Friday, September 20, 2019

Managing Water Resources Using - Water Radioactive Isotopes Monitoring and Risk Mapping-Juniper Pubishers

Agricultural Research & Technology: Open Access Journal-Juniper Publishers

Opinion

Radioactive contamination, also called radiological contamination, is the deposition of, or presence of radioactive substances on surfaces or within solids, liquids or gases (including the human body), where their presence is unintended or undesirable. Contamination may affect a person, a place, an animal, or an object such as clothing. Following an atmospheric nuclear weapon discharge or a nuclear reactor containment breach, the air, soil, people, plants, and animals in the vicinity will become contaminated by nuclear fuel and fission products.
As far, it is scientifically proved that there is a direct correlation between the incidence of cancers and radiation exposure of the human body, water is agent that is permanently in contact with both: nature and people. From this point of view, it is extremely important to evaluate the water quality. The major objective of the proposed project is to measure and evaluate, from the radiation point of view, the quality of the natural and industrial water resulted from the mining of the radioactive and complex minerals. By achieving the proposed objectives, the project will promote conditions for environmentally sustainable, economically efficient and equitably allocated use of water resources.
The investigation will cover mountains regions where water resources have been affected by mining of the radioactive and complex minerals. The possible measurement points will be: decontamination stations, rivers, and main water confluences. First, the team research unit will optimize the number of measurement points by environmental survey tools and geological methods.
Next the research team experts will design and implement a radiation PIN-based smart sensor. Due to measurement specificity, each sensor will be calibrated in site conditions. For this action a probe sensor will be designed and implemented. The probe will be a reference measurement system and it will be used each time when a sensor will be started-up in local measurement conditions. The sensor is controlled by a microcontroller which will be also responsible for measuring some other radiation favorable parameters. For powering the entire measurement system, a solar panel-based power supply will be designed and implemented.
The data from the measuring points will be sent to a central processing unit through a measurement network. The major network support is the Internet with TCP/IP protocol. Because the measurement points are located in insulated and heavy Internet access areas, we will design and implement a radio communication dedicated device, also controlled by the same microcontroller. For linking the measurement points with first Internet access points, the Norway partner will design a transceiver that will fulfill some constrains: secure radio connection, efficient power consumption, in a license free radio communication band. The Norway partner will use a radio device that respects the main constrains list and they will add to its firmware also some specific legislation functions. It will become a specific protocol called radiation protection transmission protocol- RPTP.
The partners propose the use of ICT solutions for water management that could benefit different categories of stakeholders (public and private institutions, organizations, general public, etc) and that could improve water resources planning.
For the evaluation of the water quality from radiation isotopes of view, all measured data will be collected into a database, located in a computing center in Alba Iulia city- as central geographical point. The project aims to design and develop a dedicated software solution capable of analyzing the data gathered from the field research in order to generate different reports and statistics. Radiation data is processed, with a referee to the additional measured parameters that will be able to generate some alert messages for warning and notifications of the public and authorities. A spatial data analyzer module of the proposed software system will be able to use the data gathered and analyzed in order to create risk maps that will be used to monitor the environmental impact demonstrated by life cycle analysis and also to provide information about the effects of the climate changes in the river basins. The early warning solution is design, to take into consideration the risks involved and to provide essential information in order to set priorities for mitigation and prevention strategies that could affect communities, economies and the environment.
The project is in accordance with the call’s scope by implementing new activities of new or improved innovative water solutions in a real environment addressing in the same time 3 out of the 5 thematic priorities: water reuse and recycling; water and wastewater treatment and ecosystem services in the provision of water related services; and also 2 out of the 3 cross-cutting priorities: water governance; decision support systems and monitoring.
Acting as a decision support system for monitoring the status of the water resources, the ICT system developed in the project will deliver warning messages to the potentially affected locations to alert local and regional governmental agencies, ensuring them that they have available all the needed information to coordinate and to establish good governance and appropriate action plans for any given situation.
The main objective of the proposal is to create wide and fast deployment of sustainable innovative solutions in the water management sector based on solid research, capable of making a significant impact on the improving the air and water quality, reducing soil pollution and ecosystems change, and preventing loss of biodiversity and habitats, land.
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Thursday, September 19, 2019

Oocyte Quality and Female Infertilitye_Juniper Publishers


Abstract

Female infertility is one of the major reproductive health issue affecting majority of women worldwide. Several factors including environmental, hormonal and physical may affect the physiology of ovary to release quality grade oocyte required for fertilization and early embryonic development. The quality of oocyte is dependent on several factors within the follicular microenvironment and even after ovulation. One of the major factors that affect oocyte quality is the induction of apoptosis. Apoptosis plays a major role to eliminate majority of germ cells from the cohort of ovary during various stages of folliculogenesis. Few numbers of oocytes are selectively recruited to get ovulated during entire reproductive life span in female. Prior to ovulation, these oocytes achieve meiotic competency that may last for several months in rodents to several years in human. Inability to achieve meiotic competency within the follicular microenvironment and spontaneous egg activation (SEA) immediately after ovulation may deteriorate oocyte quality. Thus, induction of apoptosis or meiotic arrest at Metaphase-I stage (M-I) or SEA could reduce female fertility and may cause infertility.
Keywords: Apoptosis; Oocyte competency; Spontaneous egg activation; Ovary; Female infertility
Abbreviations: SEA: Spontaneous Egg Activation; M-I: Metaphase-I; M-II: Metaphase-II; M-III: Metaphase-III; PB-I: First Polar Body; PB-II: Second Polar Body; ROS: Reactive Oxygen Species

Introduction

Infertility is a one of the major reproductive health problems that has affected almost 10% of young age group worldwide. The infertility rate remains unchanged over past two decades besides having significant advancement in reproductive health sector [1]. This could be due to environmental, stress, lifestyle factor, hormonal and pathophysiological factors [2]. These factors directly or indirectly affect the physiology of ovary that is responsible for the generation of competent oocytes for fertilization and early embryonic development [3]. The increase of stress hormone induces granulosa cell apoptosis responsible for synthesis of estradiol-17β. Estradiol depletion at the level of ovary affects follicular growth and development [2]. Amelioration in follicular growth and development induces follicular atresia [4]. The increased stress causes oxidative stress and reactive oxygen species (ROS) at the level of ovary trigger germ cell depletion via apoptosis [5]. Several factors and pathways facilitate germ cell depletion at all the stages of oogenesis in mammals [6]. The large number of germ cells is eliminated from the cohort of ovary just before the attainment of puberty [4]. At puberty, less than 1% of germ cells remains in the ovary that are subjected to selective recruitment process during entire reproductive life span [7].
The selective recruitment of oocytes during puberty in response to pituitary gonadotrophin surge induces meiotic resumption from diplotene arrest in follicular oocytes by increasing the level of cyclic nucleotides as well as Mos level in granulosa cells of follicular oocytes [8]. These cyclic nucleotides and MOS/MEK/MAPK signalling pathways disrupt the gap junctions between granulosa cells and oocytes resulting in a transient decrease of oocyte adenosine 3',5'-cyclic monophosphate (cAMP) required to maintain diplotene arrest in follicular microenvironment [9]. A transient decrease of oocyte cAMP activates mitogen-activated protein kinase (MAPK) as well as cyclin dependent kinasel (Cdkl), a catalytic unit of maturation promoting factor (MPF). Further, decrease of cAMP destabilizes MPF [10]. The MPF destabilization causes meiotic resumption from diplotene arrest and oocyte progresses towards to metaphase-I stage (M-I) [11]. The M-I arrest may last for very short period of time in vivo and oocyte progresses to reach metaphase-II stage (M-II) by extruding first polar body (PB-I) at the time of ovulation [12]. However, removal of oocyte from follicular microenvironment and their culture in vitro results in spontaneous resumption of meiosis but they are unable to progress beyond M-I under in vitro culture conditions [13].
These oocytes are unfit for fertilization as they contain diploidset of chromosomes and do not posses PB-I. Further, growing body of evidences suggest that the oocytes after ovulation do not wait for fertilizing spermatozoa and quickly undergo meiotic exit from M-II arrest so called spontaneous activation in several mammalian species [14,15]. The spontaneous activation is possibly due to premature release of calcium (Ca++) from internal stores and increase of cytosolic free calcium. A moderate increase of cytosolic free calcium triggers downstream pathway to destabilize MPF [16]. MPF destabilization results spontaneous activation by initiating the extrusion of second polar body (PB-II). These oocytes are of poor quality and their use limits reproductive outcome and may trigger infertility problems [17].

Apoptosis and oocyte quality

Apoptosis plays a major role in follicular atresia and eliminates majority of defective as well as surplus germ cells from the cohort of ovary [18,19]. By this way, ovary keeps only few numbers of germ cells (less than 1%) for selective recruitment during entire reproductive lifespan. As the aging occurs, decline of number of follicles below threshold level may cause infertility [20,21]. Studies suggest that the good quality of oocyte is ovulated first and as the maternal aging occurs, poor quality oocytes are remained in the ovary. These oocytes are more fragile and susceptible towards apoptosis that reduces reproductive outcome (Figure 1) [22-24]. Women are more frequently exposed to various kinds of stress during their reproductive period [25]. The psychological stress, lifestyle changes and various other factors stimulate the release of stress hormone and reactive oxygen species (ROS) [2]. The increased level of stress hormone and ROS induce apoptosis not only in granulosa cells but also in follicular oocytes [5,26]. There are several players and both as death receptors as well as mitochondria-mediated pathways involved in oocyte apoptosis within the follicle of the ovary [27,28]. Indeed, apoptosis plays a major role in determining the quality of follicular oocytes that directly affects reproductive outcome of a female and induces infertility [4].

Meiotic maturation arrest and oocyte quality

Meiotic maturation is required for the follicular oocytes to achieve developmental competency [29]. The achievement of meiotic competency starts with the resumption from diplotene arrest in follicular oocytes and ends with extrusion of PB-I [16]. Any defect during the achievement of meiotic competency does not allow the follicular oocyte to progress meiosis [30]. These compromised oocytes are arrested at M-I stage and do not progress to extrude PB-I [12,13,31]. Further, M-II arrested oocytes even after insemination do not get activated [32]. These oocytes are of poor quality due to meiotic maturation arrest either at M-I stage or at M-II stage under in vitro culture conditions (Figure 1B) [3,33]. The meiotic maturation failure could be possibly due to maintenance of high level of stabilized MPF. The high level of stabilized MPF is required for the maintenance of meiotic arrest [34,35]. The meiotic maturation arrest may cause infertility in human [3].

Spontaneous activation and oocyte quality

The oocyte after ovulation are generally arrested at M-II stage and posses PB-I in most of the mammalian species [3538]. Growing body evidences suggest that oocyte do not wait for fertilizing spermatozoa and quickly undergo spontaneous exit from M-II arrest in several mammalian species including human [39-42]. The initiation of extrusion of PB-II starts but never gets completely extrude (Figure 1C). Oocytes are further arrested at Metaphase-III (M-III) like stage [43].The SEA could be due to abortive increase of cytosolic free calcium and activation of downstream pathway to destabilize MPF [37,38,44]. A moderate increase of cytosolic free Ca++ is good enough to trigger SEA but not sufficient to induce full activation process [37,44]. These oocytes are not fit for fertilization since the chromosomes are scattered throughout the cytoplasm. A large amount of cytoplasm goes towards the side of polar body formation but PB-II never completely extruded [11]. These oocytes are of poor quality and cannot be used for any assisted reproductive technology (ART) program including somatic cell nuclear transfer program (SCNT) during animal cloning [36,11].

Conclusion

Good quality of oocytes is the right choice for fertilization and early embryonic development. Deterioration in oocyte quality may occur due to the onset of apoptosis in the follicular oocytes. Majority of oocytes are eliminated from ovary via apoptosis during follicular atresia. Only few oocytes remain in the ovary that are selectively recruited for ovulation during entire reproductive life of a female. Prevention of MPF destabilization may cause meiotic maturation arrest in follicular oocytes. After ovulation, oocyte quality undergoes Ca++ mediated MPF destabilization that causes SEA in several mammalian species including human. Thus, apoptosis in oocytes, meiotic maturation arrest and SEA may deteriorate oocyte quality after ovulation. Poor quality oocyte directly impacts the reproductive outcome and causes female infertility.


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Wednesday, September 18, 2019

Utility of Noninvasive Serum Biomarkers of Liver Fibrosis in Infants with Biliary Atresia_Juniper Publishers



Authored by Mostafa M Sira

Abstract


Background: Biliary Atresia (BA) is the most common cause of chronic cholestasis in infants It is a destructive inflammatory obliterative cholangiopathy that affects varying lengths of both intrahepatic and extrahepatic bile ducts. Even after a successful surgery, scARGHing of the liver can continue, resulting in cirrhosis and its complications.
Aim: The aim of this study is to evaluate different serological markers derived from routine investigations in the prediction of liver fibrosis in infants with BA.
Methods: This retrospective study included a total of 147 infants with proved diagnosis of BA. We employed six noninvasive scores (FIB-4, FibroQ, King’s score, APRI, GUCI and AAR). Liver fibrosis was classified into 5 grades. For further descriptive purpose, we arbitrarily divided fibrosis grades into early (F1, F2 and F3) and advanced (F4 and F5) fibrosis.
Results: FIB-4, FibroQ and King’s score correlated significantly with fibrosis grade (P values were 0.007 and 0.015 respectively) while there was no significant correlation with other studied scores (P value >0.05). FIB-4, FibroQ and King’s score were significantly higher in patients with advanced fibrosis compared to early fibrosis and at cutoff values of 0.0098, 0.0085 and 0.115 respectively they were able to discriminate those with advanced fibrosis with acceptable sensitivity (61.9%-64.3%) and specificity (60.0%-62.9%).
Conclusion: Conclusion: FIB-4, FibroQ and King’s score, but not APRI, GUCI and AAR, correlated significantly with fibrosis and could predict those with advanced fibrosis with relatively acceptable performance. These markers may be of help in predicting advanced fibrosis and in long term follow up of infants with BA and reduce the need for repeated liver biopsy.
Keywords: AAR; APRI; Biliary atresia; FIB-4; FibroQ; GUCI; King’s score; Liver fibrosis; Noninvasive; Serological markers
Abbreviations: BA: Biliary Atresia; AAR: AST/ALT Ratio; ALP: Alkaline Phosphatase; ALT: Alanine Transaminase; APRI: AST-To-Platelet Ratio Index; AST: Aspartate Transaminase; AUROC: Area Under ROC; FIB-4: Fibrosis-4; FibroQ: Fibro-Quotient; GGT: Gammaglutamyl Transpeptidase; GUCI: Göteborg University Cirrhosis Index; INR: International Normalized Ratio; NPV: Negative Predictive Value; PPV: Positive Predictive Value; ROC: Receiver Operating Characterstic

Introduction

Biliary Atresia (BA) is the most common cause of chronic cholestasis in infants and the most frequent cause for surgery in cholestatic jaundice in this age group. It is a destructive inflammatory obliterative cholangiopathy that affects varying lengths of both intrahepatic and extrahepatic bile ducts [1]. If not treated, BA leads to biliary cirrhosis, hepatic failure and death within the first two years of life [2,3].
The etiology of BA has been a subject of intense investigation. However, the precise etiology remains largely unknown [4]. The initial event may be a viral infection, which targets the biliary epithelium [5]. This is followed by activation of immune cells and release of proinflammatory cytokines that perpetuates the injury and causes biliary destruction, which is followed by collagen deposition to produce the atresia phenotype [6]. Some studies suggested the involvement of biliary morphogenesis genes [7,8] or very recently discovered biliary toxin; biliatrisone [9,10].
The principal treatment of BA is based on surgical reconstruction of bile flow by Kasai portoenterostomy. However, such interventions can be insufficient to prevent further hepatic injury. Even after a successful surgery, scARGHing of the liver can continue, resulting in cirrhosis over the years. This is probably due to the ongoing inflammatory process [11].
Complications of progressive fibrosis and cirrhosis such as esophageal varices may endanger the patient’s life and necessitates urgent intervention [11]. Furthermore, the success of Kasai portoenterostomy is largely dependent on the absence of advanced fibrosis or cirrhosis [12]. For that, noninvasive prediction of liver fibrosis in such patients, avoiding the risks of repeated liver biopsy [13,14] and its limitations including sampling error, and inter- and intra-observer variability in interpretation [15], would be of value during monitoring and follow up of this devastating disease [16]. The aim of the current study was to evaluate different serological markers derived from routine laboratory investigations in the prediction of liver fibrosis in infants with BA.

Patients and Methods

Study population and data collection

This retrospective study included 147 infants with surgically proved BA attending the Department of Pediatric Hepatology, Gastroenterology and Nutrition in the period between year 2010 and 2015. Preoperative demographic (age and sex), laboratory data including total and direct bilirubin, transaminases (alanine transaminase; ALT and aspartate transaminase; AST), biliary enzymes (gammaglutamyl transpeptidase; GGT and alkaline phosphatase; ALP), total proteins, serum albumin, international normalized ratio (INR) and platelets count were collected. Hepatic histopathological features in the form of portal fibrosis, were also revised. Due to the retrospective nature of the study, an informed consent was not needed. The study was approved by the Research Ethics Committee of the National Liver Institute, Menofiya University, Egypt.

Laboratory investigations

Fifteen milliliters venous blood samples were taken by sterile venipuncture, without frothing and after minimal venous stasis using disposable syringes. The blood samples were distributed as follows: 5 ml of venous blood were delivered in a vacutainer plain test tube. Blood was left for a sufficient time to clot; serum was then separated after centrifugation at 3000 rpm/min for 10 min for liver function tests. Five milliliters of venous blood were delivered in a vacutainer plastic tube containing EDTA for complete blood count (CBC). Five milliliters of venous blood were delivered in a vacutainer plastic tube containing Sodium Citrate for INR. CBC was performed on Sysmex KX-21 (Wakinohamakaigandori, Kobe, Hyogo, Japan). Liver function tests [ALT, AST,albumin, total protein, total bilirubin, direct bilirubin, ALP and GGT] were conducted using Integra 400 autoanalyzer (Roche- Diagnostics, Mannheim, Germany). Prothrombin time and INR were conducted using Sysmex CA 1500 coagulometer
infection received peg-interferon and ribavirin treatment for 48 weeks, out of nine patients showed Resistance to the treatment. Blood sampling were made on at start and end of the treatment. Based on the therapeutic response to antiviral treatment, those 18 patients could divide into two groups: Treated (Responder, R) 9 patients, and Resistant (Non-responder, NR) 9 patients.

Liver biopsy

Ultrasonography-guided liver biopsy was done for all patients using a tru-cut needle. Biopsy specimens were fixed in formalin and embedded in paraffin. Five-micron thick sections were cut and stained with Hematoxylin-Eosin, Mason-Trichrome, Orcein and Perls’ stains for routine histopathological evaluation. Portal fibrosis was assessed using a semi-quantitative histopathological score as described by Russo et al. [17].

Calculation of the selected non-invasive serological scores

The employed scores was calculated as follows; AST-toplatelet ratio index (APRI) was calculated according to the formula; APRI = AST / upper limit of normal x 100 / platelet count (109/L) [18]; Fibrosis-4 (FIB-4) = Age (years) x AST / platelet count (109/L) x (ALT)1/2 [19]; Fibro-quotient (FibroQ) index using this formula 10 × (age in years × AST × INR)/(ALT × platelet count) [20]; King’s score using this formula Age (years) x AST (IU/L) x INR/platelet count (109/L) [21]; AST/ALT ratio (AAR) [22]; Göteborg University Cirrhosis Index (GUCI) using the formula (Normalized ASTxINRx100)/platelet count (109/L) [23].

Statistical Analysis

This retrospective study included 147 infants with surgically proved BA attending the Department of Pediatric Hepatology, Gastroenterology and Nutrition in the period between year 2010 and 2015. Preoperative demographic (age and sex), laboratory data including total and direct bilirubin, transaminases (alanine transaminase; ALT and aspartate transaminase; AST), biliary enzymes (gammaglutamyl transpeptidase; GGT and alkaline phosphatase; ALP), total proteins, serum albumin, international normalized ratio (INR) and platelets count were collected. Hepatic histopathological features in the form of portal fibrosis, were also revised. Due to the retrospective nature of the study, an informed consent was not needed. The study was approved by the Research Ethics Committee of the National Liver Institute, Menofiya University, Egypt.

Results

Study population’s characteristics

The current study included 147 infants with BA. Their mean age was 76 ± 41 days and 55% were females. Other baseline laboratory parameters and histopathological fibrosis grades were as presented in Table 1.

Distribution of serological scores according to fibrosis grades

The selected scores were compared according the individual fibrosis grades. In all the six scores, the values were at its lowest in F1 and was highest in F5 except for FibroQ and AAR, the values were lower than that of F4, yet, there was no significant statistical difference among the different grades of fibrosis (Figure 1). On the other hand, correlation analysis revealed a significant positive correlation of FIB-4, FibroQ and King’s scores with fibrosis grades (P values were 0.007 and 0.015 respectively) while there was no significant correlation with the other studied scores (P value >0.05) as shown in Table 2.
APRI: AST-to-platelet ratio index; FIB-4: Fibrosis-4; FibroQ: Fibro-quotient; AAR: AST/ALT ratio; GUCI: Göteborg University Cirrhosis Index.

Comparison between early and advanced fibrosis

For descriptive purpose, we arbitrarily divided fibrosis grades into early (F1, F2 and F3) and advanced (F4 and F5) fibrosis. Again, FIB-4, FibroQ and King’s scores showed a significantly higher values in those with advanced fibrosis (P values were 0.007, 0.017 and 0.009 respectively) while there was no significant difference using the other studied scores (P value >0.05) as shown in Table 3.

Performance of FIB-4, FibroQ and King’s scores in discriminating advanced fibrosis


The three scores (a cutoff value of 0.0098 for FIB-4; 0.0085 for FibroQ and 0.115 for King’s score) showed nearly a comparable performance in discriminating advanced fibrosis (Table 4).

Discussion

The prognosis of chronic cholestatic diseases depends, in part, on the extent of liver fibrosis [24,25], while it markedly influences the outcome of Kasai protoenterostomy in infants with BA [12]. In addition, it identifies those in need of liver transplantation whether in those who performed a previous Kasai operation or not [26,27] For that follow up of fibrosis progression is of utmost importance. Liver biopsy, being the gold standard in assessment of liver fibrosis, is not largely accepted when repeated, especially in the pediatric population. For that , the use of noninvasive predictor of liver fibrosis is needed [28,29].
Several noninvasive markers and scores have been applied satisfactorily in hepatitis C virus [18] and non-alcoholic fatty liver diseases [30], while studies on its use in BA are very limited. APRI score has been used in predicting liver fibrosis in BA. Yet, the results are contradictory. Kim et al. [31] reported that APRI significantly discriminated F3 and F4 Metavir score in infants with BA. AUROC for F≥3 and F=4 were 0.92 and 0.91, respectively. Distinct optimal cutoff values of APRI for F≥3 and F=4 were obtained (1.01 and 1.41, respectively). In addition, Grieve et al. [16] using a cutoff value of 1.22 [AUC 0.83] showed a sensitivity of 75% and a specificity of 84% for macroscopic cirrhosis. Native liver survival was significantly different but improved only for those with the lowest APRI quartile (P=0.009). Similar results were also reported by Yang et al. [32].
On the other hand, Lind et al. [33] found that APRI did not significantly differ in various fibrosis Metavir scores (P = 0.89) and was not correlated with transplant-free survival (r=0.08; P=0.67) in infants with BA. Our results are in agreement with that of Lind et al where APRI value neither differ significantly with different Russo fibrosis grades (P = 0.445) nor correlated with fibrosis (r=0.15; P = 0.07). Nonetheless, APRI values increased successively as fibrosis increases with its lowest in F1 and highest in F5.
Other scores have been used in predicting fibrosis in HCV, all of which are dependent on the routine laboratory tests regularly performed in these patients. Leung et al. [34] found that APRI performed better than FIB-4 in predicting fibrosis studied in children with cystic fibrosis liver disease. In the current study, contrary to APRI, FIB-4 was significantly correlated with fibrosis in BA (P = 0.007) and was significantly higher in those with advanced fibrosis (Russo F4 and F5; P=0.007). With AUROC of 0.644, FIB-4 could predict advanced fibrosis with 61.9% sensitivity and 61.9% specificity. On the other hand, Chen et al. [35] reported that FIB-4 failed to correlate with fibrosis stage. This may be due to the small number of patients in Chen’s study (n = 24) compared to our study (n = 147).
GUCI and AAR were able to predict fibrosis in HCV and hepatocellular carcinoma in addition to predicting response to antiviral therapy [36-38]. In our study, both scores were not correlated with liver fibrosis (P = 0.063 and 0.523 for GUCI and AAR respectively) and could not discriminate advanced from early fibrosis. Unfortunately, there are no reported studies for their use in BA.
On the other hand, FibroQ and King’s score showed a significant positive correlation with fibrosis grade (P = 0.015 for both) and at a cutoff value of 0.085 and 0.115 respectively, both could discriminate advanced fibrosis from early fibrosis with comparable sensitivity (64.3% for both) and specificity (60.0% and 62.9% respectively). King’s score has been used in assessing fibrosis in chronic hepatitis B [39] and hepatitis C [21] but no reports about its use in predicting fibrosis in BA. Combining the three scores (FIB-4, FibroQ and King’s score) did not improve the performance compared to the performance of each score individually. Although statistically significant, the performance of these scores was found to be better in adult studies with chronic hepatitis C. This may be due to the fibrogenic nature of BA and the relatively high platelet counts even in cases with advanced fibrosis [40] which may influence the performance of platelet count-based scores.
In conclusion, FIB-4, FibroQ and King’s, but not APRI, GUCI or AAR, correlated significantly with fibrosis grade in infants with BA. These noninvasive serological markers, which are derived from simple routine laboratory tests, may be of help in predicting advanced fibrosis and in long term follow up of infants with BA, and minimize the need for repeated follow up liver biopsies.


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Tuesday, September 17, 2019

Is Telomere Shortening a Genetic Factor That Predisposes to Diabetes Mellitus 2 and Oxidative Stress, or do They Induce It? A Telomere Shortening Predisposes to T2DM_Juniper Publishers






Authored by Murillo Ortiz Blanca

Abstract

Telomeres are structures at the ends of eukaryotic chromosomes and consist of tandemly repeated DNA sequences. Telomeres shorten with each cell division, and it is well known that telomere length in peripheral blood mononuclear cells (PBMCs) decreases with age. High oxidative stress can lead to accelerated telomere shortening, which causes premature cell senescence. In summary, this review shows the short Telomere Length has been identified in a limited number of population studies as a risk factor for development of T2DM. Also, it is importantly to notice the antioxidant properties of Curcumin which may play a key role in the prevention and treatment of premature aging while preserving the length of the telomeres.
Keywords: Telomere shortening; Oxidative stress; Genetic factor; Diabetes mellitus 2
Abbreviations: T2DM: Diabetes Mellitus 2; PBMCs: Cryopreserved Human Peripheral Blood Mononuclear Cells; WBCs: White Blood Cells;NO: Nitric Oxide; TBARS: Thiobarbituric Acid Reactive Substances

Introduction

Diabetes mellitus 2 and telomere shortening

Diabetes Mellitus 2 (T2DM) is a multifactorial complex disorder which is emerging as a major cause of morbidity and mortality [1]. Telomeres are structures located at the extreme ends of chromosomes and are considered as indicators of biological age [2]. Increased telomere shortening has been demonstrated in several diseases, including diabetes type [3-6]. Telomere shortening increases with the diabetes duration, in our study, we established the potential importance of telomere dynamics in T2DM. We associated the time of disease duration closely in parallel to the progressive increased of inflammation and/or oxidative stress and both played a direct role in telomere shortening [7]. However, a study based on Chinese population found no relationship between Telomere Length and either the onset time or the Diabetes Mellitus 2 duration [8]. Genetic regulation of telomere could potentially explain telomere shortening and also an increased risk for Diabetes Mellitus 2. Zee et al. [9], analyzed 11 telomere pathway genes and their relationship to the development of Diabetes Mellitus 2. A total of eleven tSNPs within TERF1, TNKS, TEP1, ACD and TERF2 were associated with Diabetes Mellitus 2 risk [9]. These findings suggest that genetic variation within the telomere pathway gene loci examined may be a useful predictor for Diabetes Mellitus 2 risk assessment [10,11]. Paik JK, et al. [12], did not observe an association between the selected TL-related SNPs and the presence of Hypertension and Coronary Heart Disease in [12]. These findings tell us the great importance of telomere dynamics in T2DM and the need for translational research.

Discussion

Oxidative stress and Telomere Length

Endogenous factors that cause telomere shortening are aging inflammation and oxidative stress. Telomere attrition (expressed in WBCs) can serve as a biomarker of the cumulative oxidative stress and inflammation [13,14]. The association of UCP2 gene involved in the production of reactive oxygen species and functional promoter variant in mitochondria with the telomere length implies a link between mitochondrial production of reactive oxygen species and shorter telomere length in Diabetes Mellitus 2 [15]. Oxidative stress exerts a major influence on telomere dynamics by two principal mechanisms; firstly, the GGG triples on the telomere sequence are highly sensitive to the hydroxyl radical. Masi et al. [16] demonstrated that antioxidant defenses are important to maintain telomere integrity, potentially reducing the progression of vascular ageing in patients with T2DM. Secondly in contrast to genomic DNA, telomeric DNA was reported to be deficient in the repair of single-strand breaks. Consequently telomeres appear to be especially vulnerable to the accumulation of ROS-induced DNA- strand breaks [17,18].

Prospective treatment for diabetes mellitus 2

Recent studies propose that telomere shortening and abnormal telomerase activity occur in patients with diabetes mellitus 2 and targeting the telomere-telomerase system has become a prospective treatment for diabetes mellitus [19]. Dietary supplementation of antioxidants has been proposed as alternative treatment to reduce oxidative stress caused by obesity and diabetes. Different studies have shown that curcumin has antioxidant and antihyperglycemic properties in diabetes and obese animal models [20-24]. Hyperglycemia modifies oxygen consumption rate, NO synthesis and increases TBARS levels in mitochondria from the liver and kidneys of diabetic mice, whereas curcumin may has a protective role against these alteration [25-27]. Antioxidant properties of curcumin could play a key role in the prevention and treatment of chronic inflammation diseases [28]. Zhou et al. [29] demonstrated that diet ingredients significantly have an impact on inflammation and oxidative stress markers, which probably also have an effect on Telomere Length. Diabetes patients with normal plasma glucose levels had longer Telomere Length [29].

Conclusion

Telomere Length has been identified in a limited number of population studies as a risk factor for development of T2DM, antioxidant defences are important to maintain telomere integrity, Curcumin which may play a key role in the prevention and treatment of premature aging while preserving the length of the telomeres.




Managing Water Resources Using - Water Radioactive Isotopes Monitoring and Risk Mapping-Juniper Pubishers

Agricultural Research & Technology: Open Access Journal - Juniper Publishers Opinion Radioactive contamination, also called rad...