the drug release rate was markedly accelerated. MTT assay showed that the copolymer had negligible cytotoxicity whereas the DOX-PMs displayed high toxicity for tumour cells such as B16F10, HepG2 and HeLa cell lines. The results demonstrated that these pH-sensitive polymeric micelles could be used as potential anti-cancer drug carriers for cancer chemotherapy with controlled release.