Search

Context The traditional drying method, sun drying, for Chrysanthemum morifolium Ramat. cv. Hang-ju (Compositae) (HJ) is widely replaced by sulphur fumigation (SF), which has an unknown effect on its efficacy. Objective To investigate protective effects of nonfumigated HJ (NHJ) and sulphur-fumigated HJ (SHJ) water extracts against oxidative stress and lipid peroxidation. Materials and methods Sprague-Dawley rats were administered high-fat diet to induce hyperlipidaemia and randomly divided into eight groups (n = 6): control, fenofibrate, NHJ and SHJ extracts (1, 2 or 4 g crude drugs/kg/d; intragastric administration for 8 weeks). Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected. Human umbilical vein endothelial cells (HUVECs) were treated with NHJ and SHJ extracts (50, 100 or 200 μg/mL) for 24 h, followed by oxidized low-density lipoprotein (ox-LDL, 20 μg/mL) for 2 h in vitro. Cellular reactive oxygen species (ROS), SOD and MDA levels and apoptosis were evaluated. Results NHJ was more effective than SHJ in decreasing serum TG, TC, LDL-C, LDL/HDL and MDA while increasing serum HDL-C and SOD levels at high doses. SHJ (IC50=19.9 mg/mL) suppressed HUVEC growth stronger than NHJ (IC50=186.7 mg/mL). At 200 μg/mL, NHJ was more effective than SHJ in downregulating ROS and MDA levels, reducing HUVECs apoptosis rate and elevating SOD activity in ox-LDL-treated HUVECs. Conclusions SF causes oxidative damage and attenuates antioxidative activity in ox-LDL-treated HUVECs, which promotes lipid peroxidation. SF is not recommended for processing HJ.

Huntington's disease is an autosomal dominant hereditary neurodegenerative disease characterized by progressive dystonia, chorea and cognitive or psychiatric disturbances. The leading cause is the Huntington gene mutation on the patient's chromosome 4 that produces a mutated protein. Recently, attention has focused on the relationship between microRNAs and Huntington's disease's pathogenesis. In Huntington's disease, microRNAs can interact with various transcription factors; dysregulated microRNAs may be associated with the Cytosine deoxynucleotide-Adenine ribonucleotides-Guanine ribonucleotide length and Huntington's disease's progression and severity. This study explores the role of microRNAs in the pathogenesis of Huntington's disease through bioinformatics analysis. By analyzing data from the Gene Expression Omnibus database, we identified a total of 9 differentially expressed microRNA. Subsequently, target genes and long non-coding RNAs were predicted, and a comprehensive regulatory network centered on microRNA was constructed. The microRNA integrated regulatory network, Homo sapiens (hsa)-miR-144-3p, interacted with the largest number of long non-coding RNAs, including X-inactive specific transcript and taurine upregulated gene 1. The miRNAs, hsa-miR-10b-5p and hsa-miR-196a-5p, regulated most of the target genes, including class I homeobox and brain-derived neurotrophic factor genes. Additionally, 59 Gene Ontology terms and eight enrichment pathways were identified by analyzing the target genes of hsa-miR-196a-5p and hsa-microRNA-10b-5p. In conclusion, hsa-miR-10b-5p and hsa-miR-196a-5p were significantly and differentially expressed in Huntington's disease, the long non-coding RNAs X-inactive specific transcript, taurine upregulated gene 1, and target genes such as homeobox or brain-derived neurotrophic factor may play critical roles in the pathogenesis of Huntington's disease.

The purpose of our study was to review and evaluate the efficacy and safety of nerve combing without neurovascular decompression for trigeminal neuralgia. A retrospective review of 298 patients with trigeminal neuralgia between August 2007 and August 2016 was conducted. The patients were divided into two groups: the A group was treated by nerve combing (34 patients) and the B group received microvascular decompression (264 patients). Surgical outcomes and postoperative complications were compared between the two groups. Pain was completely relieved in 88.2% of group A patients and 92.8% of group B after surgery. The median duration of follow-up was 60 months (range 10–115 months) in group A and 62 months (range 12–118 months) in group B. 72.7% and 86.4% of cases were completely relieved in groups A and B, respectively. There were no statistically significant differences in the surgical outcomes between the two groups. Almost all patients experienced some degree of numbness or hypesthesia (76.5%). The rate of facial numbness in group A was significantly higher than that in group B. This study demonstrated that nerve combing without neurovascular decompression is a safe and effective treatment for trigeminal neuralgia. However, a majority of patients treated with nerve combing experienced some degree of facial numbness.

Ethnopharmacological relevance Eucommia ulmoides (E. ulmoides) leaves are included in the Chinese Pharmacopoeia, and are traditionally used to treat hypertension, obesity, diabetes, and other diseases. Numerous pharmacological studies have shown that E. ulmoides has a good effect on lowering blood lipids and can improve obesity and nonalcoholic fatty liver. Aim To study the mechanism of E. ulmoides leaves in regulating nonalcoholic fatty liver disease by combining prediction and validation. Methods Using network pharmacology, and molecular docking to predict E. ulmoides in regulating the action mechanism and potential active ingredients of nonalcoholic fatty liver, large hole adsorption resin enrichment active sites, in vitro experiments were performed to verify its fat-lowering effect and mechanism. Results The major components of E. ulmoides leaves exhibited good combination with lipid metabolism-regulating core proteins, particularly flavonoids. EUL 50 significantly reduced lipid accumulation, and increased PPARγ. Compared with the control group, the autophagy level increased after the administration of EUL 50. PPARγ decreased significantly after the addition of chloroquine (CQ, autophagy inhibitor). Conclusion The active ingredients in E. ulmoides leaves regulating nonalcoholic fatty liver disease are mainly flavonoids and phenolics. EUL 50 may play a role in lowering lipids by regulating PPARγ expression through inducing autophagy.

Four new gallate derivatives—ornusgallate A, ent-cornusgallate A, cornusgallate B and C (1a, 1b, 2, 3)—were isolated from the wine-processed fruit of Cornus officinalis. Among them, 1a and 1b are new natural compounds with novel skeletons. Their chemical structures were elucidated by comprehensive spectroscopy methods including NMR, IR, HRESIMS, UV, ECD spectra and single-crystal X-ray diffraction analysis. The in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. As the result, all compounds exhibited anti-inflammatory activities at attested concentrations. Among the tested compounds, compound 2 exhibited the strongest anti- inflammatory activity.

Metabolic-associated fatty liver disease (MAFLD), also known as the hepatic manifestation of metabolic disorders, has become one of the most common chronic liver diseases worldwide. The associations between some oral resident microbes and MAFLD have been described. However, changes to the oral microbial community in patients with MAFLD remain unknown. In this study, variations to the supragingival microbiota of MAFLD patients were identified. The microbial genetic profile of supragingival plaque samples from 24 MAFLD patients and 22 healthy participants were analyzed by 16S rDNA sequencing and bioinformatics analysis. Clinical variables, including indicators of insulin resistance, obesity, blood lipids, and hepatocellular damage, were evaluated with laboratory tests and physical examinations. The results showed that the diversity of the supragingival microbiota in MAFLD patients was significantly higher than that in healthy individuals. Weighted UniFrac principal coordinates analysis and partial least squares discriminant analysis showed that the samples from the MAFLD and control groups formed separate clusters (Adonis, P = 0.0120). There were 27 taxa with differential distributions (linear discriminant analysis, LDA>2.0) between two groups, among which Actinomyces spp. and Prevotella 2 spp. were over-represented in the MAFLD group with highest LDA score, while Neisseria spp. and Bergeyella spp. were more abundant in the control group. Co-occurrence networks of the top 50 abundant genera in the two groups suggested that the inter-genera relationships were also altered in the supragingival plaque of MAFLD patients. In addition, in genus level, as risk factors for the development of MAFLD, insulin resistance was positively correlated with the abundances of Granulicatella, Veillonella, Streptococcus, and Scardovia, while obesity was positively correlated to the abundances of Streptococcus, Oslenella, Scardovia, and Selenomonas. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to sugar (mainly free sugar) metabolism were enriched in the supragingival plaque of the MAFLD group. In conclusion, as compared to healthy individuals, component and interactional dysbioses were observed in the supragingival microbiota of the MAFLD group.

Renal fibrosis is recognized as the common route of all chronic kidney disease (CKD) progressing to end-stage renal disease (ESRD). Additionally, accumulating evidence suggests that epithelial-mesenchymal transition (EMT) plays a significant role in the process of renal fibrogenesis. Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been widely used to treat type 2 diabetes. Recent studies have demonstrated that the GLP-1 analogs could also exert protective effects in cardiac fibrosis models. However, the effects of liraglutide on the progression of CKD remain largely unknown. In the present study, we investigated the effects of liraglutide on the progression to renal fibrosis induced by unilateral ureteral obstruction (UUO) and EMT of rat renal tubular epithelial cells (NRK-52E) induced with recombinant transforming growth factor-beta 1 (TGF-β1). The results indicated that UUO increased collagen deposition and the mRNA expression of fibronectin (FN) and collagen type I alpha 1 (Col1α1) in the obstructed kidney tissues. The effects were blunted in liraglutide-treated UUO mice compared with control mice. The upregulation of Snail1 and alpha smooth muscle actin (α-SMA), and downregulation of E-cadherin revealed that EMT occurred in the UUO kidneys, and these effects were ameliorated following liraglutide treatment. Additionally, liraglutide treatment decreased the expression of TGF-β1 and its receptor (TGF-β1R) and inhibited the activation of its downstream signaling molecules (pSmad3 and pERK1/2). The in vitro results showed that the EMT and extracellular matrix (ECM) secretion of NRK-52E cells were induced by TGF-β1. In addition, the Smad3 and ERK1/2 signaling pathways were highly activated in cells cultured with TGF-β1. All these effects were attenuated by liraglutide treatment. However, the protective effects of liraglutide were abolished by co-incubation of the GLP-1 receptor (GLP-1R) antagonist exendin-3 (9-39). These results suggest that liraglutide attenuates the EMT and ECM secretion of NRK-52E cells induced by TGF-β1 and EMT and renal fibrosis induced by UUO. The potential mechanism involves liraglutide binding to and activating GLP-1R, which prevents EMT by inhibiting the activation of TGF-β1/Smad3 and ERK1/2 signaling pathways, thereby decreasing the ECM secretion and deposition. Therefore, liraglutide is a promising therapeutic agent that may halt the progression of renal fibrosis.

Objective The proportion of the super-aged population (at the age of 80 or above) in patients with chronic subdural hematoma (CSDH) and the incidence of CSDH of the population have been increasing. Since it is widely accepted that YL-1 needle is effective in CSDH treatment, this paper aimed to probe into the efficacy of YL-1 needle in minimally invasive surgery for super-aged (at the age of 80-90) CSDH patients. Methods A retrospective analysis on the clinical information of 17 super-aged CSDH patients having received the YL-1 needle puncture treatment provided by the hospital from May 2012 to December 2016 was performed. At the same time, another 19 CSDH patients (ages 60-79) who were hospitalized during the same period were randomly selected to form a control group. The same surgical treatment was provided for both groups to observe and compare the treatment efficacy. Results The patients of both groups were cured and discharged. Among the super-aged patients, there was 1 patient with postoperative hematoma recurrence, 1 patient with pneumocephalus, and 1 patient with wound infection; among the aged patients, 1 reported postoperative recurrence and 2 had pneumocephalus; The average length of stay of the super-aged group was 9.235 ± 2.948 days while that of the aged group was 7.316 ± 3.660 days, which showed no statistical difference. Conclusion The YL-1 needle puncture treatment is safe and efficacious for both the super-aged and the aged CSDH patients.

Background Daidzein is a soybean isoflavone that has been shown in previous studies to have anti-inflammatory and antioxidant effects. However, it remains unknown whether daidzein plays a protective role against concanavalin A (Con A)-induced autoimmune hepatitis (AIH). Methods In this study, an animal model of AIH was constructed by intravenous injection of Con A (15 mg/kg). Daidzein (200 mg/kg/d) was intraperitoneally administered to mice for 3 days before the Con A injection. Alpha mouse liver 12 (AML-12) cells were incubated in the absence or presence of daidzein to determine whether daidzein can alleviate Con A-induced hepatotoxicity. Results The findings showed that pretreatment with daidzein significantly reduced Con A-induced oxidative stress and hepatocyte apoptosis in Con A-induced liver injury. Pretreatment with daidzein significantly prevented the decrease of intrahepatic protein levels of phosphorylated Akt (p-Akt), phosphorylated GSK3β (p-GSK3β), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NOQ1 (NAD(P)H quinone dehydrogenase 1) in response to Con A administration. Meanwhile, malondialdehyde (MDA) production was reduced, and glutathione peroxidase (GPX), superoxide dismutase (SOD) activity, and SOD2 mRNA expression were elevated in daidzein-pretreated livers. In in vitro experiments, daidzein pretreatment prevented Con A-induced murine hepatocyte death. This effect was partly diminished by an inhibitor of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Conclusions These results indicate that daidzein pretreatment attenuates Con A-induced liver injury through the Akt/GSK3β/Nrf2 pathway. Our findings provide new insights into the use of plant-derived products for AIH treatment beyond immunosuppression.

Bone marrow stromal cells (BMSCs) can differentiate into osteoblasts. The present study investigated the osteogenic effects of estradiol, as well as the role of the c‑Jun N‑terminal kinase (JNK) signaling pathway in promoting estradiol‑enhanced osteogenesis of rat (r)BMSCs. rBMSCs were treated for 7 days with or without estradiol and further treated with or without the JNK‑specific inhibitor SP600125. The role of estrogen during rBMSC osteogenesis was evaluated by alkaline phosphatase activity and mineralized nodule formation using the Gomori method and Alizarin red S staining, respectively. Subsequently, the mRNA expression levels of transforming growth factor-β1 (TGF‑β1) and core‑binding factor α1 (Cbfα1) were evaluated by reverse transcription‑quantitative polymerase chain reaction, and TGF‑β1, Cbfα1 and phosphorylated (p)‑JNK protein expression was detected by western blotting. All groups treated with SP600125 expressed low levels of TGF‑β1 and Cbfα1 mRNA and protein, and low p‑JNK protein expression. Compared with the control cells, rBMSCs cultured with estradiol exhibited a significant upregulation in the expression levels of osteogenic genes and proteins. The present study demonstrated that estradiol enhanced osteogenic differentiation of rBMSCs and that the JNK signaling pathway was involved in this process, providing insights into the molecular mechanisms involved in rBMSC osteogenesis upon estradiol stimulation.

Objective The aim of the present study was to explore the clinical effects, including the prevention of complications, of the treatment of chronic subdural hematoma with double needle aspiration. Methods The clinical data of 31 patients with chronic subdural hematoma treated by double YL-1 needle double skull drilling and 31 controls treated by traditional drilling and drainage were analyzed retrospectively. Results In the YL-1 needle group, only 1 patient was with hematoma recurrence, 1 patient was with intracranial pneumocephalus, and the remaining patients who were followed up for 3 months achieved a clinical cure. In the traditional drilling and drainage group, 13 patients were with hematoma recurrence within 3 months after the operation and 7 patients were with postoperative intracranial pneumocephalus. Conclusions The method of double YL-1 needle is better than the traditional drilling and drainage method for the treatment of chronic subdural hematoma because it reduces the postoperative recurrence rate and complications.

The aim of this retrospective study was to evaluate the role of delayed images after forced diuresis coupled with oral hydration in abdominopelvic 18F-FDG PET/CT. Forty-six patients consisting of 17 urological diseases, 9 gynecological tumors, 18 colorectal malignancies, and 2 cancers of unknown primary site were retrospectively analyzed. All patients who presented with indeterminate or equivocal abdominopelvic foci on standard 18F-FDG PET/CT underwent a delayed abdominopelvic imaging after administration of 20 mg furosemide intravenously and extra water intake of 500 mL. PET/CT images before and after furosemide were compared with each other and their findings correlated with pathology or clinical follow-up (>6 months). On initial PET/CT, the glucose metabolism characters of lesions were disguised by radioactive urine, or some undetermined 18F-FDG accumulating foci near the urinary tract appeared. While postdiuretic PET/CT demonstrated an excellent urinary tracer washout, and hypermetabolic lesions could be clearly detected and precisely localized in all cases. On the other hand, the suspected active foci caused by potential stagnation of excreted 18F-FDG in urinary tract were eliminated. The sensitivity, specificity, and accuracy were 94.4% (34/36), 8/10, 91.3% (42/46), respectively. Furthermore, the additional lesions with surrounding invasion or locoregional metastasis were discovered in 8 of 46 (17.4%) patients only by the delayed images, including 2 gynecological and 6 rectal malignancies. Detection of abdominopelvic malignancies can be improved using delayed 18F-FDG PET/CT images after a diuretic and oral hydration.

We explore the underlying molecular mechanisms and to identify key molecules in Huntington's disease by utilizing bioinformatics methods. The gene expression profile of GSE3621 was extracted from the gene expression omnibus. Differentially expressed genes between the R6/1 transgenic mouse model of Huntington's disease and controls at different time points were screened by limma package in R. Kyoto encyclopedia of genes and genomes database. It was used to analyze the pathways of differentially expressed genes. A searching tool of the protein-protein interaction network was constructed and visualized by Cytoscape. Molecular complex detection was utilized to performed module analysis. There were 513, 483, and 528 differentially expressed genes identified at weeks 18, 22 and 27, respectively, when compared with the control samples. Also, 24 significantly enriched R. Kyoto encyclopedia of genes and genomes database pathways were identified (9 in week 18, 6 in week 22, 9 in week 27), and 31 significant modules were identified from the protein-protein interaction network (13 in week 18, 8 in week 22, 10 in week 27). Hoxd8, Atf3, and Egr2 were confirmed as transcription factors related to Huntington's disease. There are widespread gene expression changes in Huntington's disease at different time points. Some hub genes, such as Usp18, Oasl2, and Rtp4, may play important roles in the pathogenesis of Huntington's disease.

Nardilysin, a kind of metalloendopeptidase, plays an important role in numerous inflammatory diseases. Malignant cerebral infarction (Glasgow coma scale score of9) is associated with a high mortality risk. Here, we intended to investigate the relationship between serum nardilysin levels and prognosis of patients with malignant cerebral infarction.Serum nardilysin concentrations were quantified at malignant cerebral infarction diagnosis moment in 105 patients and at study entrance in 105 healthy controls. Association of nardilysin concentrations with 30-day mortality and overall survival was estimated using multivariate analyses.The patients exhibited substantially increased serum nardilysin concentrations, as compared to the controls. Nardilysin concentrations were in pronounced correlation with Glasgow coma scale scores and serum C-reactive protein concentrations. Serum nardilysin was independently predictive of 30-day mortality and overall survival. Under receiver operating characteristic curve, its high discriminatory ability was found.Rising serum nardilysin concentrations following malignant cerebral infarction are strongly related to stroke severity, inflammatory extent and a higher risk of mortality, substantializing serum nardilysin as a potential prognostic biomarker for malignant cerebral infarction.

Ten new (1-10) and seventeen known (11-27) neo-clerodane diterpenoids substituted with nicotinoyloxyl were isolated from the plant Scutellaria barbata and their structures were established by extensive spectroscopic analysis. Chemoreversal effects of these neo-clerodane diterpenoids on multidrug resistance were evaluated in breast cancer multidrug-resistant MCF-7/ADR cells that overexpress P-glycoprotein. Four compounds (11, 14, 16, and 18) exhibited better chemoreversal abilities than the classical P-gp inhibitor verapamil and the most potent compound 11 reduced IC50 value of adriamycin in MCF-7/ADR cells from 58.8 μM to 1.3 μM. Mechanistic investigations showed that compound 11 reversed multidrug resistance through suppressing the activity of P-gp and restraining the expression of P-glycoprotein. In the present study, the structure-activity relationships of neo-clerodane diterpenoids were also discussed.

A novel series of compounds obtained by fusing the acetylcholinesterase (AChE) inhibitor donepezil and the antioxidant melatonin were designed as multi-target-directed ligands for the treatment of Alzheimer's disease (AD). In vitro assay indicated that most of the target compounds exhibited a significant ability to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (eqBuChE and hBuChE), and β-amyloid (Aβ) aggregation, and to act as potential antioxidants and biometal chelators. Especially, 4u displayed a good inhibition of AChE (IC50 value of 193nM for eeAChE and 273nM for hAChE), strong inhibition of BuChE (IC50 value of 73nM for eqBuChE and 56nM for hBuChE), moderate inhibition of Aβ aggregation (56.3% at 20μM) and good antioxidant activity (3.28trolox equivalent by ORAC assay). Molecular modeling studies in combination with kinetic analysis revealed that 4u was a mixed-type inhibitor, binding simultaneously to catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 4u could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). Taken together, these results strongly indicated the hybridization approach is an efficient strategy to identify novel scaffolds with desired bioactivities, and further optimization of 4u may be helpful to develop more potent lead compound for AD treatment.

Objectives Investigate the effectiveness of alcohol septal ablation (ASA) and transaortic extended myectomy (TEM) in hypertrophic cardiomyopathy (HCM) with midventricular obstruction (MVO). Background MVO is less common than subaortic obstruction. Data on the effectiveness of ASA and TEM in MVO are lacking. Methods The clinical profiles of 22 patients undergoing ASA and 37 patients undergoing TEM were compared. No patient had apical aneurysm, abnormal chordae, mitral valve replacement or repair. Results Baseline midventricular pressure gradient and symptoms were comparable between the ASA and TEM groups. During follow-up, both groups demonstrated substantial reduction in pressure gradient (the ASA group: 79.7 ± 21.2 mm Hg to 43.7 ± 28.9 mm Hg, P

Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87 μM and 0.93 μM, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37 μM for hAChE; 1.98 μM for hBuChE; 2.62 μM for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit.

A novel family of donepezil–ferulic acid hybrids were designed, synthesized and biologically evaluated as multi-target-directed ligands against Alzheimer's disease by fusing a fragment of donepezil and ferulic acid. The in vitro assay indicated that some of these molecules exhibited potent cholinesterase inhibitory activities, outstanding radical scavenging activities and good neuroprotective effects on PC12 cells, and could penetrate into the central nervous system. Compound 5c especially showed moderate acetylcholinesterase inhibitory activity (IC50 values of 0.398 μM for electric eel acetylcholinesterase) and butyrylcholinesterase inhibitory activity (IC50 = 0.976 μM for equine serum butyrylcholinesterase). It also showed significant antioxidant activity (1.78 trolox equivalents by the ABTS method, IC50 values of 24.9 μM by the DPPH method). The kinetic study and molecular docking indicated that compound 5c interacted with both the peripheral anionic site and the catalytic binding site of acetylcholinesterase. Overall, these results indicated that compound 5c is a promising drug candidate with balanced properties for the treatment of Alzheimer's disease.

Advances in immunosuppressive therapy have significantly improved short-term but not long-term survival of cardiac transplant recipients; this is largely due to severe cardiac allograft vasculopathy (CAV). Glucagon-like peptide-1 receptor (GLP-1R)-based therapy exerts physiological effects on the cardiovascular system in addition to its traditional role in controlling glucose. We have investigated the effects of liraglutide, a GLP-1R agonist, on the development of CAV in a murine heart transplant model.Heterotopic murine cardiac transplantation was performed with a major histocompatibility complex class II-mismatched model. Recipient mice were subcutaneously administered vehicle (0.9% saline solution) or liraglutide (300 μg·kg every 12 hours) from the day of transplantation. Allografts were harvested at 2 or 8 weeks and histologically analyzed. Inflammatory infiltrates were measured by immunohistochemistry, and immunofluorescence and western blotting analyzes were used to evaluate GLP-1R expression and markers of endothelial-to-mesenchymal transition (EndMT) in cardiac allografts and human coronary artery endothelial cells challenged with transforming growth factor-beta 1.Glucagon-like peptide-1 receptor was predominantly localized to vascular endothelial cells and was upregulated in cardiac allografts after liraglutide treatment. Liraglutide ameliorated CAV and cardiac fibrosis with reduced inflammatory cell infiltration and downregulated expression of adhesion molecules. Liraglutide inhibited EndMT in allografts and attenuated EndMT by inhibiting Smad3 activation in transforming growth factor-beta 1-treated human coronary artery endothelial cells.Administration of liraglutide from the time of transplantation upregulated GLP-1R in the transplanted heart and reduced cardiac fibrosis, inflammation, and CAV development. Therefore, liraglutide may be a novel therapy for CAV.

Myocarditis can be caused by several infectious and noninfectious causes. Treatment for myocarditis is still a difficult task in clinical practice. The gut microbiota is related to cardiovascular diseases such as atherosclerosis and hypertension. However, little is known about the role of the gut microbiota in myocarditis. In our study, we tested the hypothesis that gut dysbiosis is associated with myocarditis. We focused on whether fecal microbiota transplantation (FMT) can be used as an effective treatment for myocarditis. We used an experimental autoimmune myocarditis (EAM) mouse model. Fecal samples were isolated from the control and EAM groups for bacterial genome analysis. We observed an increase in microbial richness and diversity in the myocarditis mice. These changes were accompanied by an increased Firmicutes/Bacteroidetes ratio. We also evaluated the efficacy of FMT for the treatment of myocarditis. EAM mouse guts were repopulated with fecal contents from an untreated male mouse donor. We found that myocardial injury was improved by diminished inflammatory infiltration, showing that IFN-γ gene expression in the heart tissue and CD4+IFN-γ+ cells in the spleen were decreased after FMT in EAM mice. We also found that FMT was able to rebalance the gut microbiota by restoring the Bacteroidetes population and reshaping the microbiota composition. Myocarditis is associated with gut microbiota dysbiosis and characterized by an increased F/B ratio. FMT treatment can rebalance the gut microbiota and attenuate myocarditis. Thus, FMT may be a potential therapeutic strategy for the treatment of myocarditis.

A new flavonol glycoside, kaempferol-3-O-β-D-(2-O-E-p-coumaroyl)-glucopyranosyl-7-O-α-l-rhamnopyranoside (1), along with eleven known compounds including five flavonol glycosides (2-6), one phenolic glycoside (7), two megastigmane glycosides (8 and 9), two triterpenoids (10 and 11) and one alditol (12), was isolated from the aerial parts of Euonymus fortunei. Their structures were determined on the basis of spectroscopic analysis and chemical evidence. Compounds 2-4, 7, 8, and 10-12 were evaluated their antimicrobial activities against Ureaplasma urealyticumin vitro, but all tested compounds have no useful activities against Ureaplasma urealyticum.

Two new hederagenin-type saponins, staunoside G (1) and staunoside H (2), along with twelve known triterpenoid saponins, were isolated from stems of Stauntonia obovatifoliola Hayata ssp. intermedia. Their structures were determined by analysis of HR-EI-MS, and 1D- and 2D-NMR data, and comparison with those in literature. The two new compounds showed moderate cytotoxicities against three tumor cells, i.e., A549 (lung carcinoma), 4T1 (mammary carcinoma), and HeLa (cervical carcinoma).

A series of 3-Schiff base-4-hydroxycoumarin derivatives (1–20) have been designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies indicated that most of the derivatives exhibited significant abilities to inhibit monoamine oxidase (MAO), self-induced and Cu2+-induced β-amyloid (Aβ1–42) aggregati006Fn, as well acting as potential biometal chelators and antioxidants. Moreover, these derivatives were capable of decreasing reactive oxygen species (ROS) and showed good neuroprotective effects in PC12 cells and could penetrate the central nervous system (CNS). In particular, compound 4 exhibited high potency to monoamine oxidase (IC50, 0.673 μM for hMAO-A, 0.711 μM for hMAO-B), good antioxidant activity (1.34 trolox equivalents by ABTS method, 45.8 μM of IC50 by DPPH method), and it also displayed a significant ability to inhibit self-induced and Cu2+-induced Aβ1–42 aggregation (60.1%, 20 μM and 45.7%, 50 μM). Taken together, these results suggested that compound 4 might be a promising lead compound with balanced properties for AD treatment.

Two series of acetophenone derivatives have been designed, synthesized and evaluated for human monoamine oxidase A and B inhibitory activity in vitro. Most of the tested compounds acted preferentially on MAO-B with IC50 values in the nanomolar range and weak or no inhibition of MAO-A. In particular, compounds 1j (IC50 = 12.9 nM) and 2e (IC50 = 11.7 nM) were the most potent MAO-B inhibitors being 2.76- and 2.99-fold more active than selegiline. In addition, the structure–activity relationships for MAO-B inhibition indicated that substituents at C3 and C4 of the acetophenone moiety, particularly with the halogen substituted benzyloxy, were more favorable for MAO-B inhibition. Molecular docking and kinetic studies have been carried out to explain the binding modes of MAO-B with the acetophenone derivatives. Furthermore, the representative compounds 1j and 2e showed low neurotoxicity in SH-SY5Y cells. It may be concluded that the acetophenone derivatives could be used to develop promising lead compounds for treating neurodegenerative diseases.

The MYH11 gene may be related to cell migration and adhesion, intracellular transport, and signal transduction. However, its relationship with prognosis is still uncertain. The aim of this study was to investigate correlations between MYH11 gene expression and prognosis in 58 patients with stage II and III colorectal cancer. Quantitative real-time polymerase chain reaction was performed in fresh CRC tissues to examine mRNA expression, and immunohistochemistry was performed with paraffin-embedded specimens for protein expression. On univariate analysis, MYH11 expression at both mRNA and protein levels, perineural invasion and lymphovascular invasion were related to disease-free survival (p

AIMS: To explore the risk factors of nocturia in Chinese inhabitants aged >/=40 years. METHODS: A randomized, community-based, cross-sectional study was performed on 10,160 inhabitants >/=40 years old in mainland China, via a stratified sampling approach. A questionnaire, including socio-demographics, lifestyle factors and medical history, was completed. Nocturia was defined as a threshold of two or more voids per night. Differences in prevalence between age and gender groups were ascertained by the chi-squared test. Gender-related factors were evaluated by multivariate logistic regression analysis. P /=40 years, nocturia is associated with aging, OABSS, cardiovascular disease, hypertension, and DM. Sporting activities are negatively associated with nocturia.

The aim of this study was to discuss the baseline characteristics of hemifacial spasm (HFS) associated with the vertebral artery (VA) and evaluate microvascular decompression (MVD) as a surgical treatment of the associated HFS. From February 2010 to February 2015, 118 consecutive patients with HFS underwent MVD. Of these, 29 cases of HFS were associated with VA, this series was compared with the remaining non-VA-associated HFS. Of the 29 cases of VA-associated HFS, the VA was directly compressing the root exit zone (REZ) in eight cases. In the other 21 cases, the VA contacted REZ indirectly via its branches. The symptoms were completely relieved in 26 cases (89.7%) and partially relieved in another two cases (6.9%). Between the VA-associated group and non-VA-associated group, no statistically significant difference existed in the surgical results. VA-associated HFS is not a rare condition. For all cases of VA-associated HFS, indirect compression due to VA was more common. MVD for VA-associated HFS still can achieve good results.

Six new compounds, including a new compound with an unusual 2, 4, 6-cycloheptatrien ketone skeleton (1), two new diphenylpropanoid ethers (2, 3), a new protostane-type triterpenoid (4), two new norsesquiterpene (5a, 5b), and two new natural products (6, 7), together with eleven known compounds (8–18) were isolated from the aqueous extract of Alismatis Rhizoma (AR). Their structures were elucidated by a combination of 1D and 2D NMR (1H and 13C NMR, COSY, HSQC, HMBC, and NOESY), HRESIMS spectroscopic data, experimental and calculated electronic circular dichroism (ECD) spectra. Some of the compounds were evaluated for their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells. Two protostane-type triterpenoids, compounds 4 and 17, exhibited potent inhibitory activities with the IC50 values of 39.3 and 63.9 μM compared with indomethacin. In the meanwhile, their anti-inflammatory effects were also confirmed by acute inflammation model induced by CuSO4 in zebrafish.

The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins. Among them, 13 exhibited remarkable and balanced neuroprotective potency. The protective effects of 13 against neurotoxins-induced apoptosis were confirmed with flow cytometry and staining methods. Furthermore, 13 also showed good BBB permeability and low toxicity according to in vitro BBB prediction and in vivo acute toxicity test. The results indicated that 13 is an effective and promising candidate to be further developed as disease-modifying drug for Parkinson's disease therapy.

PURPOSE: Little is known about the use of electroconvulsive therapy (ECT) for adolescent psychiatric patients in China. This study examined the frequency of ECT and the demographic and clinical correlates of adolescent psychiatric patients hospitalized in a tertiary psychiatric hospital in China. METHODS: This was a retrospective chart review of 954 inpatients aged between 13 and 17 years treated over a period of 8 years (2007-2013). Sociodemographic and clinical data were collected from the electronic chart management system for discharged patients. RESULTS: The rate of ECT use was 42.6% in the whole sample (46.5% for patients with schizophrenia, 41.8% for major depressive disorder, 57.8% for bipolar disorders, and 23.9% for other diagnoses). Use of ECT was independently and positively associated with older age, high aggression risk at time of admission, and use of antipsychotics and antidepressants. Compared with patients with schizophrenia, those with other psychiatric diagnoses were less likely to receive ECT. The above significant correlates explained 32% of the variance of ECT use (P < 0.001). Limitations of this study included the lack of data regarding the efficacy and side effects of ECT. Furthermore, the high rate of ECT applied only to 1 setting which limits the ability to extrapolate the implications of the results to other populations. CONCLUSIONS: The use of ECT was exceedingly high in adolescent patients treated in a tertiary clinical centre in China. It is unlikely that such a high rate of ECT use is found across China or that such practice reflects standard of care for psychiatrically ill adolescents. The underlying reasons for the high use of ECT at this center warrant urgent investigations.

Everted intestinal sac models were used to investigate the intestinal absorption of the 4 alkaloids(berberine, palmatine, coptisine, and epiberberine) in Fuzheng Xiaozheng Fang(FZ) at different intestine segments. The absorption parameters of each component were calculated; SPSS 20.0 software was used to analyze the data and evaluate the absorption characteristics at different intestinal segments. The results showed that all the four active ingredients conformed to zero-order absorption rate. There was significant difference in absorption rate constant (Ka) between the four ingredients at low dose and medium and high dose groups(P

A series of novel donepezil derivatives was designed, synthesized and evaluated as multifunctional acetylcholinesterase (AChE) inhibitors for the treatment of Alzheimer's disease (AD). The screening results indicated that most of the compounds exhibited potent inhibition of AChE with IC50 values in the nanomolar range. Moreover, these derivatives displayed good antioxidant, Aβ interaction, blood-brain barrier penetration (PAMPA-BBB+) and ADMET properties (in silico). Among them, 5c demonstrated excellent AChE inhibition (IC50: 85 nM for eeAChE, 73 nM for hAChE), metal chelation, and inhibitory effects on self-induced, hAChE-induced and Cu(2+)-induced Aβ1-42 aggregation (18.5%, 72.4% and 46.3%, at 20 μM). Kinetic analysis and molecular modeling studies suggested that 5c could bind simultaneously to the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. More importantly, 5c exhibited significant neuroprotective potency against Aβ1-42-induced PC12 cell injury. Furthermore, the step-through passive avoidance test showed 5c significantly reversed scopolamine-induced memory deficit and no hepatotoxicity in mice. These results indicated that 5c might be a promising drug candidate for AD therapy.

Background Genome-wide association studies (GWAS) have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between susceptibility loci and clinical recurrence of AF after catheter ablation have not been examined in Chinese Han populations. To the personalization of catheter ablation for AF, we examined whether these single nucleotide polymorphisms (SNPs) can predict clinical outcomes after catheter ablation for AF in Chinese Han population. Methods and results The association between 8 SNPs and AF was studied in 1418 AF patients and 1424 controls by the unconditional logistic regression analysis. The survival analyses were used to compare AT/AF recurrence differences among 438 AF patients, which were classified by the genotype of rs2200733. rs2200733 and rs6590357 were significantly associated with AF in Chinese Han population. In addition, rs2200733 was associated with clinical recurrence of AF after catheter ablation. In Kaplan–Meier survival analysis, the recurrence-free rates for AF with TT and with TC+CC were 35.5% and 61.9%, respectively ( P =0.0009). In multivariate Cox regression analysis, rs2200733 was strong independent risk factor for recurrence. Conclusion rs2200733 risk allele at the 4q25 predicted impaired clinical response to catheter ablation for AF in Chinese Han population. Our findings suggested rs2200733 polymorphism may be used as a clinical tool for selection of patients for AF catheter ablation.

In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of donepezil-like compounds were designed, synthesized and evaluated. In vitro studies showed that most of the designed compounds displayed potent inhibitory activities toward AChE, BuChE, MAO-B and MAO-A. Among them, w18 was a promising agent with balanced activities, which exhibited a moderate cholinesterase inhibition (IC50, 0.220 μM for eeAChE; 1.23 μM for eqBuChE; 0.454 μM for hAChE) and an acceptable inhibitory activity against monoamine oxidases (IC50, 3.14 μM for MAO-B; 13.4 μM for MAO-A). Moreover, w18 could also be a metal-chelator, and able to cross the blood–brain barrier with low cell toxicity on PC12 cells. Taken together, these results suggested that w18 might be a promising multitargeted compound for AD treatment.

4-Aryl-hexahydroquinolines prepared by Hantzsch reaction from aromatic aldehydes obtained from lignin had been proved to be excellent antioxidant property. In view of polyhydroquinoline containing similarities in structure to the biologically important compound, 1,4-dihydropyridine, their antihypertensive activities were herein determined in spontaneously hypertensive rats (SHRs) during different time. The results show that those compounds possessing excellent antioxidant activity exhibit good antihypertensive property, and the compound containing syringyl moiety exhibit better antihypertensive activity than that containing guaiacyl moiety. This study suggests that those compounds may serve as promising agents for cure hypertension and free radical-related diseases.

Corrugated tubes in a heat exchanger are analyzed by using the FEA methods. And the formula how to compute single wave’s rigidity is obtained. Besides, methods of analyzing the stability of corrugated tubes under internal compressive pressure and external pressure are proposed which include characteristic value analysis and non-linear stability analysis, thus providing theory basis for the stability research of heat exchangers.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Hypertension is one important risk factor of developing AF. The hypertensive patients had up to a 42% increased risk of developing AF and up to 70% of patients with AF had a history of hypertension. The subjects with

RATIONALE X-linked dominant hypophosphatemia rickets (XLH, OMIM 307800) is the most common hereditary hypophosphatemic rickets and characterized by growth retardation, skeletal malformations, dental dysplasia, spontaneous fractures and osteomalacia. PHEX gene was identified for XLH and novel mutations were consistent with loss of function. PATIENT CONCERNS Case1: the proband 1 III3 in family 1 was a fourteen-year-old boy with bowing of bilateral legs, obviously enlarged joints, tooth absence and difficulty in walking; X-rays showed bilateral femoral multiple fractures with sclerosis at the fracture edge. Case 2: the proband 2 III2, a five-year-old boy in family 2, showed growth retardation, dental dysplasia, gingiva abscess and bilateral legs malformations; X-rays showed low bone density, delayed bone age, bowing of legs, frayed and widened metaphyses of the distal femurs and proximal tibias. Both of their mothers suffered from skeletal malformations, tooth absence and were performed with osteotomy due to fractures of lower limb. Their biochemical parameters showed hypophosphatemia, elevated alkaline phosphatase. DIAGNOSES X-linked dominant hypophosphatemia rickets (XLH). INTERVENTIONS AND OUTCOMES Treatment with high doses of phosphate and 1,25-dihydroxyvitamin D3, the height of proband 2 increased 10 cm and femoral Multiple fracture of proband1 almost healed after treatment for 6 months and the patients's PHEX gene was investigated. LESSONS Two novel pathogenic PHEX mutations were found: c.497delG in family 1 and c.388G> T in family 2, both of which caused early termination of translation and produced truncated protein. Serum FGF23 concentration in our XLH patients were obviously higher than the normal and may be related to age to some extent. Early initiation of treatment produces better effect.

microRNAs (miRNAs) have been reported to be associated with the pathogenesis and progression of breast cancer. However, little is known about the pathways through which miRNAs regulate these processes, e.g., the interaction between miRNAs and their target genes with regard to different pathological status of breast cancer, such as histological grades. This study investigated the possible roles of miRNAs in the differentiation of histological grades of breast cancer with a computational approach. Based on a microarray dataset, 15 candidate miRNAs were identified, whose predicted target genes are enriched as differentially expressed between grade I and grade III breast tumors. Among them, 9 key miRNAs focalize their target genes on 6 central signaling pathways. The SMAD7 protein, the main inhibitory protein in the TGF-β pathway, is predicted as a target of several miRNAs and is also regulated by several other pathways that are possibly targeted by miRNAs. It was hypothesized that miRNAs participate in the differentiation of breast cancer and the TGF-β pathway acts as a major implementary pathway on which several miRNAs take effect through multiple channels. The prediction power of the predicted miRNA target genes was validated on three independent datasets. The differential expression of three miRNAs was validated by real-time PCR on breast carcinoma samples of 10 patients.

To evaluate the therapeutic effect of heated (60 degrees C) lipiodol via hepatic artery administration in a rabbit model of VX2 liver cancer.Thirty male New Zealand white rabbits were randomly divided into three groups with 10 rabbits assigned to each group. VX2 carcinoma cells were surgically implanted into the left hepatic lobe. The tumors were allowed to grow for 2 weeks, and studies were performed until the diameter of the tumors detected by ultrasonograph reached 2-3cm. Under anesthesia, trans-catheter hepatic arterial embolization was performed and doxorubicin-lipiodol (37 degrees C) (1mL), lipiodol (60 degrees C) (1mL) or control (physiological saline (37 degrees C) (1mL)) solution was injected into the hepatic arteries of animals in the three groups. One week later, the volume of the tumor was measured by ultrasonograph again. The serum of all rabbits was collected before injection and at 4 and 7 days after injection, and the level of aspartate aminotransferase (AST) was checked. The survival period of the three groups of rabbits after treatment was also recorded. During the last course of their disease, the rabbits were given analgesics to relieve suffering.The tumor growth rate in the lipiodol (60 degrees C) group (0.92+/-0.21, tumor volume from 1811+/-435 to 1670+/-564mm(3)) was significantly lower than that in the control group (3.48+/-1.17, tumor volume from 1808+/-756 to 5747+/-1341mm(3)) (P0.05) and in the doxorubicin-lipiodol (37 degrees C) group (1.69+/-0.26, tumor volume from 1881+/-641 to 2428+/-752mm(3)) (P0.05). Consequently, the survival period of the animals in the lipiodol (60 degrees C) group (41.0+/-3.0 days) was significantly greater than that in the doxorubicin-lipiodol (37 degrees C) group (38.0+/-2.5 days) (P0.05). On the other hand, there was no statistically significant difference in serum AST levels between the lipiodol (60 degrees C) group (148.2+/-11.3UL(-1)) and the doxorubicin-lipiodol (37 degrees C) group (139.7+/-12.3UL(-1)) (P0.05). However, the serum AST level in the lipiodol (60 degrees C) group was significantly higher at 4 days after injection (P0.05) than in the control group (68.6+/-6.6UL(-1)).Treatment with lipiodol (60 degrees C) resulted in an effect on serum AST levels similar to that caused by treatment with doxorubicin-lipiodol (37 degrees C). Thus, lipiodol (60 degrees C) treatment could greatly prolong the survival period of rabbits with VX2 cancer by inhibiting tumor growth.

ARC1 is an arm repeat containing a downstream gene of S-locus receptor kinase (SRK). It interacts with SRK probably in signal transduction pathway of self-incompatibility. In this study, the interaction between SRK and ARC1 proteins was tested using the expression vectors pET43.1a-ARC1 and pET43.1a-SRK E1 . The coding sequences of ARC1 gene were amplified from stigma mRNA of Brassica oleracea L. and inserted into the expression vector pET43.1a to construct the recombinant plasma pET43.1a-ARC1. The recombinant plasmid was transformed to Escherichia coli (BL21) and the expression of the recombinant protein was detected using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Using the co-immunoprecipitation theory and characteristic of 6× His Tag combined with Ni+ in pET43.1a-ARC1, a new method was proposed for testing the interaction between proteins. With this method the interaction between ARC1 and SRK was analyzed, showing that ARC1 and SRK could interact with each other to combine and form a complex. This study provides the theoretical and technical bases for further analyzing the mechanism of interaction between ARC1 and SRK proteins and for probing into interaction between ARC1 and downstream targets.

SRY-box 17 (Sox17) is a transcription factor which involved in a variety of developmental processes and can act as an antagonist of canonical Wnt/beta-catenin signaling pathway. However, the relationship between Sox17 gene expression, methylation status, and beta-catenin in breast cancer has not been established. Here we report that the expression level of Sox17 mRNA was dramatically decreased in five different breast cancer cell lines and 23 of 31 primary breast tumor samples, which significantly correlated with its methylation status. After treated with 5-aza-2'-deoxycytidine (5-aza-dC, a demethylation agent), the expression levels of Sox17 mRNA and protein were obviously increased. Restored expression of Sox17 by 5-aza-dC treatment decreased the expression level of beta-catenin in breast cancer cell lines. Furthermore, small interfering RNA (siRNA)-mediated knockdown of Sox17 in SKBR-3 and Bacp-37 cells enhanced beta-catenin expression. In 31 paired tissue samples, a significant difference between the expression level of Sox17 and beta-catenin was also observed (P0.001). Clinically, Sox17 methylation was detected in 74.3% breast tumors (84/113) and 31.9% (36/113) paired normal tissues, respectively (P0.0001). Sox17 methylation was also associated with tumor stage (P = 0.028) and lymph node metastasis (P = 0.013). These findings indicate that silencing of Sox17 due to promoter hypermethylation is a frequent event and may contribute to aberrant activation of Wnt signaling in breast cancer. Sox17 may be a valuable biomarker for the study of breast cancer carcinogenesis and progression.

Through a series of linkage analyses in a large Chinese family cohort of psoriasis, we previously identified and confirmed a non-HLA psoriasis linkage locus PSORS9 within a small region at 4q31.2–32.1. Within the critical region of the PSORS9 locus, IL-15 has been long recognized as a strong candidate gene for psoriasis. In this study, we investigated the association between IL-15 genetic polymorphisms and psoriasis in a large Chinese sample. Highly significant evidence for association was identified at a single-nucleotide polymorphism (SNP) (g.96516A → T) within the 3′-untranslated region (UTR) of the IL-15 gene ( P =0.00006, after correction for multiple testing). Haplotype analysis using the SNPs within the 3′UTR region also provided strong supporting evidence for association ( P =0.00005), where we identified a haplotype of the 3′UTR region of IL-15 associated with increased risk to psoriasis (odds ratio=1.65). This association was also supported by the results of our expression activity analyses, where we demonstrated that the identified risk haplotype is associated with an increased activity of IL-15. Therefore, we provided early evidence for the important role of IL-15 genetic variants in the pathogenesis of psoriasis, probably by increasing interleukin production and inflammation in the lesions of psoriasis.