Local Hyperthermia Versus Cryotherapy for Treatment of Plantar Warts: A Prospective Multi-centre Non-randomized Concurrent Controlled Clinical Trial.

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.

Identification of Subtype-Specific Metastasis-Related Genetic Signatures in Sarcoma.

Background: Sarcomas are heterogeneous rare malignancies constituting approximately 1% of all solid cancers in adults and including more than 70 histological and molecular subtypes with different pathological and clinical development characteristics. Method: We identified prognostic biomarkers of sarcomas by integrating clinical information and RNA-seq data from TCGA and GEO databases. In addition, results obtained from cell cycle, cell migration, and invasion assays were used to assess the capacity for Tanespimycin to inhibit the proliferation and metastasis of sarcoma. Results: Sarcoma samples (N = 536) were divided into four pathological subtypes including DL (dedifferentiated liposarcoma), LMS (leiomyosarcoma), UPS (undifferentiated pleomorphic sarcomas), and MFS (myxofibrosarcoma). RNA-seq expression profile data from the TCGA dataset were used to analyze differentially expressed genes (DEGs) within metastatic and non-metastatic samples of these four sarcoma pathological subtypes with DEGs defined as metastatic-related signatures (MRS). Prognostic analysis of MRS identified a group of genes significantly associated with prognosis in three pathological subtypes: DL, LMS, and UPS. ISG15, NUP50, PTTG1, SERPINE1, and TSR1 were found to be more likely associated with adverse prognosis. We also identified Tanespimycin as a drug exerting inhibitory effects on metastatic LMS subtype and therefore can serve a potential treatment for this type of sarcoma. Conclusions: These results provide new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provide new directions for further study of sarcoma.

IL­18 knockout alleviates atopic dermatitis­like skin lesions induced by MC903 in a mouse model.

Interleukin (IL)­18, a pro­inflammatory cytokine, plays an important role in a number of skin diseases. The aim of the present study was to investigate the role of IL­18 in the development of atopic dermatitis (AD). For this purpose, mice were divided into 4 groups (n=5/group) as follows: i) The wild­type (WT) controls; ii) IL18 knockout (KO) controls; iii) MC903­treated WT mice; and iv) MC903­treated KO mice. MC903 (4 nmol in ethanol) was topically applied daily for 15 consecutive days to the exposed skins of mice. AD­like 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 enzyme­linked immunosorbent assay. Immunohistochemistry was used to assess the expression of IL­1ß, signal transducer and activator of transcription (STAT)3 and filaggrin (FLG) in the skin lesions. RT­qPCR was performed to assess the mRNA levels of IL­1ß, IL­4, IL­9, STAT3, corticotropin­releasing hormone receptor (CRHR)1, CRHR2, TSLP and caspase­1 in the skin lesions. It was demonstrated that IL­18 may function as a pleiotropic pro­inflammatory cytokine in the development of AD­like lesions. IL­18 KO reduced aggravated AD­like lesions induced by MC903, in part by upregulating Th2 cytokines. IL­18 promoted the expression of FLG in the epidermis and CRHR2 in AD­like lesions, but downregulated the serum levels of IgE. On the whole, the findings of the present study demonstrate that IL­18 deficiency alleviates AD­induced lesions in mice.

Anti-inflammatory effects of quercetin in a mouse model of MC903-induced atopic dermatitis.

In this study, the anti-inflammatory mechanisms of Quercetin (Que) on atopic dermatitis (AD)-like skin lesions was examined. The left ear of mice was applied with MC903, followed by Que. administration daily on the ear for 8 days. Then macroscopic and histologic examination was performed to detect the severity of skin lesions. In the skin section of AD mice, we observed that Que. could reduce the expression of CCL17, CCL22, IL-4, IL-6, IFN-γ and TNF-α. In vitro, the anti-inflammatory effects of Que. were examined on human keratinocytes (HaCaT cells) treated with IFN-γ/TNF-α. To unveil the lncRNAs' regulatory role on Que-activated anti-inflammatory function, the next-generation high-throughput sequencing was performed in HaCat cells with or without Que. treatment, which profiled the expression of lncRNAs and mRNAs, the results illustrated that lnc-C7orf30-2, a lncRNA expressed differentially, was correlated with IL-6 expression. Silencing of lnc-C7orf30-2 by RiboTM lncRNA Smart Silencer proved its role on IL-6 expression. Therefore, the results here demonstrated that topical administration of Que. plays a beneficial role in controlling AD symptoms, which may serve as potential candidate for AD treatment.

Interleukin-18 exacerbates skin inflammation and affects microabscesses and scale formation in a mouse model of imiquimod-induced 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-1ß, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1ß, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC). RESULTS: Acanthosis (98.46 ±â€Š14.12 vs. 222.68 ±â€Š71.10 µm, P < 0.01) and dermal cell infiltration (572.25 ±â€Š47.45 vs. 762.47 ±â€Š59.59 cells/field, P < 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83 ±â€Š5112.09 vs. 4093.19 ±â€Š2591.88 µm, P < 0.01) and scales (100,935.24 ±â€Š41,167.77 vs. 41,604.41 ±â€Š14,184.10 µm, P < 0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1ß, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased. CONCLUSIONS: IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.

Melanocyte activation and skin barrier disruption induced in melasma patients after 1064 nm Nd:YAG laser treatment.

Melasma is a frequently acquired hyperpigmentary skin disorder, for which several therapies are available. Among them, 1064 nm QS Nd:YAG laser therapy is an effective method, but the recurrence rate of laser treatment is still high. The aim of the present study was to elucidate the mechanism of the high relapse rate of melasma after 1064 nm Nd:YAG laser treatment. Twenty-five female melasma patients were treated with 1064 nm Nd:YAG laser for 10 times. The lesional skin and non-lesional skin were evaluated by means of a reflectance confocal laser scanning microscope before and after laser treatment. Melanin content and transepidermal water loss (TEWL) were measured by an MPA9 skin multifunction tester accordingly. The melanin index value was significantly decreased in the lesional skin after laser treatment, while the non-lesional skin had no difference. The dendritic cells were observed at the level of the dermal-epidermal junction (DEJ) in the lesions of 8 patients before laser treatment, while after laser treatment, the dendritic cells were observed in all 25 subjects. Moreover, there was significant difference between the TEWL value of the lesions before and after laser treatment. Furthermore, the TEWL value was higher in lesions of the 8 subjects which had dendritic cells compared with other 17 subjects which had no dendritic cells, no matter before or after laser treatment. The relapse patients of melasma had higher TEWL value compared with the non-relapse patients. Melanocyte activation and skin barrier disruption may be related to the high relapse rate of melasma after laser treatment.

DNAJA4 deficiency enhances NF-kappa B-related growth arrest induced by hyperthermia in human keratinocytes.

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 30min 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-α4; IL-1B,5 TNFAIP36 and IL-87 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.

MicroRNA-210 promotes angiogenesis in acute myocardial infarction.

MicroRNA-210 (miRNA-210) has been reported to be associated with angiogenesis and may serve important roles in acute myocardial infarction (AMI), which remain unclear. The present study sought to evaluate the efficacy of miRNA­210 in AMI and to examine the potential associated mechanisms. AMI models were established in Sprague­Dawley rats. The expression of miRNA­210 was upregulated via transfection with lentivirus­mediated agonists and quantitative analysis was performed using the reverse transcription­quantitative polymerase chain reaction (RT­qPCR). Immunoblotting and RT­qPCR were separately used to detect the expression levels of hepatocyte growth factor (HGF) in heart samples, while only the protein expression level of ß­myosin heavy chain (ß­MHC) was assessed. The expression of HGF in human umbilical vein endothelial cells under hypoxic conditions was silenced by transfecting with small interfering RNA, as demonstrated by the determination of associated protein expression levels. The microvessel density (MVD) of the infarcted myocardium was selected to be the angiogenesis efficacy endpoint, which was evaluated by platelet endothelial cell adhesion molecule immunostaining. Markedly increased expression of HGF was observed among the AMI rats receiving miRNA­210 agonists, demonstrated via quantitative analyses using RT­qPCR or western blotting. Promotion of angiogenesis was observed with the increased MVD. Improved cardiac function in the rats was subsequently noted, as they exhibited improved left ventricular fractional shortening and left ventricular ejection fraction percentages, which may result from improved cardiac contractility indicated by attenuating the increase in ß­MHC protein expression. Overexpression of miRNA­210 appeared to be an advantageous therapeutic tool for treating AMI, primarily due to its promoting effects on angiogenesis in the infarcted myocardium by stimulating HGF expression and inducing improved left ventricular remodeling, leading to improved cardiac function.

Prognostic significance of ACP5 expression in patients with lung adenocarcinoma.

INTRODUCTION: Tartrate-resistant acid phosphatase 5 (ACP5), which is essential for bone resorption and osteoclast differentiation, promotes cell motility through the modulation of focal adhesion kinase phosphorylation. This study seeks to elucidate the association of ACP5 expression and the clinicopathologic characteristics of patients with lung adenocarcinoma (AD). METHODS: The expression of ACP5 was measured by Immunohistochemistry and Western blot analysis in lung AD and matched tumor-adjacent tissues, and the χ2 test was applied to analyze the correlation between ACP5 expression and clinicopathologic features. Using the Kaplan-Meier method, univariate and multivariate regression analysis was to explore the correlation between ACP5 expression and overall survival (OS). RESULTS: We found that ACP5 was frequently upregulated in lung AD tissues. The high expression of ACP5 was significantly related to lymph node status, tumor-node-metastasis (TNM) stage, and differentiation. From the results of univariate survival analysis, it indicated that the patients with high expression of ACP5 expression had a significantly lower OS than the patients with low expression of ACP5 expression. As it showed in Multivariate Cox regression analysis, the high expression of ACP5 expression was an independent prognostic factor for OS. CONCLUSIONS: Our results suggest that high expression of ACP5 correlates with tumor progression and may serve as a potential prognostic biomarker in lung AD.

Circular RNA expression profiles reveal that hsa_circ_0018289 is up-regulated in cervical cancer and promotes the tumorigenesis.

Circular RNAs (circRNAs) are a type of non-coding RNAs that have been identified as critical regulators in various diseases, especially in cancers. However, the expression profiles and functions of circRNAs in cervical cancer are still unclear. In present study, human circRNAs microarray were performed to screen the circRNAs expression in cervical cancer tissue. Microarray analysis revealed 45 significantly expressed circRNAs with 4 fold change. Among these up-regulated circRNAs, hsa_circ_0018289 was validated to be significantly up-regulated in 35 pairs of cervical cancer tissue compared with adjacent normal tissue and cell lines. Loss-of-function experiments revealed that, in vitro and in vivo, hsa_circ_0018289 knockdown inhibited the proliferation, migration and invasion of cervical cancer cells. Via bioinformatics prediction program and luciferase reporter assays, hsa_circ_0018289 was observed to directly bind to miR-497. Taken together, the results indicate that hsa_circ_0018289 plays important role in cervical cancer proliferation, migration and invasion, suggesting the miRNA 'sponge' of hsa_circ_0018289 and its oncogenic role on cervical cancer tumorigenesis.

Long Noncoding RNA PVT1 Facilitates Cervical Cancer Progression via Negative Regulating of miR-424.

Emerging evidence suggests that the long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) gene is involved in the pathogenesis of cervical cancer. However, the potential mechanism is rarely reported. Our study found that PVT1 was upregulated in cervical cancer tissue and cell lines. After transfecting PVT1 siRNA, the proliferation, migration, and invasion of cervical cancer cells were markedly decreased. miRNA expression profiles demonstrate that miR-424 was markedly downregulated in cervical cancer tissue. Bioinformatics analysis revealed that miR-424 was potentially targeted by PVT1, which was confirmed by dual-luciferase reporter assay. Pearson's correlation analysis showed that PVT1 expression was negatively related to miR-424 expression in glioma cancer tissues. Finally, lowered expression of miR-424 could recover the tumor-suppressive effects of PVT1 knockdown in cervical cancer cell lines. Our results reveal a tumor-promoting role for PVT1, acting as a competing endogenous RNA (ceRNA) or a molecular sponge in negatively modulating miR-424, which might provide a novel therapeutic target for cervical cancer.

The outcomes of intravascular ultrasound-guided drug-eluting stent implantation among patients with complex coronary lesions: a comprehensive meta-analysis of 15 clinical trials and 8,084 patients.

OBJECTIVE: The effects of intravascular ultrasound (IVUS)-guided drug-eluting stent (DES) implantation in patients with complex coronary artery lesions remains to be controversial. This study sought to evaluate the outcomes of IVUS guidance in these patients. METHODS: The EMBASE, Medline, and other internet sources were searched for relevant articles. The primary endpoint was major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction (MI), and target-vessel revascularization (TVR). The incidence of definite/probable stent thrombosis (ST) was analyzed as the safety endpoint. RESULTS: Fifteen clinical trials involving 8.084 patients were analyzed. MACE risk was significantly decreased following IVUS-guided DES implantation compared with coronary angiography (CAG) guidance (odds ratio [OR] 0.63, 95% confidence intervals [CI]: 0.53-0.73, p<0.001), which might mainly result from the lower all-cause mortality risk (OR 0.52, 95% CI: 0.40-0.67, p<0.001), MI (OR 0.70, 95% CI: 0.56-0.86, p=0.001), and TVR (OR 0.53, 95% CI: 0.40-0.70, p<0.001). The subgroup analyses indicated better outcomes of IVUS guidance in DES implantation for these patients with left main disease or bifurcation lesions. CONCLUSION: IVUS guidance in DES implantation is associated with a significant reduction in MACE risk in patients with complex lesions, particularly those with left main disease or bifurcation lesions. More large and powerful randomized trials are still warranted to guide stenting decision making.

The clinical outcomes of triple antiplatelet therapy versus dual antiplatelet therapy for high-risk patients after coronary stent implantation: a meta-analysis of 11 clinical trials and 9,553 patients.

BACKGROUND: The optimal antiplatelet regimen after in-coronary intervention among patients presenting with complex coronary artery lesions or acute coronary syndrome (ACS) has remained unclear. This study sought to evaluate the clinical outcomes of triple antiplatelet treatment (TAPT) (cilostazol added to aspirin plus clopidogrel) in these patients. METHODS: The PubMed, EMBASE, MEDLINE, and other Internet sources were searched for relevant articles. The primary end point was major adverse cardiac events (MACE), including all-cause mortality, myocardial infarction, and target vessel revascularization. The incidence of definite/probable stent thrombosis and bleeding were analyzed as the safety end points. RESULTS: Eleven clinical trials involving 9,553 patients were analyzed. The risk of MACE was significantly decreased following TAPT after stent implantation in the ACS subgroup (odds ratio [OR]: 0.72; 95% confidence interval [CI]: 0.61-0.85; P<0.001), which might mainly result from the lower risk of all-cause mortality in this subset (OR: 0.62; 95% CI: 0.48-0.80; P<0.001). The risk of bleeding was not increased with respect to TAPT. CONCLUSION: TAPT after stent implantation was associated with feasible benefits on reducing the risk of MACE, especially on reducing the incidence of all-cause mortality among patients suffering from ACS, without higher incidence of bleeding. Larger and more powerful randomized trials are still warranted to prove the superiority of TAPT for such patients.

[Hepatic lineage differentiation of hepatic progenitor cells by bone morphogenetic protein or leukemia inhibitory factor].

OBJECTIVE: To search for the optimal approach for hepatocyte-directed differentiation of hepatic progenitor cells and investigate the molecular mechanism of the hepatic differentiation. METHODS: Hepatic progenitor cells were infected with recombinant adenovirus which containing human LIF, BMP2 or BMP9 gene. The maturation and differentiation of progenitor cells were examined by PAS staining and ICG uptake methods at 4, 7 and 10 days post infection. The production of Albumin (Alb) was measured by luciferase activity at day 4, 7, 10 and 14. RESULTS: PAS staining assay revealed that BMP2 and BMP9 enhanced glycogen storage in hepatic progenitor cells most obviously at day 7. The percentages of positive cells were 30% and 45% respectively at 7 days post-infection. Meanwhile, 40% and 30% cells were positive by ICG uptake assay after BMP2 and BMP9 induction. Luciferase activity indicated that BMP9 induced ALB-Luc activity most significantly at day 7. However, less inductive activity was found in LIF-treated group. CONCLUSION: These results indicated tuat hepatic progenitor cells were differentiated into hepatocyte-like cells by BMPs and LIF induction.