Zhiqiang Yin

Systematic Review and Meta-Analysis on the Association between IL-1B Polymorphisms and Cancer Risk

Background Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, is emerging as a key mediator of carcinogenesis that characterizes host-environment interactions. Epidemiological studies investigating the association between two polymorphisms of IL-1B (−511C/T and +3954C/T) and cancer susceptibility have shown conflicting results. The aim of this study is to derive a more precise estimation of the relationship. Methods Related studies were identified through a systematic literature search of PubMed and Web of Science from their inception to September 15, 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for the IL-1B −511C/T and +3954C/T polymorphisms and cancer risk were calculated. Heterogeneity among studies and publication bias were also tested. Results The meta-analysis included 91 case-control studies in 85 publications, 81 studies for the −511C/T (19547 cases and 23935 controls) and 26 studies for the +3954C/T polymorphisms (8083 cases and 9183). The pooled results indicated that IL-1B +3954C/T (dominant model: OR = 1.15, 95% CI: 1.01–1.30) was significantly associated with increased overall cancer risk, especially among hospital-based case-control studies (dominant model: OR = 1.30, 95% CI: 1.02–1.66). As for −511C/T, we observed an inverse relationship in cervical cancer (dominant model: OR = 1.74, 95% CI: 1.35–2.23) and hepatocellular carcinoma (dominant model: OR = 0.68, 95% CI: 0.47–0.99). Moreover, −511C/T was associated with risk of specific subtypes of gastric carcinoma. Conclusion This meta-analysis suggested that both the IL-1B –511C/T and +3954C/T polymorphisms might modulate cancer susceptibility. Further well-designed studies based on larger sample sizes should be performed to confirm the findings.

The Effect of Conditioned Media of Adipose-Derived Stem Cells on Wound Healing after Ablative Fractional Carbon Dioxide Laser Resurfacing

Objective. To evaluate the benefits of conditioned medium of Adipose-derived stem cells (ADSC-CM) on wound healing after fractional carbon dioxide laser resurfacing (FxCR) on human skin. Materials and Methods. Nineteen subjects were treated with FxCR on the bilateral inner arms. ADSC-CM was applied on FxCR site of one randomly selected arm. Transepidermal water loss (TEWL), skin color, and gross-elasticity of FxCR site on both arms were measured. Skin samples were taken by biopsy from three subjects 3 weeks after treatment for histopathological manifestations and mRNA expressions of procollagen types I and III, elastin genes were noted. Results. The index of erythema, melanin, and TEWL of the ADSC-CM-treated skin were significantly lower than those of the control side. The mRNA expression of type III procollagen in ADSC-CM-treated group at 3 weeks posttreatment was 2.6 times of that of the control group. Conclusion. Application of allograft ADSC-CM is an effective method for enhancing wound healing after FxCR, by reducing transient adverse effects such as erythema, hyperpigmentation, and increased TEWL.

A meta-analysis comparing long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole

Abstract As the most frequently used systemic antifungal agents for onychomycosis, terbinafine and itraconazole have both proved to have the conditions of recurrence in various degrees during follow-up period after end of therapy; very little is known about their comparative recurrences after long-term follow-up. We conducted a meta-analysis of available trials to compare the long-term recurrences of toenail onychomycosis after successful treatment with terbinafine versus itraconazole. Meta-analysis was performed by the Review Manager version 5.0.25. Risk ratio and 95% confidence intervals were calculated by the fixed effect model. Five trials and total 251 eligible patients were included in this meta-analysis. The combined risk ratio of the meta-analysis comparing terbinafine with itraconazole for mycological recurrence rate was 0.44 (95% CI 0.29–0.66), which suggests that itraconazole therapy is more likely to produce mycological recurrence compared with terbinafine therapy.

MiR-23a regulates DNA damage repair and apoptosis in UVB-irradiated HaCaT cells

BACKGROUND MiRNAs remain at a constant level under physiological conditions. However, how the expression of miRNAs is regulated and what are the roles of miRNAs in response to UVB damage to skin cells is still not fully understood. In our preliminary study, we observed that miR-23a was upregulated following a treatment with a DNA repair agent and UVB exposure. OBJECTIVE To investigate the regulation and function of miR-23a in response to UVB-induced injury in human keratinocyte cell line (HaCaT) cells. METHODS The changes in expression of miR-23a after UVB irradiation of HaCaT cells were measured by qRT-PCR. The level of miR-23a expression was also modulated by transfecting with a miR-23a mimic or an inhibitor. Cell viability was assessed by the CCK-8 assay. Immunofluorescence staining and Southwestern dot blotting were used to detect the levels of cyclobutane pyrimidine dimers (CPDs). Flow cytometry, Hoechst staining, and measurements of caspase-3 activity were employed to measure the incidence of apoptosis. The mRNA and protein expression levels of genes related to DNA reparation and apoptosis, such as topoisomerase-1, caspase-7, and STK4, were analyzed by qRT-PCR and Western blotting, respectively. RESULTS MiR-23a expression was remarkably up-regulated at 4 h and 24 h after the UVB irradiation of HaCaT cells. UVB-induced apoptosis was increased by down-regulation of miR-23a. UVB-induced removal of CPDs was accelerated by miR-23a up-regulation and delayed by miR-23a down-regulation. Forced over-expression of miR-23a decreased the expression of UVB-induced topoisomerase-1\caspase7\STK4 at both the mRNA and protein levels, and these effects were reversed by down-regulation of miR-23a. CONCLUSION The protection of HaCaT cells against UVB damage is afforded by miR-23a through regulation of topoisomerase-1\caspase7\STK4, and this miRNA may be a novel therapeutic target in skin diseases related to UVB radiation.

Baicalin protects human skin fibroblasts from ultraviolet A radiation-induced oxidative damage and apoptosis

Reactive oxygen species (ROS) are an important factor in the development of skin photodamage after ultraviolet A (UVA) radiation. A flavonoid antioxidant, baicalin, can selectively neutralize super-oxide anion (O2−) while having no significant effect on •OH. Fibroblasts are a key component of skin dermis. In the present study, we investigated the protective effects of baicalin on human skin fibroblasts (HSFs) under UVA induced oxidative stress. Fluorescence microscopy and flow cytometry were used to assay the intracellular O2−, NO, ROS concentrations and the mitochondrial membrane potential. Cell viability was determined using the Cell Counting Kit-8 (CCK-8). The concentrations of cellular MDA, SOD, GSH, T-AOC, and 8-oxo-dG were also measured. Cellular apoptosis was measured by flow cytometry and caspase-3 detection. The results revealed that UVA radiation could cause oxidative stress and apoptosis in HSFs. Interestingly, the use of baicalin after UVA radiation significantly reduced the level of intracellular O2−, NO, and ROS, stabilized the mitochondrial membrane potential, and attenuated production of MDA and 8-oxo-dG. These efficiently enhanced the antioxidative defense system and protected the HSFs from subsequent oxidative stress damage and apoptosis. In other words, baicalin decreased the excessive generation of intracellular ROS and NO, and elevated the cellular antioxidative defense, which eventually mitigate the UVA-induced apoptosis. Based on our results, baicalin may have applications in the treatment of skin photodamage caused by UVA irradiation.

Palmitic Acid Induces Production of Proinflammatory Cytokines Interleukin-6, Interleukin-1β, and Tumor Necrosis Factor-α via a NF-κB-Dependent Mechanism in HaCaT Keratinocytes

To investigate whether palmitic acid can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with palmitic acid at pathophysiologically relevant concentrations. Secretion levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), NF-κB nuclear translocation, NF-κB activation, Stat3 phosphorylation, and peroxisome proliferator-activated receptor alpha (PPARα) mRNA and protein levels, as well as the cell proliferation ability were measured at the end of the treatment and after 24 hours of recovery. Pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF-κB) and goat anti-human IL-6 polyclonal neutralizing antibody were used to inhibit NF-κB activation and IL-6 production, respectively. Our results showed that palmitic acid induced an upregulation of IL-6, TNF-α, IL-1β secretions, accompanied by NF-κB nuclear translocation and activation. Moreover, the effect of palmitic acid was accompanied by PPARα activation and Stat3 phosphorylation. Palmitic acid-induced IL-6, TNF-α, IL-1β productions were attenuated by NF-κB inhibitor PDTC. Palmitic acid was administered in amounts able to elicit significant hyperproliferation and can be attenuated by IL-6 blockage. These data demonstrate for the first time that palmitic acid can stimulate IL-6, TNF-α, IL-1β productions in HaCaT keratinocytes and cell proliferation, thereby potentially contributing to acne inflammation and pilosebaceous duct hyperkeratinization.

Genetic Variation in a MicroRNA-502 Minding Site in SET8 Gene Confers Clinical Outcome of Non-Small Cell Lung Cancer in a Chinese Population

Background Genetic variants may influence microRNA-target interaction through modulate their binding affinity, creating or destroying miRNA-binding sites. SET8, a member of the SET domain-containing methyltransferase, has been implicated in a variety array of biological processes. Methods Using Taqman assay, we genotyped a polymorphism rs16917496 T>C within the miR-502 binding site in the 3′-untranslated region of the SET8 gene in 576 non-small cell lung cancer (NSCLC) patients. Functions of rs16917496 were investigated using luciferase activity assay and validated by immunostaining. Results Log-rank test and cox regression indicated that the CC genotype was associated with a longer survival and a reduced risk of death for NSCLC [58.0 vs. 41.0 months, P = 0.031; hazard ratio = 0.44, 95% confidential interval: 0.26–0.74]. Further stepwise regression analysis suggested rs16917496 was an independently favorable factor for prognosis and the protective effect more prominent in never smokers, patients without diabetes and patients who received chemotherapy. A significant interaction was observed between rs16917496 and smoking status in relation to NSCLC survival (P<0.001). Luciferase activity assay showed a lower expression level for C allele as compared with T allele, and the miR-502 had an effect on modulation of SET8 gene in vitro. The CC genotype was associated with reduced SET8 protein expression based on immunostaining of 192 NSCLC tissue sample (P = 0.007). Lower levels of SET8 were associated with a non-significantly longer survival (55.0 vs. 43.1 months). Conclusion Our data suggested that the rs16917496 T>C located at miR-502 binding site contributes to NSCLC survival by altering SET8 expression through modulating miRNA-target interaction.

The Protective Effect of Baicalin against UVB Irradiation Induced Photoaging: An In Vitro and In Vivo Study

Objective This study was aimed to evaluate the anti-photoaging effects of baicalin on Ultraviolet B (UVB)-induced photoaging in the dorsal skin of hairless mice and premature senescence in human dermal fibroblasts. Methods We established in vivo and in vitro photoaging models by repeated exposures to UVB irradiation. By HE staining, masson staining, immunohistostaing and real-time RT-PCR, we analyzed epidermal thickness, collagen expression and the mRNA and protein levels of type I collagen, type III collagen, interstitial collagenase (MMP-1 and MMP-3) in UVB exposed dorsal mice skin. The aging condition in human dermal fibroblasts was determined by senescence-associated β-galactosidase (SA-β-gal) staining. Cell viability was determined using the Cell Counting Kit-8 (CCK-8). The G1 phase cell growth arrest was analyzed by flow cytometry. The senescence-related protein levels of p16INK-4a, p21WAF-1, and p53 and protein levels of phosphorylated histone H2AX were estimated by Western blotting. Results Topically application of baicalin treatment reduced UVB-induced epidermal thickening of mouse skin and also result in an increase in the production of collagen I and III, and a decrease in the expression of MMP-1 and MMP-3. Compared with the UVB-irradiated group, we found that the irradiated fibroblasts additionally treated with baicalin demonstrated a decrease in the expression of SA-β-gal, a increase in the cell viability, a decrease in the G1 phase cell proportion, a downregulation in the level of senescence-associated and γ-H2AX proteins. However, Baicalin had no difference in the normal fibroblasts without UVB irradiation and long-term Baicalin incubation of UVB-SIPS fibroblasts gave no effects on the cell proliferation. Conclusions Taken together, these results suggest that baicalin significantly antagonizes photoaging induced by UVB in vivo and in vitro, indicating the potential of baicalin application for anti-photoaging treatment.

Baicalin modulates microRNA expression in UVB irradiated mouse skin

This study aimed to evaluate the effects of baicalin on ultraviolet radiation B (UVB)-mediated microRNA (miRNA) expression in mouse skin. We determined miRNA expression profiles in UVB irradiated mice, baicalin treated irradiated mice, and untreated mice, and conducted TargetScan and Gene Ontology analyses to predict miRNA targets. Three miRNAs (mmu-miR-125a-5p, mmu-miR-146a, and mmu-miR-141) were downregulated and another three (mmu-miR-188-5p, mmu-miR-223 and mmu-miR-22) were upregulated in UVB irradiated mice compared with untreated mice. Additionally, these miRNAs were predicted to be related to photocarcinogenesis, hypomethylation and apoptosis. Three miRNAs (mmu-miR-378, mmu-miR-199a-3p and mmu-miR-181b) were downregulated and one (mmu-miR-23a) was upregulated in baicalin treated mice compared with UVB irradiated mice, and they were predicted to be related to DNA repair signaling pathway. These deregulated miRNAs are potentially involved in the pathogenesis of photodamage, and may aid treatment and prevention of UVB-induced dermatoses.

A genetic polymorphism in pre-miR-27a confers clinical outcome of non-small cell lung cancer in a Chinese population.

Background Recent evidence indicates that microRNAs (miRNAs) can function as tumor suppressors and oncogenes. Single nucleotide polymorphisms (SNPs) at miRNA genes can influence the maturation of miRNAs or miRNA-mediated transcriptional regulation. Our objective was to investigate the association of SNPs in deregulated miRNAs with clinical outcome in patients with non-small cell lung cancer (NSCLC) in a Chinese population. Methods Deregulated miRNAs in NSCLC and their SNPs were identified through public databases. A single SNP, rs895819 in pre-miR-27a, was found suitable for selection. TaqMan assays were performed for genotyping and to assess the effect on the overall survival (OS) and chemotherapy response in 576 NSCLC patients. Results Log-rank test and Cox regression analysis indicated that the G allele of rs895819 was associated with shorter survival and increased risk of death in NSCLC [dominant model: 22.0 vs. 46.0 months, P<0.001; adjusted hazard ratio (HR) = 1.71, 95% confidential interval (CI): 1.12–2.26]. Further stepwise regression analysis suggested that this SNP was an independently unfavorable factor for the prognosis of NSCLC and the effect remained significant in subgroup analysis stratified by clinical parameters and treatment status. Moreover, multivariate logistic regression analysis showed that the subjects with AG/GG genotypes of rs895819 had significantly decreased response rate to platinum-based chemotherapy compared to those with the AA genotype. Conclusion Our results suggest that the pre-miR-27a rs895819 polymorphism may influence NSCLC patients’ clinical outcome. Further large sample studies should be used to validate our findings.