bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative Splice Variants, a New Class of Protein Cancer Biomarker Candidates: Findings in Pancreatic Cancer and Breast Cancer with Systems Biology Implications
Authors: Omenn Gilbert S. , Yocum Anastasia K. , Menon Rajasree
Published: June 2013

Alternative splicing plays an important role in protein diversity without increasing genome size. Earlier thought to be uncommon, splicing appears to affect the majority of genes. Alternative splice variants have been detected at the mRNA level in many diseases. We have designed and demonstrated a discovery pipeline for alternative splice variant (ASV) proteins from tandem MS/MS datasets. We created a modified ECgene database with entries from exhaustive three-frame translation of Ensembl transcripts and gene models from ECgene, with periodic updates. The human database has 14 million entries; the mouse database, 10 million entries. We match MS/MS findings against these potential translation products to identify and quantify known and novel ASVs. In this review, we summarize findings and systems biology implications of biomarker candidates from a mouse model of human pancreatic ductal adenocarcinoma [28] and a mouse model of human Her2/neu-induced breast cancer [27]. The same approach is being applied to human tumors, plasma, and cell line studies of other cancers.
Separating the Drivers from the Driven: Integrative Network and Pathway Approaches Aid Identification of Disease Biomarkers from High-Throughput Data
Authors: McDermott Jason E. , Costa Michelle , Janszen Derek , Singhal Mudita , Tilton Susan C.
Published: June 2013

The recent advances in high-throughput data acquisition have driven a revolution in the study of human disease and determination of molecular biomarkers of disease states. It has become increasingly clear that many of the most important human diseases arise as the result of a complex interplay between several factors including environmental factors, such as exposure to toxins or pathogens, diet, lifestyle, and the genetics of the individual patient. Recent research has begun to describe these factors in the context of networks which describe relationships between biological components, such as genes, proteins and metabolites, and have made progress towards the understanding of disease as a dysfunction of the entire system, rather than, for example, mutations in single genes. We provide a summary of some of the recent work in this area, focusing on how the integration of different kinds of complementary data, and analysis of biological networks and pathways can lead to discovery of robust, specific and useful biomarkers of disease and how these methods can help shed light on the mechanisms and etiology of the diseases being studied.
Infectious Agents and Xenobiotics in the Etiology of Primary Biliary Cirrhosis
Authors: Selmi Carlo , De Santis Maria , Cavaciocchi Francesca , Gershwin M. Eric
Published: June 2013

Primary biliary cirrhosis (PBC)is a chronic autoimmune cholestatic liver disease that manifests a latitudinal gradient in prevalence and incidence. The mechanisms leading to the initiation and perpetuation of PBC remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. PBC is also characterized by a high concordance rate in monozygotic twins and is considered a model autoimmune disease because of several features common to other conditions and the relatively homogeneous serological and biochemical features. From a diagnostic standpoint, PBC is characterized by the highest specificity of serum autoantibodies directed at mitochondrial proteins. Several risk factors have been suggested to be associated with PBC, including exposure to infectious agents and chemical xenobiotics that will be critically discussed in the present review article.
Correlation between Eicosanoids in Bronchoalveolar Lavage Fluid and in Exhaled Breath Condensate
Authors: Antczak Adam , Piotrowski Wojciech , Marczak Jerzy , Ciebiada Maciej , Gorski Pawel , Barnes Peter J.
Published: June 2013

Exhaled breath condensate (EBC) has been increasingly used as a new and non-invasive method to study airway inflammation. In this study we have compared the concentrations of lipid mediators in EBCwith concentrations in bronchoalveolar lavage fluid (BALF).

We included 37 patients undergoing bronchoscopy (12 sarcoidosis, 12 COPD, 6 lung cancer, 5 chronic cough, 1 Wegener’s granulomatosis, 1 sclerodermia). Patients were not allowed to have exacerbation or any change in concomitant medication for at least 4 weeks prior to the study. In all patients, EBC was collected immediately prior to the bronchoscopy.

The levels of cys-LTs, LTB4, 8-isoprostane were significantly higher in BALF compared to EBC (p < 0.0001, p < 0.001, p < 0.0001 for cys-LTs, LTB4, 8-isoprostane respectively). Moreover, there was a strong positive correlation between both leukotriene B4and 8-isoprostane in BALF and EBC (r= 0.53 andr= 0.79, p < 0.01, respectively) in patients with sarcoidosis and COPD but there was no correlation between eicosanoids BALF and EBC in patients with chronic cough and lung cancer.

This is the first study to compare EBC and BALF in different lung diseases which demonstrated significant correlations between the levels of eicosanoids in BALF and EBCin patientswith COPD and sarcoidosis. EBC may be useful inmeasuring inflammation in several inflammatory lung diseases.
Association of PPARγ2(Pro12Ala) and Neuropeptide Y (Leu7Pro) Gene Polymorphisms with Obstructive Sleep Apnea in Obese Asian Indians
Authors: Bhushan Bharat , Guleria Randeep , Misra Anoop , Luthra Kalpana , Kumar Guresh
Published: June 2013

Background:Obstructive sleep apnea (OSA) is prevalent in 7.5% in urban Asian Indians.Peroxisome proliferator activated receptor gamma2 (PPARγ2)has been implicated in adipocyte differentiation.Neuropeptide Y (NPY)is also considered as a candidate gene for excess body fat accumulation. The association ofPPARγ2 (Pro12Ala)andNPY (Leu7Pro)gene polymorphisms with OSA has not been studied in Asian Indians.

Objective:To study the distribution ofPPARγ2 (Pro12Ala)andNPY (Leu7Pro)polymorphism in Asian Indians with and without OSA.

Methods and results:This study was carried out in 252 obese subjects [(body mass index (BMI > 25 kg/m2)]; 142 with OSA and 110 without OSA. Measurements included anthropometric and biochemical parameters (fasting blood glucose, lipid profile, various circumferences and skin-fold thicknesses).PPARγ2 (Pro12Ala) and NPY (Leu7Pro) genepolymorphisms were studied in all subjects. The frequency of the variantallele (Ala12) of PPARγ2 genewas significantly higher in subjects with OSA (14.4%) when compared with subjects without OSA (5.5%; χ2= 9.7;p= 0.001). The distribution of the variantallele (Pro7)ofNPY genewas comparable in subjects with OSA (3.5%) and without OSA (3.6%; χ2= 0.001,p= 0.94).

Conclusion:This study reveals a significantly higher frequency ofPPARγ2 (Ala12) allelein obese Asian Indians with OSA when compared to obese Asian Indians without OSA.
Gingival Crevicular Fluid Calprotectin, Osteocalcin and Cross-Linked N-Terminal Telopeptid Levels in Health and Different Periodontal Diseases
Authors: Becerik Sema , Afacan Beral , Öztürk Veli Özgen , Atmaca Harika , Emingil Gülnur
Published: June 2013

Aim:The aim of the present study was to investigate gingival crevicular fluid (GCF) calprotectin, osteocalcin and cross-linked N-terminal telopeptide (NTx) levels in health along with different periodontal diseases.

Material and methods:Twenty chronic periodontitis (CP), 20 generalized aggressive periodontitis (G-AgP), 20 gingivitis and 20 healthy subjects were included. Probing depth, clinical attachment level, plaque index and papillary bleeding index was recorded. GCF calprotectin, osteocalcin and NTx levels were analyzed by enzyme-linked immunosorbent assay (ELISA).

Results:CP, G-AgP and gingivitis groups had higher GCF calprotectin total amount compared to healthy subjects (p< 0.008). CP and G-AgP groups had similar, but higher levels compared to gingivitis groups (p< 0.008). CP and G-AgP groups had lower GCF osteocalcin total amount compared to gingivitis and healthy groups (p< 0.008). CP group had higher GCF NTx but lower osteocalcin total amount and osteocalcin/NTx ratio than the G-AgP group (p< 0.008)

Conclusions:Our results suggest that elevated GCF calprotectin levels play a role as a reliable inflammatory marker in the pathogenesis of periodontal disease. Fluctuating GCF levels of osteocalcin and NTx might point out to the abnormal bone turnover in periodontitis. Our data document for the first time the role of NTx in the pathogenesis of different periodontal diseases.
Association of CD28 IVS3 +17T/C Polymorphism with Soluble CD28 in Rheumatoid Arthritis
Authors: Ledezma-Lozano I. Y. , Padilla-Martínez J. J. , Leyva-Torres S. D. , Parra-Rojas I. , Ramírez-Dueñas M. G. , Pereira-Suárez Ana Laura , Rangel-Villalobos H. , Ruiz-Quezada S. L. , Sánchez-Hernández P. E. , Muñoz-Valle J. F.
Published: June 2013

Objective:Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity.

Methods:We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients.

Methods:We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients.

Results:RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p= 0.032 OR = 1.59, C.I. 1.02–2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p= 0.026). The RA patients showed higher sCD28 serum levels than HS (p= 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p= 0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272;p= 0.016), was found.

Conclusion:The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.
A Longitudinal Study of the Effects of ART on Plasma Chemokine Levels in Malaysian HIV Patients
Authors: Chew Constance S. N. , Cherry Catherine L. , Kamarulzaman Adeeba , Yien Tan Hong , Aghafar Zayd , Price Patricia
Published: June 2013

Objectives: Chemokines influence the migration of leukocytes to secondary lymphoid tissue and sites of inflammation. In HIV patients, they are implicated in inflammatory complications of antiretroviral therapy (ART), notably Immune Reconstitution Disease (IRD) and Sensory Neuropathy (SN). However most chemokines have not been monitored as patients begin ART or correlated with IRD and SN.

Methods: Plasma chemokine levels were assessed longitudinally using commercial ELISAs in 69 patients treated in Kuala Lumpur, Malaysia. Plasma was available at baseline and after 6, 12, 24 and 48 weeks on ART. Chemokine genotypes were assessed using allele-specific fluorescent probes. IRD were diagnosed in 15 patients. 30 patients were screened for SN using the ACTG BPNS tool after six months on ART. SN was detected in 8 patients.

Results: Plasma CXCL10 levels decreased on ART compared to baseline (p= 0.002–0.0001), but remain higher than healthy controls (p≤ 0.0001). The decline was clearer in patients without IRD. CCL5 levels rose on ART but remained similar to controls. CCL2 levels were higher in patients than controls after week 12. Plasma chemokine levels were not affected by CD4+ T-cell counts or any genotypes tested. Several patients with SN displayed higher CCL5 levels throughout therapy compared to patients without neuropathy. Levels of other chemokines and chemokine genotypes were not associated with SN.

Conclusions: Chemokines are differentially affected by ART. CXCL10 and CCL5 may influence IRD and CCL5 warrants further investigation for an effect in SN. These trends are not influenced by chemokine genotypes investigated here.
Gender Differences in Animal Models of Posttraumatic Stress Disorder
Authors: Cohen Hagit , Yehuda Rachel
Published: June 2013

Epidemiological studies report higher prevalence rates of stress-related disorders such as acute stress disorder and post-traumatic stress disorder (PTSD) in women than in men following exposure to trauma. It is still not clear whether this greater prevalence in woman reflects a greater vulnerability to stress-related psychopathology. A number of individual and trauma-related characteristics have been hypothesized to contribute to these gender differences in physiological and psychological responses to trauma, differences in appraisal, interpretation or experience of threat, coping style or social support. In this context, the use of an animal model for PTSD to analyze some of these gender-related differences may be of particular utility. Animal models of PTSD offer the opportunity to distinguish between biological and socio-cultural factors, which so often enter the discussion about gender differences in PTSD prevalence.

In this review, we present and discuss sex-differences in behavioral, neurochemical, neurobiological and pharmacological findings that we have collected from several different animal studies related to both basal conditions and stress responses. These models have used different paradigms and have elicited a range of behavioral and physiological manifestations associated with gender. The overall data presented demonstrate that male animals are significantly more vulnerable to acute and chronic stress, whereas females are far more resilient. The stark contradiction between these findings and contemporary epidemiological data regarding human subjects is worthy of further study. The examination of these gender-related differences can deepen our understanding of the risk or the pathophysiology of stress-related disorders.
Peripheral Blood Based Discrimination of Ulcerative Colitis and Crohn’s Disease from Non-IBD Colitis by Genome-Wide Gene Expression Profiling
Authors: Sipos Ferenc , Galamb Orsolya , Wichmann Barnabás , Krenács Tibor , Tóth Kinga , Leiszter Katalin , Műzes Györgyi , Zágoni Tamás , Tulassay Zsolt , Molnár Béla
Published: June 2013

A molecular diagnostic assay using easily accessible peripheral blood would greatly assist in the screening and diagnosis of ulcerative colitis (UC) and Crohn’s disease (CD). Transcriptional profiles in blood/biopsy samples from 12 UC (6/12), 9 CD (5/9), 6 non-inflammatory bowel disease (non-IBD) colitis (6/0), and 11 healthy (11/11) patients were assessed by Affymetrix HGU133Plus2.0 microarrays. Prediction analysis of microarrays, discriminant and ROC analyses were performed, the results were validated by RT-PCR and immunohistochemistry using also an independent set of samples (15 blood samples, 45 biopsies). A set of 13 transcripts was differentially expressed in IBD, non-IBD controls and healthy blood samples (100% specificity and sensitivity). Validated difference was found in 16 transcripts between UC, non-IBD and normal blood, and 4 transcripts between CD, non-IBD and normal samples. UC and CD blood cases could be also distinguished by 5 genes with 100% specificity and sensitivity. Some disease associated alterations in blood transcripts were also detected in colonic tissue. IBD subtypes may be discriminated from non-IBD (diverticulitis, infective and ischemic colitis)in vitrofrom peripheral blood by screening for differential gene expression revealed in this study. Transcriptional profile alterations in peripheral blood can be located in diseased colon.
NF-kB Expression in IgA Nephropathy Outcome
Authors: Silva G. E. B. , Costa R. S. , Ravinal R. C. , Ramalho L. Z. , dos Reis M. A. , Coimbra T. M. , Dantas M.
Published: June 2013

Some studies have demonstrated the involvement of nuclear factor-kappa B (NF-kB) in the pathogenesis of glomerulonephritis. The aim of our study was twofold: (1) to analyze the prognostic value of NF-kB expression in primary IgA nephropathy (IgAN) and (2) to compare the results of NF-kB expression by immunohistochemistry (IHC) and southwestern histochemistry (SWH). We analyzed 62 patients diagnosed with IgAN from 1987 to 2003. We used monoclonal antibodies to CD68 and mast cell tryptase and polyclonal antibodies to TGF-β1, α-SMA and NF-kB p65. We used SWH for thein situdetection of activated NF-kB. The results showed that NF-kB expression (mainly by SWH) correlated with clinical and histological parameters. An unfavorable clinical course of IgAN was significantly related to tubular NF-kB expression by SWH, but not by IHC. The Kaplan-Meier curves demonstrated that increased NF-kB expression, which was measured by IHC and SWH, decreased renal survival. In conclusion, the increased expression of NF-kB in the tubular area may be a predictive factor for the poor prognosis of patients with IgAN. Compared with IHC, NF-kB expression determined by SWH was correlated with a larger number of parameters of poor disease outcome.
A Polymorphism Within the Connective Tissue Growth Factor (CTGF) Gene has No Effect on Non-Invasive Markers of Beta-Cell Area and Risk of Type 2 Diabetes
Authors: Pivovarova Olga , Fisher Eva , Dudziak Katarzyna , Ilkavets Iryna , Dooley Steven , Slominsky Petr , Limborska Svetlana , Weickert Martin O. , Spranger Joachim , Fritsche Andreas , Boeing Heiner , Pfeiffer Andreas F. H. , Rudovich Natalia
Published: June 2013

Chromosomal locus 6q23 is strongly linked to type 2 diabetes (T2DM) and related features including insulin secretion in various ethnic populations. Connective tissue growth factor (CTGF) gene is an interesting T2DM candidate gene in this chromosome region. CTGF is a key mediator of progressive pancreatic fibrosis up-regulated in type 2 diabetes. In contrast,CTGFinactivation in mice compromises islet cell proliferation during embryogenesis. The aim of our study was to investigate an impact ofCTGFgenetic variation on pancreatic beta-cell function and T2DM pathogenesis. We studied the effect of a commonCTGFpolymorphism rs9493150 on the risk of the T2DM development in three independent German cohorts. Specifically, the association betweenCTGFpolymorphism and non-invasive markers of beta-cell area derived from oral glucose tolerance test was studied in subjects without diabetes. Neither in the Metabolic Syndrome Berlin Potsdam (MESYBEPO) study (n= 1026) (OR = 0.637, CI (0.387–1.050);p= 0.077) nor in the European Prospective Investigation into Cancer and Nutrition-Potsdam (EPIC-Potsdam) (n= 3049) cohort (RR = 0.77 CI (0.49–1.20),p= 0.249 for the recessive homozygote in general model), a significant association with increased diabetes risk was observed. The risk allele of rs9493150 had also no effect on markers of beta-cell area in the combined analysis of the MESYBEPO and Tübingen Family Study (n= 1826). In conclusion, the polymorphism rs9493150 in the 5’-untranslated region of theCTGFgene has no association with T2DM risk and surrogate markers of beta-cell area.
Abnormal Expression of Matrix Metalloproteinase-9 (MMP9) Correlates with Clinical Course in Chinese Patients with Endometrial Cancer
Authors: Yu Fang , Jiang Qingping , Zhou Ying , Yang Zhen , Yu Xiaoli , Wang Hao , Liu Zhen , Wang Lijing , Fang Weiyi , Guo Suiqun
Published: June 2013

Aims and background: The aim of the present study was to analyze the expression of matrix metalloproteinase-9 (MMP9) in endometrial cancer and its correlation with clinicopathologic features in Chinese patients, including the survival of patients with endometrial cancer.

Methods: Using immunohistochemistry analysis, we analyzed MMP9 protein expression in clinicopathologically characterized 128 endometrial cancer (EC) cases with age ranging from 30 to 85 years (median=51.6 years) and 30 endometrial atypical hyperplasia (EAH) and 30 normal endometrium (NE). Cases with greater than or equal to 6 and less than 6 with the score value of cytoplasmic MMP9 immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of MMP9 and clinical features was analyzed in EC cases.

Results: Immunohistochemical analysis revealed that the protein expression of MMP9 detected in EC tissues was higher than that in the EAH tissues and NE tissues (P=0.006). In addition, high levels of MMP9 protein were positively correlated with the status of lymph node metastasis (P=0.044) and the histopathological grade (P<0.05) of EC patients. Patients with higher MMP9 expression did not correlate with EC patients' clinical outcome in China. Multivariate analysis suggested that status of lymph node metastasis and depth of myometrial invasion, but not MMP9 expression level, were significantly correlated with patients' survival.

Conclusion: MMP9 is highly expressed in ECs and correlates with the progression of ECs, but not be helpful in predicting the prognosis of EC patients.
PTPN2 is Associated with Crohn’s Disease and Its Expression Is Regulated by NKX2-3
Authors: Yu Wei , Hegarty John P. , Berg Arthur , Kelly Ashley A. , Wang Yunhua , Poritz Lisa S. , Franke Andre , Schreiber Stefan , Koltun Walter A. , Lin Zhenwu
Published: June 2013

PTPN2 is a risk gene for Crohn's disease (CD). We investigated whether PTPN2 genetic variants (rs2542151 and rs2542152) were associated with CD in a familial IBD registry. Both rs2542151 and rs2542152 are associated with CD, but not ulcerative colitis (UC). mRNA expression levels of PTPN2 were significantly increased in intestinal tissues (p=0.0493), and nearly significantly increased in B cells (p=0.0889) from CD patients, but not significantly altered in UC. cDNA microarray results found that PTPN2 was down-regulated by NKX2-3 knockdown in human cells. We confirmed this observation by RT-PCR analyses in NKX2-3 knockdown in B cells from IBD patients and human intestinal microvascular endothelial cells (HIMEC). In addition, we found that mRNA expression of another IBD-associated gene, NKX2-3, was increased in intestinal tissues and B cells from CD patients, but not significantly increased in UC patients. A positive correlation was observed between mRNA expression of PTPN2 and NKX2-3 in B cells and in intestinal tissues from both CD and UC patients. These results suggest that PTPN2 may have an important role in CD pathogenesis and may represent a potential diagnostic and therapeutic target for IBD.
Soluble Mesothelin-Related Peptides Levels in Patients with Malignant Mesothelioma
Authors: Franko Alenka , Dolzan Vita , Kovac Viljem , Arneric Niko , Dodic-Fikfak Metoda
Published: June 2013

Soluble mesothelin-related peptides (SMRP) are a potential tumor marker for malignant mesothelioma. The aim of this study was to determine the differences in SMRP levels in patients with malignant mesothelioma before treatment and in various responses to treatment and to investigate whether SMRP level could be useful in evaluating tumor response to treatment. The study included patients with malignant mesothelioma treated at the Institute of Oncology Ljubljana between March 2007 and December 2009. Blood samples were collected before treatment and/or in various responses to treatment. SMRP levels were determined using ELISA assay based upon a combination of two monoclonal antibodies. Mann-Whitney test was used to determine the differences in SMRP levels in various responses to treatment.

Median SMRP was 2.80 nmol/L (range 0.00–34.80) before treatment, 0.00 nmol/L (range 0.00–0.00) in complete response, 0.48 nmol/L (range 0.00–4.40) in partial response, 1.65 nmol/L (range 0.00–20.71) in stable disease and 7.15 nmol/L (range 0.44–31.56) in progressive disease. Pre-treatment SMRP levels were significantly higher than in stable disease, partial response and complete response (p=0.006), as were SMRP levels in progressive disease compared to stable disease, partial response and complete response (p= 0.006), as were SMRP levels in progressive disease compared to stable disease, partial response and complete response (p< 0.001).

Our findings suggest that SMRP may be a useful tumor marker for detecting the progression of malignant mesothelioma and evaluating tumor response to treatment.
Serum Homocysteine, Vitamin B12, Folic Acid Levels and Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism in Vitiligo
Authors: Yasar Ali , Gunduz Kamer , Onur Ece , Calkan Mehmet
Published: June 2013

The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.
Circulating Levels of High Molecular Weight (HMW) Adiponectin and Total Adiponectin in Relation to Fat Distribution, Oxidative Stress and Inflammation in Asian Indians
Authors: Indulekha K. , Surendar J. , Anjana R.M. , Gokulakrishnan K. , Balasubramanyam M. , Aravindhan V. , Mohan V.
Published: June 2013

Aim: To look at the association of total and high molecular weight (HMW) adiponectin with markers of fat distribution, oxidative stress and inflammation in Asian Indians.

Methods: A total of 120 subjects were chosen randomly from Chennai Urban Rural Epidemiological Study. Fasting HMW adiponectin levels, TNF-alpha and oxidized LDL were measured using ELISA. High sensitivity C reactive protein (hsCRP) was measured by a high sensitive nephelometric assay. Lipid peroxidation was measured by Tbars assay and protein carbonyl content was assessed by DNPH assay. Visceral and subcutaneous fat areas were assessed by computed tomography (CT) scan.

When stratified based on the tertiles of visceral fat, the levels of total (p= 0.03) and HMW adiponectin (p= 0.007) were highest in the first tertile followed by tertiles 2 and 3 whereas in tertiles of subcutaneous fat, there was no such trend. With increasing tertiles of Tbars, the levels of total (p= 0.03) and HMW adiponectin decreased (p= 0.002). The levels of HMW (p< 0.001) but not total adiponectin was also found to decrease with increasing tertiles of Protein carbonyl content. The levels of Total (p= 0.02) and HMW adiponectin (p= 0.004) were highest in the first tertile of oxidized LDL followed by tertile 2 and tertile 3. With increasing tertiles of TNF-alpha total (p= 0.01) and HMW adiponectin (p= 0.004) was found to decrease. With increasing tertiles of hs-CRP, Total (p= 0.005) and HMWadiponectin (p= 0.007)was found to decrease.

Conclusion: Oxidative stress markers, visceral but not subcutaneous fat and inflammation are associated with total and HMW adiponectin levles in Asian Indians.
Effect of Non Surgical Periodontal Therapy on Gingival Crevicular Fluid and Serum Visfatin Concentration in Periodontal Health and Disease
Authors: Raghavendra N.M. , Pradeep A.R. , Kathariya Rahul , Sharma Anuj , Rao Nishanth S. , Naik Savitha B.
Published: June 2013

Visfatin is a pleiotropic mediator which acts as growth factor, cytokine, enzyme involved in energy including nicotinamide adenine dinucleotide metabolism and has been recently demonstrated to exert several pro-inflammatory functions. The purpose of this study is to evaluate the Visfatin concentration in gingival crevicular fluid (GCF) and serum in patients with chronic periodontitis, and to evaluate the effect of non-surgical periodontal therapy on the GCF and serum visfatin concentration. 30 subjects (age range: 25 to 52 years) were selected and divided into two groups based on the gingival index, probing depth, periodontal attachment level, and radiologic parameters (bone loss): group 1 (15 subjects with healthy periodontium), group 2 (15 subjects with chronic periodontitis), while, Group 2 patients after 8 weeks of the treatment (scaling and root planning, SRP) constituted group 3. GCF samples (by microcapillary pipettes) and serum samples (by venipuncture) were collected to estimate the levels of Visfatin using enzyme linked immunosorbent assay kit. The mean Visfatin concentration in GCF and serum was observed to be the highest in group 2 and lowest in group 1. While concentration in group 3 was similar to group 1. The concentration of Visfatin in GCF and serum decreased after SRP. The Visfatin concentration in GCF and serum found to be highest in chronic periodontitis group and decreases after treatment. Hence Visfatin values can be considered as an “inflammatory marker” can be explored in future as a potential therapeutic target in the treatment of periodontal disease.
Replication of Relevant SNPs Associated with Cardiovascular Disease Susceptibility Obtained from GWAs in a Case-Control Study in a Canarian Population
Authors: Esparragón Francisco Rodríguez , Companioni Osmel , Bello Miguel García , Ríos Nisa Buset , Pérez José Carlos Rodríguez
Published: June 2013

Recent genome-wide single nucleotide polymorphism (SNP) association studies (GWAS) have identified a number of SNPs that were significantly associated with coronary artery disease (CAD) and myocardial infarction (MI). We tested for replication of the previously described association with CAD in our case-control datasets of SNPs variants located at 1p13.1, 2q33.1, 10q11.1, 9p21, and 21q22. We observed a small significant risk associated of the SNP rs10757274 with CAD in the PROCAGENE study. Besides, the multilocus combination rs10757274 and rs1333048 gave a near significant result. We confirmed that the SNP rs10757274 showed association with CAD in the PROCAGENE study, although after applying the Bonferroni correction was not longer significant. Independent replication studies in other populations are needed to unequivocally confirm the association.
Poly Thymidine Polymorphism and Cystic Fibrosis in a Non-Caucasian Population
Authors: Tabaripour Reza , Niaki Haleh Akhavan , Douki Mohammad Reza Esmaeeli , Bazzaz Javad Tavakkoly , Larijani Bagher , Yaghmaei Parichehr
Published: June 2013

Background:Cystic fibrosis is a monogenic recessive disorder found predominantly in Caucasian population. This disease arises from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this study we consider poly T polymorphism c.1210-12T[5], c.1210-12T[7], c.1210-12T[9] (T5, T7, T9) in the intron 8 of CFTR gene in normal individuals and cystic fibrosis patients in the north of Iran.

Material and methods:40 CF patients and 40 normal individuals were screened for poly T polymorphism in intron 8 of CFTR gene using Reverse Dot Blot method which was also used to detect p.Phe508del among CF patients.

Results:T7allele is the most prevalent in both normal and CF patients. Its abundance is approximately 75%. T9and T5represent approximately 20% and 5% of alleles respectively. T7/ T7genotype is the most present in both normal and CF patients with 72.5% and 60% prevalence respectively. p.Phe508del was present in 13 CFTR alleles belonging to 7 patients with either homozygote T9/ T9, T7/ T7or compound heterozygote T7/ T9genotypes.

Conclusion:Contrary to the Caucasians, T7allele is more frequent in Northern Iranian CF patients. The presence of p.Phe508del and T7allele in the same framework is reported for the first time in this part of the world. Further investigations of other populations will help to understand whether p.Phe508del arose by selection pressure in this part of the world or was imported from European countries. The abundance of T5, T7, T9alleles indicates that this polymorphism can be used as one of the informative markers for detection of normal and mutant alleles in prenatal diagnosis or carrier assessment in families with previous history of the disease in regions with high degree of CFTR mutation heterogeneity.
Cord Blood Levels of IL-6, IL-8 and IL-10 May Be Early Predictors of Bronchopulmonary Dysplasia in Preterm Newborns Small for Gestational Age
Authors: Rocha Gustavo , Proença Elisa , Guedes Ana , Carvalho Carmen , Areias Augusta , Ramos João Pedro , Rodrigues Teresa , Guimarães Hercília
Published: June 2013

Introduction: Various cytokines have been associated to the occurrence of bronchopulmonary dysplasia (BPD) in preterm neonates.

AIM: To establish an association between cord blood cytokines and BPD, so that they could be used, in clinical practice, as early markers of BPD.

Material and methods: Preterms less than 30 weeks gestational age, were analysed by ELISA microassay for venous cord blood IL-1β, IL-6, IL-8, TNF-αand IL-10, and compared between the BPD and non-BPD groups.

Results: One hundred and fifty neonates completed the study; 31 (21%) small for gestational age (SGA); 16 were deceased before 28 days of life; 36 developed mild BPD and 20 developed moderate/severe BPD. Elevated cord blood IL-8 was associated with death or moderate/severe BPD. SGA patients with moderate/severe BPD presented higher cord blood values of IL-8, lower IL-6 and IL-10 when compared with SGA without moderate/severe BPD; and higher IL-8 levels when compared with patients without moderate/severe BPD.

Conclusion: These results support an association between cord blood IL-8 and moderate/severe BPD, independently of the intra-uterine growth; and the association of cord blood IL-6 and IL-10 and moderate/severe BPD in SGA preterm newborns.
Combined Analysis of AFP and HCCR-1 as an Useful Serological Marker for Small Hepatocellular Carcinoma: A Prospective Cohort Study
Authors: Zhang Guoxin , Ha Seon-Ah , Kim Hyun K. , Yoo Jinah , Kim Sanghee , Lee Youn S. , Hur Soo Y. , Kim Yong W. , Kim Tae E. , Park Yong G. , Wang Jing , Yang Yang , Xu Zekuan , Song Eun Y. , Huang Zuhu , Jirun Peng , Zhongtian Jin , Shishi Qiao , Zhuqingqing Cui , Lei Gong , Kim Jin W.
Published: June 2013

Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world. The only serological marker widely used for the diagnosis of HCC is alpha-fetoprotein (AFP). Despite that AFP is widely used for the diagnosis of HCC, it has a limit as a serological marker due to its low sensitivity and specificity. The human cervical cancer proto-oncogene 1 (HCCR-1) was previously reported as a new biomarker for HCC. To further evaluate the HCCR-1 as a biomarker for HCC, we conducted the prospective cohort study. We evaluated the significance of simultaneous measurement of 2 tumor markers in the diagnosis of HCC in China, Japan and Korea. Two markers for HCC, AFP and HCCR-1, were measured in the sera obtained from 1,338 patients at the time of initial diagnosis of HCC. Of the 1338 HCC patients, 616 (46%) and 686 (51.3%) were sero-positive for AFP and HCCR-1, respectively. The positive rate for HCC was increased up to 74.1% in combined use of AFP and HCCR-1. Many cases (54%) for AFP-negative HCC were positive for HCCR-1 and vice versa. More importantly, the diagnostic rate for small HCC (< 2 cm) was signiﬁcantly improved in the combined analysis of AFP and HCCR-1 to 56.9% although it was only 40.1% and 23.4% in the single analysis of HCCR-1 and AFP, respectively. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be signiﬁcantly improved in the combined use of HCCR-1 and AFP.
Nanoscaffolds for Guided Cardiac Repair: The New Therapeutic Challenge of Regenerative Medicine
Authors: Ventrelli Letizia , Ricotti Leonardo , Menciassi Arianna , Mazzolai Barbara , Mattoli Virgilio
Published: June 2013

Cardiovascular diseases represent the leading cause of death and disability in the world. At the end‐stage of heart failure, heart transplantation remains the ultimate option. Therefore, due to the numerous drawbacks associated with this procedure, new alternative strategies to repair the wounded heart are required. Cell therapy is a potential option to regenerate functional myocardial tissue. The characteristics of the ideal cardiac cell therapy include the use of the proper cell type and delivery methods as well as the choice of a suitable biomaterial acting as a cellular vehicle. Since traditional delivery methods are characterized by several counter backs, among which low cell survival, new engineered micro‐ and nanostructured materials are today extensively studied to provide a good cardiac therapy. In this review, we report the most recent achievements in the field of cell therapy for myocardial infarction treatment and heart regeneration, focusing on the most commonly used cell sources, the traditional approaches used to deliver cells at the damaged site, and a series of novel technologies based on recent advancements of bioengineering, highlighting the tremendous potential that nanoscaffolds have in this framework.
Mechanisms of Chronic State of Inflammation as Mediators That Link Obese Adipose Tissue and Metabolic Syndrome
Authors: Fuentes Eduardo , Fuentes Francisco , Vilahur Gemma , Badimon Lina , Palomo Iván
Published: June 2013

The metabolic syndrome is a cluster of cardiometabolic alterations that include the presence of arterial hypertension, insulin resistance, dyslipidemia, and abdominal obesity. Obesity is associated with a chronic inflammatory response, characterized by abnormal adipokine production, and the activation of proinflammatory signalling pathways resulting in the induction of several biological markers of inflammation. Macrophage and lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Adiponectin can either act directly on macrophages to shift polarization and/or prime human monocytes into alternative M2-macrophages with anti-inflammatory properties. Meanwhile, the chronic inflammation in adipose tissue is regulated by a series of transcription factors, mainly PPARs and C/EBPs, that in conjunction regulate the expression of hundreds of proteins that participate in the metabolism and storage of lipids and, as such, the secretion by adipocytes. Therefore, the management of the metabolic syndrome requires the development of new therapeutic strategies aimed to alter the main genetic pathways involved in the regulation of adipose tissue metabolism.
Recombinant Varicella-Zoster Virus Vaccines as Platforms for Expression of Foreign Antigens
Authors: Gray Wayne L.
Published: June 2013

Varicella-zoster virus (VZV) vaccines induce immunity against childhood chickenpox and against shingles in older adults. The safety, efficacy, and widespread use of VZV vaccines suggest that they may also be effective as recombinant vaccines against other infectious diseases that affect the young and the elderly. The generation of recombinant VZV vaccines and their evaluation in animal models are reviewed. The potential advantages and limitations of recombinant VZV vaccines are addressed.
eNOS Gene Variants and the Risk of Premature Myocardial Infarction
Authors: Zigra Aggeliki-Maria , Rallidis Loukianos S. , Anastasiou Georgia , Merkouri Efrossyni , Gialeraki Argyri
Published: June 2013

BACKGROUND: Endothelial nitric oxide synthase (eNOS) as well as nitric oxide play an important role in the regulation of cardiovascular function. There are limited and controversial data regarding the impact of polymorphisms of eNOS gene that is implicated in the vasoconstrictive properties of the endothelium in the pathogenesis of premature myocardial infarction (MI).

OBJECTIVE: We examined whether two common polymorphisms of eNOS gene (G894T and T786C) are associated with the development of premature MI.

METHODS: We recruited 107 patients with premature MI and compared them to 103 age- and sex- matched controls. All patients underwent coronary angiogram and were classified into the subgroup of patients with ‘normal’ or ‘near normal’ coronary arteries and the subgroup of patients with significant coronary artery disease (≥ 50% stenosis in lumen diameter of coronary arteries). The genetic polymorphisms of eNOS gene were assayed with polymerase chain reaction and reverse hybridization.

RESULTS: Nineteen patients (17.8%) had ‘normal’ or ‘near normal’ coronary arteries. A significantly higher frequency of homozygosity for the 786C (32%) and the 894T (21%) alleles of the eNOS gene in patients who develop early MI in the setting of angiographically 'normal' or 'near normal' coronary arteries were found.

CONCLUSIONS: Our data suggest that the T786C and the G894T genetic polymorphisms are associated with the development of MI in very young individuals, whose coronary arteries are characterized by very small atheromatic burden.
Detecting and Defending against Replication Attacks in Wireless Sensor Networks
Authors: Chen Xiang-yi , Meng Li-xia , Zhan Yong-zhao
Published: June 2013

Wireless sensor networks are susceptible to node replication attacks due to their unattended nature. Existing replicas detection schemes can be further improved in regard of detection probabilities, detection overheads, and the balance of detection overheads among sensor nodes. In this paper, we make the following contributions: first, we point out the unrealistic assumption that the replica node would behave honestly as the benign sensor nodes; thus the existing detection schemes would fail if the replica nodes cheat or collude with the compromised node. Then, we propose a location-binding symmetric key scheme forcing the replica nodes to be inserted only in the vicinity of the compromised node. Later, a detecting scheme is presented to inspect the location claims within the neighborhood. Finally, analysis shows that our scheme helps to detect and defend against replication attacks effectively and efficiently. Extensive simulations are conducted and the results show that the detection overheads are low and evenly distributed among all the sensor nodes.
The Search for a Genetic Factor Associating with Immune Restoration Disease in HIV Patients Co-Infected withMycobacterium tuberculosis
Authors: Affandi Jacquita S. , Kumar Manoj , Agarwal Upasna , Singh Sarman , Price Patricia
Published: June 2013

BACKGROUND: Up to 43% of HIV-infected patients co-infected withMycobacterium tuberculosisexperience exacerbations of tuberculosis (TB) after commencing antiretroviral therapy (ART). These are termed immune restoration disease (IRD). It is unclear why individual susceptibility varies.

OBJECTIVE: We investigate if single nucleotide polymorphisms (SNP) in genes encoding cytokines, chemokines and their receptors associate with development of an IRD event in patients of two different ethnicities.

METHODS: DNA samples were available from small well-characterised groups of HIV patients treated in Cambodia (TB-IRD,n= 17; HIV+TB+controls, n = 55) and India (TB-IRD,n= 19; HIV+TB+controls,n= 43). HIV patients with a TB diagnosis but no evidence of IRD were included to control for susceptibility to TB per se. Sixteen SNP implicated in inflammation or mycobacterial disease were genotyped.

RESULTS: Susceptibility to TB-IRD associated with carriage of TNFA-1031*T (rs1799964;P=0.05) and SLC11A1 D543N*G (rs17235409;P=0.04) in Cambodian patients and carriage of IL18-607*G (rs1946518;P=0.02) and VDR FokI (F/f)*T (rs10735810;P=0.05) in Indian patients.

CONCLUSIONS: Associations between polymorphisms in immune-related genes and TB-IRD were found, but none were common across two ethnicities.
Crosstalk between Endoplasmic Reticulum Stress and Protein Misfolding in Neurodegenerative Diseases
Authors: Pereira Cláudia M. F.
Published: June 2013

Under physiological conditions, the endoplasmic reticulum (ER) is a central subcellular compartment for protein quality control in the secretory pathway that prevents protein misfolding and aggregation. Instrumental in protein quality control in the ER is the unfolded protein response (UPR), which is activated upon ER stress to reestablish homeostasis through a sophisticated transcriptionally and translationally regulated signaling network. However, this response can lead to apoptosis if the stress cannot be alleviated. The presence of abnormal protein aggregates containing specific misfolded proteins is recognized as the basis of numerous human conformational disorders, including neurodegenerative diseases. Here, I will highlight the overwhelming evidence that the presence of specific aberrant proteins in Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), prion diseases, and Amyotrophic Lateral Sclerosis (ALS) is intimately associated with perturbations in the ER protein quality control machinery that become incompetent to restore protein homeostasis and shift adaptive programs toward the induction of apoptotic signaling to eliminate irreversibly damaged neurons. Increasing our understanding about the deadly crosstalk between ER dysfunction and protein misfolding in these neurodegenerative diseases may stimulate the development of novel therapeutic strategies able to support neuronal survival and ameliorate disease progression.
Understanding the Complexity of Temperature Dynamics in Xinjiang, China, from Multitemporal Scale and Spatial Perspectives
Authors: Xu Jianhua , Chen Yaning , Li Weihong , Liu Zuhan , Wei Chunmeng , Tang Jie
Published: June 2013

Based on the observed data from 51 meteorological stations during the period from 1958 to 2012 in Xinjiang, China, we investigated the complexity of temperature dynamics from the temporal and spatial perspectives by using a comprehensive approach including the correlation dimension (CD), classical statistics, and geostatistics. The main conclusions are as follows (1) The integer CD values indicate that the temperature dynamics are a complex and chaotic system, which is sensitive to the initial conditions. (2) The complexity of temperature dynamics decreases along with the increase of temporal scale. To describe the temperature dynamics, at least 3 independent variables are needed at daily scale, whereas at least 2 independent variables are needed at monthly, seasonal, and annual scales. (3) The spatial patterns of CD values at different temporal scales indicate that the complex temperature dynamics are derived from the complex landform.