Neu5Gc regulates decidual macrophages leading to abnormal embryo implantation.

Repeated implantation failure (RIF) is one of the most prominent problems in the field of assisted reproduction. Neu5Gc on the surface of decidual macrophages (dMΦ) leads to different activation patterns of dMΦ, which affects embryo implantation and development. Cmah-/- (Neu5Gc-deficient) mice induced to produce anti-Neu5Gc antibodies in vivo were given a special diet rich in Neu5Gc and their fertility was monitored. The long-term diet rich in Neu5Gc induced the decrease of endometrial receptivity of female mice. The pregnancy rate of female mice fed the normal diet was 63.6% (n = 11) and the average number of embryos was 9.571 ± 1.272, while the pregnancy rate of female mice fed the diet rich in Neu5Gc was 36.4% (n = 11) and the average number of embryos in pregnant mice was 5.750 ± 3.304. The intake of Neu5Gc and the production of anti-Neu5Gc antibody led to M1 polarization of endometrial dMΦ and abnormal embryo implantation.

Vasoprotective Effects of Hyperoside against Cerebral Ischemia/Reperfusion Injury in Rats: Activation of Large-Conductance Ca2+-Activated K+ Channels.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and ß1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and ß1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels ß1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.

Simultaneous determination of five alkaloids from Rauvolfia vomitoria in rat plasma by LC-MS/MS: Application to a comparative pharmacokinetic study in normal and type 2 diabetic rats.

Rauvolfia vomitoria is widely distributed in the tropical regions of Africa and Asia, and has been used in traditional folk medicine in China. Indole alkaloids were found to be major bioactive components, while the effects of diabetes mellitus on the pharmacokinetic parameters of the components have not been reflected in vivo. In this study, an efficient and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of five ingredients of R. vomitoria in rats. Detection was implemented in multiple-reaction-monitoring mode with an electrospray positive-ionization source. Validation parameters were all in accordance with the current criterion. The established method was effectively employed to compare the pharmacokinetic behaviors of five alkaloids (reserpine, yohimbine, ajmaline, ajmalicine, and serpentine) between normal and type 2 diabetic rats. The single-dose pharmacokinetic parameters of the five alkaloids were determined in normal and diabetic rats after oral administration of 100 and 200 mg/kg body weight. The results indicated that diabetes mellitus significantly altered the pharmacokinetic characteristics of yohimbine, ajmaline, and ajmalicine after oral administration in rats. This is an attempt to provide some evidence for clinicians that may serve as a guide for the use of antidiabetic medicine in clinical practice.

Predicting factors of central lymph node metastasis and BRAFV600E mutation in Chinese population with papillary thyroid carcinoma.

OBJECTIVE: The aim of this study was to evaluate the predictive factors of central lymph node metastasis (CLNM) and BRAFV600E mutation in Chinese patients with papillary thyroid carcinoma (PTC). METHODS: A total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at our hospital were enrolled. Those patients were divided into PTC > 10 mm and papillary thyroid microcarcinoma (PTMC) groups by tumor size. The BRAFV600E mutation was examined by quantitative real-time PCR. Univariate and multivariate analyses were used to examine risk factors associated with CLNM and the BRAFV600E mutation. RESULTS: The frequency of CLNM was 53% (505/943). Both univariate and multivariate analyses suggested that the risk factors for CLNM in PTC patients were male, younger age, and larger tumor size (P < 0.05). Coexistent Hashimoto thyroiditis (HT) was an independent protective factor against CLNM when the tumor was > 10 mm (P = 0.006). Stratified analysis revealed that male, age ≤ 30 years, and tumor size > 5 mm were independent risk factors for CLNM. The BRAFV600E mutation rate was 85%. Multivariate logistic regression analysis revealed that age (P < 0.001) and coexistent HT (P = 0.005) were independent predictive factors of BRAFV600E mutation in PTC patients. Only age was a risk factor for the BRAFV600E mutation when the tumor was > 10 mm (P = 0.004). In the PTMC group, the BRAFV600E mutation was significantly correlated with tumor size (P < 0.001) and coexistent HT (P = 0.03). Stratified analysis revealed that age > 30 years and tumor size > 5 mm were independent predictive factors of BRAFV600E mutation. Furthermore, the incidence of CLNM was significantly higher in BRAFV600E mutation-positive patients (P = 0.009) when the tumor was ≤ 5 mm. CONCLUSION: The factors male, younger age (≤ 30 years), large tumor size (> 5 mm), and coexistent HT are independent predicative factors for CLNM. The BRAFV600E mutation is associated with both large size and without HT in PTMC patients, age > 30 years in the PTC > 10 mm group. The BRAFV600E mutation was an independent risk factor for CLNM when the tumor was ≤ 5 mm. For optimal management, these features should be comprehensively evaluated to determine the initial surgical approach for PTC patients.

Influence of El Niño events on sea surface salinity over the central equatorial Indian Ocean.

The El Niño event is a major large-scale air-sea interaction phenomenon over the tropical Pacific region. Previous studies classified El Niño into three types - canonical El Niño, El Niño Modoki I, and El Niño Modoki II. This research reveals that different types of El Niño present dramatic effects on the interannual variability of sea surface salinity over the central equatorial Indian Ocean in the boreal autumn. The decreasing (increasing) sea surface salinity during the canonical El Niño and the EI Niño Modoki I (the EI Niño Modoki II) events is identified. The salinity budget analysis is performed to identify the dominant factors responsible for the variability of sea surface salinity over the central Indian Ocean. The results indicate that the wind-driven anomalous zonal advection plays an important role in sea surface salinity variability during the El Niño events associated with the forcing from the anomalous Walker circulation over the equatorial Indian Ocean.

Effect of human pegivirus route of transmission on the genetic distribution of the virus: an institution based cross-sectional study.

INTRODUCTION: Human pegivirus (HPgV), formally called GB virus C (GBV-C), is a member of the pegivirus genus in Flaviviridae family. High prevalence of HPgV infection is seen among sex workers, blood transfusion recipients and intravenous drug users (IDUs). So far, there are seven genotypes and many subtypes identified in different countries. The predominant genotype in Asia including China is genotype 3, although genotype 7 has been reported recently in China. The aim of this study was to evaluate the effect of the transmission routes of HPgV infection on the genotype distribution of the virus, to determine the prevalence rate, and identify the dominant genotype among men who have sex with men (MSM) and IDUs co-infected with human immunodeficiency virus type one (HIV-1) in Guangzhou, China. METHODS: A total of 131 MSM and 70 IDUs co-infected with HIV-1 were randomly selected in Guangdong Dermatology Hospital. HPgV RNA was detected by nested reverse transcriptase polymerase chain reaction (RT-PCR) using primers. The PCR products were sequenced and phylogenetically analyzed by using MEGA6.06 version software to determine the genotypes. Chi-square and Fisher exact test were implemented for comparing the proportion between different variables. RESULTS: The prevalence of HPgV infection was 32.9% among IDUs and 18.3% in MSM with a statistically significant difference between the two groups (p = 0.02). In IDU group, 82.6% infected with genotype 3 and the rest (17.4%) were categorized to genotype 7. Similarly, in MSM group, 83.3% belonged to genotype 3, and the remaining 16.7% were classified as sub-genotype 2a and 2b. CONCLUSION: In Guangzhou, China, the prevalence rate of HPgV infection in IDUs was higher than MSM. The dominant genotype in the two groups was genotype 3. Our results indicated that routes of transmission did not affect the genotype distribution but did affect the prevalence rate of HPgV infection.

Sodium pheophorbide a has photoactivated fungicidal activity against Pestalotiopsis neglecta.

Sodium pheophorbide a (SPA) is a natural photosensitizer. To explore its antifungal activity and mechanism, we studied its inhibitory effects on spore germination and mycelial growth of Pestalotiopsis neglecta. We used sorbitol, 2-thiobarbituric acid (TBA) and electron microscopy to determine its effects on cell wall integrity, cell membrane lipid peroxidation and mycelial morphology. Finally, the effects of SPA on enzyme activity in mycelia were determined. The results showed that SPA effectively inhibited spore germination and mycelial growth of P. neglecta under light conditions (4000 lx, 24 h). Scanning electron microscopy (SEM) revealed that SPA treatment resulted in a roughened, twisted and knotted mycelial surface and abnormal mycelial growth. SPA influenced cell wall integrity, and the content of MDA, a cell membrane lipid peroxidation product was significantly increased (P < 0.05). SPA also significantly inhibited SOD, POD and PG activity, but enhanced PPO activity (P < 0.05). In conclusion, SPA may have potential to become a biological pesticide.

One New Phenolic Compound from Castanea mollissima Shells and its Suppression of HepatomaCell Proliferation and Inflammation by Inhibiting NF-κB Pathway.

Shells of Castanea mollissima (CMS), an agricultural remain and often considered waste from chestnut processing industry, have been proven a resource for traditional Chinese medicine. One new phenol, named castanolB(1), andsix known phenolic compounds (2⁻7) were isolated froma water-soluble extract of CMS. Their chemical structures were determined using preparative HPLC and various spectral analyses, and then were compared to literatures, which indicated the first identification of the seven compounds from C. mollissima. The physicochemical property of compound (2) was also reported for the first time. After antiproliferative screening of compounds (1⁻7) on LPS-induced SMMC-7721 and HepG2 hepatoma cells, castanolB (1) showed the best suppression. CastanolB(1) also significantly induced cell apoptosis. Furthermore, castanolB (1) decreasedsecretion of TNF-α and IL-6. Mechanistically, TLR4⁻NF-κB pathway was inhibited bycastanolB (1) with downregulation of TLR4, IKKß, and NF-κB p65. This study presents a new phenol and shows its profiles of anticancer and anti-inflammation via inhibiting the TLR4⁻NF-κB pathway.

The atherogenic actions of LPC on vascular smooth muscle cells and its LPA receptor mediated mechanism.

Lysophosphatidylcholine (LPC) is a bioactive lipid constituent of oxidized low density lipoprotein (ox-LDL). It regulates various cellular functions, including migration of circulating monocytes, expression of endothelial adhesion molecules, proliferation and migration of vascular smooth muscle cells (VSMCs). LPC can also be hydrolyzed into lysophosphatidic acid (LPA) by autotaxin (ATX) which possesses lysophospholipase D (lyso-PLD) activity. The aim of this study was to explore the effects of LPC on proliferation and migration of human artery smooth muscle cells (HASMCs) and the involvement of LPC-ATX-LPA pathway in these processes. In vitro, we found that LPC and LPA stimulated HASMCs proliferation and migration. Knockdown of LPA1 by siRNA and inhibit Gi protein with pertussis toxin (PTX) showed the contrary results. Silencing of LPC receptor genes did not significantly affect the LPC induced proliferation and migration. We detected the higher expressed mRNA and protein of ATX in HASMCs, and measured lyso-PLD activity. In atherosclerotic rabbit model, we observed high LPC level and high lyso-D activity in blood, and high expression of LPA1 in aorta walls. We also found that neointima appeared to be thickened and mRNA expressions of LPA1 appeared to be increased. These results revealed that LPC was converted into LPA by ATX to induce the proliferation and migration in HASMCs through LPA1/Gi/o/MAP Kinase signaling pathway. Our research suggested that LPC-ATX-LPA system contributed to the atherogenic action induced by ox-LDL. LPA1 antagonist may be considered as a potential therapeutic and preventative drug for cardiovascular disease.

P110ß Inhibition Reduces Histone H3K4 Di-Methylation in Prostate Cancer.

INTRODUCTION AND AIMS: Epigenetic alteration plays a major role in the development and progression of human cancers, including prostate cancer. Histones are the key factors in modulating gene accessibility to transcription factors and post-translational modification of the histone N-terminal tail including methylation is associated with either transcriptional activation (H3K4me2) or repression (H3K9me3). Furthermore, phosphoinositide 3-kinase (PI3 K) signaling and the androgen receptor (AR) are the key determinants in prostate cancer development and progression. We recently showed that prostate-targeted nano-micelles loaded with PI3 K/p110beta specific inhibitor TGX221 blocked prostate cancer growth in vitro and in vivo. Our objective of this study was to determine the role of PI3 K signaling in histone methylation in prostate cancer, with emphasis on histone H3K4 methylation. METHODS: PI3 K non-specific inhibitor LY294002 and p110beta-specific inhibitor TGX221 were used to block PI3 K/p110beta signaling. The global levels of H3K4 and H3K9 methylation in prostate cancer cells and tissue specimens were evaluated by Western blot assay and immunohistochemical staining. A synthetic androgen R1881 was used to stimulate AR activity in prostate cancer cells. A castration-resistant prostate cancer (CRPC) specific human tissue microarray (TMA) was used to assess the global levels of H3K4me2 methylation by immunostaining approach. RESULTS: Our data revealed that H3K4me2 levels were significantly elevated after androgen stimulation. With RNA silencing and pharmacology approaches, we further defined that inhibition of PI3 K/p110beta activity through gene-specific knocking down and small chemical inhibitor TGX221 abolished androgen-stimulated H3K4me2 methylation. Consistently, prostate cancer-targeted delivery of TGX221 in vivo dramatically reduced the global levels of H3K4me2 as assessed by immunohistochemical staining on tissue section of mouse xenografts from CRPC cell lines 22RV1 and C4-2. Finally, immunostaining data revealed a strong H3K4me2 immunosignal in CRPC tissues compared to primary tumors and benign prostate tissues. CONCLUSIONS: Taken together, our results suggest that PI3 K/p110beta-dependent signaling is involved in androgen-stimulated H3K4me2 methylation in prostate cancer, which might be used as a novel biomarker for disease prognosis and targeted therapy. Prostate 77:299-308, 2017. © 2016 Wiley Periodicals, Inc.

Risk Factors of Lymphnode Metastasis in Patients with Thyroid Papillary Carcinoma Associated with Graves Disease.

Objective To summarize the characteristics of lymph node metastasis in patients with papillary thyroid carcinoma accompanied with Graves disease,and to provide evidence for clinical treatment. Methods Totally 98 patients with papillary thyroid carcinoma and Graves disease who had been treated in Peking Union Medical College Hospital from January 2004 to December 2013 were divided into the lymph node metastasis positive group (n=34) and lymph node metastasis negative group (n=64). The general information,blood biochemical results,pathological results,and prognoses were compared between these two groups. Results These two groups showed no significant differences in gender (χ2=0.2113,P=0.6458),age (t=1.7000,P=0.0922),tumor diameter (t=1.2559,P=0.2122),and multifocal tumors (χ2=1.9170,P=0.1661). The median level of thyrotropin receptor antibody (TR-Ab) value in the lymph node metastasis positive group was 4.84 U/L,which was significantly higher than that in the negative group which was 2.99 U/L (t=2.0169,P=0.0465). There were no significant differences in serum thyroid stimulating hormone (t=0.0257,P=0.9800),free triiodothyronine (t=1.3610,P=0.1770),free thyroxine (t=0.0082,P=0.9930),thyroid peroxidase antibody (t=0.0177,P=0.9860),and thyroglobulin antibody levels (t=1.1450,P=0.2550) between two groups. The postoperative pathological results showed that tumor capsular invasion rate (26.5% vs. 9.38%;χ2=5.006,P=0.0253) and lymph node recurrence rate (14.7% vs. 1.56%;χ2=4.583,P=0.0323) were significantly higher in the positive group than in the negative group. The distal metastasis rate in the positive group and negative group were 5.88% and 0,respectively. Conclusions There is no definite association between lymph node metastasis and tumor size in patients with thyroid papillary carcinoma associated with Graves disease. The risk factors for lymph node metastasis include TR-Ab and tumor capsular invasion,with a higher incidence of lymph nodes recurrence.

Beneficial and side effects of arginine vasopressin and terlipressin for septic shock.

Arginine vasopressin (AVP) and its analog, terlipressin (TP), were all demonstrated beneficial for septic shock. What advantages and disadvantages that AVP and TP have for septic shock as well as the mechanism, however, are not completely known. With cecal ligation and puncture-induced septic shock rats and lipopolysaccharide-induced septic shock rabbits, we systematically compared the beneficial and side effects of AVP and TP, in septic shock and the sex difference, and investigated their relationship to Rho kinase and calcium sensitivity. The results indicated that low dose of TP (2.6 µg/kg/h) in combination with norepinephrine (NE) improving vascular reactivity and animal survival were superior to a small dose of AVP (0.03 U/kg/h) in septic shock rats and rabbits. This improving effect of AVP and TP on vascular reactivity was closely related to the activation of Rho-kinase and Rho-kinase-mediating vascular calcium sensitization. A small dose of TP did not result in hyponatremia, did not increase blood bilirubin and decrease platelet count, whereas AVP did. Animal survival and vascular reactivity in female rats after TP or AVP administration were slightly better than male rats, while there were no significant differences. It was suggested that a small dose of TP has better beneficial effect and less side effects on septic shock than AVP. AVP and TP improving vascular reactivity is closely related to Rho-kinase activation and calcium sensitivity improvement. TP or plus NE may be more appropriate for early emergency care for severe septic shock than AVP.

Comparison of contrast-enhanced SPACE and CISS in evaluating cavernous sinus invasion by pituitary macroadenomas on 3-T magnetic resonance.

PURPOSE: SPACE (sampling perfection with application-optimized contrasts by using different flip angle evolutions) and CISS (constructive interference in steady state) are 3-dimensional sequences that can increase the signal intensity of cavernous sinus. The purpose of this study was to determine whether contrast-enhanced (CE) SPACE and CE CISS can well demonstrate cavernous sinus invasion (CSI) by pituitary macroadenoma and which one performed better. METHODS: In 56 cavernous sinuses from 28 patients with pituitary macroadenoma, CSI grades and image quality were assessed by using CE SPACE and CISS. The assessment results were compared with Knops' classification on T1-weighted images. The interreader agreement of assessment results were analyzed with k statistics. Qualitative analyses were compared using the Wilcoxon signed-ranks test. RESULTS: Two radiologists were in substantial agreement of CSI evaluation on both CE SPACE (k = 0.87) and CE CISS (k = 0.83). The evaluation results on CE SPACE (k = 0.76) were more coincident with Knops' classification than CE CISS (k = 0.71). Identification of CSI worked well with either CE SPACE or CE CISS, but CE SPACE performed better (mean, 3.48 ± 0.61 vs 3.28 ± 0.80; P < 0.05). Contrast-enhanced SPACE had significantly higher image scores than CE CISS in description of the relationship between pituitary adenoma and internal carotid artery (mean, 3.26 ± 0.93 vs 2.96 ± 1.01; P < 0.05). Contrast-enhanced CISS demonstrated more susceptibility artifacts (10.7% vs 0%; P < 0.05) and vessel flow artifacts (53.6% vs 0%; P < 0.05). There was no significant difference regarding contrast enhancement of pituitary adenoma and cavernous sinus (mean, 3.07 ± 1.12 vs 3.04 ± 0.96; P > 0.05). CONCLUSIONS: Contrast-enhanced SPACE is superior than CE CISS for identification of CSI by pituitary macroadenoma.

Superconductivity in a layered Ta4Pd3Te16 with PdTe2 chains.

Superconductivity in low-dimensional compounds has long attracted much interest. Here we report superconductivity in a low-dimensional ternary telluride Ta4Pd3Te16 in which the repeating layers contain edge-sharing octahedrally coordinated PdTe2 chains along the crystallographic b axis. Measurements of electrical resistivity, magnetic susceptibility and specific heat on the Ta4Pd3Te16 crystals, grown via a self-flux method, consistently demonstrate bulk superconductivity at 4.6 K. Further analyses of the data indicate significant electron-electron interaction, which allows electronic Cooper pairing in the present system.

Anomalous Eu valence state and superconductivity in undoped Eu3Bi2S4F4.

We have synthesized a novel europium bismuth sulfofluoride, Eu3Bi2S4F4, by solid-state reactions in sealed evacuated quartz ampules. The compound crystallizes in a tetragonal lattice (space group I4/mmm, a = 4.0771(1) Å, c = 32.4330(6) Å, and Z = 2), in which CaF2-type Eu3F4 layers and NaCl-like BiS2 bilayers stack alternately along the crystallographic c axis. There are two crystallographically distinct Eu sites, Eu(1) and Eu(2) at the Wyckoff positions 4e and 2a, respectively. Our bond valence sum calculation, based on the refined structural data, indicates that Eu(1) is essentially divalent, while Eu(2) has an average valence of ∼ +2.64(5). This anomalous Eu valence state is further confirmed and supported, respectively, by Mössbauer and magnetization measurements. The Eu(3+) components donate electrons into the conduction bands that are mainly composed of Bi 6px and 6py states. Consequently, the material itself shows metallic conduction and superconducts at 1.5 K without extrinsic chemical doping.

RAD18 mediates resistance to ionizing radiation in human glioma cells.

Radioresistance remains a major challenge in the treatment of glioblastoma multiforme (GBM). RAD18 a central regulator of translesion DNA synthesis (TLS), has been shown to play an important role in regulating genomic stability and DNA damage response. In the present study, we investigate the relationship between RAD18 and resistance to ionizing radiation (IR) and examined the expression levels of RAD18 in primary and recurrent GBM specimens. Our results showed that RAD18 is an important mediator of the IR-induced resistance in GBM. The expression level of RAD18 in glioma cells correlates with their resistance to IR. Ectopic expression of RAD18 in RAD18-low A172 glioma cells confers significant resistance to IR treatment. Conversely, depletion of endogenous RAD18 in RAD18-high glioma cells sensitized these cells to IR treatment. Moreover, RAD18 overexpression confers resistance to IR-mediated apoptosis in RAD18-low A172 glioma cells, whereas cells deficient in RAD18 exhibit increased apoptosis induced by IR. Furthermore, knockdown of RAD18 in RAD18-high glioma cells disrupts HR-mediated repair, resulting in increased accumulation of DSB. In addition, clinical data indicated that RAD18 was significantly higher in recurrent GBM samples that were exposed to IR compared with the corresponding primary GBM samples. Collectively, our findings reveal that RAD18 may serve as a key mediator of the IR response and may function as a potential target for circumventing IR resistance in human GBM.

MiR-181c modulates the proliferation, migration, and invasion of neuroblastoma cells by targeting Smad7.

MicroRNAs (miRNAs) function as key regulators of gene expression in various cancers. In this study, the aim is to explore the roles and regulation mechanism of miR-181c in neuroblastoma (NB) cells. We found that miR-181c was downregulated in metastatic NB tissues, compared with primary NB tissues. Then functional studies indicated that miR-181c overexpression inhibited NB cell proliferation, migration, and invasion, while miR-181c inhibition increased cell proliferation, migration, and invasion. EGFP reporter assay, real-time polymerase chain reaction and western blot analysis validated that Smad7 was a direct target of miR-181c. MiR-181c reduced Smad7 expression at both mRNA and protein levels. Finally, functional assays showed that the effect of Smad7 knockdown on cells was similar to that of miR-181c overexpression. Importantly, Smad7 overexpression could restore the antitumor effects that were induced by miR-181c. In conclusion, our results demonstrated that miR-181c inhibits NB cell growth and metastasis-related traits through the suppression of Smad7, functioning as a tumor suppressor. Moreover, our results suggested that miR-181c may serve as an important therapeutic target for NB patients.

Synthesis, anti-tumor activity, and structure-activity relationships of curcumol derivatives.

Using curcumol that was extracted from the volatile oil of Rhizoma Curcumae as the raw material, its derivatives were synthesized and purified. The structures of these compounds were confirmed by (1)H, (13)C NMR, and mass spectral data. The test compounds were evaluated for their in vitro anti-tumor activity against gastric cancer cell lines SGC-7901 and lung carcinoma cell line H460 by methyl thiazolyl tetrazolium chromatometry. Distinct structure-activity relationships of these curcumol derivatives were also revealed for inhibiting cell proliferation. Presence of electron-withdrawing groups or amino could increase the activity significantly, whereas esterification of 8-hydroxy diminished the anti-tumor activity. Many of the tested candidates exhibited higher inhibition efficiency than curcumol, suggesting that structural modifications could enhance its activity effectively.

Effect of IL-17 on pulmonary artery smooth muscle cells and connective tissue disease-associated pulmonary arterial hypertension.

OBJECTIVE: To explore the role of interleukin (IL)-17 in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and to investigate its possible mechanism on pulmonary artery smooth muscle cells (PASMCs). METHODS: Enzyme-linked immunosorbent assay (ELISA) were used to compare levels of serum IL-17 in patients with CTD-PAH and healthy controls (HCs). After treatment for 3 months, the serum IL-17 levels were tested in CTD-PAH. ELISA and immunohistochemistry were used to compare levels of serum IL-17 and numbers of pulmonary artery IL-17+ cells, respectively, in a rat model of monocrotaline-induced PAH and untreated rats. Proliferation, migration, and inflammatory factors expression of PASMCs were assessed after stimulation with different concentrations of IL-17 for various time periods. Proteins in the mitogen-activated protein kinase (MAPK) pathway were examined by western blot. RESULTS: Levels of IL-17 were upregulated in patients with CTD-PAH compared to HCs. After 3 months of treatment, serum IL-17 levels were downregulated with pulmonary artery pressure amelioration. Moreover, serum IL-17 levels and numbers of IL-17+ cells infiltrating lung arterioles were increased in PAH model rats. IL-17 could dose- and time-dependently promote proliferation and migration of PASMCs as well as time-dependently induce IL-6 and intercellular cell adhesion molecule-1 (ICAM-1) expression. The levels of MKK6 increased after IL-17 treatment. Inhibition of MAPK decreased proliferation of PASMCs. CONCLUSION: Levels of IL-17 may increase in CTD-PAH, and IL-17 promotes proliferation, migration, and secretion of IL-6 and ICAM in PASMCs, respectively, which likely involves the p-38 MAPK pathway.

BRAFV600E mutation does not predict lymph node metastases and recurrence in Chinese papillary thyroid microcarcinoma patients.

OBJECT: Previous studies suggest BRAFV600E mutation is a marker for poor prognosis in papillary thyroid cancer, however, its ability to further risk stratify papillary thyroid microcarcinoma (PTMC) remains controversial. We aimed to explore the association between BRAFV600E mutation and the clinicopathological features and recurrence in Chinese PTMC patients. METHODS: We retrospectively reviewed 2094 PTMC patients who underwent surgery and had a valid BRAFV600E mutation test result. Among them, 1292 patients had complete follow-up data. The mutation incidence was determined. Moreover, the clinicopathological characteristics, disease-free survival (DFS), and response to therapy distribution were compared between the mutation and non-mutation groups. RESULTS: BRAFV600E mutation was observed in 90.6 % of all patients and 89.2 % of patients with complete follow-up data. No significant difference was observed in lymph node metastases (LNM) number categories between the mutation and non-mutation groups among all patients (P = 0.329) and 1292 patients (P = 0.408). Neither the 3-year DFS (97.9 % vs. 98.0 %, P = 0.832) nor the response to therapy distribution (P > 0.05) indicated a significant difference between the mutation and non-mutation groups. The 3-year DFS differs among patients having different LNM number categories (99.8 % vs. 98.5 % vs. 77.3 %, P < 0.001). Multivariate analysis revealed that high-volume (over 5) LNM (Total thyroidectomy (TT): OR = 4.000, 95 % CI 2.390-6.694, P < 0.001; Unilateral thyroidectomy (UT): OR = 4.183, 95 % CI 1.565-11.190, P = 0.004), rather than BRAFV600E mutation (P > 0.05), was an independent risk factor of response to therapy. CONCLUSIONS: Our results suggested that BRAFV600E mutation could not accurately predict LNM or the recurrence of Chinese PTMC patients. Moreover, high-volume LNM is significantly associated with PTMC prognosis.