• Title/Summary/Keyword: Specific Disease Prediction

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In silico Design of Discontinuous Peptides Representative of B and T-cell Epitopes from HER2-ECD as Potential Novel Cancer Peptide Vaccines

  • Manijeh, Mahdavi;Mehrnaz, Keyhanfar;Violaine, Moreau;Hassan, Mohabatkar;Abbas, Jafarian;Mohammad, Rabbani
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5973-5981
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    • 2013
  • At present, the most common cause of cancer-related death in women is breast cancer. In a large proportion of breast cancers, there is the overexpression of human epidermal growth factor receptor 2 (HER2). This receptor is a 185 KDa growth factor glycoprotein, also known as the first tumor-associated antigen for different types of breast cancers. Moreover, HER2 is an appropriate cell-surface specific antigen for passive immunotherapy, which relies on the repeated application of monoclonal antibodies that are transferred to the patient. However, vaccination is preferable because it would stimulate a patient's own immune system to actively respond to a disease. In the current study, several bioinformatics tools were used for designing synthetic peptide vaccines. PEPOP was used to predict peptides from HER2 ECD subdomain III in the form of discontinuous-continuous B-cell epitopes. Then, T-cell epitope prediction web servers MHCPred, SYFPEITHI, HLA peptide motif search, Propred, and SVMHC were used to identify class-I and II MHC peptides. In this way, PEPOP selected 12 discontinuous peptides from the 3D structure of the HER2 ECD subdomain III. Furthermore, T-cell epitope prediction analyses identified four peptides containing the segments 77 (384-391) and 99 (495-503) for both B and T-cell epitopes. This work is the only study to our knowledge focusing on design of in silico potential novel cancer peptide vaccines of the HER2 ECD subdomain III that contain epitopes for both B and T-cells. These findings based on bioinformatics analyses may be used in vaccine design and cancer therapy; saving time and minimizing the number of tests needed to select the best possible epitopes.

Disease Progression from Chronic Hepatitis C to Cirrhosis and Hepatocellular Carcinoma is Associated with Increasing DNA Promoter Methylation

  • Zekri, Abd El-Rahman Nabawy;Nassar, Auhood Abdel-Monem;El-Rouby, Mahmoud Nour El-Din;Shousha, Hend Ibrahim;Barakat, Ahmed Barakat;El-Desouky, Eman Desouky;Zayed, Naglaa Ali;Ahmed, Ola Sayed;Youssef, Amira Salah El-Din;Kaseb, Ahmed Omar;El-Aziz, Ashraf Omar Abd;Bahnassy, Abeer Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6721-6726
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    • 2013
  • Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

The Classification System and Information Service for Establishing a National Collaborative R&D Strategy in Infectious Diseases: Focusing on the Classification Model for Overseas Coronavirus R&D Projects (국가 감염병 공동R&D전략 수립을 위한 분류체계 및 정보서비스에 대한 연구: 해외 코로나바이러스 R&D과제의 분류모델을 중심으로)

  • Lee, Doyeon;Lee, Jae-Seong;Jun, Seung-pyo;Kim, Keun-Hwan
    • Journal of Intelligence and Information Systems
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    • v.26 no.3
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    • pp.127-147
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    • 2020
  • The world is suffering from numerous human and economic losses due to the novel coronavirus infection (COVID-19). The Korean government established a strategy to overcome the national infectious disease crisis through research and development. It is difficult to find distinctive features and changes in a specific R&D field when using the existing technical classification or science and technology standard classification. Recently, a few studies have been conducted to establish a classification system to provide information about the investment research areas of infectious diseases in Korea through a comparative analysis of Korea government-funded research projects. However, these studies did not provide the necessary information for establishing cooperative research strategies among countries in the infectious diseases, which is required as an execution plan to achieve the goals of national health security and fostering new growth industries. Therefore, it is inevitable to study information services based on the classification system and classification model for establishing a national collaborative R&D strategy. Seven classification - Diagnosis_biomarker, Drug_discovery, Epidemiology, Evaluation_validation, Mechanism_signaling pathway, Prediction, and Vaccine_therapeutic antibody - systems were derived through reviewing infectious diseases-related national-funded research projects of South Korea. A classification system model was trained by combining Scopus data with a bidirectional RNN model. The classification performance of the final model secured robustness with an accuracy of over 90%. In order to conduct the empirical study, an infectious disease classification system was applied to the coronavirus-related research and development projects of major countries such as the STAR Metrics (National Institutes of Health) and NSF (National Science Foundation) of the United States(US), the CORDIS (Community Research & Development Information Service)of the European Union(EU), and the KAKEN (Database of Grants-in-Aid for Scientific Research) of Japan. It can be seen that the research and development trends of infectious diseases (coronavirus) in major countries are mostly concentrated in the prediction that deals with predicting success for clinical trials at the new drug development stage or predicting toxicity that causes side effects. The intriguing result is that for all of these nations, the portion of national investment in the vaccine_therapeutic antibody, which is recognized as an area of research and development aimed at the development of vaccines and treatments, was also very small (5.1%). It indirectly explained the reason of the poor development of vaccines and treatments. Based on the result of examining the investment status of coronavirus-related research projects through comparative analysis by country, it was found that the US and Japan are relatively evenly investing in all infectious diseases-related research areas, while Europe has relatively large investments in specific research areas such as diagnosis_biomarker. Moreover, the information on major coronavirus-related research organizations in major countries was provided by the classification system, thereby allowing establishing an international collaborative R&D projects.

CHANGING THE ANIMAL WORLD WITH NIR : SMALL STEPS OR GIANT LEAPS\ulcorner

  • Flinn, Peter C.
    • Proceedings of the Korean Society of Near Infrared Spectroscopy Conference
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    • 2001.06a
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    • pp.1062-1062
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    • 2001
  • The concept of “precision agriculture” or “site-specific farming” is usually confined to the fields of soil science, crop science and agronomy. However, because plants grow in soil, animals eat plants, and humans eat animal products, it could be argued (perhaps with some poetic licence) that the fields of feed quality, animal nutrition and animal production should also be considered in this context. NIR spectroscopy has proved over the last 20 years that it can provide a firm foundation for quality measurement across all of these fields, and with the continuing developments in instrumentation, computer capacity and software, is now a major cog in the wheel of precision agriculture. There have been a few giant leaps and a lot of small steps in the impact of NIR on the animal world. These have not been confined to the amazing advances in hardware and software, although would not have occurred without them. Rapid testing of forages, grains and mixed feeds by NIR for nutritional value to livestock is now commonplace in commercial laboratories world-wide. This would never have been possible without the pioneering work done by the USDA NIR Forage Research Network in the 1980's, following the landmark paper of Norris et al. in 1976. The advent of calibration transfer between instruments, algorithms which utilize huge databases for calibration and prediction, and the ability to directly scan whole grains and fresh forages can also be considered as major steps, if not leaps. More adventurous NIR applications have emerged in animal nutrition, with emphasis on estimating the functional properties of feeds, such as in vivo digestibility, voluntary intake, protein degradability and in vitro assays to simulate starch digestion. The potential to monitor the diets of grazing animals by using faecal NIR spectra is also now being realized. NIR measurements on animal carcasses and even live animals have also been attempted, with varying degrees of success, The use of discriminant analysis in these fields is proving a useful tool. The latest giant leap is likely to be the advent of relatively low-cost, portable and ultra-fast diode array NIR instruments, which can be used “on-site” and also be fitted to forage or grain harvesters. The fodder and livestock industries are no longer satisfied with what we once thought was revolutionary: a 2-3 day laboratory turnaround for fred quality testing. This means that the instrument needs to be taken to the samples rather than vice versa. Considerable research is underway in this area, but the challenge of calibration transfer and maintenance of instrument networks of this type remains. The animal world is currently facing its biggest challenges ever; animal welfare, alleged effects of animal products on human health, environmental and economic issues are difficult enough, but the current calamities of BSE and foot and mouth disease are “the last straw” NIR will not of course solve all these problems, but is already proving useful in some of these areas and will continue to do so.

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Evaluation of Biochemical Recurrence-free Survival after Radical Prostatectomy by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) Score

  • Aktas, Binhan Kagan;Ozden, Cuneyt;Bulut, Suleyman;Tagci, Suleyman;Erbay, Guven;Gokkaya, Cevdet Serkan;Baykam, Mehmet Murat;Memis, Ali
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2527-2530
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    • 2015
  • Background: The cancer of the prostate risk assessment (CAPRA) score has been defined to predict prostate cancer recurrence based on the pre-clinical data, then pathological data have also been incorporated. Thus, CAPRA post-surgical (CAPRA-S) score has been developed based on six criteria (prostate specific antigen (PSA) at diagnosis, pathological Gleason score, and information on surgical margin, seminal vesicle invasion, extracapsular extension and lymph node involvement) for the prediction of post-surgical recurrences. In the present study, biochemical recurrence (BCR)-free probabilities after open retropubic radical prostatectomy (RP) were evaluated by the CAPRA-S scoring system and its three-risk level model. Materials and Methods: CAPRA-S scores (0-12) of our 240 radical prostatectomies performed between January 2000-May 2011 were calculated. Patients were distributed into CAPRA-S score groups and also into three-risk groups as low, intermediate and high. BCR-free probabilities were assessed and compared using Kaplan-Meier analysis and Cox proportional hazards regression. Ability of CAPRA-S in BCR detection was evaluated by concordance index (c-index). Results: BCR was present in 41 of total 240 patients (17.1%) and the mean follow-up time was $51.7{\pm}33.0$ months. Mean BCR-free survival time was 98.3 months (95% CI: 92.3-104.2). Of the patients in low, intermediate and high risk groups, 5.4%, 22.0% and 58.8% had BCR, respectively and the difference among the three groups was significant (P = 0.0001). C-indices of CAPRA-S score and three-risk groups for detecting BCR-free probabilities in 5-yr were 0.87 and 0.81, respectively. Conclusions: Both CAPRA-S score and its three-risk level model well predicted BCR after RP with high c-index levels in our center. Therefore, it is a clinically reliable post-operative risk stratifier and disease recurrence predictor for prostate cancer.

Breast Cancer Trend in Iran from 2000 to 2009 and Prediction till 2020 using a Trend Analysis Method

  • Zahmatkesh, Bibihajar;Keramat, Afsaneh;Alavi, Nasrinossadat;Khosravi, Ahmad;Kousha, Ahmad;Motlagh, Ali Ghanbari;Darman, Mahboobeh;Partovipour, Elham;Chaman, Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1493-1498
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    • 2016
  • Background: Breast cancer is the most common cancer in women worldwide with a rising incidence rate in most countries. Considering the increase in life expectancy and change in lifestyle of Iranian women, this study investigated the age-adjusted trend of breast cancer incidence during 2000-2009 and predicted its incidence to 2020. Materials and Methods: The 1997 and 2006 census results were used for the projection of female population by age through the cohort-component method over the studied years. Data from the Iranian cancer registration system were used to calculate the annual incidence rate of breast cancer. The age-adjusted incidence rate was then calculated using the WHO standard population distribution. The five-year-age-specific incidence rates were also obtained for each year and future incidence was determined using the trend analysis method. Annual percentage change (APC) was calculated through the joinpoint regression method. Results: The bias adjusted incidence rate of breast cancer increased from 16.7 per 100,000 women in 2000 to 33.6 per 100,000 women in 2009. The incidence of breast cancer had a growing trend in almost all age groups above 30 years over the studied years. In this period, the age groups of 45-65 years had the highest incidence. Investigation into the joinpoint curve showed that the curve had a steep slope with an APC of 23.4% before the first joinpoint, but became milder after this. From 2005 to 2009, the APC was calculated as 2.7%, through which the incidence of breast cancer in 2020 was predicted as 63.0 per 100,000 women. Conclusions: The age-adjusted incidence rate of breast cancer continues to increas in Iranian women. It is predicted that this trend will continue until 2020. Therefore, it seems necessary to prioritize the prevention, control and care for breast cancer in Iran.

A Measurement System for Color Environment-based Human Body Reaction (색채 환경 기반의 인체 반응 정보 측정 시스템)

  • Kim, Ji-Eon;Jeong, Chang-Won;Joo, Su-Chong
    • Journal of Internet Computing and Services
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    • v.17 no.2
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    • pp.59-65
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    • 2016
  • The result of analyzing the cognitive reaction due to the color environment has been applied to various filed especially in medical field. Moreover, the study about the identification of patient's condition and examination the brain activity by collecting the bio-signal based on the color environment is being actively conducted. Even though, there were a variety of experiments by convention the color environment using a light or LED color, it still has a problem that affects the psychological information. Therefore, our proposed system using a HMD (Head Mounting display) to provide a completed color environment condition. This system uses the BMS(Biomedical System) to collect the biometric information which responds to the specific color condition and the human body response information can be measured by the development the Memory and Attention test on Mobile phone. The collection of Biometric information includes electro cardiogram(ECG), respiration, oxygen saturation (Sp02), Bio-impedance, blood pressure will store in the database. In addition, we can verify the result of the human body reaction in the color environment by Memory and Attention application. By utilizing the reaction of the human body information that is collected thought the proposed system, we can analyze the correlation between the physiological information and the color environment. And we also expect that this system can apply to the medical diagnosis and treatment. For future work, we will expand the system for prediction and treatment of Alzheimer disease by analyzing the visualization data through the proposed system. We will also do evaluation on the effectiveness of the system for using in the rehabilitation program.

Class prediction of an independent sample using a set of gene modules consisting of gene-pairs which were condition(Tumor, Normal) specific (조건(암, 정상)에 따라 특이적 관계를 나타내는 유전자 쌍으로 구성된 유전자 모듈을 이용한 독립샘플의 클래스예측)

  • Jeong, Hyeon-Iee;Yoon, Young-Mi
    • Journal of the Korea Society of Computer and Information
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    • v.15 no.12
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    • pp.197-207
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    • 2010
  • Using a variety of data-mining methods on high-throughput cDNA microarray data, the level of gene expression in two different tissues can be compared, and DEG(Differentially Expressed Gene) genes in between normal cell and tumor cell can be detected. Diagnosis can be made with these genes, and also treatment strategy can be determined according to the cancer stages. Existing cancer classification methods using machine learning select the marker genes which are differential expressed in normal and tumor samples, and build a classifier using those marker genes. However, in addition to the differences in gene expression levels, the difference in gene-gene correlations between two conditions could be a good marker in disease diagnosis. In this study, we identify gene pairs with a big correlation difference in two sets of samples, build gene classification modules using these gene pairs. This cancer classification method using gene modules achieves higher accuracy than current methods. The implementing clinical kit can be considered since the number of genes in classification module is small. For future study, Authors plan to identify novel cancer-related genes with functionality analysis on the genes in a classification module through GO(Gene Ontology) enrichment validation, and to extend the classification module into gene regulatory networks.

Prediction Model of Exercise Behaviors in Patients with Arthritis (by Pender's revised Health Promotion Model) (관절염 환자의 운동행위 예측모형 (Pender의 재개정된 건강증진 모형에 의한))

  • Lim, Nan-Young;Suh, Gil-Hee
    • Journal of muscle and joint health
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    • v.8 no.1
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    • pp.122-140
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    • 2001
  • The aims of this study were to understand and to predict the determinent factors affecting the exercise behaviors and physical fitness by testing the Pender's revised health promotion model, and to help the patients with rheumatoid arthritis and osteoarthritis perform the continous exercise program, and to help them maximize the physical effect such as muscle strength, endurance, and functional status and mental effects including self efficacy and quality of life, and improve the physical and mental well being, and to provide a basis for the nursing intervention strategies. Of the selected variables in this study, the endogenous variables included the physical fitness, exercise score, exercise participation, perceived benefits of action, perceived barriers of action to exercise, activity-related affect(depression) and perceived self-efficacy, interpersonal influences(family support), situational factors(duration of arthritis, fatigue) and the exogenous variables included personal sociocultural factor(education level), personal biologic factor(body mass index), personal psychologic factor(perceived health status) and prior related behavior factors(previous participation in exercise, life-style). We analyzed the clinical records of 208 patients with rheumatoid arthritis and degenerative arthritis who visited the outpatient clinics at H university hospital in Seoul. Data were composed of self reported qustionnaire and good of fitness score which were obtained by padalling the ergometer of bicycle for 9 minutes. SPSS Win 8.0 and Window LISREL 8.12a were used for statistical analysis. Of 75 hypothetical paths that influence on physical fitness, exercise participation, exercise score, perceived benefits of action, perceived barriers of action to exercise, activity-related affect(depression) and perceived self-efficacy, interpersonal influences(family support), situational factors(duration of arthritis, fatigue), 40 were supported. The physical fitness was directly influenced by life-style, perceived health status, education level, family support, fatigue, which explained 12% of physical fitness. The exercise participation were directly influenced by life-style, education level, past exercise behavior, perceived benefits of action, perceived barriers of action, depression and duration of arthritis, which explained 47% of exercise participation. Exercise score were directly affected by perceived self efficacy. BMI, life-style, past exercise behavior, perceived benefits of action, family support, perceived health status. perceived barriers of action, and fatigue, which explained 70%. Perceived benefits of action was directly influenced by BMI, life-style, which explained 39%. Perceived barriers of action were directly influeced by past exercise behavior, perceived health status, which explained 7%. Perceived self efficacy were directly influeced by level of education, perceived health status, life-style, which explained 57%. Depression were directly influeced by past exercise behavior, BMI, life-style, which explained 27%. Family support were directly influeced by life-style, perceived health status, which explained 29%. Fatigue were directly influeced by BMI, life-style, perceived health status. which explained 41%. Duration of arthritis were directly influeced by life-style, past exercise behavior, BMI, which explained 6%. In conclusion, important variables for physical fitness were life-style, and variable affecting exercise participation were life-style. Perceived self-efficacy of exercise was a significant predictor of exercise score. BMI, Life-style, perceived benefits of action, family support, past exercise behavior showed direct effects on perceived self-efficacy. Therefore, disease related factor should be minimized for physical performance and well being in nursing intervention for patients with rheumatoid arthritis, and plans to promote and continue exercise should be seeked to reduce disability. In addition, Exercise program should be planned and performed by the exact evaluation of exercise according to the ability of the patients and the contents to improve the importance of exercise and self efficacy in self control program, dedicated educational program should be involved. This study suggest that the methods to reduce the disease related factors, the importance of daily life-style, recognition of benefit of exercise, and educational program to promote self efficacy should be considered in the exercise behavior promotion and nursing intervention for continous performance. The significance of this study is also thought to provide patients with chronic arthritis the specific data for maximal physical and mental well being through exercise, chronic therapeutic procedure, daily adaptation and confrontation in nursing intervention.

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Manganese and Iron Interaction: a Mechanism of Manganese-Induced Parkinsonism

  • Zheng, Wei
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2003.10a
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    • pp.34-63
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    • 2003
  • Occupational and environmental exposure to manganese continue to represent a realistic public health problem in both developed and developing countries. Increased utility of MMT as a replacement for lead in gasoline creates a new source of environmental exposure to manganese. It is, therefore, imperative that further attention be directed at molecular neurotoxicology of manganese. A Need for a more complete understanding of manganese functions both in health and disease, and for a better defined role of manganese in iron metabolism is well substantiated. The in-depth studies in this area should provide novel information on the potential public health risk associated with manganese exposure. It will also explore novel mechanism(s) of manganese-induced neurotoxicity from the angle of Mn-Fe interaction at both systemic and cellular levels. More importantly, the result of these studies will offer clues to the etiology of IPD and its associated abnormal iron and energy metabolism. To achieve these goals, however, a number of outstanding questions remain to be resolved. First, one must understand what species of manganese in the biological matrices plays critical role in the induction of neurotoxicity, Mn(II) or Mn(III)? In our own studies with aconitase, Cpx-I, and Cpx-II, manganese was added to the buffers as the divalent salt, i.e., $MnCl_2$. While it is quite reasonable to suggest that the effect on aconitase and/or Cpx-I activites was associated with the divalent species of manganese, the experimental design does not preclude the possibility that a manganese species of higher oxidation state, such as Mn(III), is required for the induction of these effects. The ionic radius of Mn(III) is 65 ppm, which is similar to the ionic size to Fe(III) (65 ppm at the high spin state) in aconitase (Nieboer and Fletcher, 1996; Sneed et al., 1953). Thus it is plausible that the higher oxidation state of manganese optimally fits into the geometric space of aconitase, serving as the active species in this enzymatic reaction. In the current literature, most of the studies on manganese toxicity have used Mn(II) as $MnCl_2$ rather than Mn(III). The obvious advantage of Mn(II) is its good water solubility, which allows effortless preparation in either in vivo or in vitro investigation, whereas almost all of the Mn(III) salt products on the comparison between two valent manganese species nearly infeasible. Thus a more intimate collaboration with physiochemists to develop a better way to study Mn(III) species in biological matrices is pressingly needed. Second, In spite of the special affinity of manganese for mitochondria and its similar chemical properties to iron, there is a sound reason to postulate that manganese may act as an iron surrogate in certain iron-requiring enzymes. It is, therefore, imperative to design the physiochemical studies to determine whether manganese can indeed exchange with iron in proteins, and to understand how manganese interacts with tertiary structure of proteins. The studies on binding properties (such as affinity constant, dissociation parameter, etc.) of manganese and iron to key enzymes associated with iron and energy regulation would add additional information to our knowledge of Mn-Fe neurotoxicity. Third, manganese exposure, either in vivo or in vitro, promotes cellular overload of iron. It is still unclear, however, how exactly manganese interacts with cellular iron regulatory processes and what is the mechanism underlying this cellular iron overload. As discussed above, the binding of IRP-I to TfR mRNA leads to the expression of TfR, thereby increasing cellular iron uptake. The sequence encoding TfR mRNA, in particular IRE fragments, has been well-documented in literature. It is therefore possible to use molecular technique to elaborate whether manganese cytotoxicity influences the mRNA expression of iron regulatory proteins and how manganese exposure alters the binding activity of IPRs to TfR mRNA. Finally, the current manganese investigation has largely focused on the issues ranging from disposition/toxicity study to the characterization of clinical symptoms. Much less has been done regarding the risk assessment of environmenta/occupational exposure. One of the unsolved, pressing puzzles is the lack of reliable biomarker(s) for manganese-induced neurologic lesions in long-term, low-level exposure situation. Lack of such a diagnostic means renders it impossible to assess the human health risk and long-term social impact associated with potentially elevated manganese in environment. The biochemical interaction between manganese and iron, particularly the ensuing subtle changes of certain relevant proteins, provides the opportunity to identify and develop such a specific biomarker for manganese-induced neuronal damage. By learning the molecular mechanism of cytotoxicity, one will be able to find a better way for prediction and treatment of manganese-initiated neurodegenerative diseases.

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