Search results for: mismatch repair protein

Authors: Abhimanyu Thakur, Youngjin Lee

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Glioma is a lethal brain cancer whose early diagnosis and prognosis are limited due to the dearth of a suitable technique for its early detection. Current approaches, including magnetic resonance imaging (MRI), computed tomography (CT), and invasive biopsy for the diagnosis of this lethal disease, hold several limitations, demanding an alternative method. Recently, extracellular vesicles (EVs) have been used in numerous biomarker studies, majorly exosomes and microvesicles (MVs), which are found in most of the cells and biofluids, including blood, cerebrospinal fluid (CSF), and urine. Remarkably, glioma cells (GMs) release a high number of EVs, which are found to cross the blood-brain-barrier (BBB) and impersonate the constituents of parent GMs including protein, and lncRNA; however, biophysical properties of EVs have not been explored yet as a biomarker for glioma. We isolated EVs from cell culture conditioned medium of GMs and regular primary culture, blood, and urine of wild-type (WT)- and glioma mouse models, and characterized by nano tracking analyzer, transmission electron microscopy, immunogold-EM, and differential light scanning. Next, we measured the biophysical parameters of GMs-EVs by using atomic force microscopy. Further, the functional constituents of EVs were examined by FTIR and Raman spectroscopy. Exosomes and MVs-derived from GMs, blood, and urine showed distinction biophysical parameters (roughness, adhesion force, and stiffness) and different from that of regular primary glial cells, WT-blood, and -urine, which can be attributed to the characteristic functional constituents. Therefore, biophysical features can be potential diagnostic biomarkers for glioma.

Keywords: glioma, extracellular vesicles, exosomes, microvesicles, biophysical properties

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Authors: Danutė Jablonskytė-Raščė, Audronė MankevičIenė, Laura Masilionytė

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During the period 2009–2015, in Joniškėlis Experimental Station of the Lithuanian Research Centre for Agriculture and Forestry, the effect of ecologic fertilizers Ekoplant, bio-activators Biokal 01 and Terra Sorb Foliar and their combinations on the formation of the productivity elements, grain yield and quality of winter wheat, spelt (Triticum spelta L.), and common wheat (Triticum aestivum L.) was analysed in ecological agro-system. The soil under FAO classification – Endocalcari-Endo-hypogleyic-Cambisol. In a clay loam soil, ecological fertilizer produced from sunflower hull ash and this fertilizer in combination with plant extracts and bio-humus exerted an influence on the grain yield of spelt and common wheat and their mixture (increased the grain yield by 10.0%, compared with the unfertilized crops). Spelt grain yield was by on average 16.9% lower than that of common wheat and by 11.7% lower than that of the mixture, but the role of spelt in organic production systems is important because with no mineral fertilization it produced grains with a higher (by 4%) gluten content and exhibited a greater ability to suppress weeds (by on average 61.9% lower weed weight) compared with the grain yield and weed suppressive ability of common wheat and mixture. Spelt cultivation in a mixture with common wheat significantly improved quality indicators of the mixture (its grain contained by 2.0% higher protein content and by 4.0% higher gluten content than common wheat grain), reduced disease incidence (by 2-8%), and weed infestation level (by 34-81%).

Keywords: common and spelt-wheat, ecological fertilizers, bio-activators, productivity elements, yield, quality

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Authors: Jelena Filipović, Milenko Košutić, Vladimir Filipović

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In the last decades urban population is characterized by sedentary lifestyles, low physical activity and "fast food". These changes in diet and physical non activity have been associated with the increase of chronic non diseases. Bread is one of the most popularly wheat products consumed worldwide. Spelt wheat has shown potential in various food applications, including bread, pasta, breakfast cereal and other products of altered nutritional characteristics compared to conventional wheat products. It has very high protein content and even 30 to 60% higher concentration of mineral elements Fe, Zn, Cu, Mg and P compared to Triticum Aestivum. Spelt wheat is growing without the use of pesticides in harsh ecological conditions and it is an old cultivar. So it can be used for organic and health safe food. Changes in the formulation of bread with the aim to improve their nutritional and functional properties usually lead to changes in the dough properties which is related reflected to the quality of the finished product. The aim of this paper is researching the impact of adding yeast extract to bread on sensory characteristics and consumer acceptance of a new product as a key factor for successful marketing of a new product. The sensory analysis of bread with 5% yeast extract is as follows: the technological quality is very good (3.8) and the color of the product is excellent (4.85). Based on data consumers survey declared that they liked the taste of bread with 5% yeast extract (74%), consumers marked the product as likeable (70%), and 75% of the total number of respondents would buy this new product. This paper is promoting a new type of bread with 5% yeast extract (Z score 0.80) to improve diet and novel functional product which intended for consumers conscious about their health and diet.

Keywords: bread, yeast extract, sensory analysis, consumer survey, score analysis Z

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Authors: Ujene Ikem Godspower

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Acts of terror perpetrated either by state or non-state actors are considered a social ill and impugn on the collective well-being of the society. As such, there is the need for social reparations, which is meant to ensure the healing of the social wounds resulting from the atrocities committed by errant individuals under different guises. In order to ensure social closure and effectively repair the damages done by anomic behaviors, society must ensure that justice is served and those whose rights and privileges have been denied and battered are given the necessary succour they deserve. With regards to the ongoing terrorism in the Northeast, the moves to rehabilitate and reintegrate Boko Haram members have commenced with the establishment of Operation Safe Corridor,1 and a proposed bill for the establishment of “National Agency for the Education, Rehabilitation, De-radicalisation and Integration of Repentant Insurgents in Nigeria”2. All of which Nigerians have expressed mixed feelings about. Some argue that the endeavor is lacking in ethical decency and justice and totally insults human reasoning. Terrorism and counterterrorism in Nigeria have been enmeshed in gross human rights violations both by the military and the terrorists, and this raises the concern of Nigeria’s ability to fairly and justiciably implement the deradicalization and reintegration efforts. On the other hand, there is the challenge of the community dwellers that are victims of terrorism and counterterrorism and their ability to forgive and welcome back their immediate-past tormentors even with the slightest sense of injustice in the process of terrorists reintegration and rehabilitation. With such efforts implemented in other climes, the Nigeria’s case poses a unique challenge and commands keen interests by stakeholders and the international community due to the aforementioned reasons. It is therefore pertinent to assess the communities’ level of involvement in the cycle of reintegration- hence, the objective of this paper. Methodologically as a part of my larger PhD thesis, this study intends to explore the three different local governments (Michika in Adamawa, Chibok in Borno, and Yunusari in Yobe), all based on the intensity of terrorists attacks. Twenty five in-depth interview will be conducted in the study locations above featuring religious leaders, Community (traditional) leaders, Internally displaced persons, CSOs management officials, and ex-Boko Haram insurgents who have been reintegrated. The data that will be generated from field work will be analyzed using the Nvivo-12 software package, which will help to code and create themes based on the study objectives. Furthermore, the data will be content-analyzed, employing verbatim quotations where necessary. Ethically, the study will take into consideration the basic ethical principles for research of this nature. It will strictly adhere to the principle of voluntary participation, anonymity, and confidentiality.

Keywords: boko haram, reintegration, rehabilitation, terrorism, victimology

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Authors: Naim Izet Kajtazi

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Context: Frequently, the cause of raised intracranial pressure remains unresolved and rarely is related to spinal tumors, moreover less to spinal medulloblastoma without primary brain focus. Process: An 18-year-old woman had a 3-month history of headaches and impaired vision. Neurological examination revealed bilateral sixth cranial nerve palsies with bilateral papilloedema of grade III. No focal brain or spine lesion was found on imaging. Consecutive lumbar punctures showed high opening pressure and subsequent increasing protein level. The meningeal biopsy was negative. At one point, she developed an increasing headache, vomiting and back pain. Spine MRI showed diffuse nodular leptomeningeal enhancement with the largest nodule at T6–T7. Malignant cells were detected in cerebrospinal fluid. She underwent laminectomy with excisional biopsy, and pathology showed medulloblastoma WHO grade IV. Outcome: She was treated with chemotherapy and craniospinal irradiation and made a good recovery. Relevance: Primary spinal leptomeningeal medulloblastoma is extremely rare, especially without primary brain focus, but may cause increased intracranial pressure, even in the early microscopic phases, and it should be considered in the differential diagnosis if conventional and aggressive treatment of idiopathic intracranial hypertension fails. We assume that arachnoiditis from tumor seeding caused increased intracranial pressure. Appropriate neurosurgical intervention and surgical biopsy are mandated if a suspicious lesion is detected. Consider proper rescreening of the whole neuroaxis in refractory cases of intracranial hypertension.

Keywords: CNS infection, IIH, headache, primary spinal leptomeningeal medulloblastoma

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Authors: Shadia Al-Bahlani, Khadija Al-Bulushi, Zuweina Al-Hadidi, Buthaina Al-Dhahl, Nadia Al-Abri

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Breast cancer is the most common cancer in women worldwide. Triple-Negative Breast Cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. However, the role of calpain in cisplatin (CDDP)-induced apoptosis in TNBC cells is not fully understood. Here, TNBC (MDA-MB231) cells were treated with different concentration of CDDP (0, 20 & 40 µM) and calpain activation and apoptosis were measured by western blot and Hoechst Stain respectively. In addition, calpain modulation by either activation and/or inhibition and its effect on CDDP-induced apoptosis were assessed by the same above approaches. Our findings showed that CDDP induced endoplasmic reticulum stress and thus Calcium release and subsequently activate calpain α-fodrin cleavage indicated by the increase in GRP78 and Calmodulin protein expression and respectively in MDA-MB231 cells. It also induced apoptosis as measured by Hoechst stain and caspase-12 cleavage. Calpain activation by both Cyclopiazonic acid and Thapsigargin showed similar effect and enhanced the sensitivity of these cells to CDDP treatment. On the other hand, calpain inhibition by either specific siRNA and/or exogenous inhibitor (Calpeptin) had an adverse effect where it attenuated calpain activation and thus CDDP- induced apoptosis in these cells. Altogether, these findings suggested that calpain activation play an essential role in sensitizing the TNBC cells to CDDP-induced apoptosis. This might lead to the discovery of novel treatment to over this aggressive type of breast cancer.

Keywords: calpain, cisplatin, apoptosis, breast cancer

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Authors: T. Arkle, D. Pournaras, S. Lam, B. Kumar

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Introduction: Fundoplication is widely recognised as the best surgical option for gastro-oesophageal reflux disease (GORD) in the general population. However, there is controversy surrounding the use of conventional fundoplication in obese patients. Whilst the intra-operative failure of fundoplication, including wrap disruption, is reportedly higher in obese individuals, the more significant issue surrounds symptom recurrence post-surgery. Could a bariatric procedure be considered in obese patients for weight management, to treat the GORD, and to also reduce the risk of recurrence? Roux-en-Y gastric bypass, a widely performed bariatric procedure, has been shown to be highly successful both in controlling GORD symptoms and in weight management in obese patients. Furthermore, NICE has published clear guidelines on eligibility for bariatric surgery, with the main criteria being type 3 obesity or type 2 obesity with the presence of significant co-morbidities that would improve with weight loss. This study aims to identify the proportion of patients who undergo conventional fundoplication for GORD and/or hiatus hernia, which would have been eligible for bariatric surgery referral according to NICE guidelines. Methods: All patients who underwent fundoplication procedures for GORD and/or hiatus hernia repair at a single NHS foundation trust over a 10-year period will be identified using the Trust’s health records database. Pre-operative patient records will be used to find BMI and the presence of significant co-morbidities at the time of consideration for surgery. This information will be compared to NICE guidelines to determine potential eligibility for the bariatric surgical referral at the time of initial surgical intervention. Results: A total of 321 patients underwent fundoplication procedures between January 2011 and December 2020; 133 (41.4%) had available data for BMI or to allow BMI to be estimated. Of those 133, 40 patients (30%) had a BMI greater than 30kg/m², and 7 (5.3%) had BMI >35kg/m². One patient (0.75%) had a BMI >40 and would therefore be automatically eligible according to NICE guidelines. 4 further patients had significant co-morbidities, such as hypertension and osteoarthritis, which likely be improved by weight management surgery and therefore also indicated eligibility for referral. Overall, 3.75% (5/133) of patients undergoing conventional fundoplication procedures would have been eligible for bariatric surgical referral, these patients were all female, and the average age was 60.4 years. Conclusions: Based on this Trust’s experience, around 4% of obese patients undergoing fundoplication would have been eligible for bariatric surgical intervention. Based on current evidence, in class 2/3 obese patients, there is likely to have been a notable proportion with recurrent disease, potentially requiring further intervention. These patient’s may have benefitted more through undergoing bariatric surgery, for example a Roux-en-Y gastric bypass, addressing both their obesity and GORD. Use of patient written notes to obtain BMI data for the 188 patients with missing BMI data and further analysis to determine outcomes following fundoplication in all patients, assessing for incidence of recurrent disease, will be undertaken to strengthen conclusions.

Keywords: bariatric surgery, GORD, Nissen fundoplication, nice guidelines

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Authors: Anyaphat Srithanasuwan, Noppason Pangprasit, Montira Intanon, Phongsakorn Chuammitri, Witaya Suriyasathaporn, Ynte H. Schukken

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Streptococcus uberis is one of the most common mastitis-causing pathogens, with a wide range of intramammary infection (IMI) durations and pathogenicity. This study aimed to compare shared or unique virulence factor gene clusters distinguishing persistent and transient strains of S. uberis. A total of 139 S. uberis strains were isolated from three small-holder dairy herds with a high prevalence of S. uberis mastitis. The duration of IMI was used to categorize bacteria into two groups: transient and persistent strains with an IMI duration of less than 1 month and longer than 2 months, respectively. Six representative S. uberis strains, three from each group (transience and persistence) were selected for analysis. All transient strains exhibited multi-locus sequence types (MLST), indicating a highly diverse population of transient S. uberis. In contrast, MLST of persistent strains was available in an online database (pubMLST). Identification of virulence genes was performed using whole-genome sequencing (WGS) data. Differences in genomic size and number of virulent genes were found. For example, the BCA gene or alpha-c protein and the gene associated with capsule formation (hasAB), found in persistent strains, are important for attachment and invasion, as well as the evasion of the antimicrobial mechanisms and survival persistence, respectively. These findings suggest a genetic-level difference between the two strain types. Consequently, a comprehensive study of 139 S. uberis isolates will be conducted to perform an in-depth genetic assessment through WGS analysis on an Illumina platform.

Keywords: Streptococcus Uberis, mastitis, whole genome sequence, intramammary infection, persistent S. Uberis, transient s. Uberis

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Authors: Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Zobov, Vladimir Reznik

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Among hepatic pyrimidine used as a means of stimulating protein synthesis and recovery of liver cells in her damaged toxic and infectious etiology. When an experimental toxic hepatitis hepatoprotective activity detected some pyrimidine derivatives. There are literature data on oksimetiluratcila hepatoprotective effect. For analogs of pyrimidine nucleobases - drugs Methyluracilum pentoxy and hepatoprotective effect of weakly expressed. According to the American scientists broad spectrum of biological activity, including hepatoprotective properties, have a 2,4-dioxo-5-arilidenimino uracils. Influenced Xymedon medicinal preparation (1- (beta-hydroxyethyl) -4,6-dimethyl-1,2-dihydro-2-oksopirimidin) developed as a means of stimulating the regeneration of tissue revealed increased activity of microsomal oxidases human liver. In studies on the model of toxic liver damage in rats have shown hepatoprotective effect xymedon and stimulating its impact on the recovery of the liver tissue. Hepatoprotective properties of the new compound in the series of pyrimidine derivatives L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropirimidine-2-one synthesized on the basis Xymedon preparation were firstly investigated on rats under the carbon tetrachloride action. It was shown the differences of biochemical parameters from the reference value and severity of structural-morphological liver violations decreased in comparison with control group under the influence of the compound injected before exposure carbon tetrachloride. Hepatoprotective properties of the investigated compound were more pronounced in comparison with Xymedon.

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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Authors: Larisa Gheber

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Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.

Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics

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Authors: S. Noreen, S. Ahmad

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Salinity is one of the most important environmental factors that limit the production of crop plants to the greatest proportion than any other ones. Salt-induced changes in growth, pigment concentration, water status, malondialdehydes (MDA) and H₂O₂ content, enzymatic and non-enzymatic antioxidants, Na⁺, K⁺ content and yield attributes were examined in the glasshouse on ten pea (Pisum Sativum L.) accessions, namely ‘13240’, ‘18302’, ‘19666’, ‘19700’, ‘19776’, ‘19785’, ‘19788’, ‘20153’, ‘20155’, ‘26719’ were subjected to non-stress (0 mM NaCl) and salt stress (100 mM and150 mM NaCl) in pots containing sand medium. The results showed that salt stress at level150 mM substantially reduced biomass production, leaf water status, pigment concentration (chlorophyll ‘a’, ‘b’, ‘carotenoid content’ total chlorophyll), K⁺ content, quantum yield and yield attributes as compared to plants treated with 100 mM NaCl. Antioxidant enzymes, Catalase (CAT), Peroxidase (POD), Superoxide dismutase (SOD) and Ascorbate peroxidase (APX), proline content, total soluble protein, total amino acids, Malondialdehyde content (MDA), Hydrogen peroxide (H₂O₂) content and Na⁺ uptake markedly enhanced due to the influence of salt stress. On the basis of analyses (expressed as percent of control), of 10 accessions of pea plant, two were ranked as salt tolerant namely (‘19666’, ‘20153’), four were moderately tolerant namely (‘19700’, ‘19776’, ‘19785’, ‘20155’), and three were salt sensitive namely (‘13240’, ‘18302’, ‘26719’) at 150 mM NaCl level.

Keywords: antioxidant enzymes, ion uptake, pigment concentration, salt stress, yield attributes

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Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

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Objective: Endothelial progenitor cells (EPCs) have reparative potential in overcoming the endothelial dysfunction and reducing cardiovascular risk. EPC depletion has been demonstrated in the setting of established atherosclerotic diseases. With this background, we evaluated whether reduced EPCs population are associated with endothelial dysfunction, subclinical atherosclerosis and inflammatory markers in ankylosing spondylitis (AS) patients without any known traditional cardiovascular risk factor in AS patients. Methods: Levels of circulating EPCs (CD34+/CD133+), brachial artery flow-mediated dilatation, carotid intima-media thickness (CIMT) and inflammatory markers i.e erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tissue necrosis factor (TNF)–α, interleukin (IL)-6, IL-1 were assessed in 30 AS patients (mean age33.41 ± 10.25; 11 female and 19 male) who fulfilled the modified New York diagnostic criteria with 25 healthy volunteers (mean age 29.36± 8.64; 9 female and 16 male) matched for age and sex. Results: EPCs (CD34+/CD133+) cells were significantly (0.020 ± 0.001% versus 0.040 ± 0.010%, p<0.001) reduced in patients with AS compared to healthy controls. Endothelial function (7.35 ± 2.54 versus 10.27 ±1.73, p=0.002), CIMT (0.63 ± 0.01 versus 0.35 ± 0.02, p < 0.001) and inflammatory markers were also significantly (p < 0.01) altered as compared to healthy controls. Specifically, CD34+CD133+cells were inversely multivariate correlated with CRP and TNF-α and endothelial dysfunction was positively correlated with reduced number of EPC. Conclusion: Depletion of EPCs population is an independent predictor of endothelial dysfunction and early atherosclerosis in AS patients and may provide additional information beyond conventional risk factors and inflammatory markers.

Keywords: endothelial progenitor cells, atherosclerosis, ankylosing spondylitis, cardiovascular

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Authors: Hussein M. Elmehdi

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In this paper, we present the results of our recent experiments done to examine the effect of air bubbles, which were introduced to bio-samples during preparation, on the rheological properties of soft biological materials. To effectively achieve this, we three samples each prepared with differently. Our soft biological systems comprised of three types of flour dough systems made from different flour varieties with variable protein concentrations. The samples were investigated using ultrasonic waves operated at low frequency in transmission mode. The sample investigated included dough made from bread flour, wheat flour and all-purpose flour. During mixing, the main ingredient of the samples (the flour) was transformed into cohesive dough comprised of the continuous dough matrix and air pebbles. The rheological properties of such materials determine the quality of the end cereal product. Two ultrasonic parameters, the longitudinal velocity and attenuation coefficient were found to be very sensitive to properties such as the size of the occluded bubbles, and hence have great potential of providing quantitative evaluation of the properties of such materials. The results showed that the magnitudes of the ultrasonic velocity and attenuation coefficient peaked at optimum mixing times; the latter of which is taken as an indication of the end of the mixing process. There was an agreement between the results obtained by conventional rheology and ultrasound measurements, thus showing the potential of the use of ultrasound as an on-line quality control technique for dough-based products. The results of this work are explained with respect to the molecular changes occurring in the dough system as the mixing process proceeds; particular emphasis is placed on the presence of free water and bound water.

Keywords: ultrasound, soft biological materials, velocity, attenuation

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Authors: E. Riani, T. T. Irawadi, S. Nurjanah, K. Syamsu, E. G. Said, Suprihatin, M. R. Cordova

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Especially coastal, Indonesian and Chinese communities have utilized sandfish to improve reproduction quality of men. This study aimed to examine the nutrition on sandfish flesh that has the potency to improve reproduction quality of men. The materials used were sandfish with weight of 200-500 g, and then analysis of proximate, analysis of amino acid, analysis of fatty acid and analysis of mineral contained in the sandfish were performed. The results showed that protein content (39.96%) was the main component of the flesh; the carbohydrate and fat were 25.43% and 4.18%, respectively. Sandfish powder contains several essential amino acids and nonessential amino acids. Nine of ten amino acids needed by human body are contained in sandfish powder, i.e. arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, tryptophan, threonine and valine; only tryptophan that are not contained in sandfish powder. Sandfish powder contains saturated fatty acid kaproat, kaprilat, kaprat, laurat, miristat, stearat, arakhidat and behenat; monosaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA). MUFA is composed of fatty acid oleat, while PUFA is composed fatty acid omega 3 (linonenat, eicosapentaenoic acid and docosahexaenoic acid) and omega 6 (linoleat and arakhidonat). The minerals contained in sandfish powder are macrominerals and microminerals. Based on the findings, the nutrition in sandfish powder has a good potency to improve reproduction of men, especially PUFA for the maturation of spermatozoa, zinc for production function and spermatogenesis, motility of spermatozoa, acromoson reaction; Mg for transformation of genetic information and motility of spermatozoa; calcium for spermatogenesis, capacity and fertilization of spermatozoa. Thus, sandfish flesh powder has the potency to improve reproduction quality of men.

Keywords: sandfish flesh powder, nutrition, reproduction quality, men

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Authors: Paria Baharvand, Mohammad Reza Abbasi, Soha Namazi

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Introduction: Uremic pruritus (UP) is one of the major complaints in hemodialysis patients. The aim of this randomized clinical trial study was the evaluation of the anti-pruritus effect of Melatonin on hemodialysis patients with UP. Methods: This multi-centered double, blinded randomized clinical trial study was conducted on hemodialysis patients with UP that referred to the dialysis department of Imam Khomeini Hospital, Labbafinezhad Hospital and Ghiasi Hospital in Tehran, Iran, in 2018. Forty participants were enrolled and block randomization was performed by using a randomized list and divided into 2 groups of twenty patients. Evaluation of the 12-Item Pruritus Severity Scale (12-PSS), Visual analog scale (VAS), and Calculation of the affected body surface area for pruritus extent (BSA %) was performed every week. The Melatonin group received a 10 mg soft gel capsule, and the placebo group received a soft gel capsule placebo after dinner. For statistical analysis used by SPSS version 21(IRCT20180714040462N1). Results: 38 hemodialysis patients enrolled in this study. The mean age in the placebo group and in the Melatonin group was 55.88 ± 11.70 and 54.52 ± 13.00 years (p> 0.05). Also, 46% of all participants were female. Aspartate transaminase, alanine transaminase and C-reactive protein have significant differences between the two groups (p< 0.05). VAS score reduction in the two groups had a statistically significant (CI 95% = -1.71, P= 0.015(.The results of BSA% showed Melatonin had a significant effect on the decrease of the pruritus extent compared to placebo (CI 95% = -22.82, P= 0.001(. Conclusion: According to the results of this study and the preliminary effects of Melatonin on uremic pruritus, we suggest performing advanced clinical trials studies.

Keywords: Melatonin, Uremic Pruritus, hemodialysis, anti-pruritus

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Authors: Aydan Atalar, Nurcan Cetinkaya

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Corn stover is leftover of the leaves, stalk, husks and tassels in the field after harvesting the grain combined. Corn stover is a low-quality roughage but has mostly been used as roughage source for feeding ruminant animals in developing countries including Turkey; however, it can also be used to make biofuels as in developed countries. The objectives of the present study were to improve the digestibility of corn stover by the treatment of white rod fungus mainly Pleurotus osteritus (PO), Pleurotus eryingii (PE) and Lantinula edudes (LE) at different incubation times and also to determine the most effective fungus and incubation time to prepare fermeted corn stover for ruminant nutrition. The choped corn stover was treated with PO, PE and LE and incubated for 10, 20, 30 and 40 days in incubator at 26 0C. After each incubation time dry matter(DM), organic matter(OM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), neutral detergent lignin (ADL), in-vitro true dry matter digestibility (IVTDMD) and organic matter digestibility (IVTOMD) were determined. The mean IVTDMD and IVTOMD levels were increased by PO, PE and LE treatments in increasing order of incubation times. The obtained IVTDM values were 59.45, 60.51, 60.82 and 60.18 %; 59.45, 70.55, 67.18 and 66.96 %; 59.45, 70.55, 67.18 and 66,96 %; 59.45, 74.90, 69.18 % ; 59.45, 76.50, 71.24 and 73.04 for control, PO, PE and LE treatments at 0, 10, 20, 30 and 40 days incubation times respectively. The obtained IVTOMD values were 56.45,60.26,60.82and 60.18 %; 56.45, 68.70, 67.18 and 66.96 %; 56.45, 71.26, 69.18 and 69.28 %; 56.45, 73.23, 71.24 and 73.04 % for control, PO, PE and LE treatments at 0, 10, 20, 30 and 40 days incubation times respectively. The most effective fungus was PO and the incubation time was 30 days. In conclusion, PO treatment of corn stover with 30 days incubation may be used to prepare fermented corn stover for ruminant nutrition.

Keywords: biological treatment, corn stover, digestibility, Lantinula edudes, Pleurotus eryingii, Pleurotus osteritus

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Authors: Damaris Estrella Castillo, Zacil ha Vilchis Zapata, Leydi Peraza Gómez

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Hearing loss is an etiologically heterogeneous condition, where almost 60% is genetic in origin, 20% is due to environmental factors, and 20% have unknown causes. However, it is now known that the gene, GJB2, which encodes the connexin 26 protein, accounts for a large percentage of non-syndromic genetic hearing loss, and variants in this gene have been identified to be a common cause of hereditary hearing loss in many populations. The literature reports that the etiology in deafness helps improve family functioning but low-income countries this is difficult. Therefore, it is difficult to contribute the right of families to know about the genetic risk in future pregnancies as well as determining the certainty of being a carrier or affected. In order to assess the impact of genetic counseling and the functionality, 100 families with at least one child with profound hearing loss, were evaluated by specialists in audiology, clinical genetics and psychology. Targeted mutation analysis for one of the two known large deletions of upstream of GJB2/GJB6 gene (35delG; and including GJB2 regulatory sequences and GJB6) were performed in patients with diagnosis of non-syndromic hearing loss. Genetic counseling was given to all parents and primary caregivers, and APGAR family test was applied before and after the counseling. We analyzed a total of 300 members (children, parents) to determine the presence of the GJB2 gene mutation. Twelve patients (carriers and affected) were positive for the mutation, from 5 different families. The subsequent family APGAR testing and genetic counseling, showed that 14% perceived their families as functional, 62 % and 24 % moderately functional dysfunctional. This shows the importance of genetic counseling in the perception of family function that can directly impact the quality of life of these families.

Keywords: family dynamics, deafness, APGAR, counseling

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Authors: Nabil Omar, Farah Jibril, Oraib Amjad

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Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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Authors: Amanat Ali, Muhammad S. Al-Siyabi, Mostafa I. Waly, Hashem Al-Kilani

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In a cross-sectional research design, we assessed the nutrient intake, nutritional status, nutritional knowledge and dietary habits of Sultan Qaboos University (SQU) student athletes. A total of 71 (49 male and 22 female) student athletes with a mean age of 21.0 ± 1.81 and 19.32 ± 0.72 years and body mass index (BMI) of 22.51 ± 1.98 and 20.34 ± 2.97 kg/m2 for male and female respectively, participated in this study. A study questionnaire consisting of 2 sections was distributed to the participants. Section I included 18 questions regarding the demographic information, whereas the Section II consisted of 20 questions regarding the nutrition knowledge. The dietary intake of participants was collected by using a 7-days food diary identifying the frequency as well as the variety of food consumption. Significant differences (P < 0.05) were observed in the main sources of nutrition information used by the male and female athletes. Male athletes mainly had most of the nutrition information from friends (17%) whereas female athletes relied mainly on the family (20%). More female athletes (20%) were using TV as a source of nutrition information as compared to male athletes (15%). Both male and female athletes had the minimum nutrition information from dietitians and physicians. Significant (P < 0.05) differences were also observed in the nutritional knowledge and dietary habits scores of male and female athletes, which were 57 % and 49 %, respectively. Male athletes were classified to have fair nutritional knowledge and dietary habits, whereas the female athletes had poor nutritional knowledge and dietary habits. The average daily energy intake of male athletes was 2595 ± 358 kcal/day. Carbohydrate, fat, and protein contributed 64%, 22%, and 14%, of the total energy intake for the male athletes, respectively. The energy and macronutrients intake of male athletes was within the recommended dietary intake. The results indicated some gaps in the nutritional knowledge of SQU student athletes and suggest that there is a need for developing strategies in counseling and teaching the athletes to improve their nutritional knowledge and dietary habits.

Keywords: nutrient assessment, nutritional knowledge, dietary habits, Omani University athletes

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Authors: Muhammad Adeel Arshad, Faiz-Ul Hassan, Yanfen Cheng

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According to FAO, enteric methane (CH4) production is about 44% of all greenhouse gas emissions from the livestock sector. Ruminants produce CH4 as a result of fermentation of feed in the rumen especially from roughages which yield more CH4 per unit of biomass ingested as compared to concentrates. Efficient ruminal fermentation is not possible without abating CO2 and CH4. Methane abatement strategies are required to curb the predicted rise in emissions associated with greater ruminant production in future to meet ever increasing animal protein requirements. Ecology of ruminal methanogenesis and avenues for its mitigation can be identified through various genomic and transcriptomic techniques. Programs such as Hungate1000 and the Global Rumen Census have been launched to enhance our understanding about global ruminal microbial communities. Through Hungate1000 project, a comprehensive reference set of rumen microbial genome sequences has been developed from cultivated rumen bacteria and methanogenic archaea along with representative rumen anaerobic fungi and ciliate protozoa cultures. But still many species of rumen microbes are underrepresented especially uncultivable microbes. Lack of sequence information specific to the rumen's microbial community has inhibited efforts to use genomic data to identify specific set of species and their target genes involved in methanogenesis. Metagenomic and metatranscriptomic study of entire microbial rumen populations offer new perspectives to understand interaction of methanogens with other rumen microbes and their potential association with total gas and methane production. Deep understanding of methanogenic pathway will help to devise potentially effective strategies to abate methane production while increasing feed efficiency in ruminants.

Keywords: Genome sequences, Hungate1000, methanogens, ruminal fermentation

Procedia PDF Downloads 139

Authors: Tanveer Hussain, Misbah Hussain, Masroor Ellahi Babar, Muhammad Traiq Pervez, Fiaz Hussain, Sana Zahoor, Rashid Saif

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Interleukin 2 (IL-2) is a cytokine which is produced by activated T cells, play important role in immune response against antigen. It act in both autocrine and paracrine manner. It can stimulate B cells and various other phagocytic cells like monocytes, lymphokine-activated killer cells and natural killer cells. Acting in autocrine fashion, IL-2 protein plays a crucial role in proliferation of T cells. IL-2 triggers the release of pro and anti- inflammatory cytokines by activating several pathways. In present study, exon 1 of IL-2 gene of four local Pakistani breeds (Dera Din Panah, Beetal, Nachi and Kamori) from two provinces was amplified by using reported Ovine IL-2 primers, yielding PCR product of 501 bp. The sequencing of all samples was done to identify the polymorphisms in amplified region of IL-2 gene. Analysis of sequencing data resulted in identification of one novel nucleotide substitution (T→A) in amplified non-coding region of IL-2 gene. Comparison of IL-2 gene sequence of all four breeds with other goat breeds showed high similarity in sequence. While phylogenetic analysis of our local breeds with other mammals showed that IL-2 is a variable gene which has undergone many substitutions. This high substitution rate can be due to the decreased or increased changed selective pressure. These rapid changes can also lead to the change in function of immune system. This pioneering study of Pakistani goat breeds urge for further studies on immune system of each targeted breed for fully understanding the functional role of IL-2 in goat immunity.

Keywords: interleukin 2, mutational analysis, phylogeny, goat breeds, Pakistan

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Authors: Aldi Nel, Cliff L. W. Jones, Justin O. G. Kemp, Peter J. Britz

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Kelp Ecklonia maxima is included in formulated abalone feeds in South Africa, but its effect on abalone growth, feed utilisation efficiency and gut-bacterial communities has not previously been investigated. An eight-month on-farm growth trial with sub-adult Haliotis midae (~43 mm shell length) fed graded levels of kelp in formulated feeds was conducted. Kelp inclusion (0.44–3.54 % of pellet dry mass) promoted faster growth (65.7 – 74.5 % total mass gain), with better feed and protein conversions (FCR: 1.4 – 1.8; PER 2.3 – 2.7), compared to abalone fed the non-supplemented feed (52.3% total mass gain; FCR: 2.1; PER 1.9; p < 0.001). The gut-bacterial communities of abalone fed kelp-supplemented feed (0.88 % of pellet dry mass) were subsequently compared with that of abalone fed a non-supplemented control diet. Abalone gut-bacterial DNA was sequenced using 16S rRNA pyrosequencing and sequences were clustered into operational taxonomic units (OTUs) at a 97 % similarity level. A supplementary 16S rRNA denaturing gradient gel electrophoresis (DGGE) analysis was conducted. The dominant OTUs differed in terms of their relative abundances, with that of an autochthonous Mollicutes strain being significantly higher (p = 0.03) in the guts of abalone fed kelp-supplemented feed. The DGGE band patterns displayed a higher within-group variability of dominant bacterial strains for abalone fed the control diet, suggesting that dietary inclusion of kelp, which is rich in fermentable polysaccharides, promotes a balanced gut-bacterial community. This may contribute to the better feed utilisation and growth in abalone fed kelp-supplemented feeds.

Keywords: abfeed, digestion, macroalgae, mariculture

Procedia PDF Downloads 284

Authors: Mahdi Farajzadeh Ajirlou

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Prior evidence of normal cardiac anatomy is desirable to relieve the anxiety of cases with a family history of congenital heart disease or to offer the option of early gestation termination or close follow-up should a cardiac anomaly be proved. Fetal heart discovery plays an important part in the opinion of the fetus, and it can reflect the fetal heart function of the fetus, which is regulated by the central nervous system. Acquisition of ventricular volume and inflow data would be useful to quantify more valve regurgitation and ventricular function to determine the degree of cardiovascular concession in fetal conditions at threat for hydrops fetalis. This study discusses imaging the fetal heart with transvaginal ultrasound, Doppler ultrasound, three-dimensional ultrasound (3DUS) and four-dimensional (4D) ultrasound, spatiotemporal image correlation (STIC), glamorous resonance imaging and cardiac catheterization. Doppler ultrasound (DUS) image is a kind of real- time image with a better imaging effect on blood vessels and soft tissues. DUS imaging can observe the shape of the fetus, but it cannot show whether the fetus is hypoxic or distressed. Spatiotemporal image correlation (STIC) enables the acquisition of a volume of data concomitant with the beating heart. The automated volume accession is made possible by the array in the transducer performing a slow single reach, recording a single 3D data set conforming to numerous 2D frames one behind the other. The volume accession can be done in a stationary 3D, either online 4D (direct volume scan, live 3D ultrasound or a so-called 4D (3D/ 4D)), or either spatiotemporal image correlation-STIC (off-line 4D, which is a circular volume check-up). Fetal cardiovascular MRI would appear to be an ideal approach to the noninvasive disquisition of the impact of abnormal cardiovascular hemodynamics on antenatal brain growth and development. Still, there are practical limitations to the use of conventional MRI for fetal cardiovascular assessment, including the small size and high heart rate of the mortal fetus, the lack of conventional cardiac gating styles to attend data accession, and the implicit corruption of MRI data due to motherly respiration and unpredictable fetal movements. Fetal cardiac MRI has the implicit to complement ultrasound in detecting cardiovascular deformations and extracardiac lesions. Fetal cardiac intervention (FCI), minimally invasive catheter interventions, is a new and evolving fashion that allows for in-utero treatment of a subset of severe forms of congenital heart deficiency. In special cases, it may be possible to modify the natural history of congenital heart disorders. It's entirely possible that future generations will ‘repair’ congenital heart deficiency in utero using nanotechnologies or remote computer-guided micro-robots that work in the cellular layer.

Keywords: fetal, cardiac MRI, ultrasound, 3D, 4D, heart disease, invasive, noninvasive, catheter

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Authors: N. Slepickova Kasalkova, P. Slepicka, L. Bacakova, V. Svorcik

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Tissue engineering includes combination of materials and techniques used for the improvement, repair or replacement of the tissue. Scaffolds, permanent or temporally material, are used as support for the creation of the "new cell structures". For this important component (scaffold), a variety of materials can be used. The advantage of some polymeric materials is their cytocompatibility and possibility of biodegradation. Poly(L-lactic acid) (PLLA) is a biodegradable,  semi-crystalline thermoplastic polymer. PLLA can be fully degraded into H₂O and CO₂. In this experiment, the effect of the surface modification of biodegradable polymer (performed by plasma treatment) on the various cell types was studied. The surface parameters and changes of the physicochemical properties of modified PLLA substrates were studied by different methods. Surface wettability was determined by goniometry, surface morphology and roughness study were performed with atomic force microscopy and chemical composition was determined using photoelectron spectroscopy. The physicochemical properties were studied in relation to cytocompatibility of human osteoblast (MG 63 cells), rat vascular smooth muscle cells (VSMC), and human stem cells (ASC) of the adipose tissue in vitro. A fluorescence microscopy was chosen to study and compare cell-material interaction. Important parameters of the cytocompatibility like adhesion, proliferation, viability, shape, spreading of the cells were evaluated. It was found that the modification leads to the change of the surface wettability depending on the time of modification. Short time of exposition (10-120 s) can reduce the wettability of the aged samples, exposition longer than 150 s causes to increase of contact angle of the aged PLLA. The surface morphology is significantly influenced by duration of modification, too. The plasma treatment involves the formation of the crystallites, whose number increases with increasing time of modification. On the basis of physicochemical properties evaluation, the cells were cultivated on the selected samples. Cell-material interactions are strongly affected by material chemical structure and surface morphology. It was proved that the plasma treatment of PLLA has a positive effect on the adhesion, spreading, homogeneity of distribution and viability of all cultivated cells. This effect was even more apparent for the VSMCs and ASCs which homogeneously covered almost the whole surface of the substrate after 7 days of cultivation. The viability of these cells was high (more than 98% for VSMCs, 89-96% for ASCs). This experiment is one part of the basic research, which aims to easily create scaffolds for tissue engineering with subsequent use of stem cells and their subsequent "reorientation" towards the bone cells or smooth muscle cells.

Keywords: poly(L-lactic acid), plasma treatment, surface characterization, cytocompatibility, human osteoblast, rat vascular smooth muscle cells, human stem cells

Procedia PDF Downloads 228

Authors: Joana Carvalho, Margarida Soares, André Ribeiro, Lucas Nascimento, Nádia Valério, Zlatina Genisheva

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Following the exponential growth of human population, a remarkable increase in the amount of fish waste has been produced worldwide. The fish processing industry generates a considerable amount of by-products which represents a considerable environmental problem. Accordingly, the reuse and valorisation of these by-products is a key process for marine resource preservation. The significant volume of fish waste produced worldwide, along with its environmental impact, underscores the urgent need for the adoption of sustainable practices. The transformative potential of utilizing fish processing waste to create industrial value is gaining recognition. The substantial amounts of waste generated by the fish processing industry present both environmental challenges and economic inefficiencies. Different added-value products can be recovered by the valorisation industries, whereas fishing companies can save costs associated with the management of those wastes, with associated advantages, not only in terms of economic income but also considering the environmental impacts. Fish processing by-products have numerous applications; the target portfolio of products will be fish oil, fish protein hydrolysates, bacteriocins, pigments, vitamins, collagen, and calcium-rich powder, targeting food products, additives, supplements, and nutraceuticals. This literature review focuses on the main valorisation ways of fish wastes and different compounds with a high commercial value obtained by fish by-products and their possible applications in different fields. Highlighting its potential in sustainable resource management strategies can play and important role in reshaping the fish processing industry, driving it towards circular economy and consequently more sustainable future.

Keywords: fish process industry, fish wastes, by-products, circular economy, sustainability

Procedia PDF Downloads 17

Authors: Leila M. Carvalho, Maria Erica S. Oliveira, Arnoud C. Neto, Elza I. Ida, Massami Shimokomaki, Marta S. Madruga

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The quality of broiler breast meat is changing as a result of the continuing emphasis on genetic selection for a more efficient meat production. Breast meat has been classified as PSE (pale, soft, exudative), DFD (dark, firm, dry) and normal color meat, and recently a third group has emerged: the so-called PFN (pale, firm, non-exudative) meat. This classification was based on pH, color and functional properties. The aim of this work was to confirm the existence of PFN and PSE meat by biochemical characterization and functional properties. Twenty four hours of refrigerated fillet, Pectoralis major, m. samples (n= 838) were taken from Cobb flocks 42-48 days old, obtained in Northeastern Brazil tropical region, the Northeastern, considered to have only dry and wet seasons. Color (L*), pH, water holding capacity (WHC), values were evaluated and compared with PSE group samples. These samples were classified as Normal (465.8), PSE meat (L*≥53; pH<5.8) and PFN (L*≥53; pH>5.8). The occurrence of control meat, PSE and PFN was 69.09%, 11.10% and 19.81%, respectively. Samples from PFN presented 4.0-5.0% higher WHC in relation to PSE meat and similar to control group. These results are explained by the fact that PSE meat syndrome occurs because of higher protein denaturation as the consequence of a simultaneous lower pH values under warm carcass sooner after slaughtering impairing the myofibril proteins functional properties. Conversely, PFN samples follow normal glycolysis rate maintaining the normal proteins activities. In conclusion, the results reported herein confirm the existence of this emerging broiler meat group with similar properties as control group and it should be considered as normal breast meat group.

Keywords: broiler breast meat, funcional properties, PFN, PSE

Procedia PDF Downloads 249

Authors: Rita Bagheri, Javed Ahmed, Humayra Bashir, M. Irfan Qureshi

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Agriculture lands suffer from a combination of stresses such as salinity and metal contamination including cadmium at the same time. Under such condition of multiple stresses, plant may exhibit unique responses different from the stress occurring individually. Thus, it would be interesting to investigate that how plant respond to combined stress at level of antioxidants and proteome expression, and identifying the proteins which are involved in imparting stress tolerance. With an approach of comparative proteomics and antioxidant analysis, present study investigates the response of Spinacia oleracea to salt (NaCl), cadmium (Cd), and their combination (NaCl+Cd) stress. Two-dimensional gel electrophoresis was used for resolving leaf proteome, and proteins of interest were identified using PDQuest software. A number of proteins expressed differentially, those indicated towards their roles in imparting stress tolerance, were digested by trypsin and analyzed on mass spectrometer for peptide mass fingerprinting (PMF). Data signals were then matched with protein databases using MASCOT. Results show that NaCl, Cd and both together (NaCl+Cd) induce oxidative stress which was highest in combined stress of Cd+NaCl. Correspondingly, the activities of enzymatic antioxidants viz., SOD, APX, GR and CAT, and non-enzymatic antioxidants had highest changes under combined stress compares to single stress over their respective controls. Among the identified proteins, several interesting proteins were identified that may be have role in Spinacia oleracia tolerance in individual and combinatorial stress of salt and cadmium. The functional classification of identified proteins indicates the importance and necessity of keeping higher ratio of defence and disease responsive proteins.

Keywords: Spinacia oleracea, Cd, salinity, proteomics, antioxidants, combinatorial stress

Procedia PDF Downloads 382

Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak

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Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.

Keywords: cancer, MyD88, TIR domains, Toll-like receptors

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Authors: Ume Habiba, Shafaqat Ali, Mujahid Farid, Muhammad Bilal Shakoor

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Copper (Cu) is an essential micronutrient for normal plant growth and development, but in excess, it is also toxic to plants. The present study investigated the influence of ethylenediaminetetraacetic acid (EDTA) in enhancing Cu uptake and tolerance as well as the morphological and physiological responses of Brassica napus L. seedlings under Cu stress. Four-week-old seedlings were transferred to hydroponics containing Hoagland’s nutrient solution. After 2 weeks of transplanting, three levels (0, 50, and 100 μM) of Cu were applied with or without application of 2.5 mM EDTA and plants were further grown for 8 weeks in culture media. Results showed that Cu alone significantly decreased plant growth, biomass, photosynthetic pigments, and gas exchange characteristics. Cu stress also reduced the activities of antioxidants, such as superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), and catalase (CAT) along with protein contents. Cu toxicity increased the concentration of reactive oxygen species (ROS) as indicated by the increased production of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in both leaves and roots. The application of EDTA significantly alleviated Cu-induced toxic effects in B. napus, showing remarkable improvement in all these parameters. EDTA amendment increased the activity of antioxidant enzymes by decreasing the concentrations of MDA and H2O2 both in leaves and roots of B. napus. Although, EDTA amendment with Cu significantly increased Cu uptake in roots, stems, and leaves in decreasing order of concentration but increased the growth, photosynthetic parameters, and antioxidant enzymes. These results showed that the application of EDTA can be a useful strategy for phytoextraction of Cu by B. napus from contaminated soils.

Keywords: antioxidants, biomass, copper, EDTA, phytoextraction, tolerance

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Authors: Said Belaaouad

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This study aimed to explore the quantitative structure-activity relationship (QSAR) of 1,2,4-Triazine-3(2H)-one derivative as a potential anticancer agent against breast cancer. The electronic descriptors were obtained using the Density Functional Theory (DFT) method, and a multiple linear regression techniques was employed to construct the QSAR model. The model exhibited favorable statistical parameters, including R2=0.849, R2adj=0.656, MSE=0.056, R2test=0.710, and Q2cv=0.542, indicating its reliability. Among the descriptors analyzed, absolute electronegativity (χ), total energy (TE), number of hydrogen bond donors (NHD), water solubility (LogS), and shape coefficient (I) were identified as influential factors. Furthermore, leveraging the validated QSAR model, new derivatives of 1,2,4-Triazine-3(2H)-one were designed, and their activity and pharmacokinetic properties were estimated. Subsequently, molecular docking (MD) and molecular dynamics (MD) simulations were employed to assess the binding affinity of the designed molecules. The Tubulin colchicine binding site, which plays a crucial role in cancer treatment, was chosen as the target protein. Through the simulation trajectory spanning 100 ns, the binding affinity was calculated using the MMPBSA script. As a result, fourteen novel Tubulin-colchicine inhibitors with promising pharmacokinetic characteristics were identified. Overall, this study provides valuable insights into the QSAR of 1,2,4-Triazine-3(2H)-one derivative as potential anticancer agent, along with the design of new compounds and their assessment through molecular docking and dynamics simulations targeting the Tubulin-colchicine binding site.

Keywords: QSAR, molecular docking, ADMET, 1, 2, 4-triazin-3(2H)-ones, breast cancer, anticancer, molecular dynamic simulations, MMPBSA calculation

Procedia PDF Downloads 97