Search results for: metabolism and excretion–toxicity

Authors: Sara Khan Mohammadi

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The world is facing a major challenge of feeding a growing population while ensuring the sustainability of food systems. The United Nations estimates that the global population will reach 9.7 billion by 2050, which means that food production needs to increase by 70% to meet the demand. However, this increase in food production should not come at the cost of environmental degradation, loss of biodiversity, and climate change. Therefore, there is a need for sustainable food systems that can provide healthy and nutritious food while minimizing their impact on the environment. Nutrition and Food Engineering: Nutrition and food engineering play a crucial role in promoting sustainable food system. Nutrition is concerned with the study of nutrients in foods, their absorption, metabolism, and their effects on health. Food engineering involves the application of engineering principles to design, develop, and optimize food processing operations. Together, nutrition and food engineering can help to create sustainable food systems by: 1. Developing Nutritious Foods: Nutritionists and food engineers can work together to develop foods that are rich in nutrients such as vitamins, minerals, fiber, and protein. These foods can be designed to meet the nutritional needs of different populations while minimizing waste. 2. Reducing Food Waste: Food waste is a major problem globally as it contributes to greenhouse gas emissions and wastes resources such as water and land. Nutritionists and food engineers can work together to develop technologies that reduce waste during processing, storage, transportation, and consumption. 3. Improving Food Safety: Unsafe foods can cause illnesses such as diarrhea, cholera, typhoid fever among others which are major public health concerns globally. Nutritionists and food engineers can work together to develop technologies that improve the safety of foods from farm to fork. 4. Enhancing Sustainability: Sustainable agriculture practices such as conservation agriculture can help reduce soil erosion while improving soil fertility. Nutritionists and food engineers can work together to develop technologies that promote sustainable agriculture practices.

Keywords: sustainable food, developing food, reducing food waste, food safety

Procedia PDF Downloads 58

Authors: S. K. Thind, Aparjot Kaur

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Heat stress is one of the major environmental factors drastically reducing wheat production. Crop heat tolerance can be enhanced by preconditioning of plants by exogenous application of osmoprotectants. Presently, the effect of trehalose pretreatment (at 1 mM, and 1.5 nM) under heat stress of 35±2˚C (moderate) and 40±2˚ (severe) for four and eight hour was conducted in wheat (Tricticum aestivum L.) genotypes viz. HD2967, PBW 175, PBW 343, PBW 621, and PBW 590. Heat stress affects wide spectrum of physiological processes within plants that are irreversibly damaged by stress. Membrane thermal stability (MTS) and cell viability was significantly decreased under heat stress for eight hours. Pretreatment with trehalose improved MTS and cell viability under stress and this effect was more promotory with higher concentration. Thermal stability of photosynthetic apparatus differed markedly between genotypes and Hill reaction activity was recorded more in PBW621 followed by C306 as compared with others. In all genotypes photolysis of water showed decline with increase in temperature stress. Trehalose pretreatment helped in sustaining Hill reaction activity probably by stabilizing the photosynthetic apparatus against heat-induced photo inhibition. Both plant growth and development were affected by temperature in both shoot and root under heat stress. The reduction was compensated partially by trehalose (1.5 mM) application. Adaption to heat stress is associated with the metabolic adjustment which led to accumulation of soluble sugars including non-reducing and reducing for their role in adaptive mechanism. Higher acid invertase activity in shoot of tolerant genotypes appeared to be a characteristic for stress tolerance. As sucrose synthase play central role in sink strength and in studied wheat genotype was positively related to dry matter accumulation. The duration of heat stress for eight hours had more severe effect on these parameters and trehalose application at 1.5 mM ameliorated it to certain extent.

Keywords: heat stress, Triticum aestivum, trehalose, membrane thermal stability, triphenyl tetrazolium chloride, reduction test, growth, sugar metabolism

Procedia PDF Downloads 308

Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

Procedia PDF Downloads 69

Authors: Mahesh M. Patil, K. A. Anu-Appaiah

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Overweight and obesity is a serious medical problem, increasing in prevalence, and affecting millions worldwide. Investigators have been trying from decades to articulate the burden of obesity and related risk factors. To answer this problem, we suggest a new therapeutic anti-obesity compounds from Garcinia xanthochymus fruit. However, there is little published scientific information on non-hydroxycitric acid Garcinia species. Our findings include biochemical characterization of the fruit; in vivo toxicity and bio-efficacy study of G. xanthochymus in high fat diet wistar rat model. We observed that Garcinia pericarp is a rich source of organic acids, polyphenols, mono- (40.63%) and poly-unsaturated fatty acids (16.45%; omega-3: 10.02%). Toxicological studies have showed that Garcinia is safe and had no observed adverse effect level up to 400 mg/kg/day. Body weight and food intake was significantly (P<0.05) reduced in oral gavage treated rats (sonicated Garcinia powder) in 13 weeks. Subcutaneous fat was significantly (P<0.05) reduced in Garcinia treated rats. Hepatocytes significantly (p<0.05) overexpressed sterol regulatory element binding protein 2, liver X receptor- α, liver X receptor- β, lipoprotein lipase and monoacylglycerol lipase. Fatty acid binding protein 1 and peroxisome proliferator activated receptor- α were down regulated as assessed by real time qPCR. Currently our research is focused on the adipocyte obesity related gene expressions, effect of Garcinia on 3T3-adipocyte cell lines and high fat diet induced mice model. This in vivo pre-clinical data suggests that G. xanthochymus may have clinical utility for the treatment of obesity. However, further studies are required to establish its potency.

Keywords: Garcinia xanthochymus, anti-obesity, high fat diet, real time qPCR

Procedia PDF Downloads 238

Authors: Ahsan Khan, Nazish Shah, Muhammad Salman

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The present study deals with the toxicological effects of copper, lead and chromium on brain and liver tissues of grass carp (Ctenopharyngodon idella). The average length of experimental fish was 8.5 ± 5.5 cm and weighed 9.5 ± 6.5 g. Grass carp was exposed to lethal concentration (LC₁₅) of copper, lead and chromium for 24, 48, 72 and 96 hours respectively. (LC₁₅) for copper was 1.5, 1.4, 1.2 and 1mgL⁻¹. Similarly, LC₁₅ of lead was 250, 235, 225 and 216mgL⁻¹ while (LC₁₅) for chromium was 25.5, 22.5, 20 and 18mgL⁻¹ respectively. During the time of exposure against various doses of heavy metals the grass carp showed some behavioral changes. In the initial stages of experiment, the rapid movements and gulping of air were observed. Several times the fish tried to jump to scat from the toxic median. In addition, the accumulation of heavy metals in different tissues of grass carp particularly in liver and brain tissues were observed. Lead was highly accumulated in brain tissue after the exposure of fish for 24 and 48 hours, while highly accumulated in liver tissues after the exposure of fish for 72 and 96 hours. Chromium was highly accumulated in the liver tissues after the exposure of fish for 24 hours while its accumulation was found highly in the brain tissues after the exposure of fish for 48, 72 and 96 hours. Similarly, accumulation of copper concentration was found highly in brain tissues after the exposure of 48 and 96 hours while its accumulation was high in liver tissues after the exposure of 24 and 72 hours. Comparatively maximum accumulation of lead was found in brain and liver tissues of grass carp followed by chromium and copper. Furthermore, accumulation of these metals caused many abnormalities like gliosis, destruction of cell, change in cell shape and shrinkage of cells in brain tissue while in liver tissues aggregation in hepatocytes, widen space between cells and also destruction of cell was observed. These experiments and observations can be useful to monitor the aquatic pollution and quality of aquatic environment system.

Keywords: brain, grass carp, liver, lethal concentration, toxicity

Procedia PDF Downloads 137

Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani

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Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.

Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.

Procedia PDF Downloads 326

Authors: Youcef Serhane, Abdelkrim Bouzaza, Dominique Wolbert, Aymen Amin Assadi

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Throughout history, the use of chemical weapons is not exclusive to combats between army corps; some of these weapons are also found in very targeted intelligence operations (political assassinations), organized crime, and terrorist organizations. To improve the speed of action, important technological devices have been developed in recent years, in particular in the field of protection and decontamination techniques to better protect and neutralize a chemical threat. In order to assess certain protective, decontaminating technologies or to improve medical countermeasures, tests must be conducted. In view of the great toxicity of toxic chemical agents from (real) wars, simulants can be used, chosen according to the desired application. Here, we present an investigation about using a photocatalytic filtering reactor (PFR) for highly contaminated environments containing diethyl sulfide (DES). This target pollutant is used as a simulant of CWA, namely of Yperite (Mustard Gas). The influence of the inlet concentration (until high concentrations of DES (1200 ppmv, i.e., 5 g/m³ of air) has been studied. Also, the conversion rate was monitored under different relative humidity and different flow rates (respiratory flow - standards: ISO / DIS 8996 and NF EN 14387 + A1). In order to understand the efficacity of pollutant neutralization by PFR, a kinetic model based on the Langmuir–Hinshelwood (L–H) approach and taking into account the mass transfer step was developed. This allows us to determine the adsorption and kinetic degradation constants with no influence of mass transfer. The obtained results confirm that this small configuration of reactor presents an extremely promising way for the use of photocatalysis for treatment to deal with highly contaminated environments containing real chemical warfare agents. Also, they can give birth to an individual protection device (an autonomous cartridge for a gas mask).

Keywords: photocatalysis, photocatalytic filtering reactor, diethylsulfide, chemical warfare agents

Procedia PDF Downloads 82

Authors: Vincent Murray

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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.

Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing

Procedia PDF Downloads 102

Authors: Amriana Hifizah, Philip Edward Vercoe, Graeme Bruce Martin, Teuku Reza Ferasy, Muhammad Hambal

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Many native forage plant species have been used in Indonesia as feed for ruminants. However, less information is available about how these plants affect productivity, let alone methane emissions. In the province of Aceh, where the traditional practice is to feed local forages to small ruminants, the farmers are not satisfied with the productivity of their livestock, and they attribute this problem to poor availability and too few options for good quality forages. Forage quality is reduced by high environmental temperatures which increase the amount of lignification. In addition to reducing productivity, these factors also increase enteric methane production. A preliminary survey about potential forage species was completed in three different districts, two of low elevation and one of high elevation: Syiah Kuala (05°30’5.08” N to 095°24’7.35” E), elevation 29 m MSL; Kajhu (05°32’34.6” N to 095°21’17.7” E), elevation 30 m MSL; Lembah Seulawah (05°28'06.4" N to 095°43' 14.2" E), elevation 254 m MSL. Information about local plants was collected in a semi-structured interview with scientists, government field officers and local farmers, in the city of Banda Aceh and in those three districts. The outcome was a list 40 species that could be useful, of which 21 were selected for further study. The selection process was based on several criteria: high availability, high protein content, low toxicity, and evidence of secondary metabolites (eg, history of medicinal plants for both human and animals). For some of the selected medicinal plants, there is experimental evidence of effects on methane production during rumen fermentation. Subsequently, the selected forages were tested for their effects on rumen fermentation in vitro, using batch culture. The data produced will be used to identify forages with the potential to reduce CH4 emissions. These candidates will then be assessed for their benefits (fermentability and productivity) and potential deleterious side-effects.

Keywords: batch culture, forage, methane, rumen

Procedia PDF Downloads 312

Authors: Kanokwan Sansuwan, Orapint Jintasataporn, Srinoy Chumkam

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

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

Procedia PDF Downloads 163

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

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

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

Procedia PDF Downloads 113

Authors: Gordana Ćetković, Sanja Podunavac-Kuzmanović, Jasna Čanadanović-Brunet, Vesna Tumbas Šaponjac, Vanja Šeregelj, Jelena Vulić, Slađana Stajčić

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The color of food is one of the decisive factors for consumers. Potential toxicity of artificial food colorants has led to the consumers' preference for natural products over products with artificial colors. Natural pigments have many bioactive functions, such as antioxidant, provitamin and many other. Having this in mind, the acceptability of natural colorants by the consumers is much higher. Being present in all photosynthetic plant tissues carotenoids are probably most widespread pigments in nature. Carrot (Daucus carota) is a good source of functional food components. Carrot is especially rich in carotenoids, mainly α- and β-carotene and lutein. For this study, carrot was extracted using classical extraction with hexane and ethyl acetate, as well as supercritical CO₂ extraction. The extraction efficiency was evaluated by estimation of carotenoid yield determined spectrophotometrically. Classical extraction using hexane (18.27 mg β-carotene/100 g DM) was the most efficient method for isolation of carotenoids, compared to ethyl acetate classical extraction (15.73 mg β-carotene/100 g DM) and supercritical CO₂ extraction (0.19 mg β-carotene/100 g DM). Three carrot extracts were tested in terms of antioxidant activity using DPPH and reducing power assay as well. Surprisingly, ethyl acetate extract had the best antioxidant activity on DPPH radicals (AADPPH=120.07 μmol TE/100 g) while hexane extract showed the best reducing power (RP=1494.97 μmol TE/100 g). Hexane extract was chosen as the most potent source of carotenoids and was encapsulated in whey protein by freeze-drying. Carotenoid encapsulation efficiency was found to be high (89.33%). Based on our results it can be concluded that carotenoids from carrot can be efficiently extracted using hexane and classical extraction method. This extract has the potential to be applied in encapsulated form due to high encapsulation efficiency and coloring capacity. Therefore it can be used for dietary supplements development and food fortification.

Keywords: carotenoids, carrot, extraction, encapsulation

Procedia PDF Downloads 247

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

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

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

Procedia PDF Downloads 174

Authors: Kazam Ali, Muhammad Sagheer, Mansoor-Ul- Hasan, Abdul Rashid, Chaudhary Muhammad Shahid Hanif, Fawad Zafar Ahmad Khan, Hafiz Muhammad Aatif

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Natural extracts of two medicinal plants Nicotiana tabacum and Eucalyptus globulus were tested for their toxic and enzyme inhibition effects against three insects species of stored grains Tribolium castaneum, Trogoderma granarium and Sitophilus granarius. Responses of insects varied with exposure periods and dilution levels of acetone extracts of plants. Both plant extracts were lethal to insects but the crude leaf extract of N. tabacum evidenced strong toxic action against three tested insect species. Maximum mortality 36.30% in S. granarius, 25.96% in T. castaneum, and 21.88% in T. granarium were found at 20% dilution level, after 10 days exposure to botanical extract of N. tabacum. The impact of N. tabacum and E. globulus on the activity of esterases; acetylcholinesterase (AChE), α-carboxylesterase (α-CE), β-carboxylesterase (β-CE) and phosphatses; acid phosphatase (AcP), alkaline phosphatase (AlP) of three stored grain insect species were also studied in the survivors of toxicity assay. Whole body homogenates of insects were used for enzyme determination and consumption of high dose rate N. tabacum extract containing diet resulted in maximum 55.33% inhibition of AChE and 26.17% AlP inhibition in T. castaneum, while 44.17% of α-CE and 31.67% inhibition of β-CE activity were noted in S. granarius. Maximum inhibition 23.44% of AcP activity was found in T. granarium exposed to diet treated with the extract of E. globulus. The findings indicate that acetone extracts of N. tabacum and E. globulus are naturally occurring pesticide and facts of the enzyme inhibition relations specify that their effect changes with the insect species.

Keywords: natural extract, medicinal plant, toxic effects, enzyme inhibition, acetone extract

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Authors: Muhammad Imran, Sarfraz Shafiq, Xiangru Tang

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

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

Procedia PDF Downloads 91

Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

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Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

Procedia PDF Downloads 118

Authors: Chakrapani Pullagummi, Arun Jyothi Bheemagani, B. Chandra Sekhar Singh, Prem Kumar, A. Roja Rani

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Diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion and its action. The objective of present study was alloxan induced diabetes in S.D (Sprague Dawley) rats, treated with leaf extract of Andrographis paniculata and bark extract of Erythrina indica. Plant extract treated rats were analyzed biochemically and molecularly. on normal and diabetic rats. The changes in MDA (lipid peroxidation) and glucose (by GOD method) levels in blood of both normal and diabetic rat were analyzed. Diabetes induced rats were treated with methanolic extracts of Andrographis paniculata leaf and Erythrina indica bark which are of medicinal importance. Later after inducing diabetes the rats were treated with medicinal plant extracts, Andrographis paniculata leaf and Erythrina indica bark which are well known for their anti diabetic and antioxidative property in order to control the glucose and MDA levels. The blood plasma of diabetic and normal rats was analyzed for the levels of MDA (lipid peroxidation) and glucose levels. Results of this study suggested that the Andrographis paniculata leaf and Erythrina indica can be used as a potential natural antidiabetic agent for treating and postponing the appearance of complications that arise due to Diabetes. Molecular study deals with the analysis of binding mechanism of 2 selected natural compounds from Andrographis and Erythrina extracts against the novel target for type T2D namely PPAR-γ compared with Rosiglitazone (standard compound). The results revealed that most of the selected herbal lead compounds were effective targets against the receptors. These compounds showed favorable interactions with the amino acid residues thereby substantiating their proven efficacy as anti-diabetic compounds.

Keywords: andrographis paniculata, erythrina indica, alloxan, lipid peroxidation, blood glucose level, PPAR-γ

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Authors: Sonal Gupta, Rakhi Bansal, Javed Ali, Reema Gabrani, Shweta Dang

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Nanoemulsions (NEs) and microemulsions (MEs) have been an attractive tool for encapsulation of both hydrophilic and lipophillic actives. Both these systems are composed of oil phase, surfactant, co-surfactant and aqueous phase. Depending upon the application and intended use, both oil-in-water and water-in-oil emulsions can be designed. NEs are fabricated using high energy methods employing less percentage of surfactant as compared to MEs which are self assembled drug delivery systems. Owing to the nanometric size of the droplets these systems have been widely used to enhance solubility and bioavailability of natural as well as synthetic molecules. The aim of the present study is to assess the effect of % age of surfactants on cell viability of Vero cells (African Green Monkeys’ Kidney epithelial cells) via MTT assay. Green tea catechin (Polyphenon 60) loaded ME employing low energy vortexing and NE employing high energy ultrasonication were prepared using same excipients (labrasol as oil, cremophor EL as surfactant and glycerol as co-surfactant) however, the % age of oil and surfactant needed to prepare the ME was higher as compared to NE. These formulations along with their excipients (oilME=13.3%, SmixME=26.67%; oilNE=10%, SmixNE=13.52%) were added to Vero cells for 24 hrs. The tetrazolium dye, 3-(4,5-dimethylthia/ol-2-yl)-2,5-diphi-iiyltclrazolium bromide (MTT), is reduced by live cells and this reaction is used as the end point to evaluate the cytoxicity level of a test formulation. Results of MTT assay indicated that oil at different percentages exhibited almost equal cell viability (oilME ≅ oilNE) while surfactant mixture had a significant difference in the cell viability values (SmixME < SmixNE). Polyphenon 60 loaded ME and its PlaceboME showed higher toxicity as compared to Polyphenon 60 loaded NE and its PlaceboNE that can be attributed to the higher concentration of surfactants present in MEs. Another probable reason for high % cell viability of Polyphenon 60 loaded NE might be due to the effective release of Polyphenon 60 from NE formulation that helps in the sustenance of Vero cells.

Keywords: cell viability, microemulsion, MTT, nanoemulsion, surfactants, ultrasonication

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Authors: Kinjal H. Shah, Piyush M. Patel

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Diabetes mellitus is considered to be a serious endocrine syndrome. Synthetic hypoglycemic agents can produce serious side effects including hematological effects, coma, and disturbances of the liver and kidney. In addition, they are not suitable for use during pregnancy. In recent years, there have been relatively few reports of short-term side effects or toxicity due to sulphonylureas. Published figures and frequency of side effects in large series of patient range from about 1 to 5%, with symptoms severe enough to lead to the withdrawal of the drug in less than 1 to 2%. Adverse effects, in general, have been of the following type: allergic skin reactions, gastrointestinal disturbances, blood dyscrasias, hepatic dysfunction, and hypoglycemia. The associated disadvantages with insulin and oral hypoglycemic agents have led to stimulation in the research for locating natural resources showing antidiabetic activity and to explore the possibilities of using traditional medicines with proper chemical and pharmacological profiles. Literature survey reveals that the inhabitants of Abbottabad district of Pakistan use the dried leaf powder along with table salt and water orally for treating diabetes, skin allergy, wounds and as a blood purifier, where they pronounced the plant locally as ‘Nem.' The detailed phytochemical investigation of the Cedrela toona Roxb. leaves for antidiabetic activity has not been documented. Hence, there is a need for phytochemical investigation of the leaves for antidiabetic activity. The collection of fresh leaves and authentification followed by successive extraction, phytochemical screening, and testing of antidiabetic activity. The blood glucose level was reduced maximum in ethanol extract at 5th and 7th h after treatment. Blood glucose was depressed by 8.2% and 10.06% in alloxan – induced diabetic rats after treatment which was comparable to the standard drug, Glibenclamide. This may be due to the activation of the existing pancreatic cells in diabetic rats by the ethanolic extract.

Keywords: antidiabetic, Cedrela toona Roxb., phytochemical screening, blood glucose

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

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

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

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Authors: Sergejs Kolesovs, Pavels Semjonovs

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

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

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Authors: Marwa A. A. Ragab, Hadir M. Maher, Eman I. El-Kimary

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Co-administration of methotrexate (MTX) and aspirin (ASP) can cause a pharmacokinetic interaction and a subsequent increase in blood MTX concentrations which may increase the risk of MTX toxicity. Therefore, it is important to develop a sensitive, selective, accurate and precise method for their simultaneous determination in urine. A new hybrid chemometric method has been applied to the emission response data of the two drugs. Spectrofluorimetric method for determination of MTX through measurement of its acid-degradation product, 4-amino-4-deoxy-10-methylpteroic acid (4-AMP), was developed. Moreover, the acid-catalyzed degradation reaction enables the spectrofluorimetric determination of ASP through the formation of its active metabolite salicylic acid (SA). The proposed chemometric method deals with convolution of emission data using 8-points sin xi polynomials (discrete Fourier functions) after the derivative treatment of these emission data. The first and second derivative curves (D1 & D2) were obtained first then convolution of these curves was done to obtain first and second derivative under Fourier functions curves (D1/FF) and (D2/FF). This new application was used for the resolution of the overlapped emission bands of the degradation products of both drugs to allow their simultaneous indirect determination in human urine. Not only this chemometric approach was applied to the emission data but also the obtained data were subjected to non-parametric linear regression analysis (Theil’s method). The proposed method was fully validated according to the ICH guidelines and it yielded linearity ranges as follows: 0.05-0.75 and 0.5-2.5 µg mL-1 for MTX and ASP respectively. It was found that the non-parametric method was superior over the parametric one in the simultaneous determination of MTX and ASP after the chemometric treatment of the emission spectra of their degradation products. The work combines the advantages of derivative and convolution using discrete Fourier function together with the reliability and efficacy of the non-parametric analysis of data. The achieved sensitivity along with the low values of LOD (0.01 and 0.06 µg mL-1) and LOQ (0.04 and 0.2 µg mL-1) for MTX and ASP respectively, by the second derivative under Fourier functions (D2/FF) were promising and guarantee its application for monitoring the two drugs in patients’ urine samples.

Keywords: chemometrics, emission curves, derivative, convolution, Fourier transform, human urine, non-parametric regression, Theil’s method

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Authors: Kabrambam D. Singh, Dinabandhu Sahoo, Yallappa Rajashekar

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Evolution has caused many insects to develop resistance to several synthetic insecticides. This problem along with the persisting concern regarding the health and environmental safety issues of the existing synthetic insecticides has urged the scientific fraternity to look for a new plant-based natural insecticide with inherent eco-friendly nature. Colocasia esculenta var. esculenta (L.) Schott (Araceae family) is widely grown throughout the South- East Asian Countries for its edible corms and leaves. Various physico-chemical and spectroscopic techniques (IR, 1H NMR, 13C NMR and Mass) were used for the isolation and characterization of isolated bioactive molecule named 2, 3-dimethylmaleic anhydride (3, 4-dimethyl-2, 5-furandione). This compound was found to be highly toxic, even at low concentration, against several storage grain pests when used as biofumigant. Experimental studies on the mode of action of 2, 3-dimethylmaleic anhydride revealed that the biofumigant act as inhibitor of acetylcholinesterase enzyme in cockroach and stored grain insects. The knockdown activity of bioactive compound is concurrent with in vivo inhibition of AChE; at KD99 dosage of bioactive molecule showed more than 90% inhibition of AChE activity in test insects. The molecule proved to affect the antioxidant enzyme system; superoxide dismutase (SOD), and catalase (CAT) and also found to decrease reduced glutathione (GSH) level in the treated insects. The above results indicate involvement of inhibition of AChE activity and oxidative imbalance as the potential mode of action of 2, 3-dimethylmaleic anhydride. In addition, the study reveals computational docking programs elaborate the possible interaction of 2, 3-dimethylmaleic anhydride with enzyme acetylcholinesterase (AChE) of Periplaneta americana. Finally, the results represent that toxicity of 2, 3-dimethylmaleic anhydride might be associated with inhibition of AChE activity and oxidative imbalance.

Keywords: 2, 3-dimethylmaleic anhydride, Colocasia esculenta var. esculenta (L.) Schott, Biofumigant, acetylcholinesterase, antioxidant enzyme, molecular docking

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Authors: L. Meksem Amara, M. Ferfar, N. Meksem, M. R. Djebar

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The wheat is the cereal the most consumed in the world. In Algeria, the production of this cereal covers only 20 in 25 % of the needs for the country, the rest being imported. To improve the efficiency and the productivity of the durum wheat, the farmers turn to the use of pesticides: weed-killers, fungicides and insecticides. However this use often entrains losses of products more at least important contaminating the environment and all the food chain. Weed-killers are substances developed to control or destroy plants considered unwanted. That they are natural or produced by the human being (molecule of synthesis), the absorption and the metabolization of weed-killers by plants cause the death of these plants. In this work, we set as goal the evaluation of the effect of a weed-killer sulfonylurea, the CossackOD with various concentrations (0, 2, 4 and 9 µg) on variety of Triticum durum: Cirta. We evaluated the plant growth by measuring the leaves and root length, compared with the witness as well as the content of proline and analyze the level of one of the antioxydative enzymes: catalase, after 14 days of treatment. Sulfonylurea is foliar and root weed-killers inhibiting the acetolactate synthase: a vegetable enzyme essential to the development of the plant. This inhibition causes the ruling of the growth then the death. The obtained results show a diminution of the average length of leaves and roots this can be explained by the fact that the ALS inhibitors are more active in the young and increasing regions of the plant, what inhibits the cellular division and talks a limitation of the foliar and root’s growth. We also recorded a highly significant increase in the proline levels and a stimulation of the catalase activity. As a response to increasing the herbicide concentrations a particular increases in antioxidative mechanisms in wheat cultivar Cirta suggest that the high sensitivity of Cirta to this sulfonylurea herbicide is related to the enhanced production and oxidative damage of reactive oxygen species.

Keywords: sulfonylurea, triticum durum, oxydative stress, toxicity

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

Procedia PDF Downloads 134

Authors: Ramatu I. Sha’aba, Mathias A. Chia, Abdullahi B. Alhassan, Yisa A. Gana, Ibrahim M. Gadzama

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Globally, Diclofenac (DLC) and Ibuprofen (IBU) are the most prescribed drugs due to their antipyretic and analgesic properties. They are, however, highly toxic at elevated doses, with the involvement of an already described oxidative stress pathway. As a result, there is rising concern about the ecological fate of analgesics on non-target organisms such as Daphnia magna and Phytoplankton species. Phytoplankton is a crucial component of the aquatic ecosystem that serves as the primary producer at the base of the food chain. However, the increasing presence and levels of micropollutants such as these analgesics can disrupt their community structure, dynamics, and ecosystem functions. This study presents a comprehensive series of the physiology, antioxidant response, immobilization, and risk assessment of Diclofenac and Ibuprofen’s effects on Daphnia magna and the Phytoplankton community using a laboratory approach. The effect of DLC and IBU at 27.16 µg/L and 20.89 µg/L, respectively, for a single exposure and 22.39 µg/L for combined exposure of DLC and IBU for the experimental setup. The antioxidant response increased with increasing levels of stress. The highest stressor to the organism was 1000 µg/L of DLC and 10,000 µg/L of IBU. Peroxidase and glutathione -S-transferase activity was higher for Diclofenac + Ibuprofen. The study showed 60% and 70% immobilization of the organism at 1000 g L-1 of DLC and IBU. The two drugs and their combinations adversely impacted Phytoplankton biomass with increased exposure time. However, combining the drugs resulted in more significant adverse effects on physiological and pigment content parameters. The risk assessment calculation for the risk quotient and toxic unit of the analgesic reveals from this study was RQ Diclofenac = 8.41, TU Diclofenac = 3.68, and RQ Ibuprofen = 718.05 and TU Ibuprofen = 487.70. Hence, these findings demonstrate that the current exposure concentrations of Diclofenac and Ibuprofen can immobilize D. magna. This study shows the dangers of multiple drugs in the aquatic environment because their combinations could have additive effects on the structure and functions of Phytoplankton and are capable of immobilizing D. magna.

Keywords: algae, analgesic drug, daphnia magna, toxicity

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Authors: Boris Bajer, Andrea Havranova, Miroslav Vlcek, Richard Imrich, Adela Penesova

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Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, and also prevent cardiovascular diseases, as it showed many studies (the Finnish Diabetes Prevention Study, Diabetes Prevention Program (DPP), . the China Da Qing Diabetes Prevention Study, etc.) Therefore the aim of our study was to compare the effect of intensified lifestyle intervention on cardiometabolic parameters. Methods: It is an ongoing randomized interventional clinical study (NCT02325804) focused on the reduction of body weight/fat. Intervention: hypocaloric diet (30% restriction of calories) and physical activity 150 minutes/week. Before and after 8 weeks of intervention all patients underwent complete medical examination (measurement of physical fitness, resting metabolic rate (RMR), body composition analysis, oral glucose tolerance test, parameters of lipid metabolism, and other cardiometabolic risk factors. Results: So far 39 patients finished the intervention. The average reduction of body weight was 6,8 + 4,9 kg (0-15 kg; p=0,0006), accompanied with significant reduction of body fat percentage (p ≤ 0,0001), amount of fat mass (p=0,03), waist circumference (p=0.02). Amount of lean mass and RMR remained unchanged. Heart rate (p=0,02), systolic and diastolic blood pressure was reduced (p=0,01 p=0,02 resp.) as well as insulin sensitivity was improved. Lipid parameters also changed - cholesterol, LDL decreased (p=0,05, p=0,04 resp.), while triglycerides showed tendency to decrease (p=0,055). Liver function improved, alanine aminotrasnferase (ALT) were reduced (p=0,01). Physical fitness significantly improved (as measure VO2 max (p=0,02). Conclusion: Results of our study are in line with previous results about the beneficial effect of intensive lifestyle changes on the reduction of cardiometabolic risk factors and improvement of liver function. Supported by grants APVV 15-0228; VEGA 2/0161/16

Keywords: obesity, weight loss, diet lipids, blood pressure, liver enzymes

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Authors: Nagwa E. Abd Elazim, Maha S. El-naggar, Rania H. Mohamed, Sara M. Awad

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Background: Radiodermatitis is a common side effect of radiation therapy for breast cancer. However, there is no current consensus about effective standard therapy for the prevention and management of radiation dermatitis. Topical ectoine has demonstrated efficacy in the treatment of atopic dermatitis owing to its anti-inflammatory activity. Objective: To evaluate the efficacy of topical ectoine in comparison to traditional topical dexpanthenol treatment in the management of acute radiodermatitis in breast cancer patients undergoing adjuvant radiotherapy. Methods: Fifty patients were randomized to use either dexpanthenol 0.5% cream (25 patients), or ectoin 7% cream (25 patients), applied twice daily to the irradiated area during the radiation period and continued for 2 weeks after cessation of radiotherapy. Assessment of radiation skin toxicity using Common Terminology Criteria of Adverse Events (CTCAE) v4.0, radiation-associated symptoms, and adverse events were undertaken weekly during radiotherapy and 2 weeks after the end of radiotherapy. Results: Topical ectoine showed some clinical benefit over dexpanthenol, as shown by delayed time to onset (at week 3 versus week 2, respectively) and larger number of patients who reached grade 0 at the end of treatment (64% vs. 48%, respectively). The clinical symptoms of pain (p = 0.003) and itching (p = 0.001) attributable to radiation were less pronounced with ectoine than with dexpanthenol. Burning and hyperpigmentation were the most common side effects with ectoine. However, no significant difference between dexpanthenol and ectoine treatments was found in any of the side effects (p = 0.1). Conclusion: Ectoin was overall more effective in improving radiation dermatitis than topical dexpanthenol in breast cancer patients. Ectoin could be proposed as a preventive or curative treatment for patients undergoing postoperative irradiation for breast cancer. Further clinical studies with a larger number of patients are recommended for the confirmation of these preliminary results.

Keywords: breast cancer, dexapanthenol, ectoin, radiation dermatitis

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Authors: Kuan Yin Hsiao, Shyh Ming Kuo, Yi Jhen Wu, Chin Wen Chuang, Chuen-Fu Lin, Wei-qing Yang, Han Hsiang Huang

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Anti-tumor effects of natural products, like compounds from marine sponges and soft corals, have been investigated for decades. Polymeric nanoparticles prepared from biodegradable and biocompatible molecules, such as Hyaluronan (HA), Chitosan (CHI) and gelatin have been widely studied. Encapsulation of anti-cancer therapies by the biopolymeric nanoparticles in drug delivery system is potentially capable of improving the therapeutic effects and attenuating their toxicity. In the current study, the anti-bladder cancer effects of heteronemin extracted from the sponge Hippospongia sp. with or without HA and CHI nanoparticle encapsulation were assessed and evaluated in vitro. Results showed that IC50 (half maximal inhibitory concentration) of heteronemin toward T24 human bladder cancer cell viability is approximately 0.18 µg/mL. Both plain and HA nanoparticles-encapsulated heteronemin at 0.2 and 0.4 µg/mL significantly reduced T24 cell viability (P<0.001) while HA nanoparticles-encapsulated heteronemin showed weaker viability-inhibitory effects on L929 fibroblasts compared with plain heteronemin at the identical concentrations. HA and CHI nanoparticles-encapsulated heteronemin exhibited significantly stronger inhibitory effects against migration of T24 human bladder cancer cell than those exerted by plain heteronemin at the same concentrations (P<0.001). The flow cytometric results showed that 0.2 µg/mL HA and CHI nanoparticles-encapsulated heteronemin induced higher early apoptosis rate than that induced by plain heteronemin at the same concentration. These results show that HA and CHI nanoparticle encapsulation is able to elevate anti-migratory and apoptosis-inducing effects exerted by heteronemin against bladder cancer cells in vitro. The in vivo anti-bladder cancer effects of the compound with or without HA/CHI nanoparticle encapsulation will be further investigated and examined using murine tumor models. The data obtained from this study will extensively evaluate of the anti-bladder cancer effects of heteronemin as well as HA/CHI-encapsulated heteronemin and pave a way to develop potential bladder cancer treatment.

Keywords: heteronemin, nanoparticles, hyaluronan, chitosan, bladder cancer

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

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

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

Procedia PDF Downloads 363