Abdominal aortic aneurysm (AAA) demonstrates many features of autoimmune diseases. Y chromosome, sex-determining region of the Y chromosome (SRY) gene, androgen receptor (AR) gene, and androgen appear as potential candidates for influence of the male immune function. This study investigated Y chromosome numbers, SRY gene, AR gene, and androgen levels in male AAAs. We also investigated the correlation between Y chromosome loss (LOY) ratio, SRY expression, androgen levels, and age.

Interleukin-1 receptor antagonist (IL1RN) has been reported as a biomarker of many cancers. However, the biological function of IL1RN in papillary thyroid carcinoma (PTC) remains undetermined.

Vascular remodeling is mainly caused by excessive proliferation of vascular smooth muscle cells (VSMCs). Noncoding RNAs (ncRNAs) have emerged as important regulators in diverse pathological processes. Previous work has shown the functions and mechanisms of long noncoding RNA H19 (LncRNA H19) on VSMCs. As long noncoding RNAs (lncRNAs) are complex in their mechanisms of action, the aim of the study is to identify if there are any other molecular mechanisms of LncRNA H19 on VSMCs. In vivo studies demonstrated that cyclin D1 was overexpressed in neointima of balloon-injured artery. In vitro studies identified that the overexpression of LncRNA H19 promoted VSMCs proliferation and cyclin D1 upregulation. On the contrary, cellular proliferation and expression of cyclin D1 were inhibited in VSMCs after infection with let-7a. Furthermore, luciferase reporter assays and RNA pull-down assays were used to explore the regulatory mechanism, we found that LncRNA H19 functioned as a competing endogenous RNA (ceRNA) by sponging let-7a to promote the expression of the target gene cyclin D1. In conclusion, LncRNA H19 positively regulated cyclin D1 expression through directly binding to let-7a in VSMCs. Our findings provide new insight into the mechanism of LncRNA H19 in VSMCs proliferation and vascular remodeling, and further indicate the implications of LncRNA H19 in the diagnosis and treatment of vascular proliferative diseases.

Accidental injury due to burns is a serious and common, but preventable, occurrence in children. To analyze the characteristics of pediatric burns in the south of Liaoning province of China, a retrospective review was conducted of information, including general characteristics, demographics, etiology of burns, anatomical areas burned, and severity of injuries, obtained from medical records of pediatric burn patients admitted to the Burn Center of Anshan Hospital of the First Hospital of China Medical University from 2002 to 2011. Differences between age-groups and cause and severity of injuries were examined using Cochran-Mantel-Haenzsel (C-M-H) statistic or chi-square (χ(2)) analyses where appropriate. A total of 985 pediatric burn cases were included, with only one death. The maximal burn area recorded was 80% and the maximal third-degree burn area was 45%. The majority of burns (637/985, 64.67%) were moderate second-degree wounds, encompassing 5-14% of the total body surface area. The infant age-group (<3 years old) had the largest representation (622/985, 63.15%), with more males than females affected. Most of the injuries occurred at home in children living in the local region. Scalding accounted for 89.85% (885/985) of all injuries, with a decreasing incidence with age, whereas injuries due to flames and from electrical sources markedly increased with age. Only a minority of guardians (244/985, 24.77%) had burn prevention knowledge, and none of them knew how to provide first-aid treatment for burn injuries. These results indicate that the majority of pediatric burns occur in children less than 3 years of age from scalds received while at home. As a large proportion of these cases occurred in rural areas, programs emphasizing burn prevention and treatment knowledge should therefore be made more available to these families.

Abdominal aortic aneurysm (AAA) is life-threatening, for which efficient nonsurgical treatment strategy has not been available so far. Several previous studies investigating the therapeutic effect of mesenchymal stem cells (MSCs) in AAA indicated that MSCs could inhibit aneurysmal inflammatory responses and extracellular matrix destruction, and suppress aneurysm occurrence and expansion. Vascular smooth muscle cell (VSMC) phenotypic plasticity is reported to be predisposed in AAA initiation and progression. However, little is known about the effect of MSCs on VSMC phenotypic modulation in AAA. In this study, we investigate the therapeutic efficacy of umbilical cord mesenchymal stem cells (UC-MSCs) in elastase-induced AAA model and evaluate the effect of UC-MSC on VSMC phenotypic regulation. We demonstrate that the intravenous injection of UC-MSC attenuates elastase-induced aneurysmal expansion, reduces elastin degradation and fragmentation, inhibits MMPs and TNF-α expression, and preserves and/or restores VSMC contractile phenotype in AAA. Taken together, these results highlight the therapeutic and VSMC phenotypic modulation effects of UC-MSC in AAA progression, which further indicates the potential of applying UC-MSC as an alternative treatment candidate for AAA.

Aim: Smoking is a major risk factor for abdominal aortic aneurysm (AAA). Among the components of smoke, nicotine is known to exert pro-atherosclerotic, prothrombotic, and proangiogenic effects on vascular smooth muscle cells (VSMCs). The current study was designed to investigate the mechanisms through which nicotine induces vascular wall dysfunction and to examine whether melatonin protects against nicotine-related AAA. Methods: In this study, an enzyme-linked immunosorbent assay (ELISA) was used to measure melatonin and TNF-α levels, as well as total antioxidant status (TAS), in patients with AAA. We established a nicotine-related AAA model and explored the mechanisms underlying the therapeutic effects of melatonin. Tissue histopathology was used to assess vascular function, while western blotting (WB) and immunofluorescence staining were performed to detect protein expression. Results: We observed melatonin insufficiency in the serum from patients with AAA, particularly smokers. Moreover, melatonin level was positively correlated with antioxidant capacity. In the in vivo model, nicotine accelerated AAA expansion and destroyed vascular structure. Furthermore, OPN, LC3II, p62, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), NF-κB p65, TNF-α, phosphorylated AKT, and phosphorylated mTOR levels were increased, in vivo, following nicotine treatment, while SM22α and α-SMA levels were reduced. Additionally, melatonin attenuated the effects of nicotine on AAA and reversed changes in protein expression. Moreover, melatonin lost its protective effects following bafilomycin A1-mediated inhibition of autophagy. Conclusion: Based on our data, melatonin exerts a beneficial effect on rats with nicotine-related AAA by downregulating the AKT-mTOR signaling pathway, improving autophagy dysfunction, and restoring the VSMC phenotype.

The proinflammatory cytokine, interleukin-6 (IL-6), plays a critical role in many chronic inflammatory diseases, particularly inflammatory bowel disease. To investigate the regulation of IL-6 gene expression at the molecular level, genomic DNA sequencing of Jinghai yellow chickens (Gallus gallus) was performed to detect single-nucleotide polymorphisms (SNPs) in the region -2200 base pairs (bp) upstream to 500 bp downstream of IL-6. Transcription factor binding sites and CpG islands in the IL-6 promoter region were predicted using bioinformatics software. Twenty-eight SNP sites were identified in IL-6. Four of these 28 SNPs, three [-357 (G > A), -447 (C > G), and -663 (A > G)] in the 5' regulatory region and one in the 3' non-coding region [3177 (C > T)] are not labelled in GenBank. Bioinformatics analysis revealed 11 SNPs within the promoter region that altered putative transcription factor binding sites. Furthermore, the C-939G mutation in the promoter region may change the number of CpG islands, and SNPs in the 5' regulatory region may influence IL-6 gene expression by altering transcription factor binding or CpG methylation status. Genetic diversity analysis revealed that the newly discovered A-663G site significantly deviated from Hardy-Weinberg equilibrium. These results provide a basis for further exploration of the promoter function of the IL-6 gene and the relationships of these SNPs to intestinal inflammation resistance in chickens.

Background: Toll-like receptor 4 (TLR4) and matrix metalloproteinase 2 (MMP2) play important roles in aortic pathophysiology. We aimed to evaluate the contribution of TLR4 and MMP2 polymorphisms individually and complex interactions between gene and risk factors in susceptibility to aortic aneurysm (AA) and its subtypes. Methods: KASP method was adopted to detect TLR4rs11536889, rs1927914 and MMP2rs2285053 polymorphisms in 498 controls and 472 AA patients, including 212 abdominal AA (AAA) and 216 thoracic AA (TAA). Results: In the overall analysis, MMP2rs2285053 TC genotype was correlated with TAA risk (P = 0.047, OR = 1.487). Stratified analysis revealed an increased AA risk in males with TLR4rs1927914 TC genotype, while MMP2rs2285053 TC conferred an elevated AA risk in the subjects ≤60 years, and its TC genotype and dominant model were associated with TAA in the subjects ≤60 year. The interaction between TLR4rs1927914 and MMP2rs2285053 was associated with AAA risk (Pinteraction = 0.028, OR = 2.913). Furthermore, significant interaction between TLR4rs11536889 and dyslipidemia was observed for TAA risk, while TLR4rs1927914 could interact with hypertension and diabetes to increase the risk of AA or its subtypes. Two-way interaction effect of TLR4rs1927914 and MMP2rs2285053 was enhanced by diabetes or dyslipidemia. Conclusion: TLR4 and MMP2 polymorphisms and their complex interactions with cardiovascular risk factors contributed to aortic aneurysmal diseases.

The contractile to synthetic phenotypic switching of vascular smooth muscle cells (VSMCs) in response to fibroblast growth factor (FGF) has been previously described. However, the role of the inflammatory response induced by FGF signaling in VSMCs and its occurrence in atherosclerosis remains unclear. In the present study, FGF signaling promoted a contractile to secretory phenotypic transition in VSMCs. VSMCs (primary human aortic smooth muscle cells) treated with FGF exhibited a decrease in the protein expression levels of factors involved in contractility and the secretion of various chemokines was increased, as assessed by reverse transcription‑quantitative PCR and ELISA. Additionally, inhibition of FGF signaling by silencing FGF receptor substrate 2 (FRS2) decreased the protein expression levels of various chemokines. Furthermore, VSMCs in the medial layers of arteries from apolipoprotein E‑deficient mice and human atherosclerotic samples exhibited an increase in FGF signaling that was identified to be associated with an increase in the protein expression levels of pro‑inflammatory molecules, including C‑C motif chemokine ligand 2, C‑X‑C motif chemokine ligand (CXCL) 9, CXCL10 and CXCL11, compared with wild‑type mice and healthy control samples, respectively. The present results suggested that FGF signaling induced dedifferentiation of contractile VSMCs and the transition to a secretory phenotype, which may be involved in the progression of atherosclerosis. Collectively, the present results suggested that the FGF signaling pathway may represent a novel target for the treatment of atherosclerosis.

Inflammation plays a significant role in the pathogenesis of human abdominal aortic aneurysm (AAA). AEBP1 can promote activation of the NF-κB pathway, subsequently affecting the expression of NF-κB target genes, including inflammatory cytokines and matrix metalloproteinases (MMPs). Our objective was to examine the role of AEBP1 in the development of AAA and characterize the underlying mechanism.

Interleukin 6 (IL-6) is an immunoregulatory cytokine involved in various inflammatory and immune responses. To investigate the effects of single nucleotide polymorphisms (SNPs) and haplotypes of IL-6 on resistance to Eimeria tenella (E. tenella), SNPs in the 5' regulatory region of IL-6 were detected with direct sequencing, and the effects of SNPs and haplotypes on resistance to E. tenella were analyzed by the least square model in Jinghai yellow chickens. Nineteen SNPs were identified in the 5' regulation region of IL-6, among which three SNPs were newly discovered. The SNP association analysis results showed that nine of the SNPs were significantly associated with E. tenella resistance indexes; the A-483G locus was significantly associated with the GSH-Px, IL-2, and IL-17 indexes (p < 0.05); the C-447G locus was significantly associated with the SOD, GSH-Px, IL-17, and IL-2 indexes (p < 0.05); and the G-357A locus had significant effects on the CAT and IL-16 indexes (p < 0.05). Haplotype analysis showed that H2H3 and H2H5 were favorable haplotype combinations with good coccidium resistance. Furthermore, we used qRT-PCR and observed that the expression of IL-6 in the infection group was higher than that in the control group in the liver, proventriculus, small intestine, thymus, kidney, and bursa of Fabricius and extremely significantly different than that in the cecum especially (p < 0.01). In summary, SNPs and haplotypes in the 5' regulatory region of IL-6 have important effects on E. tenella resistance, and the results will provide a reference for molecular marker selection of E. tenella resistance in Jinghai yellow chickens.

Cancer stem cells (CSCs) have been proven to influence drug resistance, recurrence, and metastasis in tumors. Our study aimed to identify stemness-related prognostic biomarkers for new therapeutic strategies in adrenocortical carcinoma.

Background: Vascular smooth muscle cells (VSMC) underwent phenotypic switching upon stimulation signals, and this is the prerequisite for their proliferation and migration. Previous work revealed that miR-455 may be involved in vascular stenosis. Thus, this study aimed to explore potential targets and mechanisms underlying the dynamics of miR-455 in vascular stenosis. Methods: miR-455 and PTEN expression levels were studied in normal and stenosis tissue, as well as in VSMC in proliferation model. Manipulating miR-455 expression levels was achieved by transfection of either miR-455 mimic or inhibitor, and its effect on cell proliferation was studied by CCK-8 assay. Its effect on gene expression was studied by RT-qPCR and western blot. The expression regulation mechanism was studied by luciferase reporter system. Finally, the effect of miR-455 on regulating vascular stenosis was studied using a rat balloon-injured carotid artery stenosis model. Results: High expression levels of miR-455 were detected in both stenosis arterial tissues and VSMC proliferation models. In contrast, the expression levels of PTEN were downregulated in these systems. miR-455 transfected VSMC showed higher levels of proliferation and decreased levels of PTEN. Potential binding sites between miR-455 and PTEN 3'UTR were predicted and confirmed. NF-kB p65 was found to bind directly on miR-455 promoter region and regulate its transcription. The progression of arterial stenosis could be delayed by introducing miR-455 antagomir. Conclusions: The p65/miR-455/PTEN signaling pathway plays a crucial role in regulating VSMC proliferation and vascular stenosis. This indicated that miR-455 is a novel target that would help improve treatment outcomes in patients suffering from vascular stenosis.

Triggering receptor expressed on myeloid cells-1 (TREM-1) has been reported as a biomarker in many cancers. However, the biological function of TREM-1 in papillary thyroid carcinoma (PTC) remains unknown.

Inflammation and excessive proliferation of vascular smooth muscle cells (VSMCs) have key roles in various vascular disorders, including restenosis, atherosclerosis and pulmonary artery hypertension. However, the underlying mechanism remains unclear. The present study investigated the role of nuclear factor-κB (NF-κB) and microRNA (miRNA) in the regulation of VSMC proliferation under inflammatory conditions. It was demonstrated that miR‑17 stimulated the proliferation of VSMCs, enhanced cell cycle G1/S transition, and increased levels of proliferating cell nuclear antigen and E2F1. By directly targeting the retinoblastoma (RB) protein mRNA-3' untranslated region, miR‑17 suppressed the expression of RB. Activation of NF-κB p65 resulted in increased miR‑17 expression in VSMCs, whereas inactivation of NF-κB p65 resulted in decreased expression of miR‑17 in VSMCs. NF-κB p65 signalling directly regulates miR‑17 promoter activity. NF-κB p65 activation also suppressed RB expression, which was abrogated by miR‑17 inhibitor. Taken together, the present results indicated that VSMC proliferation is regulated by activation of the NF-κB p65/miR‑17/RB pathway. As NF-κB p65 signalling is activated in and is a master regulator of the inflammatory response, the present findings may provide a mechanism for the excessive proliferation of VSMCs under inflammation during vascular disorders and may identify novel targets for the treatment of vascular diseases.