Displaying publications 41 - 60 of 1426 in total

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  1. Leow, V.M., Faizah, M.S., Yang, K.F., Hasnan, M.N., Manisekar, S.S.
    MyJurnal
    Tuberculous (TB) biliary stricture with calcified liver nodules rendering obstructive jaundice is a rare clinical phenomenon. Recently, we encountered a young patient with obstructive jaundice who was investigated in a general hospital. He was sent to our hospital for subsequent management after undergoing a series of investigations and biliary stenting. The radiological imagings performed revealed multiple calcified lesions in the liver with proximal bile duct strictures. Blood investigations, tumor markers and tuberculous work up were not remarkable. Subsequently, he underwent laparotomy and biliary reconstruction. Postoperatively, he was discharged well. Histopathological examination of the hepatoduodenal nodes showed chronic infections and granulomatous lymphadenitis, suspicious of a mycobacterium infection.
    Matched MeSH terms: Biomarkers, Tumor
  2. Menon R, Mohd Noor FS, Draman CR, Seman MR, Ghani AS
    Saudi J Kidney Dis Transpl, 2012 Sep;23(5):1109-14.
    PMID: 22982937 DOI: 10.4103/1319-2442.100972
    Diabetic nephropathy (DN) has become the most common cause of end-stage renal failure. Early referral and specific nephrology treatment could delay the disease progression and should reduce the treatment cost, mortality and morbidity rate in these patients. This is a single-center, retrospective review of all DN patients referred to the nephrology clinic in Hospital Sultan Ahmad Shah, Temerloh, from 2000 to 2009, to study and define the clinical characteristics of DN patients at the time of the referral to the nephrology clinic. A total of 75 patient case records were reviewed. Forty-three (57.3%) of them were males, with a median age of 64.3 ± 8.5 years at the time of referral. Only 14.7% of them had blood pressure lower than 125/75 mmHg. Co-morbid and disease-related complications were also commonly diagnosed and 28.4% (n = 21) had ischemic heart disease, 23% (n = 17) had diabetic retinopathy and 20.3% (n = 15) had diabetic neuropathy. The mean serum creatinine at the time of referral was 339.8 ± 2.3 μmol/L, gylcated hemoglobin A 1c (HbA1C) was 8.1 ± 2.0 %, serum fasting glucose was 9.6 ± 4.7 mmol/L, serum cholesterol was 5.4 ± 1.2 mmol/L and hemoglobin level was 10.6 ± 2.9 g/dL. Although female patients were less frequently seen in the early stages of chronic kidney disease (CKD), they comprised at least 72.7% of CKD stage 5 (male:female; 6:16, P <0.05). Twenty-nine percent (n=22) of them were referred at CKD stage 5, 48% (n=36) were at CKD stage 4, 17.3% (n=13) were at CKD stage 3, 4% (n=3) were at CKD stage 2 and 1.3% (n=1) was at CKD stage 1. Advanced CKD patients were frequently prescribed with more antihypertensives. CKD stage 5 patients were prescribed with two-and-half types of antihypertensive as compared to two types of anti-hypertensive in CKD stage 2 and stage 3. Furthermore, ACE-inhibitors (ACE-I) were less frequently prescribed to them. Only 22.7% (n=5) of CKD stage 5 patients received ACE-I and 30% (n=11) in CKD stage 4 patients as compared to 53.4% (n=7) in CKD patients stage 3. This review shows that DN patients were referred late to the nephrologists and the overall disease management was suboptimal. Antihypertensive requirement was also increased and ACEIs were less frequently prescribed in the advanced diabetic nephropathy patients.
    Study site: Nephrology Clinic, Hospital Sultan Ahmad Shah, Temerloh, Pahang, Malaysia
    Matched MeSH terms: Biomarkers/blood
  3. Alshareefy Y, Cummins S, Mazzoleni A, Sharma V, Guggilapu S, Leong AWY, et al.
    Medicine (Baltimore), 2023 Nov 17;102(46):e36094.
    PMID: 37986400 DOI: 10.1097/MD.0000000000036094
    Pancreatic neuroendocrine tumors (PanNETs) are a rare subtype of pancreatic cancer and can be divided into functional (30-40%) and nonfunctional subtypes. The different subtypes of functional PanNETs (F-PanNETs) have a variety of classical presentations that raise suspicion for an underlying PanNET. It is estimated that 90% of PanNETs are sporadic, and the PI3K-Akt-mTOR and ATRX/DAXX signaling pathways have been recognized as key genetic pathways implicated in the pathogenesis. The other 10% of PanNETs may occur in the context of familial cancer syndromes such as MEN1. Chromogranin A is the most useful biomarker currently; however, several studies have shown limitations with its use, especially its prognostic value. Synaptophysin is a novel biomarker which has shown promising preliminary results however its use clinically has yet to be established. Blood tests assessing hormone levels, cross-sectional imaging, and endoscopic ultrasound remain at the core of establishing a diagnosis of F-PanNET. The treatment options for F-PanNETs include surgical methods such as enucleation, systemic therapies like chemotherapy and novel targeted therapies such as everolimus. The prognosis for F-PanNETs is more favorable than for nonfunctional PanNETs, however metastatic disease is associated with poor survival outcomes. Researchers should also focus their efforts on identifying novel pathways implicated in the pathogenesis of F-PanNETs in order to develop new targeted therapies that may reduce the need for surgical intervention and on the establishment of novel biomarkers that may reduce the need for invasive testing and allow for earlier detection of F-PanNETs.
    Matched MeSH terms: Biomarkers
  4. Tan MS, Cheah PL, Chin AV, Looi LM, Chang SW
    Comput Biol Med, 2021 12;139:104947.
    PMID: 34678481 DOI: 10.1016/j.compbiomed.2021.104947
    Alzheimer's Disease (AD) is a neurodegenerative disease that affects cognition and is the most common cause of dementia in the elderly. As the number of elderly individuals increases globally, the incidence and prevalence of AD are expected to increase. At present, AD is diagnosed clinically, according to accepted criteria. The essential elements in the diagnosis of AD include a patients history, a physical examination and neuropsychological testing, in addition to appropriate investigations such as neuroimaging. The omics-based approach is an emerging field of study that may not only aid in the diagnosis of AD but also facilitate the exploration of factors that influence the development of the disease. Omics techniques, including genomics, transcriptomics, proteomics and metabolomics, may reveal the pathways that lead to neuronal death and identify biomolecular markers associated with AD. This will further facilitate an understanding of AD neuropathology. In this review, omics-based approaches that were implemented in studies on AD were assessed from a bioinformatics perspective. Current state-of-the-art statistical and machine learning approaches used in the single omics analysis of AD were compared based on correlations of variants, differential expression, functional analysis and network analysis. This was followed by a review of the approaches used in the integration and analysis of multi-omics of AD. The strengths and limitations of multi-omics analysis methods were explored and the issues and challenges associated with omics studies of AD were highlighted. Lastly, future studies in this area of research were justified.
    Matched MeSH terms: Biomarkers
  5. Hussain Z, Yusoff ZM, Sulaiman SA
    Prim Care Diabetes, 2015 Aug;9(4):275-82.
    PMID: 25457621 DOI: 10.1016/j.pcd.2014.10.002
    AIMS: The aim of this study was to evaluate attitude and treatment satisfaction of women suffering from GDM and their association with glycaemic level.
    METHODS: A cross sectional study was conducted in antenatal clinic of Hospital Pulau Pinang, Malaysia from June to December 2013 on the sample of 175 patients. Data was collected through modified version of Diabetes Integration Scale (ATT-19) and Diabetes Treatment Satisfaction Questionnaires (DSTQs). Glycaemic level was evaluated in terms of Fasting Plasma Glucose (FPG). Three most recent values of FPG (mmol/l) were taken from patients medical profiles and their mean was calculated. Descriptive and inferential statistics were used for data analysis.
    RESULTS: A total of 166 patients were included in final analysis. Only 35 (21.1%) patients had positive attitude and 122 (73.5%) of patients had adequate treatment satisfaction. There was no significant association of total mean ATT-19 score with age, ethnicity, educational level, occupational status, family history and type of therapy. For treatment satisfaction statistically significant association was present only between total mean treatment satisfaction score and educational level. Patients with negative attitude and inadequate treatment satisfaction had higher mean glycaemic level.
    CONCLUSIONS: It is concluded that more than two folds of patients were satisfied with their ongoing treatment but majority of the patients were feeling difficulty in active coping measures for the management of GDM.
    KEYWORDS: Attitude; GDM; Glycaemic level; Treatment satisfaction

    Study site: antenatal clinic of Hospital Pulau Pinang
    Matched MeSH terms: Biomarkers/blood
  6. Lee YK, Za'aba A, Madzhi NK, Ahmad A
    PMID: 19964239 DOI: 10.1109/IEMBS.2009.5333674
    Previous works on the effects of salivary alpha amylase in respond to various stressors report encouraging findings on it being a good indicator of stress. Ellestad protocol is a clinical procedure to screen for coronary artery disease by introducing exercise induced physical stress. If a salivary based biomarker profile in accordance to a stress test protocol could be established, the critical stress state which disable rational decision making could be ascertained in a standardized procedure. This technique would serve to aid human resource management in times of critical events such as rescue, firefighting or even military, that would potentially prevent unnecessary sacrifice of human lives. In this pilot study with five healthy volunteers performing the Ellestad protocol treadmill, a measurement profile with physiologic and salivary based biomarker is obtained. It is found that the alpha amylase levels or the changes in it as workload changes from resting-walking-running at ease-exhaustive running, is relatively more significant in reflecting the stress state than heart rate and blood pressure. Moreover, it is strongly associated with mood state with correlation coefficient of 0.8 and significance of 0.01.
    Matched MeSH terms: Biomarkers/analysis
  7. Thriumani R, Zakaria A, Hashim YZH, Jeffree AI, Helmy KM, Kamarudin LM, et al.
    BMC Cancer, 2018 04 02;18(1):362.
    PMID: 29609557 DOI: 10.1186/s12885-018-4235-7
    BACKGROUND: Volatile organic compounds (VOCs) emitted from exhaled breath from human bodies have been proven to be a useful source of information for early lung cancer diagnosis. To date, there are still arguable information on the production and origin of significant VOCs of cancer cells. Thus, this study aims to conduct in-vitro experiments involving related cell lines to verify the capability of VOCs in providing information of the cells.

    METHOD: The performances of e-nose technology with different statistical methods to determine the best classifier were conducted and discussed. The gas sensor study has been complemented using solid phase micro-extraction-gas chromatography mass spectrometry. For this purpose, the lung cancer cells (A549 and Calu-3) and control cell lines, breast cancer cell (MCF7) and non-cancerous lung cell (WI38VA13) were cultured in growth medium.

    RESULTS: This study successfully provided a list of possible volatile organic compounds that can be specific biomarkers for lung cancer, even at the 24th hour of cell growth. Also, the Linear Discriminant Analysis-based One versus All-Support Vector Machine classifier, is able to produce high performance in distinguishing lung cancer from breast cancer cells and normal lung cells.

    CONCLUSION: The findings in this work conclude that the specific VOC released from the cancer cells can act as the odour signature and potentially to be used as non-invasive screening of lung cancer using gas array sensor devices.

    Matched MeSH terms: Biomarkers
  8. Chua, S.K., Singh, Devinder K.A., Rajaratnam, B.S., Mokhtar, Sabarul A., Sridharan, R., Gan, K.B., et al.
    MyJurnal
    Older adults are at risk of osteoporotic fractures. Osteoporotic vertebral fractures are associated with a reduced cross-sectional area and muscle strength of the back extensor muscles, increased intramuscular fat infiltration and thoracic and lumbar curvature alterations. This study proposed a protocol to examine in more detail the contributions of altered spinal morphological, physical performance and biochemical markers to the risk of developing osteoporotic vertebral fractures. In this cross-sectional study, we plan to recruit 100 adults aged 50 years and above from an orthopaedic clinic, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia. The fracture prediction tool (FRAX) will be used to categorise high and low risk groups. Back muscle strength will be quantified using a load cell system. Thoracolumbar curvatures will be examined using an electromagnetic tracking system and intramuscular fat infiltration in the lumbar muscles will be measured using Magnetic Resonance Imaging. The Short Physical Performance Battery and JAMA dynamometer will quantify physical performance and the European Quality of Life Questionnaire will be used to assess self-perceived quality of life. Biochemical markers of serum C terminal telopeptide and N terminal propeptide of type I procollagen will be assessed using an enzyme-linked immunosorbent assays kit. A spine-specific model using regression analysis will be developed to predict osteoporotic vertebral fractures using the measured parameters in the present study.
    Matched MeSH terms: Biomarkers
  9. Ng KL, Morais C, Bernard A, Saunders N, Samaratunga H, Gobe G, et al.
    J Clin Pathol, 2016 Aug;69(8):661-71.
    PMID: 26951082 DOI: 10.1136/jclinpath-2015-203585
    Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities.
    Matched MeSH terms: Biomarkers, Tumor/metabolism*
  10. Sakharkar MK, Kashmir Singh SK, Rajamanickam K, Mohamed Essa M, Yang J, Chidambaram SB
    PLoS One, 2019;14(9):e0220995.
    PMID: 31487305 DOI: 10.1371/journal.pone.0220995
    Parkinson's disease (PD) is an irreversible and incurable multigenic neurodegenerative disorder. It involves progressive loss of mid brain dopaminergic neurons in the substantia nigra pars compacta (SN). We compared brain gene expression profiles with those from the peripheral blood cells of a separate sample of PD patients to identify disease-associated genes. Here, we demonstrate the use of gene expression profiling of brain and blood for detecting valid targets and identifying early PD biomarkers. Implementing this systematic approach, we discovered putative PD risk genes in brain, delineated biological processes and molecular functions that may be particularly disrupted in PD and also identified several putative PD biomarkers in blood. 20 of the differentially expressed genes in SN were also found to be differentially expressed in the blood. Further application of this methodology to other brain regions and neurological disorders should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for PD. The identification of valid peripheral biomarkers for PD may ultimately facilitate early identification, intervention, and prevention efforts as well.
    Matched MeSH terms: Biomarkers*
  11. Mohd Isa SA, Md Salleh MS, Ismail MP, Hairon SM
    Asian Pac J Cancer Prev, 2019 Apr 29;20(4):1081-1087.
    PMID: 31030477
    Background: Cervical cancer is a preventable disease caused by human papillomaviruses. It is the third most
    common cancer to occur in women of reproductive age. The ADAM9 protein plays a role in basement membrane
    degradation and tumour metastasis in certain types of tumour. Thus, it has the potential to become a new targeted
    therapy. The objective of this study was to investigate ADAM9 expression in cervical cancer and to determine the
    factors associated with ADAM9-positive expression. Methods: This cross-sectional study was conducted in Hospital
    Universiti Sains Malaysia (HUSM) Kelantan, Malaysia from December 2010 to December 2012. Histological slides
    obtained from 95 cervical cancer cases diagnosed and/or treated in HUSM from 2000 to 2010 were analysed. The
    ADAM9 immunostain was then performed on the paraffin blocks. The statistical data entry and analysis were done
    using SPSS version 18.0. Multiple logistic regression analysis was performed to determine the factors associated with
    ADAM9-positive expression. Result: Of the 95 cervical cancer patients included in the study, 72 (75.8%) patients showed
    positive ADAM9 expression. The mean age of the patients was 53.89 (10.83) years old. Squamous cell carcinoma was
    the most common type of cervical cancer (n = 67, 70.5%). Factors that showed a statistically significant association
    with ADAM9-positive expression were tumour size (adjusted odds ratio [adj. OR]: 1.08; 95% confidence interval
    [CI]: 1.02, 1.13; p = 0.004), distant metastasis (adj. OR: 12.82; 95% CI: 1.91, 86.13; p = 0.009) and the histological
    type of cervical cancer (i.e. squamous cell carcinoma) (adj. OR: 7.39; 95% CI: 1.42, 38.51; p = 0.017). Conclusion:
    The ADAM9 immunostain was consistently positive in malignant cells. Thus, ADAM9 expression can be used as a
    prognostic/therapeutic indicator in aiding clinician decision-making regarding patient treatment (targeted therapy).
    Matched MeSH terms: Biomarkers, Tumor/metabolism*
  12. Elias MH, Azlan H, Sulong S, Baba AA, Ankathil R
    Cancer Rep (Hoboken), 2018 08;1(2):e1111.
    PMID: 32721103 DOI: 10.1002/cnr2.1111
    BACKGROUND: Imatinib mesylate is a molecularly targeted tyrosine kinase inhibitor drug. It is effectively used in the treatment of chronic myeloid leukemia (CML) patients. However, development of resistance to imatinib mesylate as a result of BCR-ABL dependent and BCR-ABL independent mechanisms has emerged as a daunting problem in the management of CML patients. Between these mechanisms, BCR-ABL independent mechanisms are still not robustly understood.

    AIM: To investigate the correlation of HOXA4 and HOXA5 promoter DNA hypermethylation with imatinib resistance among CML patients.

    METHODS AND RESULTS: Samples from 175 Philadelphia positive CML patients (83 good response and 92 BCR-ABL non-mutated imatinib resistant patients) were subjected to Methylation Specific High Resolution Melt Analysis for methylation levels quantification of the HOXA4 and HOXA5 promoter regions. Receiver operating characteristic curve analysis was done to elucidate the optimal methylation cut-off point followed by multiple logistic regression analysis. Log-Rank analysis was done to measure the overall survival difference between CML groups. The optimal methylation cut-off point was found to be at 62.5% for both HOXA4 and HOXA5. Chronic myeloid leukemia patients with ≥63% HOXA4 and HOXA5 methylation level were shown to have 3.78 and 3.95 times the odds, respectively, to acquire resistance to imatinib. However, overall survival of CML patients that have ≤62% and ≥ 63% methylation levels of HOXA4 and HOXA5 genes were found to be not significant (P-value = 0.126 for HOXA4; P-value = 0.217 for HOXA5).

    CONCLUSION: Hypermethylation of the HOXA4 and HOXA5 promoter is correlated with imatinib resistance and with further investigation, it could be a potential epigenetic biomarker in supplement to the BCR-ABL gene mutation in predicting imatinib treatment response among CML patients but could not be considered as a prognostic marker.

    Matched MeSH terms: Biomarkers, Tumor/blood; Biomarkers, Tumor/genetics
  13. Mohamad A, Hassan R, Husin A, Johan MF, Sulong S
    Asian Pac J Cancer Prev, 2021 Jan 01;22(1):85-91.
    PMID: 33507683 DOI: 10.31557/APJCP.2021.22.1.85
    OBJECTIVE: Chronic Lymphocytic Leukemia (CLL) is a common leukemia among Caucasians but rare in Asians population. We postulated that aberrant methylation either hypermethylation or partial methylation might be one of the silencing mechanisms that inactivates the tumour suppressor genes in CLL. This study aimed to compare the methylation status of tumour suppressor gene, ADAM12, among CLL patients and normal individuals. We also evaluated the association between methylation of ADAM12 and clinical and demographic characteristics of the participants.

    METHODS: A total of 25 CLL patients and 25 normal individuals were recruited in this study. The methylation status of ADAM12 was determined using Methylation-Specific PCR (MSP); whereas, DNA sequencing method was applied for validation of the MSP results.

    RESULTS: Among CLL patients, 12 (48%) were partially methylated and 13 (52%) were unmethylated. Meanwhile, 5 (20%) and 20 (80.6%) of healthy individuals were partially methylated and unmethylated, respectively. There was a statistically significant association between the status of methylation at ADAM12 and the presence of CLL (p=0.037).

    CONCLUSION: The aberrant methylation of ADAM12 found in this study using MSP assay may provide new exposure to CLL that may improve the gaps involved in genetic epigenetic study in CLL.

    Matched MeSH terms: Biomarkers, Tumor/genetics*
  14. Yong YK, Tan HY, Jen SH, Shankar EM, Natkunam SK, Sathar J, et al.
    J Transl Med, 2017 05 31;15(1):121.
    PMID: 28569153 DOI: 10.1186/s12967-017-1226-4
    BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks.

    METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD).

    RESULTS: Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P 

    Matched MeSH terms: Biomarkers/blood
  15. Jessie K, Jayapalan JJ, Rahim ZH, Hashim OH
    Electrophoresis, 2014 Dec;35(24):3504-11.
    PMID: 25223738 DOI: 10.1002/elps.201400252
    Prolonged chewing of betel quid is known to cause oral diseases, including cancer. The present study was performed to screen for aberrant proteins in the saliva of habitual betel quid chewers compared to nonchewers. Saliva of female subjects (n = 10) who had been chewing betel quid for more than 20 years and nonbetel quid chewers (n = 10) of the same gender and range of age was analyzed by gel-based proteomics. Increased structural microheterogeneity of saliva haptoglobin beta chains indicated by shifts of focused spots similar to that earlier reported in patients with oral squamous cell carcinoma, and their relatively higher abundance compared to nonbetel quid chewers, were detected in saliva protein profiles of all chewers. In addition, the majority of the betel quid chewers also showed significant higher abundance of hemopexin, alpha-1B glycoprotein, alpha1-antitrypsin, complement C3, and transthyretin. These proteins had previously been associated with several different cancers. Our data demonstrated different forms of protein aberration in the saliva of betel quid chewers, which may be indicative of early oral precancerous conditions.
    Matched MeSH terms: Biomarkers, Tumor/analysis*; Biomarkers, Tumor/chemistry
  16. Jessie K, Jayapalan JJ, Ong KC, Abdul Rahim ZH, Zain RM, Wong KT, et al.
    Electrophoresis, 2013 Sep;34(17):2495-502.
    PMID: 23784731 DOI: 10.1002/elps.201300107
    Confirmation of oral squamous cell cancer (OSCC) currently relies on histological analysis, which does not provide clear indication of cancer development from precancerous lesions. In the present study, whole saliva proteins of patients with OSCC (n = 12) and healthy subjects (n = 12) were separated by 2DE to identify potential candidate biomarkers that are much needed to improve detection of the cancer. The OSCC patients' 2DE saliva protein profiles appeared unique and different from those obtained from the healthy subjects. The patients' saliva α1-antitrypsin (AAT) and haptoglobin (HAP) β chains were resolved into polypeptide spots with increased microheterogeneity, although these were not apparent in their sera. Their 2DE protein profiles also showed presence of hemopexin and α-1B glycoprotein, which were not detected in the profiles of the control saliva. When subjected to densitometry analysis, significant altered levels of AAT, complement C3, transferrin, transthyretin, and β chains of fibrinogen and HAP were detected. The increased levels of saliva AAT, HAP, complement C3, hemopexin, and transthyretin in the OSCC patients were validated by ELISA. The strong association of AAT and HAP with OSCC was further supported by immunohistochemical staining of cancer tissues. The differently expressed saliva proteins may be useful complementary biomarkers for the early detection and/or monitoring of OSCC, although this requires validation in clinically representative populations.
    Matched MeSH terms: Biomarkers, Tumor/metabolism*; Biomarkers, Tumor/chemistry
  17. Veeraveedu PT, Sanada S, Okuda K, Fu HY, Matsuzaki T, Araki R, et al.
    Biochem Pharmacol, 2017 Aug 15;138:73-80.
    PMID: 28450225 DOI: 10.1016/j.bcp.2017.04.022
    BACKGROUND AND PURPOSE: ST2 is one of the interleukin (IL)-1 receptor family members comprising of membrane-bound (ST2L) and soluble (sST2) isoforms. Clinical trials have revealed that serum sST2 levels predict outcome in patient with myocardial infarction or chronic heart failure (HF). Meanwhile, we and others have reported that ablation of ST2 caused exaggerated cardiac remodeling in both ischemic and non-ischemic HF. Here, we tested whether IL-33, the ligand for ST2, protects myocardium against HF induced by mechanical overload using ligand specific knockout (IL-33(-/-)) mice.

    METHODS AND RESULTS: Transverse aortic constriction (TAC)/sham surgery were carried out in both IL-33 and WT-littermates. Echocardiographic measurements were performed at frequent interval during the study period. Heart was harvested for RNA and histological measurements. Following mechanical overload by TAC, myocardial mRNA expressions of Th1 cytokines, such as TNF-α were enhanced in IL-33(-/-) mice than in WT mice. After 8-weeks, IL-33(-/-) mice exhibited exacerbated left ventricular hypertrophy, increased chamber dilation, reduced fractional shortening, aggravated fibrosis, inflammation, and impaired survival compared with WT littermates. Accordingly, myocardial mRNA expressions of hypertrophic (c-Myc/BNP) molecular markers were also significantly enhanced in IL-33(-/-) mice than those in WT mice.

    CONCLUSIONS: We report for the first time that ablation of IL-33 directly and significantly leads to exacerbate cardiac remodeling with impaired cardiac function and survival upon mechanical stress. These data highlight the cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a potential therapeutic role for IL-33 in non-ischemic HF.

    Matched MeSH terms: Biomarkers/metabolism
  18. Dessie BK, Mehari B, Osman M, Gari SR, Desta AF, Melaku S, et al.
    Biometals, 2022 Dec;35(6):1341-1358.
    PMID: 36163536 DOI: 10.1007/s10534-022-00448-8
    The Akaki River in the Upper Awash Basin, which flows through Addis Ababa, the capital city of Ethiopia, has been highly polluted by sewage from factories and residential areas. A population-based cross-sectional study was used to assess the association between trace elements and kidney injury from residents living in polluted areas downstream (Akaki-Kality) versus upstream (Gullele) in Sub-Cities of Addis Ababa. A total of 95 individuals (53 from Akaki-Kality and 42 from Gullele) were included in the study. Kidney injury molecule 1 (KIM-1), lead, arsenic, cadmium, cobalt, lead, manganese, zinc, iron, copper, chromium and nickel were evaluated in residents' urine and nail samples. A large proportion (74%) of the sample population contained KIM-1, including 81% residents in Akaki-Kality and 64% residents in Gullele. KIM-1 was, however, not significantly different (p = 0.05) between the two Sub-Cities, with median of 0.224 ng/mL in Akaki-Kality and 0.152 ng/mL in Gullele. Most of the analyzed elements, except Pb, As, Cd and Co, were found in all of the nail samples, with median (µg/g) in the range of 442‒714 Fe, 97.0‒246 Zn, 11.6‒24.1 Mn, 4.49‒5.85 Cu, 1.46‒1.66 Cr and 1.22‒1.41 Ni. The high incidence of KIM-1 indicates a potential for long term renal tubular damage among residents of the Sub-Cities. The concentrations of the elements in nails were, however, not significantly associated (p = 0.05) with the corresponding levels of KIM-1 in urine. Hence, the observed KIM-1 might be related to exposure to toxic substances or factors other than those included in this study.
    Matched MeSH terms: Biomarkers
  19. Obón-Santacana M, Lujan-Barroso L, Travis RC, Freisling H, Ferrari P, Severi G, et al.
    Cancer Epidemiol Biomarkers Prev, 2016 Jan;25(1):127-34.
    PMID: 26598536 DOI: 10.1158/1055-9965.EPI-15-0822
    BACKGROUND: Acrylamide was classified as "probably carcinogenic to humans (group 2A)" by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case-control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent.

    METHODS: A nested case-control study in nonsmoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk.

    RESULTS: No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but nonstatistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95% CI, 0.96-3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94-3.83, respectively); however, no linear dose-response trends were observed.

    CONCLUSION: This EPIC nested case-control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC.

    IMPACT: It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk.

    Matched MeSH terms: Biomarkers/metabolism*
  20. Obón-Santacana M, Freisling H, Peeters PH, Lujan-Barroso L, Ferrari P, Boutron-Ruault MC, et al.
    Int J Cancer, 2016 Mar 01;138(5):1129-38.
    PMID: 26376083 DOI: 10.1002/ijc.29853
    Acrylamide, classified in 1994 by IARC as "probably carcinogenic to humans," was discovered in 2002 in some heat-treated, carbohydrate-rich foods. Four prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The purpose of this nested case-control study, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, was to evaluate, for the first time, the association between hemoglobin adducts of acrylamide (HbAA) and glycidamide (HbGA) and the risk of developing EC in non-smoking postmenopausal women. Hemoglobin adducts were measured in red blood cells by HPLC/MS/MS. Four exposure variables were evaluated: HbAA, HbGA, their sum (HbAA+HbGA), and their ratio (HbGA/HbAA). The association between hemoglobin adducts and EC was evaluated using unconditional multivariable logistic regression models, and included 383 EC cases (171 were type-I EC), and 385 controls. Exposure variables were analyzed in quintiles based on control distributions. None of the biomarker variables had an effect on overall EC (HRHbAA;Q5vsQ1 : 0.84, 95%CI: 0.49-1.48; HRHbGA;Q5vsQ1 : 0.94, 95%CI: 0.54-1.63) or type-I EC risk. Additionally, none of the subgroups investigated (BMI 
    Matched MeSH terms: Biomarkers/blood
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