Search results for: atherosclerotic biomarkers

Authors: Von Jerick Tenorio, Jonald Lucero, Marivic Vestal, Edwin Tiempo

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In patients with hostile aortic neck anatomy, the risks of proximal seal complications and stent migration remain with EVAR despite improved endograft technology. This case report discusses how the technical challenges of the hostile neck anatomy, proximal penetrating atherosclerotic ulcer (PAU) and tortuous femoral access were addressed. The CT aortogram of a 63-year-old hypertensive and diabetic man with recurring abdominal discomfort revealed a fusiform infra-renal aneurysm measuring 8.8 cm in length and 5.7 cm in diameter. The proximal landing zone only has a 3 mm healthy neck with a conicity of > 10% and a thrombus of 4 mm thick. Proximal to the aneurysm is a PAU with a circumferential mural thrombus. The right femoral artery is tortuous with > 90o angulation. A 20% oversized Endurant II endograft and Aptus Heli-FX EndoAnchors were deployed as prophylaxis for type I endoleaks and endograft migration consequent to the conical neck and proximal aneurysm extension consequent to the PAU. A stiff Backup Meier guide wire facilitated the deployment of the endograft. Coil embolization of the right internal iliac artery was performed as prophylaxis for type II endoleaks. EndoAnchors can be used as an adjunct to EVAR as prophylaxis for proximal seal complications and stent migration in patients with hostile aortic aneurysm neck anatomy and concomitant proximal PAU.

Keywords: endoAnchors, endoleaks, EVAR, hostile neck

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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Authors: Syed Mamoon Siyar, Fayaz Ali, Sajjad Ahmad, Samina Jahandad, George Kontakiotis, Hammad T. Janjuhah, Assimina Antonarakou, Waqas Naseem

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The Cretaceous Chichali Formation in the Chanda-01, Chanda-02, Chanda-03 and Mela-05 wells and the oil samples from Chanda-01 and Chanda-01 wells located in the Kohat Basin, Pakistan, were analyzed with the objectives of evaluating the hydrocarbon generation potential, source, thermal maturity and depositional of organic matter, and oil-source correlation by employing geochemical screening techniques and biomarker studies. The total organic carbon (TOC) values in Chanda-02, Chanda-03 and Mela-05 indicate, in general, poor to fair, fair and fair to good source rock potential with low genetic potential, respectively. The nature of organic matter has been determined by standard cross plots of Rock Eval pyrolysis parameters, indicating that studied cuttings from the Chichali Formation dominantly contain type III kerogen at present and show maturity for oil generation in the studied wells. The organic petrographic study also confirmed the vitrinite (type III) as a major maceral in the investigated Chichali Shales and its reflectance values show maturity for oil. The different ratios of non-biomarkers and biomarkers i.e., steranes, terpenes and aromatics parameters, indicate the marine source of organic matter deposited in the anoxic environment for the Chichali Formation in Chanda-01 and Chanda-02 wells and mixed source input of organic matter deposited in suboxic conditions for oil in the same wells. The CPI, and different biomarkers parameters such as C29 S/S+R, ββ/αα+ββ), M29/H30, Ts/Ts+Tm, H31 (S/S+R) and aromatic compounds methyl phenanthrene index (MPI) and organic petrographic analysis (vitrinite reflectance) suggest mature stage of oil generation for Chichali Shales and oil samples in the study area with little high thermal maturity in case of oils. Based on source and thermal maturity biomarkers and non-biomarkers parameters, the produced oils have no correlation with the Cretaceous Chichali Formation in the studied Chanda-01 and Chanda-02 wells in Kohat Basin, Pakistan, but it has been suggested that these oils have been generated by the strata containing high terrestrial organic input compare to Chichali Shales.

Keywords: Organic geochemistry, Chichali Shales and crude oils, Kohat Basin, Pakistan

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Authors: Andleeb Zahra, Itrat Rubab, Sumaira Malik, Amina Khan, Muhammad Jawad Khan, M. Qaiser Fatmi

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Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Recent studies have highlighted the role of miRNA in disease pathology, indicating its potential use in an early diagnostic tool. miRNAs are small, double stranded, non-coding RNAs that regulate gene expression by deregulating mRNAs. miRNAs play important roles in modifying various cellular processes such as cell growth, differentiation, apoptosis, and immune response. Dis-regulated expression of miRNAs is known to affect the cell growth, and this may function as tumor suppressors or oncogenes in various cancers. Objectives: The main objectives of this study were to characterize the extracellular miRNAs involved in oral cancer (OC) to assist early detection of cancer as well as to propose a list of genes that can potentially be used as biomarkers of OC. We used gene expression data by microarrays already available in literature. Materials and Methods: In the first step, a total of 318 miRNAs involved in oral carcinoma were shortlisted followed by the prediction of their target genes. Simultaneously, the differentially expressed genes (DEGs) of oral carcinoma from all experiments were identified. The common genes between lists of DEGs of OC based on experimentally proven data and target genes of each miRNA were identified. These common genes are the targets of specific miRNA, which is involved in OC. Finally, a list of genes was generated which may be used as biomarker of OC. Results and Conclusion: In results, we included some of pathways in cancer to show the change in gene expression under the control of specific miRNA. Ingenuity pathway analysis (IPA) provided a list of major biomarkers like CDH2, CDK7 and functional enrichment analysis identified the role of miRNA in major pathways like cell adhesion molecules pathway affected by cancer. We observed that at least 25 genes are regulated by maximum number of miRNAs, and thereby, they can be used as biomarkers of OC. To better understand the role of miRNA with respect to their target genes further experiments are required, and our study provides a platform to better understand the miRNA-OC relationship at genomics level.

Keywords: biomarkers, gene expression, miRNA, oral carcinoma

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Authors: Wenjun Zhang, Yunqing Du, Steven W. Cranford, Ming L. Wang

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The beginning of 21st century has witnessed new advancements in the design and use of new materials for biosensing applications, from nano to macro, protein to tissue. Traditional analytical methods lack a complete toolset to describe the complexities introduced by living systems, pathological relations, discrete hierarchical materials, cross-phase interactions, and structure-property dependencies. Materiomics – via systematic molecular dynamics (MD) simulation – can provide structure-process-property relations by using a materials science approach linking mechanisms across scales and enables oriented biosensor design. With this approach, DNA biosensors can be utilized to detect disease biomarkers present in individuals’ breath such as acetone for diabetes. Our wireless sensor array based on single-stranded DNA (ssDNA)-decorated single-walled carbon nanotubes (SWNT) has successfully detected trace amount of various chemicals in vapor differentiated by pattern recognition. Here, we present how MD simulation can revolutionize the way of design and screening of DNA aptamers for targeting biomarkers related to oral diseases and oral health monitoring. It demonstrates great potential to be utilized to build a library of DNDA sequences for reliable detection of several biomarkers of one specific disease, and as well provides a new methodology of creating, designing, and applying of biosensors.

Keywords: biosensor, DNA, biomarker, molecular dynamics simulation

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Authors: P. S. Seboletswe, Z. Mkhize, L. M. Katata-Seru

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Protorhus longifolia is known as a medicinal plant that has been used traditionally to treat various ailments such as hemiplegic paralysis, blood clotting related diseases, diarrhoea, heartburn, etc. The study reports a High-Performance Thin Layer Chromatography (HPTLC) fingerprint profile of Protorhus longifolia methanolic extract and its qualitative analysis of gallic acid, rutin, and quercetin. HPTLC analysis was achieved using CAMAG HPTLC system equipped with CAMAG automatic TLC sampler 4, CAMAG Automatic Developing Chamber 2 (ADC2), CAMAG visualizer 2, CAMAG Thin Layer Chromatography (TLC) scanner and visionCATS CAMAG HPTLC software. Mobile phase comprising toluene, ethyl acetate, formic acid (21:15:3) was used for qualitative analysis of gallic acid and revealed eight peaks while the mobile phase containing ethyl acetate, water, glacial acetic acid, formic acid (100:26:11:11) for qualitative analysis of rutin and quercetin revealed six peaks. HPTLC sillica gel 60 F254 glass plates (10 × 10) were used as the stationary phase. Gallic acid was detected at the R_f = 0.35; while rutin and quercetin were not evident in the extract. Further studies will be performed to quantify gallic acid in Protorhus longifolia leaves and also identify other biomarkers.

Keywords: biomarkers, fingerprint profiling, gallic acid, HPTLC, Protorhus longifolia

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Authors: Simona Capossela, Ramona Schaniel, Singer Franziska, Aquino Fournier Catharine, Daniel Stekhoven, Jivko Stoyanov

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A spinal cord injury (SCI) is a traumatic life event that often results in ageing associated health conditions such as muscle mass decline, adipose tissue increase, decline in immune function, frailty, systemic chronic inflammation, and psychological distress and depression. Psychological, oxidative, and metabolic stressors may facilitate accelerated ageing in the SCI population with reduced life expectancy. Research designs using biomarkers of aging and stress are needed to elucidate the role of psychological distress in accelerated aging. The aim of this project is a feasibility pilot study to observe changes in stress biomarkers and correlate them with aging markers in SCI patients during their first rehabilitation (longitudinal cohort study). Biological samples were collected in the SwiSCI (Swiss Spinal Cord Injury Cohort Study) Biobank in Nottwil at 4 weeks±12 days after the injury (T1) and at the end of the first rehabilitation (discharge, T4). The "distress thermometer" is used as a selfassessment tool for psychological distress. Stress biomarkers, as cortisol and protein carbonyl content (PCC), and markers of cellular aging, such as telomere lengths, will be measured. 2 Preliminary results showed that SCI patients (N= 129) are still generally distressed at end of rehabilitation, however we found a statistically significant (p< 0.001) median decrease in distress from 6 (T1) to 5 (T4) during the rehabilitation. In addition, an explorative transcriptomics will be conducted on N=50 SCI patients to compare groups of persons with SCI who have different trajectories of selfreported distress at the beginning and end of the first rehabilitation after the trauma. We identified 4 groups: very high chronic stress (stress thermometer values above 7 at T1 and T4; n=14); transient stress (high to low; n=14), low stress (values below 5 at T1 and T4; n=14), increasing stress (low to high; n=8). The study will attempt to identify and address issues that may occur in relation to the design and conceptualization of future study on stress and aging in the SCI population.

Keywords: stress, aging, spinal cord injury, biomarkers

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Authors: M. G. Tanga, P. B. Telefo, D. N. Tarla

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Even though the WHO, the EPA and other regulatory bodies have recognized the effects of acute pesticide poisoning little data exists on health effects after long-term low-dose exposures especially in Africa and Cameroon. The aim of this study was to evaluate the impact of pesticides on the hepatic functions of market gardeners in the Western Region of Cameroon by studying some biochemical parameters. Sixty six male market gardeners in Foumbot, Massangam, and Bantoum were interviewed on their health status, habits and pesticide use in agriculture, including the spray frequency, application method, and pesticide dosage. Thirty men with no history of pesticide exposure were recruited as control group. Thereafter, their blood samples were collected for assessment of hepatic function biomarkers (ALT, AST, and albumin). The results showed that 56 pesticides containing 25 active ingredients were currently used by market gardeners enrolled in our study and most of their symptoms (headache, fatigue, skin rashes, eye irritation, and nausea) were related to the use of these chemicals. Compared to the control subjects market gardeners’ ALT levels (32.9 ± 7.19 UL-1 vs. 82.11 ± 35.40 UL-1; P < 0.001) and, AST levels (40.63 ± 6.52 UL-1 vs. 112.11 UL-1 ± 47.15 UL-1; P < 0.001) were significantly increased. These results suggest that liver function tests can be used as biomarkers to indicate toxicity before overt clinical signs occur. The market gardeners’ chronic exposure to pesticides due to poor application measures could lead to hepatic function impairment. Further research on larger scale is needed to confirm these findings and to establish a mechanism of toxicity.

Keywords: biomarkers, liver, pesticides, occupational exposure

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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Authors: Ceyda Dadali, Yeşim Elmaci

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Coffee was introduced as an economic crop during the fifteenth century; nowadays it is the most important food commodity ranking second after crude oil. Desirable sensory properties make coffee one of the most often consumed and most popular beverages in the world. The coffee preparation method has a significant effect on flavor and composition of coffee brews. Three different extraction methodologies namely decoction, infusion and pressure methods have been used for coffee brew preparation. Each of these methods is related to specific granulation (coffee grind) of coffee powder, water-coffee ratio temperature and brewing time. Coffee is a mixture of 1500 chemical compounds. Chemical composition of coffee highly depends on brewing methods, coffee bean species and roasting time-temperature. Coffee contains a wide number of very important bioactive compounds, such as diterpenes: cafestol and kahweol, alkaloids: caffeine, theobromine and trigonelline, melanoidins, phenolic compounds. The phenolic compounds of coffee include chlorogenic acids (quinyl esters of hidroxycinnamic acids), caffeic, ferulic, p-coumaric acid. In coffee caffeoylquinic acids, feruloylquinic acids and di-caffeoylquinic acids are three main groups of chlorogenic acids constitues 6% -10% of dry weight of coffee. The bioavailability of chlorogenic acids in coffee depends on the absorption and metabolization to biomarkers in individuals. Also, the interaction of coffee polyphenols with other compounds such as dietary proteins affects the biomarkers. Since bioactive composition of coffee depends on brewing methods effect of coffee brewing method on bioactive compounds of coffee will be discussed in this study.

Keywords: bioactive compounds of coffee, biomarkers, coffee brew, effect of brewing

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Authors: Abdollah Sobhani, Hossein Vaseghi-Dodaran

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Proteomics is defined as the study of the component of a cell, tissue and biological fluid. This technique has the potential to identify protein biomarkers of a disease states. In this study which was performed on bovine ovarian follicular cysts (BOFC), eight proteins are over expressed in BOFC that these proteins could be useful biomarkers for BOFC. The difference between serum proteome pattern cows affected by postpartum endometritis with healthy cows revealed that concentrations orosomucoid was decreased in endometritis. The comparison proteome of brucella abortus between laboratory adapted strains and clinical isolates could be useful to better understand this disease and vaccine development. Proteomics experiments identified new proteins and pathways that may be important in future hypothesis-driven studies of glucocorticoid-induced immunosuppression. Understanding the molecular mechanisms of effective parameters on male fertility is essential for obtaining high reproductive efficiency by decreasing cost and time. The investigations on proteome of high fertility spermatozoa indicated that expression of some proteins such as casein kinase 2 (CKII) prime poly peptide and tyrosine kinase in high fertility spermatozoa was higher compared to low fertility spermatozoa. Also, some evidence has indicated that variation in protein types and amounts in seminal fluid regulates fertility indexes in dairy bull. In conclusion, proteomics is a useful technique for discovering drugs, vaccine development, and diagnosis disease by biomarkers and improvement of reproduction efficiency.

Keywords: proteomics, reproduction, biomarker, immunity

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Authors: Noreen Noreen, Aamir Ijaz, Hamza Akhtar

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Background: Screening plays a major role to detect chromosomal abnormalities, Down syndrome, neural tube defects and other inborn diseases of the newborn. Serum biomarkers in the second trimester are useful in determining risk of most common chromosomal anomalies; these test include Alpha-fetoprotein (AFP), Human chorionic gonadotropin (hCG), Unconjugated Oestriol (UEȝ)and inhibin-A. Quadruple biomarkers are worth test in diagnosing the congenital pathology during pregnancy, these procedures does not form a part of routine health care of pregnant women in Pakistan, so the median value is lacking for population in Pakistan. Objective: To determine median values of biochemical maternal serum markers in local population during second trimester maternal screening. Study settings: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP) Rawalpindi. Methods: Cross-Sectional study for estimation of reference values. Non-probability consecutive sampling, 155 healthy pregnant women, of 30-40 years of age, will be included. As non-parametric statistics will be used, the minimum sample size is 120. Result: Total 155 women were enrolled into this study. The age of all women enrolled ranged from 30 to39 yrs. Among them, 39 per cent of women were less than 34 years. Mean maternal age 33.46±2.35 SD and maternal body weight were 54.98±2.88. Median value of quadruple markers calculated from 15-18th week of gestation that will be used for calculation of MOM for screening of trisomy21 in this gestational age. Median value at 15 week of gestation were observed hCG 36650 mIU/ml, AFP 23.3 IU/ml, UEȝ 3.5 nmol/L, InhibinA 198 ng/L, at 16 week of gestation hCG 29050 mIU/ml, AFP 35.4 IU/ml, UEȝ 4.1 nmol/L, InhibinA 179 ng/L, at 17 week of gestation hCG 28450 mIU/ml, AFP 36.0 IU/ml, UEȝ 6.7 nmol/L, InhibinA 176 ng/L and at 18 week of gestation hCG 25200 mIU/ml, AFP 38.2 IU/ml, UEȝ 8.2 nmol/L, InhibinA 190 ng/L respectively.All the comparisons were significant (p-Value <0.005) with 95% confidence Interval (CI) and level of significance of study set by going through literature and set at 5%. Conclusion: The median values for these four biomarkers in Pakistani pregnant women can be used to calculate MoM.

Keywords: screening, down syndrome, quadruple test, second trimester, serum biomarkers

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Authors: Ae Ra Han, Taek Hoo Lee, Sun Zoo Kim, Hwa Young Lee

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Introduction: Ovarian endometrioma is one of the important causes of poor ovarian reserve and up to half of them have recurred. However, the treatment for recurrence prevention has limited efficiency and repeated surgical management makes worsen the ovarian reserve. To find better management for recurrence prevention, we investigated risk factors and biomarkers for the recurrence of ovarian endometrioma. Methods: The medical records of women with the history of surgical dissection for ovarian endometrioma were collected. After exclusion of the cases with concurrent hysterectomy, been menopaused during follow-up, incomplete medical record, and loss of follow-up, a total of 134 women were enrolled. Immunohistochemical staining for progesterone receptor isoform B (PR-B) and nuclear factor kappa B (NFκB) was done with the fixed tissue blocks of their endometriomas which were collected at the time of surgery. Results: Severity of dysmenorrhea and co-existence of adenomyosis had significant correlation with recurrence of endometrioma. Increased PR-B (P = .041) and decreased NFκB (P = .036) immunoreactivity were found in recurrent group. Serum CA-125 level at the time of recurrence was higher than the highest level of CA-125 during follow-up in unrecurred group (55.6 vs. 21.3 U/mL, P = .014). Conclusion: We found that the severity of dysmenorrhea and coexistence of adenomyosis are risk factors for recurrence of ovarian endometrioma, and serial follow-up of CA-125 is effective to detect and prevent the recurrence. However, to determine the possibility of immunoreactivity of PR-B and NFκB as biomarkers for ovarian endometrioma, further studies of various races and large numbers with prospective design are needed.

Keywords: endometriosis, recurrence, biomarker, risk factor

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Authors: Neda Valizadeh, Soudabeh Shafiee Ardestani, Arvin Najafi

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Objectives: The aim of this study is to evaluate the association of mid-regional pro-atrial natriuretic peptide (MRproANP), procalcitonin (PCT), proendothelin-1 (proET-1) levels with sepsis severity in Emergency ward patients. Materials and Methods: We assessed the predictive value of MRproANP, PCT, copeptin, and proET-1 in early sepsis among patients referring to the emergency ward with a suspected sepsis. Results-132 patients were enrolled in this study. 45 (34%) patients had a final diagnosis of sepsis. A higher percentage of patients with definite sepsis had systemic inflammatory response syndrome (SIRS) criteria at initial visit in comparison with no-sepsis patients (P<0.05) and were admitted to the hospital (P<0.05). PCT levels were higher in sepsis patients [P<0.05]. There was no significant differences for MRproANP or proET-1 in sepsis patients (P=0.47). Conclusion: A combination of SIRS criteria and PCT levels is beneficial for the early sepsis diagnosis in emergency ward patients with a suspicious infection disease.

Keywords: emergency, prolactin, sepsis, biomarkers

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Authors: Wael El-Deeb

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The present study aimed to investigate the diagnostic importance of acute phase proteins in urinary tract infection (UTI) in cattle. We describe the clinical, bacteriological and biochemical findings in 99 lactating cows. Blood and urine samples from diseased (n=84) and control healthy cows (n=15) were submitted to laboratory investigations. The urine analysis revealed hematuria and pyuria in UTI group. The isolated bacteria were E.coli (43/84) Corynebacterium spp, (31/84), Proteus spp. (6/84) and Streptococcus spp (4/84). The concentrations of Haptoglobin (Hp), serum amyloid A (SAA), α1-Acid glycoprotein (AGP), fibrinogen (Fb), total protein, albumen, and globulin were higher in cows with UTI when compared to healthy ones. Fifty-one of 84 cows with UTI were successfully treated. The levels of Hp, SAA, AGP, total protein, and globulin were associated with the odds of treatment failure. Conclusively, acute phase proteins could be used as diagnostic and prognostic biomarkers in cows with UTI.

Keywords: cows, urinary, infections, haptoglobin, serum Amyloid A

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Authors: B. B. Siswanto, A. Halimi, K. M. H. J. Tandayu, C. Abdillah, F. Nanda , E. Chandra

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Nowadays, modern cardiac biomarkers, such as ST2 and NT-proBNP, have important roles in predicting morbidity and mortality in heart failure patients. Abnormalities of serum electrolytes, sepsis or infection, and deteriorating renal function will worsen the conditions of patients with heart failure. It is intriguing to know whether cardiac biomarkers elevations are affected by laboratory findings in heart failure patients. We recruited 65 patients from the heart failure clinic in NCVC Harapan Kita in 2014-2015. All of them have consented for laboratory examination, including cardiac biomarkers. The findings were recorded in our Research and Development Centre and analyzed using linear regression to find whether there is a relationship between laboratory findings (sodium, potassium, creatinine, and leukocytes) and ST2 or NT-proBNP. From 65 patients, 26.9% of them are female, and 73.1% are male, 69.4% patients classified as NYHA I-II and 31.6% as NYHA III-IV. The mean age is 55.7+11.4 years old; mean sodium level is 136.1+6.5 mmol/l; mean potassium level is 4.7+1.9 mmol/l; mean leukocyte count is 9184.7+3622.4 /ul; mean creatinine level is 1.2+0.5 mg/dl. From linear regression logistics, the relationship between NT-proBNP and sodium level (p<0.001), as well as leukocyte count (p=0.002) are significant, while NT-proBNP and potassium level (p=0.05), as well as creatinine level (p=0.534) are not significant. The relationship between ST2 and sodium level (p=0.501), potassium level (p=0.76), leukocyte level (p=0.897), and creatinine level (p=0.817) are not significant. To conclude, laboratory findings are more sensitive in predicting NT-proBNP elevation than ST2 elevation. Larger studies are needed to prove that NT-proBNP correlation with laboratory findings is more superior than ST2.

Keywords: heart failure, laboratory, NT-proBNP, ST2

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Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

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Authors: H. Haseena Banu, D. Karthick, R. Stalin, E. Nandha Kumar, T. P. Sachidanandam, P. Shanthi

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Background of the study: Type 2 diabetes is emerging as the predominant metabolic disorder in the world among adults characterized mainly by the resistance of the insulin sensitive tissues towards insulin followed by the decrease in the insulin secretion. The treatment for this disease usually involves treatment with oral synthetic drugs which are known to cause several side effects. Therefore, identification of new biomarkers as therapeutic target is the need of the hour. miRNAs are small, non–protein-coding RNAs that negatively regulate gene expression by promoting degradation and/or inhibit the translation of target mRNAs and have emerged as biomarkers in predicting diabetes mellitus. Objective of the study: To elucidate the therapeutic role of gallic acid in modulating the alterations in glucose metabolism induced by miRNAs 194 and 135a in Type 2 diabetic rats. Materials and Methods: T2D was induced in rats by feeding them with a high fat diet for 2 weeks followed by intraperitoneal injection of 35 mg/kg/body weight (b.wt.) of streptozotocin. Microarrays were used to assess the expression of miRNAs in control, diabetic and gallic acid treated rats. Gene expression studies were carried out by RT PCR analysis. Results: Forty one miRNAs were differentially expressed in Type 2 diabetic rats. Among these, the expression of miRNA 194 was significantly decreased whereas miRNA 135a was significantly increased in Type 2 diabetic rats. The glucose metabolism was also altered significantly in skeletal muscle of Type 2 diabetic rats. Conclusion: T2D is associated with alterations in the expression of miRNAs in skeletal muscle. Both these miRNAs 194 and 135a play an important role in glucose metabolism in skeletal muscle of diabetic rats. Gallic acid effectively ameliorated the alterations in glucose metabolism. Hence, both these miRNAs can serve as biomarkers and therapeutic targets in diabetes mellitus. The study also establishes the role of gallic acid as therapeutic agent. Acknowledgment: The financial assistance provided in the form of ICMR women scientist by ICMR DHR INDIA is gratefully acknowledged here.

Keywords: gallic acid, high fat diet, type 2 diabetes mellitus, miRNAs

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Authors: Shu-Pin Huang, Pai-Chi Teng, Hao-Han Chang, Chia-Hsin Liu, Yung-Lun Lin, Shu-Chi Wang, Hsin-Chih Yeh, Chih-Pin Chuu, Jiun-Hung Geng, Li-Hsin Chang, Wei-Chung Cheng, Chia-Yang Li

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The emergence of immune checkpoint inhibitors (ICIs) targeting proteins like PD-1 and PD-L1 has changed the treatment paradigm of bladder cancer. However, not all patients benefit from ICIs, with some experiencing early death. There's a significant need for biomarkers associated with the PD-1 pathway in bladder cancer. Current biomarkers focus on tumor PD-L1 expression, but a more comprehensive understanding of PD-1-related biology is needed. Our study has developed a seven-gene risk score panel, employing a comprehensive bioinformatics strategy, which could serve as a potential prognostic and predictive biomarker for bladder cancer. This panel incorporates the FYN, GRAP2, TRIB3, MAP3K8, AKT3, CD274, and CD80 genes. Additionally, we examined the relationship between this panel and immune cell function, utilizing validated tools such as ESTIMATE, TIDE, and CIBERSORT. Our seven-genes panel has been found to be significantly associated with bladder cancer survival in two independent cohorts. The panel was also significantly correlated with tumor infiltration lymphocytes, immune scores, and tumor purity. These factors have been previously reported to have clinical implications on ICIs. The findings suggest the potential of a PD-1 pathway-based transcriptomic panel as a prognostic and predictive biomarker in bladder cancer, which could help optimize treatment strategies and improve patient outcomes.

Keywords: bladder cancer, programmed cell death protein 1, prognostic biomarker, immune checkpoint inhibitors, predictive biomarker

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Authors: V. Kuzhandai Velu, R. Ramesh

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Background and objectives: Acute myocardial infarction (AMI) is the most common cause of mortality and morbidity. Over the last decade, microRNAs (miRs) have emerged as a potential marker for detecting AMI. The current study evaluates the kinetics and importance of miRs in the differential diagnosis of ST-segment elevated MI (STEMI) and non-STEMI (NSTEMI) and its correlation to conventional biomarkers and to predict the immediate outcome of AMI for arrhythmias and left ventricular (LV) dysfunction. Materials and Method: A total of 100 AMI patients were recruited for the study. Routine cardiac biomarker and miRNA levels were measured during diagnosis and serially at admission, 6, 12, 24, and 72hrs. The baseline biochemical parameters were analyzed. The expression of miRs was compared between STEMI and NSTEMI at different time intervals. Diagnostic utility of miR-1, miR-133, miR-208, and miR-499 levels were analyzed by using RT-PCR and with various diagnostics statistical tools like ROC, odds ratio, and likelihood ratio. Results: The miR-1, miR-133, and miR-499 showed peak concentration at 6 hours, whereas miR-208 showed high significant differences at all time intervals. miR-133 demonstrated the maximum area under the curve at different time intervals in the differential diagnosis of STEMI and NSTEMI which was followed by miR-499 and miR-208. Evaluation of miRs for predicting arrhythmia and LV dysfunction using admission sample demonstrated that miR-1 (OR = 8.64; LR = 1.76) and miR-208 (OR = 26.25; LR = 5.96) showed maximum odds ratio and likelihood respectively. Conclusion: Circulating miRNA showed a highly significant difference between STEMI and NSTEMI in AMI patients. The peak was much earlier than the conventional biomarkers. miR-133, miR-208, and miR-499 can be used in the differential diagnosis of STEMI and NSTEMI, whereas miR-1 and miR-208 could be used in the prediction of arrhythmia and LV dysfunction, respectively.

Keywords: myocardial infarction, cardiac biomarkers, microRNA, arrhythmia, left ventricular dysfunction

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Authors: Miao Zhang, Limin Liu, Feng Zhi, Panpan Niu, Mengya Yang, Xuemei Zhu, Ying Diao, Jun Wang, Ying Zhao

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Background and Aims: Clinical studies have demonstrated that serum semicarbazide-sensitive amine oxidase (SSAO) activities positively correlate with the progression of atherosclerosis. The aim of the present study is to investigate the effect of SSAO inactivation on the development of atherosclerosis. Methods: Female LDLr knockout (KO) mice were given the Western-type diet for 6 and 9 weeks to induce the formation of early and advanced lesions, and semicarbazide (SCZ, 0.125%) was added into the drinking water to inactivate SSAO in vivo. Results: Despite no impact on plasma total cholesterol levels, abrogation of SSAO by SCZ not only resulted in the enlargement of both early (1.5-fold, p=0.0043) and advanced (1.8-fold, p=0.0013) atherosclerotic lesions, but also led to reduced/increased lesion contents of macrophages/smooth muscle cells (SMCs) (macrophage: ~0.74-fold, p=0.0002(early)/0.0016(advanced); SMC: ~1.55-fold, p=0.0003(early) /0.0001(advanced)), respectively. Moreover, SSAO inactivation inhibited the migration of circulating monocytes into peripheral tissues and reduced the amount of circulating Ly6Chigh monocytes (0.7-fold, p=0.0001), which may account for the reduced macrophage content in lesions. In contrast, the increased number of SMCs in lesions of SCZ-treated mice is attributed to an augmented synthetic vascular SMC phenotype switch as evidenced by the increased proliferation of SMCs and accumulation of collagens in vivo. Conclusion: SSAO inactivation by SCZ promotes the phenotypic switch of SMCs and the development of atherosclerosis. The enzymatic activity of SSAO may thus represent a potential target in the prevention and/or treatment of atherosclerosis.

Keywords: atherosclerosis, phenotype switch of smooth muscle cells, SSAO/VAP-1, semicarbazide

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Authors: Marina Shargorodsky

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Aim: Gestational weight gain (GWG) has been related to altering future weight-gain curves and increased risks of obesity later in life. Obesity may contribute to vascular atherosclerotic changes as well as excess cardiovascular morbidity and mortality observed in these patients. Noninvasive arterial testing, such as ultrasonographic measurement of carotid IMT, is considered a surrogate for systemic atherosclerotic disease burden and is predictive of cardiovascular events in asymptomatic individuals as well as recurrent events in patients with known cardiovascular disease. Currently, there is no consistent evidence regarding the vascular impact of excessive GWG. The present study was designed to investigate the impact of GWG on early atherosclerotic changes during late pregnancy, using intima-media thickness, as well as placental vascular circulation and inflammatory lesions and pregnancy outcomes. Methods: The study group consisted of 59 pregnant women who gave birth and underwent a placental histopathological examination at the Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Israel, in 2019. According to the IOM guidelines the study group has been divided into two groups: Group 1 included 32 women with pregnancy weight gain within recommended range; Group 2 included 27 women with excessive weight gain during pregnancy. The IMT was measured from non-diseased intimal and medial wall layers of the carotid artery on both sides, visualized by high-resolution 7.5 MHz ultrasound (Apogee CX Color, ATL). Placental histology subdivided placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion according to the criteria of the Society for Pediatric Pathology, subdividing placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion, as well as the inflammatory response of maternal and fetal origin. Results: IMT levels differed between groups and were significantly higher in Group 1 compared to Group 2 (0.7+/-0.1 vs 0.6+/-0/1, p=0.028). Multiple linear regression analysis of IMT included variables based on their associations in univariate analyses with a backward approach. Included in the model were pre-gestational BMI, HDL cholesterol and fasting glucose. The model was significant (p=0.001) and correctly classified 64.7% of study patients. In this model, pre-pregnancy BMI remained a significant independent predictor of subclinical atherosclerosis assessed by IMT (OR 4.314, 95% CI 0.0599-0.674, p=0.044). Among placental lesions related to fetal vascular malperfusion, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly higher in Group 1 than in Group 2, p=0.034). In Conclusion, the present study demonstrated that excessive weight gain during pregnancy is associated with an adverse effect on early stages of subclinical atherosclerosis, placental vascular circulation and neonatal complications. The precise mechanism for these vascular changes, as well as the overall clinical impact of weight control during pregnancy on IMT, placental vascular circulation as well as pregnancy outcomes, deserves further investigation.

Keywords: obesity, pregnancy, complications, weight gain

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: Amamra Ryma, Djebar Mohamed Reda, Moumeni Ouissem, Otmani Hadjer, Berrebbah Houria

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The problem of environmental contamination by the excessive use of organics cannot be neglected. Extensive application is usually companied with serious problems and health risk. It is established that many chemicals, in common use, can produce some toxic effects on biological systems through their mode of action or by production of free radicals that damage all cell compounds. Deltamethrin, a widely used type II pyrethroid pesticide, is one of the most common contaminants in freshwater aquatic system. In this study, we investigate the effects of deltamethrin exposure on the induction of oxidative stress to the freshwater ciliate Paramecium tetraurelia. After the treatment of paramecium cells with increasing concentrations of insecticide, we followed up the growth kinetics, generation time and the percentage response. Also, we studied the variation in biomarkers of stress such as: GSH content, GST, GPX and CAT activities. Our results showed a significant decrease in the proliferation of cells correlated by the decrease in generation number and the increase in generation time. Also, we noted an inhibition in the percentage response. The monitoring of biomarkers revealed depletion in GSH content in a proportional and dose dependent manner accompanied by an increase in the GST activity. In parallel, a strong induction in the CAT and GPX activities was noted specially for the highest dose. In summary, under the current experimental conditions, deltamethrin is highly toxic to the freshwater ciliate Paramecium tetraurelia. Exposure to low concentrations showed significant adverse on growth accompanied with the induction of oxidative damage supported by the decrease in GSH content and the intensification of the antioxidant enzymes.

Keywords: deltamethrin, Paramecium tetraurelia, growth, oxidative stress, biomarkers, antioxidant

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Authors: Yusra Pintaningrum, Ilma Fahira Basyir, Sony Hilal Wicaksono, Vito A. Damay

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Background: Coronary artery calcium (CAC) scores play an important role in improving prognostic accuracy and can be selectively used to guide the allocation of statin therapy for atherosclerotic cardiovascular disease outcomes and potentially associated with the occurrence of MACE (Major Adverse Cardiovascular Event) and MI (Myocardial Infarction). Objective: This systematic review and meta-analysis aim to analyze the findings of a study about CAC Score and statin treatment effect on MI and MACE risk. Methods: Search for published scientific articles using the PRISMA (Preferred Reporting, Items for Systematic Reviews and Meta-Analysis) method conducted on PubMed, Cochrane Library, and Medline databases published in the last 20 years on “coronary artery calcium” AND “statin” AND “cardiovascular disease” Further systematic review and meta-analysis using RevMan version 5.4 were performed based on the included published scientific articles. Results: Based on 11 studies included with a total of 1055 participants, we performed a meta-analysis and found that individuals with CAC score > 0 increased risk ratio of MI 8.48 (RR = 9.48: 95% CI: 6.22 – 14.45) times and MACE 2.48 (RR = 3.48: 95% CI: 2.98 – 4.05) times higher than CAC score 0 individual. Statin compared against non-statin treatment showed a statistically insignificant overall effect on the risk of MI (P = 0.81) and MACE (P = 0.89) in an individual with elevated CAC score 1 – 100 (P = 0.65) and > 100 (P = 0.11). Conclusions: This study found that an elevated CAC scores individual has a higher risk of MI and MACE than a non-elevated CAC score individual. There is no significant effect of statin compared against non-statin treatment to reduce MI and MACE in elevated CAC score individuals of 1 – 100 or > 100.

Keywords: coronary artery calcium, statin, cardiovascular disease, myocardial infarction, MACE

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Authors: Sumera, Sanila Amber, Fatima Javed Mirza, Amjad Ali, Saadia Zahid

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Glioblastoma multiforme (GBM) is a widely spread and fatal primary brain tumor with an increased risk of relapse in spite of aggressive treatment. The current procedures for GBM diagnosis include invasive procedures i.e. resection or biopsy, to acquire tumor mass. Implementation of negligibly invasive tests as a potential diagnostic technique and biofluid-based monitoring of GBM stresses on discovering biomarkers in CSF and blood. Therefore, we performed a comprehensive in silico analysis to identify potential circulating biomarkers for GBM. Initially, six gene and protein databases were utilized to mine brain-specific proteins. The resulting proteins were filtered using a channel of five tools to predict the secretory proteins. Subsequently, the expression profile of the secreted proteins was verified in the brain and blood using two databases. Additional verification of the resulting proteins was done using Plasma Proteome Database (PPD) to confirm their presence in blood. The final set of proteins was searched in literature for their relationship with GBM, keeping a special emphasis on secretome proteome. 2145 proteins were firstly mined as brain-specific, out of which 69 proteins were identified as secretory in nature. Verification of expression profile in brain and blood eliminated 58 proteins from the 69 proteins, providing a final list of 11 proteins. Further verification of these 11 proteins further eliminated 2 proteins, giving a final set of nine secretory proteins i.e. OPCML, NPTX1, LGI1, CNTN2, LY6H, SLIT1, CREG2, GDF1 and SERPINI1. Out of these 9 proteins, 7 were found to be linked to GBM, whereas 2 proteins are not investigated in GBM so far. We propose that these secretory proteins can serve as potential circulating biomarker signatures of GBM and will facilitate the development of minimally invasive diagnostic methods and novel therapeutic interventions for GBM.

Keywords: glioblastoma multiforme, secretory proteins, brain secretome, biomarkers

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Authors: Karima Sifi, Noureddine Soltani

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Annaba gulf is the most important touristic and economic area located on the east coast of Algeria. However, these fishery resources are threatened by the pollution due to the progress of economic activity. As part of a biomonitoring program on the quality of waters of the Gulf of Annaba, the specific activity of two biomarkers, acetylcholinesterase (AChE) and glutathion S-transferase (GST) has been measured in edible bivalve Donax trunculus. The samples have been collected during the year 2013 in two sites: El Battah, distant from polluted sources, and Sidi Salem, located near the harbor and different industrial waste. The results showed a significant inhibition of AChE activity and a significant increase in the activity of the GST in samples collected from Sidi Salem as compared to El Battah. The inhibition of the AChE and the increase of the GST in Sidi Salem are in relation with the level of exposition of this site to the pollution.

Keywords: Donax trunculus, annaba gulf, acetylcholinesterase, glutathion s-transferase, biomonitoring, pollution

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Authors: J. Hidalgo de Quintana, I. Stoner, M. Tackett, G. Doran, C. Rafferty, A. Windemuth, J. Tytell, D. Pregibon

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We have developed the Multiplexed Circulating microRNA assay that allows the detection of up to 68 microRNA targets per sample. The assay combines particle­based multiplexing, using patented Firefly hydrogel particles, with single­ step RT-PCR signal. Thus, the Circulating microRNA assay leverages PCR sensitivity while eliminating the need for separate reverse transcription reactions and mitigating amplification biases introduced by target­-specific qPCR. Furthermore, the ability to multiplex targets in each well eliminates the need to split valuable samples into multiple reactions. Results from the Circulating microRNA assay are interpreted using Firefly Analysis Workbench, which allows visualization, normalization, and export of experimental data. To aid discovery and validation of biomarkers, we have generated fixed panels for Oncology, Cardiology, Neurology, Immunology, and Liver Toxicology. Here we present the data from several studies investigating circulating and tumor microRNA, showcasing the ability of the technology to sensitively and specifically detect microRNA biomarker signatures from fluid specimens.

Keywords: biomarkers, biofluids, miRNA, photolithography, flowcytometry

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Authors: Samuel P. Prahlow, Anthony Sciuva, Katherine Bombly, Emily Wilson, Shiv Dhiman, Savita Arya

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A prevalence cohort study of atherosclerotic lesions within cadavers was performed to better understand and characterize the prevalence of atherosclerosis among Georgia residents within body donors in the Philadelphia College of Osteopathic Medicine (PCOM) - Georgia body donor program. We procured specimens from cadavers used for medical students, physical therapy students, and biomedical science students cadaveric anatomical dissection at PCOM - South Georgia and PCOM - Georgia. Tissues were prepared using hematoxylin and eosin (H&E) stainas histological slides by Colquitt Regional Medical Center Laboratory Services. One section from each of the following arteries was taken after cadaveric dissection at the site of most calcification palpated grossly (if present): left anterior descending coronary artery, left internal carotid artery, abdominal aorta, splenic artery, and hepatic artery. All specimens were graded and categorized according to the American Heart Association’s Modified and Conventional Standards for Atherosclerotic Lesions using x4, x10, x40 microscopic magnification. Our study cohort included 22 cadavers, with 16 females and 6 males. The average age was 72.54, and the median age was 72, with a range of 52 to 90 years old. The cause of death determination listing vascular and/or cardiovascular causes was present on 6 of the 22 death certificates. 19 of 22 (86%) cadavers had at least a single artery grading > 5. Of the cadavers with at least a single artery graded at greater than 5, only 5 of 19 (26%) cadavers had a vascular or cardiovascular cause of death reported. Malignancy was listed as a cause of death on 7 (32%) death certificates. The average atherosclerosis grading of the common hepatic, splenic and left internal carotid arteries (2.15, 3.05, and 3.36 respectively) were lower than the left anterior descending artery and the abdominal aorta (5.16 and 5.86 respectively). This prevalence study characterizes atherosclerosis found in five medium and large systemic arteries within cadavers from the state of Georgia.

Keywords: pathology, atherosclerosis, histology, cardiovascular

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Authors: Elena Maria Scalisi

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Currently, photodegradation by nanoparticles (NPs) is a common solution for wastewater treatment. Nanoparticles are efficient for removing organic and inorganic pollutants, heavy metals from wastewater and killing microorganisms through environmentally friendly. In this context, the major representative of photocatalytic technology for industrial wastewater treatment are TiO₂ nanoparticles (TiO₂-NPs). TiO₂-NPs have a strong catalytic activity that depends to their physicochemical properties. Thanks to their small size (between 1-100 nm), nanoparticles occupy less volume, then their surface area increases. The increase in the surface-to-volume ratio results in the increase of the particle surface energy, which improve their reactivity potential. However, these unique properties represent risks to the ecosystems and organisms when unintentionally TiO₂-NPs are release into the environment and absorbed by living organisms. Several studies confirm that there is a high level of interest concerning the safety of TiO₂-NPs in the aquatic environment, furthermore, ecotoxicological tools are useful to correctly evaluate their toxicity. In the current study, we aimed to characterize potential toxic effects of TiO₂-NP suspension to zebrafish during embryo-larval stages to evaluate parameters such as survival rates, malformation, hatching, the overall length of the larvae heartbeat, and biochemical biomarkers that reflect the acute toxicity and sublethal effects of TiO₂-NPs. Zebrafish embryos were exposed to titanium dioxide nanoparticles (TiO₂-NPs at 1mg/L, 2mg/L, and 4mg/L) from fertilization to the free swimming stage (144hpf). Every day, we recorded the toxicological endpoints, moreover, immunohistochemical analysis has been performed at the end of the exposure. In particular, we have evaluate the expression of the following biomarkers: Heat Shock Protein 70 (HSP70), Poly ADP-Ribose Polymerase-1 (PARP-1), Metallothioneins (MTs). Our results have shown that hatch ability, survival, and malformation rate were not affected by TiO₂ NPs at these exposure levels. However, TiO₂-NPs caused an increase of heartbeat and reduction of body length; at the same time, TiO₂-NPs have inducted the production of ROS and the expression of oxidative stress biomarkers HSP70 and PARP-1. Hight positivity for PARP-1 at all concentration tested was observed. As regards MT, positivity was found in the expression of this biomarker in the whole body of the embryo, with the exception of the end of the tail. Metallothioneins (MT) are biomarkers widely used in environmental monitoring programs for aquatic creatures. At the light of our results i.e. no death until the end of the experiment (144hpf), no malformation and expression of the biomarkers mentioned, it is evident that zebrafish larvae with their natural detoxification pathways are able to resist the presence of toxic substances and then they can tolerate the presence of metal concentrations. However, an excessive oxidative state can compromise cell function, therefore the uncontrolled release of nanoparticles into the environment is severe and must be constantly monitored.

Keywords: nanoparticles, embryo zebrafish, HSP70, PARP-1

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