Search results for: glucose metabolism

Authors: Kanokwan Sansuwan, Orapint Jintasataporn, Srinoy Chumkam

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Asian seabass is one of the economically important fish of Thailand and other countries in the Southeast Asia. Zinc is an essential trace metal to fish and vital to various biological processes and function. It is required for normal growth and indispensable in the diet. Therefore, the artificial diets offered to intensively cultivated fish must possess the zinc content required by the animal metabolism for health maintenance and high weight gain rates. However, essential elements must also be in an available form to be utilized by the organism. Thus, this study was designed to evaluate the application of different zinc forms, including organic Zinc (zinc amino acid complex) and inorganic Zinc (zinc sulfate), as feed additives in diets for Asian seabass. Three groups with five replicates of fish (mean weight 22.54 ± 0.80 g) were given a basal diet either unsupplemented (control) or supplemented with 50 mg Zn kg−¹ sulfate (ZnSO₄) or Zinc Amino Acid Complex (ZnAA) respectively. Feeding regimen was initially set at 3% of body weight per day, and then the feed amount was adjusted weekly according to the actual feeding performance. The experiment was conducted for 10 weeks. Fish supplemented with ZnAA had the highest values in all studied growth indicators (weight gain, average daily growth and specific growth rate), followed by fish fed the diets with the ZnSO₄, and lowest in fish fed the diets with the control. Lysozyme and superoxide dismutase (SOD) activity of fish supplemented with ZnAA were significantly higher compared with all other groups (P < 0.05). Fish supplemented with ZnSO₄ exhibited significant increase in digestive enzyme activities (protease, pepsin and trypsin) compared with ZnAA and the control (P < 0.05). However, no significant differences were observed for RNA and protein in muscle (P > 0.05). The results of the present work suggest that ZnAA are a better source of trace elements for Asian seabass, based on growth performance and immunity indices examined in this study.

Keywords: Asian seabass, growth performance, zinc amino acid complex (ZnAA), zinc sulfate (ZnSO₄)

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Authors: Jonathan Josephs-Spaulding, Hannah Rettig, Simon Graspeunter, Jan Rupp, Christoph Kaleta

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Background: Recurrent urinary tract infections (rUTIs) are a global cause of emergency room visits and represent a significant burden for public health systems. Therefore, metatranscriptomic approaches to investigate metabolic exchange and crosstalk between uropathogenic Escherichia coli (UPEC), which is responsible for 90% of UTIs, and collaborating pathogens of the urogenital microbiome is necessary to better understand the pathogenetic processes underlying rUTIs. Objectives: This study aims to determine the level in which uropathogens optimize the host urinary metabolic environment to succeed during invasion. By developing patient-specific metabolic models of infection, these observations can be taken advantage of for the precision treatment of human disease. Methods: To date, we have set up an rUTI patient cohort and observed various urine-associated pathogens. From this cohort, we developed patient-specific metabolic models to predict bladder microbiome metabolism during rUTIs. This was done by creating an in silico metabolomic urine environment, which is representative of human urine. Metabolic models of uptake and cross-feeding of rUTI pathogens were created from genomes in relation to the artificial urine environment. Finally, microbial interactions were constrained by metatranscriptomics to indicate patient-specific metabolic requirements of pathogenic communities. Results: Metabolite uptake and cross-feeding are essential for strain growth; therefore, we plan to design patient-specific treatments by adjusting urinary metabolites through nutritional regimens to counteract uropathogens by depleting essential growth metabolites. These methods will provide mechanistic insights into the metabolic components of rUTI pathogenesis to provide an evidence-based tool for infection treatment.

Keywords: recurrent urinary tract infections, human microbiome, uropathogenic Escherichia coli, UPEC, microbial ecology

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Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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Authors: Angkrit Phitchayangkoon, Ar-Aishah Dadeh

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Background: A key aim of triage is to identify the patients with high risk of cardiac arrest because they require intensive monitoring, resuscitation facilities, and early intervention. We aimed to identify the predicting factors such as initial vital signs, serum pH, serum lactate level, initial capillary blood glucose, and Modified Early Warning Score (MEWS) which affect the occurrence of cardiac arrest in an emergency department (ED). Methods: We conducted a retrospective data review of ED patients in an emergency department (ED) from 1 August 2014 to 31 July 2016. Significant variables in univariate analysis were used to create a multivariate analysis. Differentiation of predicting factors between cardiac arrest patient and non-cardiac arrest patients for occurrence of cardiac arrest in an emergency department (ED) was the primary outcome. Results: The data of 527 non-trauma patients with Emergency Severity Index (ESI) 1-3 were collected. The factors found to have a significant association (P < 0.05) in the non-cardiac arrest group versus the cardiac arrest group at the ED were systolic BP (mean [IQR] 135 [114,158] vs 120 [90,140] mmHg), oxygen saturation (mean [IQR] 97 [89,98] vs 82.5 [78,95]%), GCS (mean [IQR] 15 [15,15] vs 11.5 [8.815]), normal sinus rhythm (mean 59.8 vs 30%), sinus tachycardia (mean 46.7 vs 21.7%), pH (mean [IQR] 7.4 [7.3,7.4] vs 7.2 [7,7.3]), serum lactate (mean [IQR] 2 [1.1,4.2] vs 7 [5,10.8]), and MEWS score (mean [IQR] 3 [2,5] vs 5 [3,6]). A multivariate analysis was then performed. After adjusting for multiple factors, ESI level 2 patients were more likely to have cardiac arrest in the ER compared with ESI 1 (odds ratio [OR], 1.66; P < 0.001). Furthermore, ESI 2 patients were more likely than ESI 1 patients to have cardiovascular disease (OR, 1.89; P = 0.01), heart rate < 55 (OR, 6.83; P = 0.18), SBP < 90 (OR, 3.41; P = 0.006), SpO2 < 94 (OR, 4.76; P = 0.012), sinus tachycardia (OR, 4.32; P = 0.002), lactate > 4 (OR, 10.66; P = < 0.001), and MEWS > 4 (OR, 4.86; P = 0.028). These factors remained predictive of cardiac arrest at the ED. Conclusion: The factors related to cardiac arrest in the ED are ESI 1 patients, ESI 2 patients, patients diagnosed with cardiovascular disease, SpO2 < 94, lactate > 4, and a MEWS > 4. These factors can be used as markers in the event of simultaneous arrival of many patients and can help as a pre-state for patients who have a tendency to develop cardiac arrest. The hemodynamic status and vital signs of these patients should be closely monitored. Early detection of potentially critical conditions to prevent critical medical intervention is mandatory.

Keywords: cardiac arrest, predicting factor, emergency department, emergency patient

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Authors: Muhammad Imran, Sarfraz Shafiq, Xiangru Tang

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Alternative splicing (AS) is an important post-transcriptional regulatory mechanism to generate transcripts variability and proteome diversity in plants. Fragrant rice (Oryza sativa L.) has a high economic and nutritional value, and the application of micronutrients regulate 2-acetyl-1-pyrroline (2-AP) production, which is responsible for aroma in fragrant rice. However, no systematic investigation of AS events in response to micronutrients (Zn) has been performed in fragrant rice. Furthermore, the post-transcriptional regulation of genes involved in 2-AP biosynthesis is also not known. In this study, a comprehensive analysis of AS events under two gradients of Zn treatment in two different fragrant rice cultivars (Meixiangzhan-2 and Xiangyaxiangzhan) was performed. A total of 386 and 598 significant AS events were found in Meixiangzhan-2 treated with low and high doses of Zn, respectively. In Xiangyaxiangzhan, a total of 449 and 598 significant AS events were found in low and high doses of Zn, respectively. Go analysis indicated that these genes were highly enriched in physiological processes, metabolism, and cellular process in both cultivars. However, genotype and dose-dependent AS events were also detected in both cultivars. By comparing differential AS (DAS) events with differentially expressed genes (DEGs), we found a weak overlap among DAS and DEGs in both fragrant rice cultivars, indicating that only a few genes are post-transcriptionally regulated in response to Zn treatment. We further report that Zn differentially regulates the expression of 2-AP biosynthesis-related genes in both cultivars, and Zn treatment altered the editing frequency of SNPs in the genes involved in 2-AP biosynthesis. Finally, we showed that epigenetic modifications associated with active gene transcription are generally enriched over 2-AP biosynthesis-related genes. Taken together, our results provide evidence of the post-transcriptional gene regulation in fragrant rice in response to Zn treatment and highlight that the 2-AP biosynthesis pathway may also be post-transcriptionally regulated through epigenetic modifications. These findings will serve as a cornerstone for further investigation to understand the molecular mechanisms of 2-AP biosynthesis in fragrant rice.

Keywords: fragrant rice, 2-acetyl-1-pyrroline, gene expression, zinc, alternative splicing, SNPs

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Authors: Akram Abi, Clarissa Müller, Hans-Joachim Jördening

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Laminaribiose is a beta-1,3-glycoside which is used in the medical field for the treatment of dermatitis and also can be used as a building block for new pharmaceutics. The conventional process of laminaribiose production is the uneconomical process of hydrolysis of laminarin extracted from natural polysaccharides of plant origin. A more economical approach however is attainable by enzymatically synthesis of laminaribiose via a reverse phosphorylase reaction catalyzed by laminaribiose phosphorylase (LP) from Euglena gracilis. Different cultivation methods of Euglena gracilis and the effect on LP production have been investigated. Buffered/unbuffered heterotrophic and mixotrophic cultivations of Euglena gracilis has been carried out. Changes of biomass and LP production, glucose level and pH, cell count and shape has been monitored in the course of time. The results obtained from experiments each in three repetitions, show that in the heterotrophic cultivation of Euglena gracilis not only more biomass is produced compared to mixotrophic cultivation, but also higher specific protein concentration is achieved. Furthermore, the LP activity test showed that the protein extracted from heterotrophically cultured cells has a higher LP activity. It was also observed that the cells develop in a distinctive different shape between these two cultures and have different length to width ratios. Taking the heterotrophic culture as the more efficient cultivation method in LP production, another comparative experiment between buffered and unbuffered heterothrophic culture was carried out that showed the unbuffered culture has advantages over the other one in respect of both LP production and resulting activity. A hetrotrophic cultivation of Euglena gracilis in a 5L bioreactor with controlled operating conditions showed a distinctive improvement of all the aspects of culture compared to the shaking flask cultivations. Biomass production was improved from 5 to more than 8 g/l (dry weight) which resulted in a specific protein concentration of 45 g/l in the heterotrophic cultivation in the bioreactor. In further attempts to improve LP production, different purification methods were tested and each method was checks through an activity assay. A laminaribiose yield of 35% was achieved which was by far the highest amount amongst different methods tested.

Keywords: euglena gracilis, heterotrophic culture, laminaribiose production, mixotrophic culture

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Authors: Melba Sheila D'Souza, Anandhi Amirtharaj, Shreedevi Balachandran

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Background: Type 2 diabetes has a significant impact on individuals’ health and well-being. Glycemic control may influence self-efficacy and self-care behaviors, and reduce the risk of complications among adults with type 2 diabetes. Type 2 diabetes has substantial morbidity and mortality and 60% of adults’ poor self-care. Glycemic control is associated with reported self-efficacy and self-care behavior. Adults with type 2 diabetes with less information were less likely to take diabetes self-care. Aim: To examine the relationship between glycemic control, demographic factors, clinical factors on self-efficacy, self-care behaviors among Omani adults with type 2 diabetes. Methods: A correlational, descriptive study was used. Omani adults with type 2 diabetes (n=140) were recruited from a public hospital in Oman. The data were collected during January-March 2015. Ethical approval was given by the college research and ethics committee, College of Nursing, and the Hospital, Sultan Qaboos University Data was collected on self-efficacy, self-care behaviors and glycemic control. The study was approved by the Institution Ethics and Research Committee. Bivariate and multivariate analyses were conducted. Results: Most adults had a fasting blood glucose >7.2mmol/L (90.7%), with the majority demonstrating ‘uncontrolled or poor HbA1c of > 8%’ (65%). Variance of self-care behavior (20.6%) and 31.3% of the variance of the self-efficacy was explained by the age, duration of diabetes, medication, HbA1c and prevention of activities of living. Adults with type 2 diabetes with poor glycemic control were more likely to have poor self-efficacy and poor self-care behaviors. Conclusion: This study confirms that self-efficacy model on outcome predicts self-efficacy and self-care behavior. Higher understanding of diabetes, prevention of normal daily activities, higher ability to fit diabetes life in a positive manner and high patient-physician communication were significant with self-efficacy and self-care behaviors. Hence, glycemic control has a high effect on improving self-care behaviors like diet, exercise, medication, foot care and self-efficacy among type 2 diabetes. Implications: Using these findings to improve self-efficacy, individualized self-care management is recommended for better self-efficacy and self-care behaviors among adults with type 2 diabetes.

Keywords: self-efficacy, self-care behaviors, self-care management, glycemic control, type 2 diabetes, nurse

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Authors: Rabia Göçmen, Gülşah Kanbur, Sinan Sefa Parlat

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In this study, in the breeding Japanese quails (coturnix coturnix japonica), it was aimed to study the effects of cellular insulin receptor stimulation on the performance, some blood parameters, and hatchability features. In the study, a total of 84 breeding quails were used, which are in 6 weeks age, and whose 24 are male and 60 female. In the trial, rations which contain 2900 kcal/kg metabolic energy; crude protein of 20%, and water whose pH is calibrated to 7.45 were administered as ad-libitum, to the animals, as metformin source, metformin-HCl was used and as chrome resource, Chromium Picolinate. Trial groups were formed as control group (basal ration), metformin group (basal ration, added metformin at the level of fodder of 20 mg/kg), and chromium picolinate group (basal ration, added fodder of 1500 ppb Cr. When regarded to the results of performance at the end of trial, it is seen that live weight gain, fodder consumption, egg weight, fodder evaluation coefficient, and egg production were affected at the significant level (p < 0.05). When the results are evaluated in terms of incubation features at the end of trial, it was identified that incubation yield and hatchability are not affected by the treatments but in the groups, in which metformin and chromium picolinate are added to ration, that fertility rose at the significant level compared to control group (p < 0,05). According to the results of blood parameters and hormone at the end of the trial, while the level of plasma glucose level was not affected by treatments (p > 0.05), with the addition of metformin and chromium picolinate to ration, plasma, total control, cholesterol, HDL, LDL, and triglyceride levels were significantly affected from insulin receptor stimulators added to ration (p<0,05). Hormone level of Plasma T3 and T4 were also affected at the significant level from insulin receptor stimulators added to ration (p < 0,05).

Keywords: cholesterol, chromium picolinate, hormone, metformin, performance, quail

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Authors: Bouchiha Hanene, Rouabhi Rachid, Bouchama Khaled, Djebar Berrebbah Houraya, Djebar Mohamed Reda

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Recently, some natural products such as essentials oils (EOs) have been used in the fields as alternative to synthetic compounds, to minimize the negative impacts to the environment. This fact has led to questions about the possible impact of EOs on ecosystems. Currently in toxicology, the use of alternative models can help to understand the mechanisms of toxic action, at different levels of organization of ecosystems. Algae, protozoa and bacteria form the base of the food chain and protozoan cells are used as bioindicators often of pollution in environment. Unicellular organisms offer the possibility of direct study of independent cells with specific characteristics of individual cells and whole organisms at the same time. This unicellular facilitates the study of physiological processes, and effects of pollutants at the cellular level, which makes it widely used to assess the toxic effects of various xenobiotics. This study aimed to verify the effects of EOs of one famous plant used tremendously in our folk medicine, namely Artemisia herba alba in causing acute toxicity (24 hours) and chronic (15 days) toxicity for model cellular (Paramecium sp). To this end, cellular’s of paramecium were exposed to various concentrations (Three doses were chosen) of EOs extracted from plant (Artemisia herba alba). In the first experiment, the cellular s cultures were exposed for 48 hours to different concentrations to determine the median lethal concentration (DL50). We followed the evolution of physiological parameters (growth), biochemical (total proteins, respiratory metabolism), as well as the variations of a bio marker the GSH. Our results highlighted a light inhibition of the growth of the protozoa as well as a disturbance of the contents of total proteins and a reduction in the reduced rate of glutathione. The polarographic study revealed a stimulation of the consumption of O2 and this at the treated cells.

Keywords: essential oils, protozoa, bio indicators, toxicity, Growth, bio marker, proteins, polarographic

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Authors: Olufemi M. Alabi, Foluke A. Aderemi, Adebayo A. Adewumi, Banwo O. Alabi

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General well-being of animals is of paramount interest in some developed countries and of global importance hence the shift onto alternative housing systems for egg-type chickens as replacement for conventional battery cage system. However, there is paucity of information on the effect of this shift on physiological status of the hens to judge their health via the blood profile. Therefore, investigation was carried out on two strains of hen kept in three different housing systems in humid tropics to evaluate changes in their blood parameters. 108, 17-weeks old super black (SBL) hens and 108, 17-weeks old super brown (SBR) hens were randomly allotted to three different intensive systems Partitioned Conventional Cage (PCC), Extended Conventional Cage (ECC) and Deep Litter System (DLS) in a randomized complete block design with 36 hens per housing system, each with three replicates. The experiment lasted 37 weeks during which blood samples were collected at 18th week of age and bi-weekly thereafter for analyses. Parameters measured are packed cell volume (PCV), hemoglobin concentration (Hb), red blood counts (RBC), white blood counts (WBC) and serum metabolites such as total protein (TP), albumin (Alb), globulin (Glb), glucose, cholesterol, urea, bilirubin, serum cortisol while blood indices such as mean corpuscular hemoglobin (MCH), mean cell volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) were calculated. The hematological values of the hens were not significantly (p>0.05) affected by the housing system and strain, so also the serum metabolites except for the serum cortisol which was significantly (p<0.05) affected by the housing system only. Hens housed on PCC had higher values (20.05 ng/ml for SBL and 20.55 ng/ml for SBR) followed by hens on ECC (18.15ng/ml for SBL and 18.38ng/ml for SBL) while hens on DLS had the lowest value (16.50ng/ml for SBL and 16.00ng/ml for SBR) thereby confirming indication of stress with conventionally caged birds. Alternative housing systems can also be adopted for egg-type chickens in the humid tropics from welfare point of view with the results of this work confirming stress among caged hens.

Keywords: blood, housing, humid-tropics, layers

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Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath

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Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

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Authors: Sergejs Kolesovs, Pavels Semjonovs

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Whey and dairy wastewaters if disposed in the environment without proper treatment, cause serious environmental risks contributing to overall and particular environmental pollution and climate change. Biological treatment of wastewater is considered to be most eco-friendly approach, as compared to the chemical treatment methods. Research shows, that dairy wastewater can potentially be remediated by use of microalgae thussignificantly reducing the content of carbohydrates, P, N, K and other pollutants. Moreover, it has been shown, that use of dairy wastewaters results in higher microalgae biomass production. In recent decades microalgal biomass has entailed a big interest for its potential applications in pharmaceuticals, biomedicine, health supplementation, cosmetics, animal feed, plant protection, bioremediation and biofuels. It was shown, that lipids productivity on whey and dairy wastewater is higher as compared with standard cultivation media and occurred without the necessity of inducing specific stress conditions such as N starvation. Moreover, microalgae biomass production as usually associated with high production costs may benefit from perspective of both reasons – enhanced microalgae biomass or target substances productivity on cheap growth substrate and effective management of whey and dairy wastewaters, which issignificant for decrease of total production costs in both processes. Obviously, it became especially important when large volume and low cost industrial microalgal biomass production is anticipated for further use in agriculture of crops as plant growth stimulants, biopesticides soil fertilisers or remediating solutions. Environmental load of dairy wastewaters can be significantly decreased when microalgae are grown in coculture with other microorganisms. This enhances the utilisation of lactose, which is main C source in whey and dairy wastewaters when it is not metabolised easily by most microalgal species chosen. Our study showsthat certain microalgae strains can be used in treatment of residual sugars containing industrial wastewaters and decrease of their concentration thus approving that further extensive research on dairy wastewaters pre-treatment optionsfor effective cultivation of microalgae, carbon uptake and metabolism, strain selection and choice of coculture candidates is needed for further optimisation of the process.

Keywords: microalgae, whey, dairy wastewaters, sustainability, plant biostimulants

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Authors: Rajesh Kumar Suman, Ipseeta Ray Mohanty, Manjusha K. Borde, Ujjawala maheswari, Y. A. Deshmukh

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Background: Metabolic syndrome encompasses cluster of risk factors for cardiovascular disease which includes abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. The incidence of metabolic syndrome is on the rise globally. Objective: The present study was designed to develop a unique animal model that will mimic the pathological features seen in a large pool of individuals with diabetes and metabolic syndrome; suitable for pharmacological screening of drugs beneficial in this condition. Material and Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) at 30, 35 and 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in Wistar rats. Results: The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for our study to induce diabetes mellitus. Rat fed HFD (HF-DC) group showed significant (p < 0.001) increase in body weight on 4th and 7th week as compared with NC (Normal Control) group rats. However, the increase in body weight of HF-DC group rats was not sustained at the end of 10th weeks. Various components of metabolic syndrome such as dyslipidemia {(Increased Triglyceride, total Cholesterol, LDL Cholesterol and decreased HDL Cholesterol)}, diabetes mellitus (Blood Glucose, HbA1c, Serum Insulin, C-peptide), hypertension {Systolic Blood pressure (p < 0.001)} were mimicked in the developed model of metabolic syndrome co existing with diabetes mellitus. In addition significant cardiac injury as indicated by CPK-MB levels, artherogenic index, hs-CRP. The decline in hepatic function {(p < 0.01) increase in the level of SGPT (U/L)} and renal function {(increase in creatinine levels (p < 0.01)} when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis and inflammation in Heart, Pancreas, Liver and Kidney of HFD-DC group as compared to NC. Conclusion: The present study has developed a unique rodent model of metabolic syndrome; with diabetes as an essential component.

Keywords: diabetes, metabolic syndrome, high fat diet, streptozotocin, rats

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Authors: Shanker Kalakotla, Krishna Mohan Gottumukkala

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Diabetes is a metabolic disorder characterized by hyperglycemia, carbohydrates, altered lipids and proteins metabolism. In recent research nanotechnology is a blazing field for the researchers; latterly there has been prodigious excitement in the nanomedicine and nano pharmacological area for the study of silver nanoparticles synthesis using natural products. Biological methods have been used to synthesize silver nanoparticles in presence of medicinally active antidiabetic plants, and this intention made us assess the biologically synthesized silver nanoparticles from the seed extract of Psoralea corylfolia using 1 mM silver nitrate solution. The synthesized herbal mediated silver nanoparticles (HMSNP’s) then subjected to various characterization techniques such as XRD, SEM, EDX, TEM, DLS, UV and FT-IR respectively. In current study, the silver nanoparticles tested for in-vitro anti-diabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Herbal mediated silver nanoparticles were successfully obtained from bioreduction of silver nitrate using Psoralea corylifolia plant extract. Silver nanoparticles have been appropriately characterized and confirmed using different types of equipment viz., UV-vis spectroscopy, XRD, FTIR, DLS, SEM and EDX analysis. From the behavioral observations of the study, the female albino mice did not show sedation, respiratory arrest, and convulsions. Test compounds did not cause any mortality at the dose level tested (i.e., 2000 mg/kg body weight) doses till the end of 14 days of observation and were considered safe. It may be concluded that LD50 of the HMSNPs was 2000mg/kg body weight. Since LD50 of the HMSNPs was 2000mg/kg body weight, so the preferred dose range for HMSNPs falls between the levels of 200 and 400 mg/kg. Further In-vivo pharmacological models and biochemical investigations will clearly elucidate the mechanism of action and will be helpful in projecting the currently synthesized silver nanoparticles as a therapeutic target in treating chronic ailments.

Keywords: herbal mediated silver nanoparticles, HMSNPs, toxicity of silver nanoparticles, PTP1B in-vitro anti-diabetic assay female albino mice, 425 OECD guidelines

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Authors: Mohd Asharf Ganie, Aafia Rashid, Mohd Afzal Zargar, Showkat Ali Zargar, Syed Mudasar, Tabasum Parvaiz, Zafar Amin Shah

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Accumulating evidence suggests that Vitamin D deficiency (VDD) might at least contribute to the metabolic co-morbidities in PCOS. Hence, we aimed to study the effect of vitamin D supplementation in co-prescription with insulin sensitizers like metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS. In this open label randomized, controlled trial a total of 120 women with PCOS diagnosis (AE-PCOS 2009 Criteria) were assigned to four treatment groups (n= 30 in each): group I (metformin 1 gm/day in combination with cholecalciferol 4000 IU/day), group II (pioglitazone 30 mg/day in combination with cholecalciferol 4000 IU/day), group III (metformin 1 gm /day) and group IV (pioglitazone 30 mg/day). Vitamin D supplementation was given as 60,000 units every two weeks for 24 weeks. All the subjects were routinely evaluated for clinical, biochemical, hormonal and insulin sensitivity parameters in addition to various safety parameters especially serum calcium levels at baseline and after 24 weeks of the treatment. Our results indicate that 95.5% of PCOS women were vitamin D deficient at baseline. Serum 25 (OH) D levels increased significantly (p < 0.001) in groups I and II without any adverse effects after 24 weeks of oral administration of 4000 IU cholecalciferol daily. However, serum 25 (OH) D levels remained unchanged in group III and IV. By six months, number of menstrual cycles per year increased whereas Ferriman-Gallwey score, serum total testosterone and HOMA-IR decreased significantly (P < 0.001) in the treatment groups supplemented with cholecalciferol as compared to those treated either drug alone. No significant beneficial changes were observed on weight, BMI, blood pressure, glucose tolerance and serum lipids in any of the groups supplemented with cholecalciferol. We conclude that daily dose of 4000 IU cholecalciferol might be a useful adjunct in complex treatment of PCOS with fewer adverse events. Furthermore, pioglitazone and cholecalciferol combination seems to be marginally better although there was no statistical significance.

Keywords: PCOS, vitamin D supplementation, insulin resistance, spironolactone, metformin, pioglitazone

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Authors: Marwa Brahim, Nicolas Brosse, Nadia Boussetta, Nabil Grimi, Eugene Vorobiev

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Rapeseed plant is an established product in France which is mainly dedicated to oil production. However, the economic potential of residues from this industry (rapeseed hulls, rapeseed cake, rapeseed straw etc.), has not been fully exploited. Currently, only low-grade applications are found in the market. As a consequence, it was deemed of interest to develop a technological platform aiming to convert rapeseed residues into value- added products. Specifically, a focus is given on the conversion of rapeseed straw into valuable molecules (e.g. lignin, glucose). Existing pretreatment technologies have many drawbacks mainly the production of sugar degradation products that limit the effectiveness of saccharification and fermentation steps in the overall scheme of the lignocellulosic biorefinery. In addition, the viability of fractionation strategies is a challenge in an environmental context increasingly standardized. Hence, the need to find cleaner alternatives with comparable efficiency by implementing physical phenomena that could destabilize the structural integrity of biomass without necessarily using chemical solvents. To meet environmental standards increasingly stringent, the present work aims to study the new pretreatment strategies involving lower consumption of chemicals with an attenuation of the severity of the treatment. These strategies consist on coupling physical treatments either high voltage electrical discharges or ultrasounds to conventional chemical pretreatments (soda and organosolv). Ultrasounds treatment is based on the cavitation phenomenon, and high voltage electrical discharges cause an electrical breakdown accompanied by many secondary phenomena. The choice of process was based on a technological feasibility study taking into account the economic profitability of the whole chain after products valorization. Priority was given to sugars valorization into bioethanol and lignin sale.

Keywords: high voltage electrical discharges, organosolv, pretreatment strategies, rapeseed straw, soda, ultrasounds

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Authors: German Hernandez-Alonso, Antonio Lazcano, Arturo Becerra

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Until today, viruses remain controversial and poorly understood; about their origin, this problem represents an enigma and one of the great challenges for the contemporary biology. Three main theories have tried to explain the origin of viruses: regressive evolution, escaped host gene, and pre-cellular origin. Under the perspective of the escaped host gene theory, it can be assumed a cellular origin of viral components, like protein RNA-binding domains. These universal distributed RNA-binding domains are related to the RNA metabolism processes, including transcription, processing, and modification of transcripts, translation, RNA degradation and its regulation. In the case of viruses, these domains are present in important viral proteins like helicases, nucleases, polymerases, capsid proteins or regulation factors. Therefore, they are implicated in the replicative cycle and parasitic processes of viruses. That is why it is possible to think that those domains present low levels of divergence due to selective pressures. For these reasons, the main goal for this project is to create a catalogue of the RNA-binding domains found in all the available viral proteomes, using bioinformatics tools in order to analyze its evolutionary process, and thus shed light on the general virus evolution. ProDom database was used to obtain larger than six thousand RNA-binding domain families that belong to the three cellular domains of life and some viral groups. From the sequences of these families, protein profiles were created using HMMER 3.1 tools in order to find distant homologous within greater than four thousand viral proteomes available in GenBank. Once accomplished the analysis, almost three thousand hits were obtained in the viral proteomes. The homologous sequences were found in proteomes of the principal Baltimore viral groups, showing interesting distribution patterns that can contribute to understand the evolution of viruses and their host-virus interactions. Presence of cellular RNA-binding domains within virus proteomes seem to be explained by closed interactions between viruses and their hosts. Recruitment of these domains is advantageous for the viral fitness, allowing viruses to be adapted to the host cellular environment.

Keywords: bioinformatics tools, distant homology, RNA-binding domains, viral evolution

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Authors: Ihcen Khacheba, Amar Djeridane, Abdelkarim Kamli, Mohamed Yousfi

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Plant materials constitute an important source of natural bioactive molecules. Thus plants have been used from antiquity as sources of medicament against various diseases. These properties are usually attributed to secondary metabolites that are the subject of a lot of research in this field. This is particularly the case of phenolic compounds plants that are widely renowned in therapeutics as anti-inflammatories, enzyme inhibitors, and antioxidants, particularly flavonoïds. With the aim of acquiring a better knowledge of the secondary metabolism of the vegetable kingdom in the region of Laghouat and of the discovering of new natural therapeutics, 10 extracts from 5 Saharan plant species were submitted to chemical screening.The analysis of the preceding biological targets led to the evaluation of the biological activity of the extracts of the species Genista Corsica. The first step, consists in extracting and quantifying phenolic compounds. The second step has been devoted to stugying the effects of phenolic compounds on the kinetics catalyzed by two enzymes belonging to the class of hydrolase (the α-amylase and α-glucosidase) responsible for the digestion of sugars and finally we evaluate the antiantioxidant potential. The analysis results of phenolic extracts show clearly a low content of phenolic compounds in investigated plants. Average total phenolics ranged from 0.0017 to 11.35 mg equivalent gallic acid/g of the crude extract. Whereas the total flavonoids content lie between 0.0015 and 10.,96 mg/g equivalent of rutin. The results of the kinetic study of enzymatic reactions show that the extracts have inhibitory effects on both enzymes, with IC50 values ranging from 95.03 µg/ml to 1033.53 µg/ml for the α-amylase and 279.99 µg/ml to 1215.43 µg/ml for α-glucosidase whose greatest inhibition was found for the acetone extract of June (IC50 = 95.03 µg/ml). The results the antioxidant activity determined by ABTS, DPPH, and phosphomolybdenum tests clearly showed a good antioxidant capacity comparatively to antioxidants taken as reference the biological potential of these plants and could find their use in medicine to replace synthetic products.

Keywords: phenolic extracts, inhibition effect, α-amylase, α-glucosidase, antioxidant activity

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Authors: P. S. Percin, O. Inanli, S. Karakaya

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Bitter melon (Momordica charantia) is a medicinal vegetable, which is used traditionally to remedy diabetes. Bitter melon contains several classes of primary and secondary metabolites. In traditional Turkish medicine bitter melon is used for wound healing and treatment of peptic ulcers. Nowadays, bitter melon is used for the treatment of diabetes and ulcerative colitis in many countries. The main constituents of bitter melon, which are responsible for the anti-diabetic effects, are triterpene, protein, steroid, alkaloid and phenolic compounds. In this study total phenolics, total carotenoids and β-carotene contents of mature and immature bitter melons were determined. In addition, in vitro α-amylase and α-glucosidase activities of mature and immature bitter melons were studied. Total phenolic contents of immature and mature bitter melon were 74 and 123 mg CE/g bitter melon respectively. Although total phenolics of mature bitter melon was higher than that of immature bitter melon, this difference was not found statistically significant (p > 0.05). Carotenoids, a diverse group of more than 600 naturally occurring red, orange and yellow pigments, play important roles in many physiological processes both in plants and humans. The total carotenoid content of mature bitter melon was 4.36 fold higher than the total carotenoid content of immature bitter melon. The compounds that have hypoglycaemic effect of bitter melon are steroidal saponins known as charantin, insulin-like peptides and alkaloids. α-Amylase is one of the main enzymes in human that is responsible for the breakdown of starch to more simple sugars. Therefore, the inhibitors of this enzyme can delay the carbohydrate digestion and reduce the rate of glucose absorption. The immature bitter melon extract showed α-amylase and α-glucosidase inhibitory activities in vitro. α-Amylase inhibitory activity was higher than that of α-glucosidase inhibitory activity when IC50 values were compared. In conclusion, the present results provide evidence that aqueous extract of bitter melon may have an inhibitory effect on carbohydrate breakdown enzymes.

Keywords: bitter melon, in vitro antidiabetic activity, total carotenoids, total phenols

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Authors: Lintle Mohase, Ninikoe Lebusa, Mpho Stephen Mafa

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Wheat is an economically important cereal crop. However, the changing climatic conditions that intensify drought in production areas, and additional pest infestation, such as the Russian wheat aphid (RWA, Diuraphis noxia), severely hamper its production. Drought and pest management require an additional water supply through irrigation and applying inorganic nutrients (including silicon) as alternative strategies to mitigate the stress effects. Therefore, other approaches are needed to enhance wheat productivity during drought stress and aphid abundance. Two wheat cultivars were raised under greenhouse conditions, exposed to drought stress, and treated with silicon before infestation with the South African RWA biotype 2 (RWASA2). The morphological evaluations showed that severe drought or a combination of drought and infestation significantly reduced the plant height of wheat cultivars. Silicon treatment did not alleviate the growth reduction. The biochemical responses were measured using spectrophotometric assays with specific substrates. An evaluation of the enzyme activities associated with oxidative stress and defence responses indicated that drought stress increased NADPH oxidase activity, while silicon treatment significantly reduced it in drought-stressed and infested plants. At 48 and 72 hours sampling periods, a combination of silicon, drought and infestation treatment significantly increased peroxidase activity compared to drought and infestation treatment. The treatment also increased β-1,3-glucanase activity 72 hours after infestation. In addition, silicon and drought treatment increased glucose but reduced sucrose accumulation. Furthermore, silicon, drought, and infestation treatment combinations reduced the sucrose content. Finally, silicon significantly increased the trehalose content under severe drought and infestation, evident at 48 and 72-hour sampling periods. Our findings shed light on silicon’s ability to induce protective biochemical responses during drought and aphid infestation.

Keywords: drought, enzyme activity, silicon, soluble sugars, Russian wheat aphid, wheat

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Authors: Hamza Ikhlaq, Stephen Franks

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Background: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. The aetiology behind PCOS is poorly understood but influencing ethnic, environmental, and genetic factors have been recognised. However, literature examining the impact of ethnicity is scarce. We hypothesised Body Mass Index (BMI) and ethnicity influence the clinical, metabolic, and biochemical presentations of PCOS, with an interaction between these factors. Methods: A database of 1081 women with PCOS and a control group of 72 women were analysed. BMIs were grouped using the World Health Organisation classification into normal weight, overweight and obese groups. Ethnicities were classified into European, South Asian, and Afro-Caribbean groups. Biochemical and clinical presentations were compared amongst these groups, and statistical analyses were performed to assess significance. Results: This study revealed ethnicity significantly influences biochemical and clinical presentations of PCOS. A greater proportion of South Asian women are impacted by menstrual cycle disturbances and hirsutism than European and Afro-Caribbean women. South Asian and Afro-Caribbean women show greater measures of insulin resistance and weight gain when compared to their European peers. Women with increased BMI are shown to have an increased prevalence of PCOS phenotypes alongside increased levels of insulin resistance and testosterone. Furthermore, significantly different relationships between the waist-hip ratio and measures of insulin and glucose control for Afro-Caribbean women were identified compared to other ethnic groups. Conclusions: The findings of this study show ethnicity significantly influence the phenotypic and biochemical presentations of PCOS, with an interaction between body habitus and ethnicity found. Furthermore, we provide further data on the influences of BMI on the manifestations of PCOS. Therefore, we highlight the need to consider these factors when reviewing diagnostic criteria and delivering clinical care for these groups.

Keywords: PCOS, ethnicity, BMI, clinical

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Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

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A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

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Authors: Janneth Gonzalez, Andres Pinzon Velasco, Maria Angarita, Nicolas Mendoza

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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatory pathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, there are few studies on the neuro-protective mechanisms of tibolone, especially at the systemic (omic) level. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also use control theory to identify those reactions that control the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a change in energy source use through inhibition of folate cycle and fatty acid β-oxidation and upregulation of ketone bodies formation.We found 25 metabolic switches under PA-mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation in metabolic pathways that increase neurotoxicity and represent potential treatment targets. Finally, this study framework facilitates the understanding of metabolic regulation strategies, andit can be used for in silico exploring the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics, control theory

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Authors: Adkham Paiziev, Fikrat Kerimov

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Near Infrared Spectroscopy (NIRS) is one of the biophotonic techniques which can be used to monitor oxygenation and hemodynamics in a variety of human tissues, including skeletal muscle. In the present work, we are offering tissue oximetry (OxyPrem) to measure hemodynamic parameters of skeletal muscles in rest and exercise. Purpose: - To elaborate the new wireless, portable, noninvasive, wearable NIRS device to measure skeletal muscle oxygenation during exercise. - To test this device on brachioradialis muscle of wrestler volunteers by using combined method of arterial occlusion (AO) and NIRS (AO+NIRS). Methods: Oxyprem NIRS device has been used together with AO test. AO test and Isometric brachioradialis muscle contraction experiments have been performed on one group of wrestler volunteers. ‘Accu- Measure’ caliper (USA) to measure skinfold thickness (SFT) has been used. Results: Elaborated device consists on power supply box, a sensor head and installed ‘Tubis’ software for data acquisition and to compute deoxyhemoglobin ([HHb), oxyhemoglobin ([O2Hb]), tissue oxygenation (StO2) and muscle tissue oxygen consumption (mVO2). Sensor head consists on four light sources with three light emitting diodes with nominal wavelengths of 760 nm, 805 nm, and 870 nm, and two detectors. AO and isometric voluntary forearm muscle contraction (IVFMC) on five healthy male subjects (23,2±0.84 in age, 0.43±0.05cm of SFT ) and four female subjects (22.0±1.0 in age and 0.24±0.04 cm SFT) has been measured. mVO2 for control group has been calculated (-0.65%/sec±0.07) for male and -0.69%/±0.19 for female subjects). Tissue oxygenation index for wrestlers in average about 75% whereas for control group StO2 =63%. Second experiment was connected with quality monitoring muscle activity during IVFMC at 10%,30% and 50% of MVC. It has been shown, that the concentration changes of HbO2 and HHb positively correlated to the contraction intensity. Conclusion: We have presented a portable multi-channel wireless NIRS device for real-time monitoring of muscle activity. The miniaturized NIRS sensor and the usage of wireless communication make the whole device have a compact-size, thus can be used in muscle monitoring.

Keywords: skeletal muscle, oxygenation, instrumentation, near infrared spectroscopy

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Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

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Authors: Pablo Cid Galache, Laura Zamorano Bonilla

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Mauriac syndrome (MS) is a rare complication of type 1 diabetes mellitus (DM1). It is rela-ted to low insulin concentrations. Therefore is a complication mainly found in developing countries. The main clinical features are hepatomegaly, edema, growth and puberty delay, and the presence of elevated transaminases and serum lipids. The MS incidence is de-creasing due to the new types of insulin and intensive glycemic control. Therefore is a rare diagnosis in Europe nowadays, being described mainly in developing countries or with so-cioeconomic limitations to guarantee an adequate management of diabetes. Edema secondary to fluid retention is a rare complication of insulin treatment, especially in young patients. Its severity is variable and is mainly related to the start of a proper treatment and the improvement in glycemic control after diagnosis or after periods of poor metabolic control. Edema resolves spontaneously without requiring treatment in most cases. The Pediatric Endocrinology Unit of Hospital Motril could diagnose a 14-year-old girl who presented very poor metabolic control during the last 3 years as a consequence of the socioeconomic conditions of the country of origin during the last years. Presents up to 4 admissions for ketoacidosis during the last 12 months. After the family moved to Spain our patient began to be followed up in our Hospital. Initially presented glycated hemoglobin figures of 11%. One week after the start of treatment, the patient was admitted in the emergency room due to the appearance of generalized edema and pain in the limbs. The main laboratory abnormalities include: blood glucose 225mg/dl; HbA1C 10.8% triglycerides 543 mg/dl, total cholesterol 339 mg/dl (LDL 225) GOT 124 U/l, GPT 89U/l. Abdominal ultrasound shows mild hepatomegaly and no signs of ascites were shown. The patient presented a progressive improvement with resolution of the edema and analitical abnormalities during the next two weeks. During admission, the family received diabetes education, achieving adequate glycemic control at discharge. Nowadays the patient has a good glycemic control having glycated hemoglobin levels around 7%.

Keywords: Mauriac, diabetes, complication, developing countries

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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NASH is an increasingly prevalent chronic liver disease that can progress to hepatocellular carcinoma and now is attracting interest worldwide. The STAM™ model is a clinically-correlated murine NASH model which shows the same pathological progression as NASH patients and has been widely used for pharmacological and basic research. The multiple parallel hits hypothesis suggests abnormalities in adipocytokines, intestinal microflora, and endotoxins are intertwined and could contribute to the development of NASH. In fact, NASH patients often exhibit gut dysbiosis and dysfunction in adipose tissue and metabolism. However, the analysis of the STAM™ model has only focused on the liver. To clarify whether the STAM™ model can also mimic multiple pathways of NASH progression, we analyzed the organ crosstalk interactions between the liver and the gut and the phenotype of adipose tissue in the STAM™ model. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin 2 days after birth and feeding with high-fat diet after 4 weeks of age. The mice were sacrificed at NASH stage. Colon samples were snap-frozen in liquid nitrogen and stored at -80˚C for tight junction-related protein analysis. Adipose tissue was prepared into paraffin blocks for HE staining. Blood adiponectin was analyzed to confirm changes in the adipocytokine profile. Tight junction-related proteins in the intestine showed that expression of ZO-1 decreased with the progression of the disease. Increased expression of endotoxin in the blood and decreased expression of Adiponectin were also observed. HE staining revealed hypertrophy of adipocytes. Decreased expression of ZO-1 in the intestine of STAM™ mice suggests the occurrence of leaky gut, and abnormalities in adipocytokine secretion were also observed. Together with the liver, phenotypes in these organs are highly similar to human NASH patients and might be involved in the pathogenesis of NASH.

Keywords: Non-alcoholic steatohepatitis, hepatocellular carcinoma, fibrosis, organ crosstalk, leaky gut

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Authors: Yenny Paola Morales Cortés, Fabián Rico Rodríguez, Juan Carlos Serrato Bermúdez, Carlos Arturo Martínez Riascos

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Numerous benefits of galactooligosaccharides (GOS) as prebiotics have motivated the study of enzymatic processes for their production. These processes have special complexities due to several factors that make difficult high productivity, such as enzyme type, reaction medium pH, substrate concentrations and presence of inhibitors, among others. In the present work the production of galactooligosaccharides (with different degrees of polymerization: two, three and four) from lactose was studied. The study considers the formulation of a mathematical model that predicts the production of GOS from lactose using the enzyme β-galactosidase. The effect of pH in the reaction was studied. For that, phosphate buffer was used and with this was evaluated three pH values (6.0.6.5 and 7.0). Thus it was observed that at pH 6.0 the enzymatic activity insignificant. On the other hand, at pH 7.0 the enzymatic activity was approximately 27 times greater than at 6.5. The last result differs from previously reported results. Therefore, pH 7.0 was chosen as working pH. Additionally, the enzyme concentration was analyzed, which allowed observing that the effect of the concentration depends on the pH and the concentration was set for the following studies in 0.272 mM. Afterwards, experiments were performed varying the lactose concentration to evaluate its effects on the process and to generate the data for the adjustment of the mathematical model parameters. The mathematical model considers the reactions of lactose hydrolysis and transgalactosylation for the production of disaccharides and trisaccharides, with their inverse reactions. The production of tetrasaccharides was negligible and, because of that, it was not included in the model. The reaction was monitored by HPLC and for the quantitative analysis of the experimental data the Matlab programming language was used, including solvers for differential equations systems integration (ode15s) and nonlinear problems optimization (fminunc). The results confirm that the transgalactosylation and hydrolysis reactions are reversible, additionally inhibition by glucose and galactose is observed on the production of GOS. In relation to the production process of galactooligosaccharides, the results show that it is necessary to have high initial concentrations of lactose considering that favors the transgalactosylation reaction, while low concentrations favor hydrolysis reactions.

Keywords: β-galactosidase, galactooligosaccharides, inhibition, lactose, Matlab, modeling

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Authors: Gina Cecilia Pistol, Loredana Calin, Mariana Stancu, Veronica Chedea, Ionelia Taranu

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Inflammatory-associated diseases have an increased trend in the past decades. The pharmacological strategies aimed to treat these inflammatory diseases are very expensive and with non-beneficial results. The current trend is to find alternative strategies to counteract or to control inflammatory component of diseases. The grape by-products either seeds or pomace are rich in bioactive compounds (e.g. polyphenols) which may be beneficial in prevention of inflammation associated with cancer progression and other pathologies with inflammatory component. The in vivo models are very useful for studying the immune and inflammatory status. The domestic pig (Sus scrofa domesticus) is related to human from anatomic and physiologic point of view, representing a feasible model for studying the human inflammatory pathologies. Starting from these data, we evaluated the effect of a diet containing 5% grape seed cakes (GS) on piglets blood biochemical parameters and immune pro- and anti-inflammatory biomarkers (IL-1 beta, IL-8, TNF-alpha, IL-6, IFN-gamma, IL-10, IL-4) in spleen and lymph nodes. 12 weaned piglets were fed for 30 days with a control diet or an experimental diet containing 5% GS. At the end of trial, plasma and tissue samples (spleen and lymph nodes) were collected and the biochemical and inflammatory markers were analysed by using biochemistry analyser and ELISA techniques. Our results showed that diet included 5% GS did not influence the health status determined by plasma biochemical parameters. Only a tendency for a slight increase of the biochemical parameters associated with energetic profile (glucose, cholesterol, triglycerides) was observed. Also, GS diet had no effect on pro- and anti-inflammatory cytokines content in spleen and lymph nodes tissue. Further experiments are needed in order to investigate other rate of dietary inclusion which could provide more evidence about the effect of grape bioactive compounds on pigs used as animal model.

Keywords: animal model, inflammation, grape seed by-product, immune organs

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