Anti-obesity effect of escin: a study on high-fat diet-induced obese mice.

OBJECTIVE: Obesity is characterized by excess fat accumulation and closely associated with insulin resistance and type 2 diabetes. We aimed at exploring the potential effect and mechanism of escin for the treatment of obesity using network pharmacology, and to verify the effect of escin on obese mice. MATERIALS AND METHODS: Escin targets were predicted by DrugBank and SwissTarget database. Potential targets for the treatment of obesity were identified based on the DisGeNET database. Comparative analysis was used to investigate the overlapping genes between escin targets and obesity treatment-related targets. Using STRING database and Cytoscape to analyze interactions among overlapping genes, hub genes were identified. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted in DAVID. High-fat diet (HFD) -induced obese mice were used to observe the anti-obesity effects of escin. The body weight, relevant biochemical markers and HE staining of fat and liver tissues were determined after escin was administered for 18 weeks. RESULTS: We screened 53 overlapping genes for escin and obesity. The mechanism of intervention of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4). The screening and enrichment analysis revealed that the treatment of obesity using escin primarily involved 10 GO enriched terms and 13 related pathways. In vivo, escin can reduce the body weight of obese mice induced by HFD and improve lipid metabolism through lowering triglycerides (TG), total cholesterol (TC), and density lipoprotein (LDL) levels and increasing high density lipoprotein (HDL) levels and decreasing leptin level and increasing adiponectin (ADPN) level. Escin can regulate glucose metabolism caused by obesity through decreasing fasting glucose, postprandial blood glucose and regulating the level of insulin. These obese mice induced by HFD displayed the increased insulin resistance that was associated with the increased inflammatory cytokines, including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). Escin may antagonize the increase of MCP-1 and partially antagonize the low-grade inflammation caused by obesity. From the morphological changes of fat and liver tissues stained by HE stain, escin could decrease the size of adipocytes and improve liver necrosis and fatty degeneration in obese mice fed by HFD. CONCLUSIONS: The network pharmacology of escin in treating obesity may involve 10 hub targets (STAT3, MTOR, NR3C1, IKBKB, PTGS2, MMP9, PRKCA, PRKCD, AR, CYP3A4), 10 GO enriched terms and 13 related pathways. In vivo, escin can be potentially used to prevent or treat obesity through reducing the weight, improving glucose and lipid metabolism, partially antagonizing the low-grade inflammation, and improved insulin resistance.

Ginseng berry concentrate prevents colon cancer via cell cycle, apoptosis regulation, and inflammation-linked Th17 cell differentiation.

The Asian ginseng root (Panax ginseng C.A. Meyer) is a very commonly used herbal medicine worldwide. Ginseng fruit, including the berry (or pulp) and seed, is also valuable for several health conditions including immunostimulation and cancer chemoprevention. In this study, the anticancer and anti-proliferative effects of the extracts of ginseng berry and seed were evaluated. The ginsenosides in the ginseng berry concentrate (GBC) and ginseng seed extract (GSE) were analyzed. We then evaluated their anti-colorectal cancer potentials, including antiproliferation, cell cycle arrest, and apoptotic induction. Further investigation consisted of the berry's adaptive immune responses, such as the actions on the differentiation of T helper cells Treg, Th1, and Th17. The major constituents in GBC were ginsenosides Re and Rd, which can be compared to those in the root. The GBC significantly inhibited colon cancer cell growth, and its anti-proliferative effect involved mechanisms including G2/M cell cycle arrest via upregulation of cyclin A and induction of apoptosis via regulation of apoptotic related gene expressions. GBC also downregulated the expressions of pro-inflammatory cytokine genes. For the adaptive immune responses, GBC did not influence Th1 and Treg cell differentiation but significantly inhibited Th17 cell differentiation and thus regulated the balance of Th17/Treg for adaptive immunity. Although no ginsenoside was detected in the GSE, interestingly, it obviously enhanced colon cancer cell proliferation with the underlined details to be determined. Our results suggested that GBC is a promising dietary supplement for cancer chemoprevention and immunomodulation.

MiR-125a-5p inhibits EMT of ovarian cancer cells by regulating TAZ/EGFR signaling pathway.

OBJECTIVE: To investigate the influences of micro ribonucleic acid (miR)-125a-5p on epithelial-mesenchymal transition (EMT) of ovarian cancer cells by regulating the transcriptional co-activator with PDZ-binding motif (TAZ)/epidermal growth factor receptor (EGFR) signaling pathway. PATIENTS AND METHODS: The human ovarian cancer cells were cultured, and miR-125a-5p was repressed by inhibitor and overexpressed by miRNA mimics. The expression of EMT-related proteins was measured via Western blotting (WB). The action target of miR-125a-5p was determined through a dual-luciferase reporter gene assay. The changes in protein levels were detected via WB. RESULTS: MiR-125a-5p was down-regulated remarkably in ovarian cancer tissues. The expression level of serum miR-125a-5p in patients with ovarian cancer was lower than that in control group. After inhibition on miR-125a-5p, the expression level of E-cadherin, an epithelial indicator, was decreased, while that of Vimentin, an interstitial indicator, was increased. MiR-125a-5p contained a complementary site in the 3'-untranslated region (UTR) of TAZ messenger RNA (mRNA). The expressions of TAZ mRNA and protein in cells were down-regulated markedly after the overexpression of miR-125a-5p. The expressions of EGFR, phosphorylated EGFR (p-EGFR) and p-Akt were up-regulated in the cells transfected with miR-125a-5p mimics and those transfected with miR-125a-5p mimics overexpressing TAZ. CONCLUSIONS: MiR-125a-5p can inhibit the EMT of ovarian cancer cells by regulating the TAZ/EGFR signaling pathway.

Osteoprotegerin mediate RANK/RANKL signaling inhibition eases asthma inflammatory reaction by affecting the survival and function of dendritic cells

Introduction: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Dendritic cells (DCs) are considered the most important antigen-presenting cell in asthma airway inflammatory reaction. But whether osteoprotegerin (OPG) mediate RANK/RANKL signaling inhibition influences asthma development by affecting the survival and function of DCs remains unclear. In this study, we assessed the effects of OPG on DCs and asthma. Material and methods: BALB/c mice immunized with ovalbumin (OVA) were challenged thrice with an aerosol of OVA every second day for eight days. Dexamethasone (1.0mg/kg) or OPG (50 mig/kg) was administered intraperitoneally to OVA-immunized BALB/c mice on day 24 once a day for nine days. Mice were analyzed for effects of OPG on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. The expression of RANK and β-actin was detected by Western Blot. DCs were isolated from mouse bone morrow. Cell survival was assessed by cell counting. The content of IL-12 was detected by ELISA. Results: Results showed that OVA increased the number of inflammatory factors in BALF, elevated lung inflammation scores in mice. OPG reversed the alterations induced by OVA in the asthmatic mice. OPG inhibited the survival and function of DC via inhibition of RANK/RANKL signaling. Conclusions: This research proved inhibition of RANK/RANKL signaling by OPG could ease the inflammatory reaction in asthma, providing new evidence for the application of OPG on asthma

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Osteoprotegerin mediate RANK/RANKL signaling inhibition eases asthma inflammatory reaction by affecting the survival and function of dendritic cells.

INTRODUCTION: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Dendritic cells (DCs) are considered the most important antigen-presenting cell in asthma airway inflammatory reaction. But whether osteoprotegerin (OPG) mediate RANK/RANKL signaling inhibition influences asthma development by affecting the survival and function of DCs remains unclear. In this study, we assessed the effects of OPG on DCs and asthma. MATERIAL AND METHODS: BALB/c mice immunized with ovalbumin (OVA) were challenged thrice with an aerosol of OVA every second day for eight days. Dexamethasone (1.0mg/kg) or OPG (50µg/kg) was administered intraperitoneally to OVA-immunized BALB/c mice on day 24 once a day for nine days. Mice were analyzed for effects of OPG on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. The expression of RANK and ß-actin was detected by Western Blot. DCs were isolated from mouse bone morrow. Cell survival was assessed by cell counting. The content of IL-12 was detected by ELISA. RESULTS: Results showed that OVA increased the number of inflammatory factors in BALF, elevated lung inflammation scores in mice. OPG reversed the alterations induced by OVA in the asthmatic mice. OPG inhibited the survival and function of DC via inhibition of RANK/RANKL signaling. CONCLUSIONS: This research proved inhibition of RANK/RANKL signaling by OPG could ease the inflammatory reaction in asthma, providing new evidence for the application of OPG on asthma.

Efficacy and safety of minimal pedicle screw fixation for thoracolumbar fractures: a meta-analysis.

OBJECTIVE: Minimal and open pedicle screw fixation procedures have been widely used in the treatment of thoracolumbar fractures. However, the efficacy and safety of these approaches remain unclear. This meta-analysis was conducted to evaluate perioperative, functional and radiological outcomes of percutaneous versus open pedicle screw fixation for thoracolumbar fractures. MATERIALS AND METHODS: To obtain relevant literature, a systematic search was performed using the MEDLINE, EMBASE, and Cochrane databases. The Cowley criteria were used to evaluate the risk of bias for the included studies. A database that included patient demographic information and perioperative outcomes was established. Summary odds ratios (ORs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were estimated. Analyses were performed for the two subgroups of Chinese studies and studies from other nations. Publication bias was assessed using the funnel plot method. RESULTS: Eleven comparative observational studies that satisfied our inclusion criteria were identified via a literature search in the MEDLINE, EMBASE, and Cochrane databases. Relative to the open approach, the minimal approach was associated with less blood loss (WMD=-218.10, 95% CI: -266.31 to -169.88, p<0.00001) and shorter operative time (WMD=-15.31, 95% CI: -24.73 to -5.88, p=0.001). Evidence indicated that a significant difference was observed between Chinese studies and other studies with respect to blood loss (p=0.02). We also found that the minimal approach was associated with a lower postoperative visual analog scale (VAS) score (WMD = -1.06, 95% CI: -1.32 to -0.8, p<0.00001) and less correction loss (WMD=-0.59, 95% CI: -1.16 to 0.02, p=0.04) than the traditional open approach. No significant difference between these approaches was found with respect to complication rate (OR 0.78, 95% CI: 0.39 to 1.55, p=0.48). CONCLUSIONS: The evidence indicated that the minimal approach had better functional and radiological outcomes than the open approach. Neither approach was superior with respect to complication rate. Relative to the open approach, the minimal approach might be associated with decreased operative time, less blood loss and a shorter hospital stay.

MiR-146a inhibits proliferation and induces apoptosis in murine osteoblastic MC3T3-E1 by regulating Bcl2.

OBJECTIVE: The dysregulation of proliferation and apoptosis plays a significant role in the pathogenesis of hormone-induced osteonecrosis of femoral head (ONFH). The research aimed to explore the regulatory role of miR-146a in dexamethasone (DEX)-induced proliferation and apoptosis change in MC3T3-E1 cells from murine osteoblastic. MATERIAL AND METHODS: In this study, MC3T3-E1 was co-cultured with 10-7 DEX for 6 h, then RT-PCR was employed to test the expression level of miR-146a and Bcl2. CCK8 assay and flow cytometry were adopted to verify miR-146a could regulate proliferation and apoptosis. After transfected MC3T3-E1 with mimics and inhibitor, RT-PCR and Western blot was used to detect Bcl2 expression level. RESULTS: In DEX treated MC3T3-E1 cells showed higher MiR-146a expression level and lower Bcl2 expression level. MiR-146a could inhibit proliferation and promotes apoptosis in murine osteoblastic MC3T3-E1 cells. Additionally, Bcl2 gene is regulated by MiR-146a. CONCLUSIONS: The MiR-146a expression level increased, while Bcl2 has low expression level in dexamethasone treated MC3T3-E1 cells. MiR-146a regulates proliferation and apoptosis of mouse bone cells. The low expression level of Bcl2 in DEX treated MC3T3-E1 cells is caused by increased MiR-146a level.

MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1

Purpose. The objective of the study was to investigate the role of microRNA-9 (miR-9) targeting forkhead box O1 (FOXO1) in the proliferation, migration, and invasion of breast cancer cells. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expressions of miR-9 and FOXO1 mRNA in breast cancer tissues, normal breast tissues, breast cancer cell lines, and normal breast epithelial cells. After the up-regulation of miR-9 expression, qRT-PCR and Western blotting were used to determine the expression of FOXO1. The luciferase reporter gene assay was used to validate the target gene. The CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay were used to investigate the changes in the proliferation, migration, and invasion of breast cancer cells, respectively. Results. MicroRNA-9 expression was significantly up-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). FOXO1 mRNA and protein expressions were substantially down-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). There can be a negative correlation between miR-9 and FOXO1 mRNA in breast cancer. Luciferase reporter gene assay indicated that miR-9 can down-regulate FOXO1 expression at a post-transcriptional level through binding specifically to FOXO1 3′UTR. The results of CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay revealed that the inhibition of miR-9 can suppress MCF7 cell proliferation, migration, and invasion. Additionally, the expression of miR-9 increased significantly whilst that of FOXO1 decreased substantially as the disease progressed (P < 0.05). Conclusions. Our study provides evidence that miR-9 can promote the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1 (AU)

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MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

PURPOSE: The objective of the study was to investigate the role of microRNA-9 (miR-9) targeting forkhead box O1 (FOXO1) in the proliferation, migration, and invasion of breast cancer cells. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expressions of miR-9 and FOXO1 mRNA in breast cancer tissues, normal breast tissues, breast cancer cell lines, and normal breast epithelial cells. After the up-regulation of miR-9 expression, qRT-PCR and Western blotting were used to determine the expression of FOXO1. The luciferase reporter gene assay was used to validate the target gene. The CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay were used to investigate the changes in the proliferation, migration, and invasion of breast cancer cells, respectively. RESULTS: MicroRNA-9 expression was significantly up-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). FOXO1 mRNA and protein expressions were substantially down-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). There can be a negative correlation between miR-9 and FOXO1 mRNA in breast cancer. Luciferase reporter gene assay indicated that miR-9 can down-regulate FOXO1 expression at a post-transcriptional level through binding specifically to FOXO1 3'UTR. The results of CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay revealed that the inhibition of miR-9 can suppress MCF7 cell proliferation, migration, and invasion. Additionally, the expression of miR-9 increased significantly whilst that of FOXO1 decreased substantially as the disease progressed (P < 0.05). CONCLUSIONS: Our study provides evidence that miR-9 can promote the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

Antidiabetic drug metformin mitigates ovarian cancer SKOV3 cell growth by triggering G2/M cell cycle arrest and inhibition of m-TOR/PI3K/Akt signaling pathway.

OBJECTIVE: Metformin is one of most extensively prescribed oral hypoglycemic drug and has received increased attention in recent times for its antitumorigenic potential. Many possible mechanisms have been proposed for the ability of metformin to overturn cancer growth in vitro and in vivo. The objective of the present study was to evaluate the anticancer activity of metformin against ovarian SKOV3 cancer cells. MATERIALS AND METHODS: Anticancer activity and IC50 value of metformin were determined by MTT assay. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was estimated by Western blotting. RESULTS: Results indicated that metformin exhibited an IC50 of 20 mM against ovarian SKOV3 cancer cell line. Metformin also caused DNA damage in SKOV3 cells and also prompted ROS-mediated alterations in mitochondrial membrane potential. Nonetheless, it triggered cell cycle arrest of SKOV3 at G2/M checkpoint. The activation of the PI3K/AKT/mTOR pathway plays a vital role in ovarian cancer tumorigenesis, progression and chemotherapy resistance. The results showed that metformin significantly inhibited the expression levels of key proteins of PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: We propose that metformin exhibits anticancer activity in SKOV3 cells and may prove beneficial in the management of ovarian cancers.

A functional magnetic resonance imaging study of the neuronal specificity of an acupoint: acupuncture at Rangu (KI 2) and its sham point.

The neuronal specificity of acupoints has not been entirely supported by the results of previous functional magnetic resource imaging studies. This study tested the specificity of an acupoint using right Rangu (KI 2) and its sham acupoint. The results showed specific cerebral response patterns and thus provided the evidence of the existence of acupoint neuronal specificity.

The determinations of nucleosome positioning.

OBJECTIVE: Nucleosomes are the basic packaging units of chromatin, determinants of nucleosome organization playing a major role in genome packaging. Although a wide variety of nucleosome organization factors have been considered separately across the whole or partial human genomic regions, it is unclarified that what the major determinants and their roles in scale are when being put all together. And it is also unknown that what the similarities and differences of determinants between different genomic features such as genes of different expression levels or genomic regions with different functions. MATERIALS AND METHODS: We detected commonalities and characteristics of nucleosome positioning determinants in different genes and regions with 1591486 nucleosomes identified by ourselves in human CD4+ cell. RESULTS: It was found that a distinct linear combination of about 20 nucleosome-positioning factors explained nucleosome occupancy for each genomic feature. In those linear combinations, 6 DNA sequence attributes (Roll stiffness and Twist stiffness, CT and AG, CG and shift stiffness) and a histone modification (H4R3me2) are shared. And other factors are varied. Roll stiffness and Twist stiffness are the most important features. They are dominant, alone explaining 96.61-98.45% of the positioning weight in each genomic feature. The characteristic factors in each combination are larger in number, but weaker in power. Numerous histone modifications play a subtle role for nucleosome positioning. CONCLUSIONS: The present study provides a more accurate positioning nucleosome-map with higher resolution and a dramatically simplified means to predict and understand intrinsic nucleosome occupancy in different genomic features in human CD4+ cell. Roll stiffness and Twist stiffness are the two most important determinants in all genomic features. They may dominate because they both determine the degree of DNA bending and correlates with many other DNA structural characteristics. Histone modifications play a role of subtle allocation for nucleosome occupancy.

Tumor recurrence and drug resistance properties of side population cells in high grade ovary cancer.

INTRODUCTION: The presence of subset of cancer stem cells (CSCs) called "Side population" (SP) cells has been identified in several solid tumors, responsible for treatment failure especially chemotherapy, and cancer relapse. The present study was aimed to isolate and characterize cancer stem like cells side population cells from high grade ovarian cancer. METHODS: The collected cancer samples were analyzed for presence of SP cells by FACS using Hoechst 33342 exclusion technique. Further the FACS sorted SP and non-SP cells were subjected to analysis of stem cell surface protein expression by western blot and immunocytochemistry, drug resistance and sphere formation assay. RESULTS: By FACS, we have identified 3.7% of cancer stem cell like side population cells in ovarian cancer whose prevalence was reduced to 0.5% upon treatment with verapamil an inhibitor of ABC transporter. Further, these sorted SP cells showed over expression of ABCG2 (ABC transporter), stem cell proteins such as CD144, CD44, EpCAM and antiapoptotic factor Bcl-2. Also the SP cells showed high resistance to chemotherapy drugs, have high survival rate and they are highly potential to form tumor spheres. CONCLUSION: Our data suggest that ovarian cancer contain small sub-population of side population cells which shares some characteristics of stem cells. The co-expression of ABC transporters and stem cells surface markers in SP cells may associate with resistance to chemotherapeutic agents, apoptosis and also supports a role for these cells in tumor recurrence, metastasis and invasion.

Nuclear loss of protein arginine N-methyltransferase 2 in breast carcinoma is associated with tumor grade and overexpression of cyclin D1 protein.

Human protein arginine N-methyltransferase 2 (PRMT2, HRMT1L1) is a protein that belongs to the arginine methyltransferase family, and it has diverse roles in transcriptional regulation through different mechanisms depending on its binding partners. In this study, we provide evidences for the negative effect of PRMT2 on breast cancer cell proliferation in vitro and in vivo. Morever, cyclin D1, one of the key modulators of cell cycle, was found to be downregulated by PRMT2, and PRMT2 was further shown to suppress the estrogen receptor α-binding affinity to the activator protein-1 (AP-1) site in cyclin D1 promoter through indirect binding with AP-1 site, resulting in the inhibition of cyclin D1 promoter activity in MCF-7 cells. Furthermore, a positive correlation between the expression of PRMT2 and cyclin D1 was confirmed in the breast cancer tissues by using tissue microarray assay. In addition, PRMT2 was found to show a high absent percentage in breast caner cell nuclei and the nuclear loss ratio of PRMT2 was demonstrated to positively correlate with cyclin D1 expression and the increasing tumor grade of invasive ductal carcinoma. Those results offer an essential insight into the effect of PRMT2 on breast carcinogenesis, and PRMT2 nuclear loss might be an important biological marker for the diagnosis of breast cancer.

Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac muscle cells

Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.

Compressive behaviour of bovine cancellous bone and bone analogous materials, microCT characterisation and FE analysis.

Compressive behaviour of bovine cancellous bone and three open-cell metallic foams (AlSi7Mg (30 ppi and 45 ppi); CuSn12Ni2 (30 ppi)) has been studied using mechanical testing, micro-focus computed tomography and finite element modelling. Whilst the morphological parameters of the foams and the bone appear to be similar, the mechanical properties vary significantly between the foams and the bone. Finite element models were built from the CT images of the samples and multi-linear constitutive relations were used for modelling of the bone and the foams. The global responses of the bone and foam samples were reasonably well captured by the FE models, whilst the percentage of yielded elements as a measure of damage evolution during compression seems to be indicative of the micro-mechanical behaviour of the samples. The damage evolution and distribution patterns across the bone and the foams are broadly similar for the strain range studied, suggesting possible substitution of trabecular bones with appropriate foams for biomechanical studies.

Extended magnetic reconnection across the dayside magnetopause.

The extent of where magnetic reconnection (MR), the dominant process responsible for energy and plasma transport into the magnetosphere, operates across Earth's dayside magnetopause has previously been only indirectly shown by observations. We report the first direct evidence of X-line structure resulting from the operation of MR at each of two widely separated locations along the tilted, subsolar line of maximum current on Earth's magnetopause, confirming the operation of MR at two or more sites across the extended region where MR is expected to occur. The evidence results from in-situ observations of the associated ion and electron plasma distributions, present within each magnetic X-line structure, taken by two spacecraft passing through the active MR regions simultaneously.

Reconnection at high latitudes: antiparallel merging.

New investigations have renewed the debate on the occurrence of magnetic reconnection of Earth's dayside magnetopause. Here, we show for the first time strong evidence for a high-latitude reconnection site, located on initially closed field lines, where the magnetic field orientations inside and outside the magnetopause are close to antiparallel. The evidence centers on repeated sampling of the ion diffusion region and associated null magnetic field by four spacecraft in formation, together with simultaneous monitoring of the local magnetosheath behavior by a fifth spacecraft.

Hypoxia-ischaemia is involved in the pathogenesis of vulvar lichen sclerosus.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disease, the pathogenesis of which is poorly understood. AIM: To evaluate the role of hypoxia-ischaemia (HI) in vulvar LS. METHODS: Samples from five patients with vulvar LS and five control subjects were collected for analysis by transmission electron microscopy (TEM) to reveal the ultrastructural changes of organelles and dermal blood capillaries. Samples from 37 patients with vulvar LS and 12 control subjects were collected for immunohistochemistry to detect the expression of vascular endothelial growth factor (VEGF) and the hypoxia markers hypoxia-inducible factor (HIF)-1alpha and glucose transporter (Glut)-1. RESULTS: Using TEM, the mitochondria of basal cells and vascular endothelial cells in vulvar LS tissue were found to be swollen with loss of cristae, and the rough endoplasmic reticulum had luminal swelling and ribosomal detachment. Damage to vascular endothelial cells, disorganization of capillary architecture and loss of capillaries were also seen. By immunohistochemistry, moderate to intense staining of VEGF was seen in almost 90% of control sections vs. about 55% of LS sections. Glut-1 expression was negative or weak in 75% of control sections vs. moderate to very strong in about 80% of vulvar LS sections. Nuclear staining of HIF-1alpha was not found in LS or control tissue. CONCLUSIONS: HI is involved in the pathogenesis of vulvar LS.

Intraparenchymal epidermoid cysts in the brain: diagnostic value of MR diffusion-weighted imaging.

AIM: To evaluate the value of magnetic resonance (MR) diffusion-weighted imaging (DWI) and apparent diffusion coefficients (ADC) maps in the diagnosis of intraparenchymal epidermoid cysts (ECs). MATERIALS AND METHODS: Six cases of histopathologically proven intraparenchymal ECs were studied. All patients were examined with conventional MR (T1WI, T2WI, contrast-enhanced T1WI) and DWI sequences. Along with the mean ADC values (mADC) of the ECs, the cerebrospinal fluid (CSF) and grey matter (GM) were measured. Qualitative and quantitative assessments, as well as MRI findings, were retrospectively analysed using a double blind method by three radiologists in consensus. RESULTS: Four lesions were located in the cerebellum, among them, one was accompanied by an arachnoid cyst; one huge lesion crossed the parenchyma of the frontal and temporal lobes; the other was located in the left temporal lobe. Two lesions had a homogeneous CSF-like intensity on both T1WI and T2WI. The other four were of mixed-intensity on both T1WI and T2WI. All lesions were strikingly hyperintense on DWI, and iso- or slightly hypointense on ADC (relative to the brain). The mADCs of the ECs were significantly higher than that of GM, but significantly lower than that of CSF. Three cases (3/6) were accurately diagnosed using conventional MR sequences without DWI, but in the remaining three cases, correct diagnosis could only be made with help of DWI. CONCLUSION: DWI sequences can facilitate the diagnosis of intraparenchymal ECs, thus alerting surgeons of the risk of chemical meningitis at surgery. The MR findings of intraparenchymal ECs are basically as the same as those of extracerebral ECs, but the former is likely to have a mixed signal. The hyperintense signal of ECs on DWI is probably caused by the T2 shine-through effect in tumour tissue.