Search results for: metabolism and excretion–toxicity

Authors: Jin-Ming Wu, Te-Wei Ho, Yu-Wen Tien

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Background: The aim of this population-based study was to determine the occurrence of diabetes and exocrine pancreatic insufficiencies (EPI) on non-diabetes subjects receiving distal pancreatectomy (DP). Method: A nationwide cohort study between 2000 and 2010 was collected from the Taiwan National Health Insurance Research Database. Among 3264 DP patients, we identified 1410 non-diabetes and 966 non-diabetes non-EPI. Results. Of 1410 non-diabetes DP subjects, 312 patients (22.1%) developed newly-diagnosed diabetes after PD. On a multiple logistic regression model, co-morbid hyperlipidemia (odds ratio, 1.640; 95% CI, 1.362–2.763; P < 0.001) and pancreatitis (odds ratio, 2.428; 95% CI, 1.889–3.121; P < 0.001) significantly contributed to higher incidences of diabetes after DP. Moreover, 380 subjects (39.3%) developed EPI, and pancreatic cancer is the statistically significant risk factor (odds ratio, 4.663; 95% CI, 2.108–6.085; P < 0.001). Conclusion: The patients with co-morbid hyperlipidemia and chronic pancreatitis had higher rates of newly-diagnosed diabetes after DP, moreover, pancreatic cancer subjects had higher rates of pancreatic exocrine insufficiency after DP. The clinicians should be alert to follow up glucose metabolism and clinical symptoms of fat intolerance for DP patients.

Keywords: distal pancreatectomy, National database, diabetes, exocrine insufficiency

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Authors: Daniel Osorio, Janneth Gonzalez, Andres Pinzon

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In this work, proteins and metabolic pathways associated with the neuroprotective response mediated by the synthetic neurosteroid tibolone under a palmitate-induced inflammatory model were identified by flux balance analysis (FBA). Three different metabolic scenarios (‘healthy’, ‘inflamed’ and ‘medicated’) were modeled over a gene expression data-driven constructed tissue-specific metabolic reconstruction of mature astrocytes. Astrocyte reconstruction was built, validated and constrained using three open source software packages (‘minval’, ‘g2f’ and ‘exp2flux’) released through the Comprehensive R Archive Network repositories during the development of this work. From our analysis, we predict that tibolone executes their neuroprotective effects through a reduction of neurotoxicity mediated by L-glutamate in astrocytes, inducing the activation several metabolic pathways with neuroprotective actions associated such as taurine metabolism, gluconeogenesis, calcium and the Peroxisome Proliferator Activated Receptor signaling pathways. Also, we found a tibolone associated increase in growth rate probably in concordance with previously reported side effects of steroid compounds in other human cell types.

Keywords: astrocytes, flux balance analysis, genome scale metabolic reconstruction, inflammation, neuroprotection, tibolone

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Authors: Babarina Maria, Andropova Margarita

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Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disorder with an estimated prevalence of 0.25 per 1000 individuals. The most common cause of HypoPT is the loss of active parathyroid tissue following thyroid or parathyroid surgery. Sometimes permanent postoperative HypoPT occures, manifested by hypocalcemia in combination with low levels of PTH during 6 months or more after surgery. Cognitive impairments in patients with hypocalcemia due to chronic HypoPT are observed, and this can lead to problems and challenges in everyday living: memory loss and impaired concentration, that may be the cause of poor compliance. Clinical case: Patient K., 66 years old, underwent thyroidectomy in 2013 (at the age of 55) because of papillary thyroid cancer T1NxMx, histopathology findings confirmed the diagnosis. 5 years after the surgery, she was followed up on an outpatient basis, TSH levelsonly were monitored, and the dose of levothyroxine was adjusted. In 2018 due to, increasing complaints include tingling and cramps in the arms and legs, memory loss, sleep disorder, fatigue, anxiety, hair loss, muscle pain, tachycardia, positive Chvostek, and Trousseau signs were diagnosed during examination, also in blood analyses: total Ca 1.86 mmol/l (2.15-2.55), Ca++ 0.96 mmol/l (1.12-1.3), P 1.55 mmol/l (0.74-1.52), Mg 0.79 mmol/l (0.66-1.07) - chronic postoperative HypoPT was diagnosed. Therapy was initiated: alfacalcidol 0.5 mcg per day, calcium carbonate 2000 mg per day, cholecalciferol 1000 IU per day, magnesium orotate 3000 mg per day. During the case follow-up, hypocalcemia, hyperphosphatemia persisted, hypercalciuria15.7 mmol/day (2.5-6.5) was diagnosed. Dietary recommendations were given because of the high content of phosphorus rich foods, and therapy was adjusted: the dose of alfacalcidol was increased to 2.5 mcg per day, and the dose of calcium carbonate was reduced to 1500 mg per day. As part of the screening for complications of hypoPT, data for cataracts, Fahr syndrome, nephrocalcinosis, and kidney stone disease were not obtained. However, HypoPT compensation was not achieved, and therefore hydrochlorothiazide 25 mg was initiated, the dose of alfacalcidol was increased to 3 mcg per day, calcium carbonate to 3000 mg per day, magnesium orotate and cholecalciferol were continued at the same doses. Therapeutic goals were achieved: calcium phosphate product <4.4 mmol2/l2, there were no episodes of hypercalcemia, twenty-four-hour urinary calcium excretion was significantly reduced. Conclusion: Timely prescription, careful explanation of drugs usage rules, and monitoring and maintaining blood and urine parameters within the target contribute to the prevention of HypoPT complications development and life-threatening events.

Keywords: hypoparathyroidism, hypocalcemia, hyperphosphatemia, hypercalciuria

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Authors: Pannaga Pavan Jutur

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Parachlorella kessleri, a marine unicellular green alga belonging to class Trebouxiophyceae, accumulates large amounts of oil, i.e., lipids under nutrient-deprived (-N, -P, and -S) conditions. Understanding their metabolic imprints is important for elucidating the physiological mechanisms of lipid accumulations in this microalga subjected to nutrient deprivation. Metabolic and lipidomic profiles were obtained respectively using gas chromatography-mass spectrometry (GC-MS) of P. kessleri under nutrient starvation (-N, -P and -S) conditions. Relative quantities of more than 100 metabolites were systematically compared in all these three starvation conditions. Our results demonstrate that in lipid metabolism, the quantities of neutral lipids increased significantly followed by the decrease in other metabolites involved in photosynthesis, nitrogen assimilation, etc. In conclusion, the metabolomics and lipidomic profiles have identified a few common metabolites such as citric acid, valine, and trehalose to play a significant role in the overproduction of oil by this microalga subjected to nutrient deprivation. Understanding the entire system through untargeted metabolome profiling will lead to identifying relevant metabolites involved in the biosynthesis and degradation of precursor molecules that may have the potential for biofuel production, aiming towards the vision of tomorrow’s bioenergy needs.

Keywords: algae, biofuels, nutrient stress, omics

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Authors: Dipali Nagaonkar, Mahendra Rai

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Chitosan, a carbohydrate polymer at nanoscale level has gained considerable momentum in drug delivery applications due to its inherent biocompatibility and non-toxicity. However, conventional synthetic strategies for chitosan nanoparticles mainly rely upon physicochemical techniques, which often yield chitosan microparticles. Hence, there is an emergent need for development of controlled synthetic protocols for chitosan nanoparticles within the nanometer range. In this context, we report the green synthesis of size controlled chitosan nanoparticles by using Pongamia pinnata (L.) leaf extract. Nanoparticle tracking analysis confirmed formation of nanoparticles with mean particle size of 85 nm. The stability of chitosan nanoparticles was investigated by zetasizer analysis, which revealed positive surface charged nanoparticles with zeta potential 20.1 mV. The green synthesized chitosan nanoparticles were further explored for encapsulation and controlled release of antioxidant biomolecule, quercetin. The resulting drug loaded chitosan nanoparticles showed drug entrapment efficiency of 93.50% with drug-loading capacity of 42.44%. The cumulative in vitro drug release up to 15 hrs was achieved suggesting towards efficacy of green synthesized chitosan nanoparticles for drug delivery applications.

Keywords: Chitosan nanoparticles, green synthesis, Pongamia pinnata, quercetin

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Authors: Arif İsmailov, Naila Hasanova, Gunay Orujalieva

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Homocysteine (HCY) is an indicator of prognostic value in monitoring regenerative processes in osteoporosis and osteoporotic fractures. The osteoporosis is known to be a serious health and economic problem, especially for women in the postmenopausal period. The study was carried out on patients 45-83 years old divided into 3 groups: group I – 14 patients with osteoporosis , group II – 15 patients with non-osteoporotic fractures, group III – 25 patients with osteoporotic fractures. The control group consisted of practically healthy 14 people. A blood sample was taken at 3 stages to monitor the dynamics of HCY level: on the 1st day before treatment, on the 10th day of treatment and 1 month after it. Blood levels of Hcy were determined at a wavelength of 450 nm by the ELİSA(Cloud Clone Corp.Elisa kits,USA). The statistical evaluation was performed by using SPSS 26.0 program (IBM SPSS Inc., USA).The results showed that on the 1st day before the treatment HCY concentration was statistically increased 2.7 times(PU = 0.108) in group I, 5.6 times (PU <0.001) in group II and 6.5 times (PU <0.001) in group III compared to the control group. Thus, the average value of HCY in group I was 1.76 ± 0.56 μg/ml; in group II – 3.57 ± 0.62 μg/ml; in group III – 4.2 ± 0.50 μg/ml. HCY level increases more sharply after fractures,especially in osteoporotic patients. In treatment period Vitamin D plays an important role in synthesis of the Cystathionine β‐synthase enzyme, which regulates HCY metabolism. Increased Hcy levels could lead to an increase in the risk of fracture through the interference in collagen cross-linking.

Keywords: homocysteine, osteoporosis, osteoporotic fractures, Vitamin D

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Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur

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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.

Keywords: small peptides, cyclooxygenase, inflammation, substrate

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Authors: Ikram Kamal, Mohamed Blaghen

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Pollution caused by petroleum hydrocarbons in terrestrial and aquatic environment is a common phenomenon that causes significant ecological and social problems. Biosurfactant applications in the environmental industries are promising due to their biodegradability, low toxicity and effectiveness in enhancing biodegradation and solubilization of low solubility compounds. Currently, the main application is for enhancement of oil recovery and hydrocarbon bioremediation due to their biodegradability and low critical micelle concentration (CMC). In this study we have investigated the potential of bacterial strains collected aseptically from the lagoon Marchika (water and soil) in Nador, Morocco; for the production of biosurfactants. This study also aimed to optimize the biosurfactant production process by changing the variables that influence the type and amount of biosurfactant produced by these microorganisms such as: carbon sources and also other physical and chemical parameters such as temperature and pH. Emulsification index, methylene blue test and thin layer chromatography (TLC) revealed the ability of strains used in this study to produce compounds that could emulsify gasoline. In addition a GC/MS was used to separate and identify different biosurfactants purified.

Keywords: petroleum hydrocarbons, biosurfactant, biodegradability, critical micelle concentration, lagoon Marchika

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Authors: Xiran Wang, Johanna Trinkl, Thomas Hoffmann, Wilfried Schwab

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Malonyltransferases (MATs) are enzymes that play a key role in the biosynthesis of secondary metabolites in plants, such as flavonoids and anthocyanins. As a kind of flavonoid-rich fruit, strawberries are an ideal model to study MATs. From Goodberry metabolome data, in the hybrid generation of 2 strawberries various, Fragaria × ananassa cv. 'Senga Sengana' and 'Candonga', we found the malonylated flavonoid concentration is significantly higher in 'Senga Sengana' compared with 'Candonga'. Therefore, we aimed to identify and characterize the malonyltransferases responsible for the different malonylated flavonoid concentrations in two different strawberry cultivars. In this study, we have found 6 MATs via genome mapping, metabolome analysis, gene cloning, and enzyme assay from strawberries, which catalyzed the malonylation of flavonoid substrates: quercetin-3-glucoside, kaempferol-3-glucoside, pelargonidin-3-glucoside, and cyanidin-3-glucoside. All four compounds reacted with FaMATs to varying degrees. These MATs have important implication into strawberries’ flavonoid biosynthesis, and also provide insights into insights into flavonoid biosynthesis, potential applications in agriculture, plant science, and pharmacy, and information on the regulation of secondary metabolism in plants.

Keywords: malonyltransferase, strawberry, flavonoid biosynthesis, enzyme assay

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Authors: Congping Lin

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Intracellular transport in fungi has a number of important roles in, e.g., filamentous fungal growth and cellular metabolism. Two basic mechanisms for intracellular transport are motor-driven trafficking along microtubules (MTs) and diffusion. Mathematical modelling has been actively developed to understand such intracellular transport and provide unique insight into cellular complexity. Based on live-cell imaging data in Ustilago hyphal cells, probabilistic models have been developed to study mechanism underlying spatial organization of molecular motors and organelles. In particular, anther mechanism - stochastic motility of dynein motors along MTs has been found to contribute to half of its accumulation at hyphal tip in order to support early endosome (EE) recycling. The EE trafficking not only facilitates the directed motion of peroxisomes but also enhances their diffusive motion. Considering the importance of spatial organization of early endosomes in supporting peroxisome movement, computational and experimental approaches have been combined to a whole-cell level. Results from this interdisciplinary study promise insights into requirements for other membrane trafficking systems (e.g., in neurons), but also may inform future 'synthetic biology' studies.

Keywords: intracellular transport, stochastic process, molecular motors, spatial organization

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Authors: Ashleigh Williams

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Micro- and nanoplastics’ (MNLPs) omnipresence and ecological accumulation is evident when surveying recent environmental impact studies. For example, in 2014 it was estimated that at least 52.3 trillion plastic microparticles are floating at sea, and scientists have even found plastics present remote Arctic ice and snow (5,6). Plastics have even found their way into precipitation, with more than 1000 tons of microplastic rain precipitating onto the Western United States in 2020. Even more recent studies evaluating the chemical safety of reusable plastic bottles found that hundreds of chemicals leached into the control liquid in the bottle (ddH2O, ph = 7) during a 24-hour time period. A consequence of the increased abundance in plastic waste in the air, land, and water every year is the bioaccumulation of MNLPs in ecosystems and trophic niches of the animal food chain, which could potentially cause increased direct and indirect exposure of humans to MNLPs via inhalation, ingestion, and dermal contact. Though the detrimental, toxic effects of MNLPs have been established in marine biota, much less is known about the potentially hazardous health effects of chronic MNLP ingestion in humans. Recent data indicate that long-term exposure to MNLPs could cause possible inflammatory and dysbiotic effects. However, toxicity seems to be largely dose-, as well as size-dependent. In addition, the transcytotic uptake of MNLPs through the intestinal epithelia in humans remain relatively unknown. To this point, the goal of the current study was to investigate the mechanisms of micro- and nanoplastic uptake and transcytosis of Polystyrene (PE) in human stem-cell derived, physiologically relevant in vitro intestinal model systems, and to compare the relative effect of particle size (30 nm, 100 nm, 500 nm and 1 µm), and concentration (0 µg/mL, 250 µg/mL, 500 µg/mL, 1000 µg/mL) on polystyrene MNLP uptake, transcytosis and intestinal epithelial model integrity. Observational and quantitative data obtained from confocal microscopy, immunostaining, transepithelial electrical resistance (TEER) measurements, cryosectioning, and ELISA cytokine assays of the proinflammatory cytokines Interleukin-6 and Interleukin-8 were used to evaluate the localization and transcytosis of polystyrene MNPs and its impact on epithelial integrity in human-derived intestinal in vitro model systems. The effect of Microfold (M) cell induction on polystyrene micro- and nanoparticle (MNP) uptake, transcytosis, and potential inflammation was also assessed and compared to samples grown under standard conditions. Microfold (M) cells, link the human intestinal system to the immune system and are the primary cells in the epithelium responsible for sampling and transporting foreign matter of interest from the lumen of the gut to underlying immune cells. Given the uptake capabilities of Microfold cells to interact both specifically and nonspecific to abiotic and biotic materials, it was expected that M- cell induced in vitro samples would have increased binding, localization, and potentially transcytosis of Polystyrene MNLPs across the epithelial barrier. Experimental results of this study would not only help in the evaluation of the plastic toxicity, but would allow for more detailed modeling of gut inflammation and the intestinal immune system.

Keywords: nanoplastics, enteroids, intestinal barrier, tissue engineering, microfold (M) cells

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Authors: Adineh Tajmousavilangerudi, Ali Zein Alabiden Tlais, Raffaella Di Cagno

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The SARS-Cov-2 pandemic has exposed our vulnerability to new illnesses and novel viruses that attack our immune systems, particularly in the elderly. The vaccine is being gradually introduced over the world, but new strains of the virus and COVID-19 will emerge and continue to cause illness. Aging is associated with significant changes in intestinal physiology, which increases the production of inflammatory products, alters the gut microbiota, and consequently establish inadequate immune response to minimize symptoms and disease development. In this context, older people who followed a Mediterranean-style diet, rich in polyphenols and dietary fiber, performed better physically and mentally (1,2). This demonstrates the importance of the human gut microbiome in transforming complex dietary macromolecules into the most biologically available and active nutrients, which in turn help to regulate metabolism and both intestinal and systemic immune function (3,4). The role of lactic acid fermentation is prominent also as a powerful tool for improving the nutritional quality of the human diet by releasing nutrients and boosting the complex bioactive compounds and vitamin content. the PhD project aims to design fermented and functional foods/beverages capable of modulating human immune function via the gut microbiome.

Keywords: functional bevarage, fermented beverage, gut microbiota functionality, immun system

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Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

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Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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Authors: Raquel M. De sousa, Sofiane Labidi, Allan Kardec D. Barros, Alex O. Barradas Filho, Aldalea L. B. Marques

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Several parameters are established in order to measure biodiesel quality. One of them is the iodine value, which is an important parameter that measures the total unsaturation within a mixture of fatty acids. Limitation of unsaturated fatty acids is necessary since warming of a higher quantity of these ones ends in either formation of deposits inside the motor or damage of lubricant. Determination of iodine value by official procedure tends to be very laborious, with high costs and toxicity of the reagents, this study uses an artificial neural network (ANN) in order to predict the iodine value property as an alternative to these problems. The methodology of development of networks used 13 esters of fatty acids in the input with convergence algorithms of backpropagation type were optimized in order to get an architecture of prediction of iodine value. This study allowed us to demonstrate the neural networks’ ability to learn the correlation between biodiesel quality properties, in this case iodine value, and the molecular structures that make it up. The model developed in the study reached a correlation coefficient (R) of 0.99 for both network validation and network simulation, with Levenberg-Maquardt algorithm.

Keywords: artificial neural networks, biodiesel, iodine value, prediction

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Authors: Abdelkarim Mahdhi, Fdhila Kais, Faouzi Lamari, Zeineb Hmila, Fathi Kamoun, Maria Ángeles Esteban, Amina Bakhrouf

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Pathogenic bacteria are considered to be responsible for several infectious diseases in aquaculture. To overcome diseases in fish culture, the use of antimicrobial drugs as strategy, have been adopted. The use of probiotic was a promising approach to avoid the risk associated to pathogenic bacteria. To find a biological control treatment against pathogens, we undertook this investigation to study the maintain of the probiotic properties of Bacillus sp., such as viability, adhesive ability to abiotic surface, antibacterial activity and pathogenicity/toxicity, under marine starvation conditions. Our data revealed that the tested strains maintained their capacity to inhibit pathogens in vivo and in vitro conditions. These strains maintain their adhesive capacity to polystyrene and do not demonstrate the pathogenic or toxic effect to the host. The obtained results give insight about the effect of starvation conditions on the physiological responses of these Bacillus strains that can be considered as a potential candidate’s probiotic.

Keywords: bacillus, probiotic, cell viability, starvation conditions

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Authors: Rasha Saad, Jean Frederic Weber, Fatimah Bebe, Sadia Sultan

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The goal of study was to screen the effects of candesartan and four endophytic fungi for their potential in microbial biotransformation. In this experiment, four types of unidentified fungi with the codes of TH2L1, TH2R10, TH1P35 and TH1S46 were used in screening process by MECFUS (Microtiter plate, Elicitors, Combination, Freeze-drying, UHPLC, Statistical analysis) protocol. The experiment was carried out by using 96-well microtiter plate (MTP) with different media and elicitors. Various media with two concentrations of Potato Dextrose Broth (PDB) and elicitors used were to induce the production of secondary metabolites from the fungi as well as the biotransformation of the drug compound. After incubation, cultures were extracted by freeze drying method and finally analyzed by ultra-High performance Liquid Chromatography (uHPLC). The extracts analyzed by uHPLC followed by LC/Ms, demonstrated the presence of biotransformation products from the drug compound and elicitation of the secondary metabolism from the fungi by the occurrence of the additional peaks. From the four fungi, TH1S46 showed highly potential produced secondary metabolites as well as the biotransformation of candesartan. For other fungi, they responded when candesartan was introduced. Moreover, the additional peaks produced in uHPLC need to be further investigation by using LC-MS or NMR.

Keywords: biotransformation, candesartan, endophytes, secondary metabolites

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Authors: Zahra Salehi Shahrbabaki, Zahra Chavoshzadeh, Fahimeh Abdollahimajd, Samin Sharafian, Tolue Mahdavi, Mahnaz Jamee

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Background: Inborn errors of immunity (IEIs) are monogenic diseases of the immune the system with broad clinical manifestations. Despite the increasing genetic advancements, the diagnosis of IEIs still leans on clinical diagnosis. Dermatologic manifestations are observed in a large number of IEI patients and can lead to proper approach, prompt intervention and improved prognosis. Methods: This cross-sectional study was carried out between 2018 and 2020 on IEIs at a Children's tertiary care center in Tehran, Iran. Demographic details (including age, sex, and parental consanguinity), age at onset of symptoms and family history of IEI with were recorded. Results :212 patients were included. Cutaneous findings were reported in (95 ,44.8%) patients. and 61 of 95 (64.2%) reported skin lesions as the first clinical presentation. Skin infection (69, 72.6%) was the most frequent cutaneous manifestation, followed by an eczematous rash (24, 25 %). Conclusions: Skin manifestations are common feature in IEI patients and can be readily recognizable by healthcare providers. This study tried to provide information on prognostic consequences.

Keywords: primary immuno deficiency, inborn errror of metabolism, skin manifestation, skin infection

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Authors: Suman Som, Abhijit Maity, Sunil B. Daschakraborty, Sujit Chaudhuri, Manik Pradhan

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Background: Helicobacter pylori is a common and important human pathogen and the primary cause of peptic ulcer disease and gastric cancer. Currently H. pylori infection is detected by both invasive and non-invasive way but the diagnostic accuracy is not up to the mark. Aim: To set up an optimal diagnostic cut-off value of 13C-Urea Breath Test to detect H. pylori infection and evaluate a novel c-PDR methodology to overcome of inconclusive grey zone. Materials and Methods: All 83 subjects first underwent upper-gastrointestinal endoscopy followed by rapid urease test and histopathology and depending on these results; we classified 49 subjects as H. pylori positive and 34 negative. After an overnight, fast patients are taken 4 gm of citric acid in 200 ml water solution and 10 minute after ingestion of the test meal, a baseline exhaled breath sample was collected. Thereafter an oral dose of 75 mg 13C-Urea dissolved in 50 ml water was given and breath samples were collected upto 90 minute for 15 minute intervals and analysed by laser based high precisional cavity enhanced spectroscopy. Results: We studied the excretion kinetics of 13C isotope enrichment (expressed as δDOB13C ‰) of exhaled breath samples and found maximum enrichment around 30 minute of H. pylori positive patients, it is due to the acid mediated stimulated urease enzyme activity and maximum acidification happened within 30 minute but no such significant isotopic enrichment observed for H. pylori negative individuals. Using Receiver Operating Characteristic (ROC) curve an optimal diagnostic cut-off value, δDOB13C ‰ = 3.14 was determined at 30 minute exhibiting 89.16% accuracy. Now to overcome grey zone problem we explore percentage dose of 13C recovered per hour, i.e. 13C-PDR (%/hr) and cumulative percentage dose of 13C recovered, i.e. c-PDR (%) in exhaled breath samples for the present 13C-UBT. We further explored the diagnostic accuracy of 13C-UBT by constructing ROC curve using c-PDR (%) values and an optimal cut-off value was estimated to be c-PDR = 1.47 (%) at 60 minute, exhibiting 100 % diagnostic sensitivity , 100 % specificity and 100 % accuracy of 13C-UBT for detection of H. pylori infection. We also elucidate the gastric emptying process of present 13C-UBT for H. pylori positive patients. The maximal emptying rate found at 36 minute and half empting time of present 13C-UBT was found at 45 minute. Conclusions: The present study exhibiting the importance of c-PDR methodology to overcome of grey zone problem in 13C-UBT for accurate determination of infection without any risk of diagnostic errors and making it sufficiently robust and novel method for an accurate and fast non-invasive diagnosis of H. pylori infection for large scale screening purposes.

Keywords: 13C-Urea breath test, c-PDR methodology, grey zone, Helicobacter pylori

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Authors: Giti Sabri, Sohrab Imani, Ali Ahadiyat, Aref Maroof, Yahya Ostadi

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Recently, there has been a growing interest in research concerning the possible use of plant extracts as alternatives to synthetic insecticides. In this research, the insecticidal effects of Carum copticum essential oils against rice weevil adults were investigated in laboratory condition. Essential oils was extracted through distillation with water using Clevenger apparatus. Tests of randomized complete block included six concentrations and three replications for essential oils (fumigant toxicity) along with control treatment in condition of 27±1ºC degrees Celsius temperature, relative humidity of 65 ± 5 percent and darkness. LC50 values were calculated by SPSS.21.0 software which presented the value of LC50 of Carum copticum essential oils after 48 hurs, 187.35± 0.40 µl/l air on rice weevil adults. Results showed that increasing the concentration of essential oils increased the mortality rate cases. The results also showed that essential oils of Carum copticum are effective biological sources which can effectively protect stored grain from infestation by the rice weevil; although for application of these combinations further research may be needed.

Keywords: insecticidial effects, essential oil, Carum copticum, Sitophilus oryzae

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Authors: Abdelbary Prince, Said Moussa, Hyungkyu Kim, Eman Gouda, Jin Han

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We compared the dynamic alterations of mitochondrial proteome of control, ischemia-reperfusion (IR) and ischemic preconditioned (IPC) rabbit hearts. Using 2-DE, we identified 29 mitochondrial proteins that were differentially expressed in the IR heart compared with the control and IPC hearts. For two of the spots, the expression patterns were confirmed by Western blotting analysis. These proteins included succinate dehydrogenase complex, Acyl-CoA dehydrogenase, carnitine acetyltransferase, dihydrolipoamide dehydrogenase, Atpase, ATP synthase, dihydrolipoamide succinyltransferase, ubiquinol-cytochrome c reductase, translation elongation factor, acyl-CoA dehydrogenase, actin alpha, succinyl-CoA Ligase, dihydrolipoamide S-succinyltransferase, citrate synthase, acetyl-Coenzyme A dehydrogenase, creatine kinase, isocitrate dehydrogenase, pyruvate dehydrogenase, prohibitin, NADH dehydrogenase (ubiquinone) Fe-S protein, enoyl Coenzyme A hydratase, superoxide dismutase [Mn], and 24-kDa subunit of complex I. Interestingly, most of these proteins are associated with the mitochondrial respiratory chain, antioxidant enzyme system, and energy metabolism. The results provide clues as to the cardioprotective mechanism of ischemic preconditioning at the protein level and may serve as potential biomarkers for detection of ischemia-induced cardiac injury.

Keywords: ischemic preconditioning, mitochondria, proteome, cardioprotection

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Authors: Akwu A. Nneka, Naidoo, Yougasphree

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A significantly high number of microbes exist in higher plants; these microbes include bacteria, fungi, and actinomycetes. There are reports on the benefits of endophytic fungi and their products of metabolism to the host plant and man, consequently, it is expedient to explore the changes that could arise as a result of manipulating their growth media. Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is an indigenous Southern African plant, that belongs to a genus with known medicinal properties. Three media were used to culture the endophytic fungi viz., Potato Dextrose Agar (PDA), Malt Extract Agar (MEA), and Bacteriological Agar (BA) were used singly, and supplemented with three dilutions of the leaves and stem bark extracts. The manipulated growth media composition had a significant effect on the diversity of the isolated fungal populations. Several endophytic fungi were isolated; their distribution and diversity revealed a significant relatedness with the manipulated media. The media supplemented with the plant extracts was observed to give a significant increase in the growth rate and yield of the endophytes. To the best of our knowledge, this is the first study describing the endophytic fungi present in the leaves and stem bark of G. lasiocarpa E. Mey. ex Harv.

Keywords: Grewia lasiocarpa, plant-based extracts, endophytic fungi, Malvaceae

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Authors: Premrudee Kanchanapiya, Supachai Songngam, Thanapol Tantisattayakul

Abstract:

Perfluorooctanoic acid (PFOA) is one of per- and polyfluoroalkyl substances (PFAS) that have increasingly attracted concerns due to their global distribution in environment, persistence, high bioaccumulation, and toxicity. It is important to study the effective treatment to remove PFOA from contaminated water. The feasibility of using commercial coconut shell activated carbon produced in Thailand to remove PFOA from water was investigated with regard to their adsorption kinetics and isotherms of powder activated carbon (PAC-325) and granular activated carbon (GAC-20x50). Adsorption kinetic results show that the adsorbent size significantly affected the adsorption rate of PFOA, and GAC-20x50 required at least 100 h to achieve the equilibrium, much longer than 3 h for PAC-325. Two kinetic models were fitted to the experimental data, and the pseudo-second-order model well described the adsorption of PFOA on both PAC-325 and GAC-20x50. PAC-325 trended to adsorb PFOA faster than GAC-20x50, and testing with the shortest adsorption times (5 min) still yielded substantial PFOA removal (~80% for PAC-325). The adsorption isotherms show that the adsorption capacity of PAC-325 was 0.80 mmol/g, which is 83 % higher than that for GAC-20x50 (0.13 mmol/g), according to the Langmuir fitting.

Keywords: perfluorooctanoic acid, PFOA, coconut shell activated carbons, adsorption, water treatment

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Authors: Rui Sang, Fei Deng, Alexander Engel, Ewa M. Goldys, Wei Deng

Abstract:

In this study, we brought together X-ray induced photodynamic therapy (X-PDT) and chemo-drug (5-FU) for the treatment on colorectal cancer cells. This was achieved by developing a lipid-polymer hybrid nanoparticle delivery system (FA-LPNPs-VP-5-FU). It was prepared by incorporating a photosensitizer (verteporfin), chemotherapy drug (5-FU), and a targeting moiety (folic acid) into one platform. The average size of these nanoparticles was around 100 nm with low polydispersity. When exposed to clinical doses of 4 Gy X-ray radiation, FA-LPNPs-VP-5-FU generated sufficient amounts of reactive oxygen species, triggering the apoptosis and necrosis pathway of cancer cells. Our combined X-PDT and chemo-drug strategy was effective in inhibiting cancer cells’ growth and proliferation. Cell cycle analyses revealed that our treatment induced G2/M and S phase arrest in HCT116 cells. Our results indicate that this combined treatment provides better antitumour effect in colorectal cancer cells than each of these modalities alone. This may offer a novel approach for effective colorectal cancer treatment with reduced off-target effect and drug toxicity.

Keywords: pdt, targeted lipid-polymer nanoparticles, verteporfin, colorectal cancer

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Authors: Sajjad Negahban, Ruihe Wang, Baojiang Sun

Abstract:

Gas-lift dual gradient drilling is a solution for deepwater drilling challenges. As well, Continuous development of drilling technology leads to increase employment of mineral oil based drilling fluids and synthetic-based drilling fluids, which have adequate characteristics such as: high rate of penetration, lubricity, shale inhibition and low toxicity. The paper discusses utilization of nitrified mineral oil base drilling for deepwater drilling and for more accurate prediction of pressure in DGD at marine riser, solubility and bubble pressure were considered in steady state hydraulic model. The Standing bubble pressure and solubility correlations, and two models which were acquired from experimental determination were applied in hydraulic model. The effect of the black oil correlations, and new solubility and bubble pressure models was evaluated on the PVT parameters such as oil formation volume factor, density, viscosity, volumetric flow rate. Eventually, the consequent simulated pressure profile due to these models was presented.

Keywords: solubility, bubble pressure, gas-lift dual gradient drilling, steady state hydraulic model

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Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

Abstract:

Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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Authors: S. Alqarni, J. C. McCann, A. Palladino, J. J. Loor

Abstract:

Seven fistulated Holstein cows were used from 3 weeks prepartum to 4 weeks postpartum to determine the relative abundance of 7 different species of ruminal microorganisms. The prepartum diet was based on corn silage. In the postpartum, diet included ground corn, grain by-products, and alfalfa haylage. Ruminal digesta were collected at five times: -14, -7, 10, 20, and 28 days around parturition. Total DNA from ruminal digesta was isolated and real-time quantitative PCR was used to determine the relative abundance of bacterial species. Eubacterium ruminantium and Selenomonas ruminantium were not affected by time (P>0.05). Megasphaera elsdenii and Prevotella bryantii increased significantly postpartum (P<0.001). Conversely, Butyrivibrio proteoclasticus decreased gradually from -14 through 28 days (P<0.001). Fibrobacter succinogenes was affected by time being lowest at day 10 (P=0.02) while Anaerovibrio lipolytica recorded the lowest abundance at -7 d followed by an increase by 20 days postpartum (P<0.001). Overall, these results indicate that changes in diet after parturition affect the abundance of ruminal bacteria, particularly M. elsdenii (a lactate-utilizing bacteria) and P. bryantii (a starch-degrading bacteria) which increased markedly after parturition likely as a consequence of a higher concentrate intake.

Keywords: rumen bacteria, transition cows, rumen metabolism, peripartal period

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Authors: G. A. Gevorgyan, K. A. Ghazaryan, T. H. Derdzyan

Abstract:

The heavy metal pollution of the soils around the mining area near Shamlugh town and related risks to human health were assessed. The investigations showed that the soils were polluted with heavy metals that can be ranked by anthropogenic pollution degree as follows: Cu>Pb>As>Co>Ni>Zn. The main sources of the anthropogenic metal pollution of the soils were the copper mining area near Shamlugh town, the Chochkan tailings storage facility and the trucks transferring are from the mining area. Copper pollution degree in some observation sites was unallowable for agricultural production. The total non-carcinogenic chronic hazard index (THI) values in some places, including observation sites in Shamlugh town, were above the safe level (THI<1) for children living in this territory. Although the highest heavy metal enrichment degree in the soils was registered in case of copper, the highest health risks to humans especially children were posed by cobalt which is explained by the fact that heavy metals have different toxicity levels and penetration characteristics.

Keywords: Armenia, copper mine, heavy metal pollution of soil, health risks

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Authors: Rama Bhattacharyya, S. N. Ojha, Umesh K. Singh

Abstract:

Anthropogenic control on groundwater chemistry has emerged as a critical concern now-a-days, especially in the industrial areas. In view of this, a comprehensive study on the distribution of the heavy metal in the groundwater was conducted to investigate the impact of urbanization in the aquatic media. Water samples either from well or borehole from Fourty different sites in and around, Durgapur, West Bengal were collected for this purpose. The samples were analyzed using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for Calcium (Ca), Cobalt (Co), Chromium (Cr), Copper (Cu), Iron (Fe), Potassium (K), Magnesium (Mg), Manganese (Mn), Sodium (Na), Nickel (Ni), Lead (Pb), Zinc (Zn) content and the levels were compared with WHO specified maximum contaminant level as well as permissible limits given by the Bureau of Indian Standards (BIS). The result obtained from the present study indicates a significant risk to the population of this important emerging ‘smart city’ of eastern India. Because of the toxicity of these metals and the fact that for many tube-wells, dug-wells and bore-wells are the only sources of the water supply for a major fraction of the population in this environment. In this study, an attempt has been made to develop metal contamination risk map.

Keywords: heavy metals, ground water, maximum contamination level, ICP-MS

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Authors: Mansouri Ouarda, Adbdennour Cherif, Boukarma Ziad

Abstract:

Environmental and biological monitoring are used for the evaluation of exposure to industrial chemicals, and provide a tool for assessing workers’ exposure to chemicals. The organs or tissues where the first biological effects can be observed with increasing amounts of lead toxicity. This study aims at evaluating the effect of the metal element-trace; lead, on the sex hormones in male workers, exposed to this metal on the level of the manufacturing plant of lead accumulators. The results indicate a significant reduction of the testosterone concentration in exposed workers compared to the control. However, the rate of LH was strongly increased at the individuals exposed to Pb. A significant difference concerning the rate of FSH, the hormone Prolactin and cortisol was recorded. The indicators of the lead poisoning indicate a very highly significant increase in the value of Pbs which vary between (142-796 µg/L) among which 50% of the workers present a high lead poisoning and the value of PPZ which vary between (43-554µg/L). The biochemical parameters show a significant increase in the rate of the créatinine, the urea and the acid urique. The hepatic results show no significant differentiation in the rate of TGO and TGP between both groups of study. However the rates of the enzyme phosphatase alkaline, triglyceride, and cholesterol a significant difference were registered.

Keywords: hormons, parameters, physilogical, Pbs, PPZ

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Authors: S. Khosravi, X. Chelius, A. Unger, D. Rieger, J. Frickel, T. Sachsenheimer, C. Luechtenborg, R. Schieweck, B. Bruegger, B. Westermann, T. Klecker, W. Neupert, M. E. Harner

Abstract:

The use of Saccharomyces cerevisiae as a model organism to study eukaryotic cell functions has been used successfully for decades. Like virtually all eukaryotic cells, they contain mitochondria as essential organelles performing various functions, including participation in lipid metabolism. They are separated from the cytosol by a double membrane system consisting of the mitochondrial inner membrane (MIM) and the mitochondrial outer membrane (MOM). This physical separation of the mitochondria requires an exchange of metabolites, proteins, and lipids. Proteinaceous contact sites are thought to be important for this communication. Recently, it was found that Cqd1, in cooperation with Cqd2, controls the distribution of Coenzyme Q within the cell. In this study, a contact site is described, formed by the MOM protein complex Por1-Om14 and the UbiB protein kinase-like MIM protein Cqd1. The present results suggest the additional involvement of Cqd1 in the homeostasis of phospholipids. Moreover, we show that overexpression of the UbiB family proteins also causes tethering of the mitochondria to the endoplasmatic reticulum. Due to the conservation of the subunits of this contact site to higher eukaryotes, its identification in S. cerevisiae might provide promising avenues for further research in other organisms.

Keywords: contact sites, mitochondrial architecture, mitochondrial proteins, yeast mitochondria

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